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  • 1
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    Springer
    Publication Date: 2018-03-05
    Description: Uncertainty in measurement is very important in the process of conformity assessment. As it is generally declared, based on the measured value of a property of an item, there is always the risk of incorrect decisions, which are of two types: an item accepted as “conforming” may actually be “non-conforming”, and an item rejected as “non-conforming” may actually be “conforming”. In order to reduce the risks associated with decision-making, it is required to reduce the measurement uncertainty to an acceptable level termed as “target uncertainty”. In order to reduce the uncertainty of a particular measurement, it would be necessary to focus on decreasing the uncertainties arising from the relevant components. There are always different solutions to reduce the uncertainties arising from each inclusive component. Each of these solutions imposes a different cost on the measurement system. Therefore, a solution should be selected, among several possible alternatives, to reduce the uncertainties arising from each relevant component and to impose the lowest cost to the measurement system to “target uncertainty”. Accordingly, in this paper through a case study, a model is presented that can reduce uncertainty with the lowest possible cost to the optimally needed level using a mathematical optimization technique. The mathematical model presented in this paper can be used in measurement uncertainty optimization in many laboratories, which require a reduction in uncertainty and the risks associated with decision-making based on measurement results. Furthermore, the use of the proposed model will help to reduce the unnecessary costs of analysis in different laboratory centers.
    Print ISSN: 0949-1775
    Electronic ISSN: 1432-0517
    Topics: Chemistry and Pharmacology
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  • 2
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    Springer
    Publication Date: 2018-03-05
    Description: Unfortunately, Eq. 3 was incorrectly presented in the original publication.
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    Electronic ISSN: 1432-0517
    Topics: Chemistry and Pharmacology
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  • 3
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    Springer
    Publication Date: 2018-03-05
    Print ISSN: 0949-1775
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    Topics: Chemistry and Pharmacology
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  • 4
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    Springer
    Publication Date: 2018-03-05
    Print ISSN: 0949-1775
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    Topics: Chemistry and Pharmacology
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  • 5
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    Springer
    Publication Date: 2018-03-05
    Print ISSN: 0949-1775
    Electronic ISSN: 1432-0517
    Topics: Chemistry and Pharmacology
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  • 6
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    Springer
    Publication Date: 2018-03-05
    Description: The results of trueness verification for blood lead measurement were analyzed in a 2016 nationwide external quality assessment (EQA) survey, in order to evaluate current approaches of blood lead measurement in Chinese Laboratories and their traceability to certified reference materials (CRMs). A panel of 2 frozen whole blood CRMs with values assigned by an absolute quantitative method was provided to 12 laboratories with satisfactory performances from the 2015 blood lead EQA scheme. Participants were required to measure the samples 5 times each day for 3 consecutive days and report all 15 data, which were then calculated for means and standard deviations. Data were statistically analyzed by adopted method groups, before comparing with the assigned values to assess the trueness of blood lead measurement using different approaches. Eleven laboratories reported on schedule, rendering a reporting rate of 91.7 %. The target values for the two batches were (37.6 ± 2.7) μg/L and (124.6 ± 4.5) μg/L, respectively. By the evaluation criterion of target value ± 20 µg/L, the pass rates were 72.7 % for the lower concentration and 54.5 % for the higher concentration, while 5 out of 11 laboratories delivered satisfactory results for both CRMs. The overall performance of the few participating laboratories in this EQA survey was basically acceptable by CLSI standard on the whole, yet barely desirable for the higher concentration. Therefore, trueness verification of blood lead measurement with CRMs is potentially necessary for national EQA schemes, which can be imperative as part of the validation procedures of analytical methods in clinical settings.
    Print ISSN: 0949-1775
    Electronic ISSN: 1432-0517
    Topics: Chemistry and Pharmacology
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  • 7
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    Springer
    Publication Date: 2018-03-05
    Description: Accreditation of calibration laboratories is a means for achieving competence recognition and assuring customers that their calibration services are accurate and reliable. Moreover, it is a powerful tool for a National Metrology Institute (NMI), enabling the formal acceptance of its measurement results. It could be especially useful when calibration activities are performed in well-developed laboratories, which have participated successfully in interlaboratory comparisons but have been awaiting the publication of Calibration and Measurement Capabilities in the BIPM Key comparison database. This paper describes establishment and implementation of a quality management system in the NMI of Montenegro called Bureau of Metrology (MBM) that complies with ISO/IEC 17025. We have presented the results of the first audit evaluation, corrective actions, preparation of quality management documentation, measurement traceability, as well as advantages of being accredited. Our experience of implementing ISO/IEC 17025 for the accreditation of national calibration laboratories established within the MBM shows that strategic planning, establishment of long-term objectives, as well as the commitment to fulfilling standard requirements are the basis for acceptable calibration results. International acceptance of confidence and reliability of calibration services and measurement results provided by the MBM laboratories represents a useful marketing tool for promoting the image of the institution.
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    Electronic ISSN: 1432-0517
    Topics: Chemistry and Pharmacology
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  • 8
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    Springer
    Publication Date: 2018-03-05
    Description: This article discusses the accuracy of the gravimetric measurement method of total particulate matter concentration in waste gases where the basic assumption is that sample collection of dust-laden gas is done in a grid with a finite number of points in the conduit’s measurement plane. In this standard approach, the sample is assumed to be representative for dust-laden gas in the conduit, and consequently, the total particulate matter concentration measured for the sample is considered the mean concentration in the conduit. The article investigates this assumption against the standard-imposed number of sampling points and in view of spatial distributions of particulate matter concentration in industrial plants which—being continuous—are not identified in measuring practice. Possible distributions were simulated both for particulate matter concentration and for gas velocity in rectangular conduits, and the following were calculated: (a) an accurate mean particulate matter concentration in the measurement plane, based on its definition employing continuous distributions of particulate matter concentration and gas velocity and (b) the concentration in a sample, i.e. measured concentration. Measurement deviation between those concentrations was determined, which is specific for cumulative gas sampling. Using the obtained set of possible deviations, an estimation method was suggested for the relevant uncertainty component of the gravimetric method, which so far has not been taken into account in the industrial measurement accuracy analyses. It turns out that the level of this uncertainty component for measuring the mean particulate matter concentration in the conduit (resulting from “measurement discretization”) is not to be ignored.
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    Topics: Chemistry and Pharmacology
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  • 9
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    Springer
    Publication Date: 2018-03-05
    Electronic ISSN: 1432-0509
    Topics: Medicine
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  • 10
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    Springer
    Publication Date: 2018-03-05
    Electronic ISSN: 1432-0509
    Topics: Medicine
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  • 11
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    Springer
    Publication Date: 2018-03-05
    Description: The International Organization for Standardization (ISO) has published ISO 17034:2016 on the general requirements for the competence of reference material producers (RMPs). Previously, these requirements were addressed in ISO Guide 34:2009, originally developed by the ISO Committee on Reference Materials (ISO/REMCO). The need for an International Standard was triggered as several accreditation bodies could not accredit to a guide, at all, while in other countries ISO Guide 34 could only serve as accreditation standard in combination with ISO/IEC 17025. For the transformation into a conformity assessment standard of the ISO/IEC 17000 series, the ISO Committee on Conformity assessment (ISO/CASCO) and ISO/REMCO joined forces. A Joint Working Group, formed by experts and stakeholders from both committees, finalised the transformation within 2 years. During the transformation, the structure of ISO 17034 has been aligned with other ISO/IEC 17000 series standards and the content of ISO 17034 has been harmonised with the recent editions of other relevant ISO Guides. Requirements for the production of reference materials (RMs) were elaborated on more clearly in the new standard, specifying the requirements for (non-certified) reference materials and the additional requirements for certified reference materials. The new International Standard ISO 17034:2016 supersedes ISO Guide 34:2009.
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    Electronic ISSN: 1432-0517
    Topics: Chemistry and Pharmacology
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  • 12
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    Springer
    Publication Date: 2018-03-05
    Description: Sum parameters (otherwise known as composite parameters) describe similar chemical, physicochemical or biological characteristics of different substances, substance groups or mixtures of substances. These might contain the same chemical element. Such parameters are total organic carbon or total bound nitrogen. Chemical oxygen demand is a shared chemical characteristic—the oxidizability of constituents by dichromate. The focus of the paper is on the uncertainty estimation of the determination of chemical sum parameters in water samples from method validation derived data—total organic carbon, chemical oxygen demand, biochemical oxygen demand, total bound nitrogen and total suspended solids. The results for the measurement uncertainty estimations according to ISO 21748 and ISO 11352, as only applicable to the field of water analysis, are presented and compared. Based on the results obtained and the experimental design, the use of ISO 11352 for the measurement uncertainty estimation is recommended. This international standard employs fewer determinations (a minimum number of eight measurements are required, compared to fifteen), fewer working days (one compared to five) and easier measurement uncertainty components’ calculations and even gives opportunity for routine laboratories to use standard solutions over the more expensive certified reference materials for the measurement uncertainty estimation during the method validation in water analysis.
    Print ISSN: 0949-1775
    Electronic ISSN: 1432-0517
    Topics: Chemistry and Pharmacology
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  • 13
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    Springer
    Publication Date: 2018-03-05
    Description: There are several drug products that bind phosphate or bile acid in the gastrointestinal (GI) tract to exert their therapeutic efficacy. In vitro binding studies are used to assess bioequivalence (BE) of these products. The objective of this study is to identify the common deficiencies in Abbreviated New Drug Applications (ANDAs) for these products. Deficiencies were compiled from ANDAs containing in vitro binding BE studies. The deficiencies were classified into eight categories: Pre-Study Method Validation, During-Study Sample Analysis, Study Design, Study Procedure, Dissolution/Disintegration, Analytical Site Inspection, Data Submission, and Formulations. Within each category, additional subcategories were defined to characterize the deficiencies. A total of 712 deficiencies from 95 ANDAs for 11 drug products were identified and included in the analysis. The four categories with the most deficiencies were During-Study Sample Analysis (27.8%), Pre-Study Method Validation (17.3%), Data Submission (16.7%), and Study Design (15.7%). For the During-Study Sample Analysis category, failure to submit complete raw data or analytical runs ranked as the top deficiency (32.8%). For the Study Design category, using an unacceptable alternate study design (26.8%) was the most common deficiency. Within this category, other commonly occurring deficiencies included incorrect/insufficient number of absorbent concentrations, failure to pre-treat drug product with acid, insufficient number of replicates in study, incorrect calculation of k1 and k2 values, incorrect dosage form or pooled samples used in the study, and incorrect pH of study medium. The review and approval of these products may be accelerated if these common deficiencies are addressed in the original ANDA submissions.
    Electronic ISSN: 1550-7416
    Topics: Chemistry and Pharmacology
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  • 14
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    Springer
    Publication Date: 2018-03-05
    Description: Intranasal administration could be an attractive alternative route of administration for the delivery of drugs to the central nervous system (CNS). However, there are always doubts about the direct transport of therapeutics from nasal cavity to the CNS since there are only limited studies on the understanding of direct nose-to-brain transport. Therefore, this study aimed to (1) investigate the existence of nose-to-brain transport of intranasally administered HIV-1 replication inhibitor DB213 and (2) assess the direct nose-to-brain transport of unbound HIV-1 replication inhibitor DB213 quantitatively by a pharmacokinetic approach. Plasma samples were collected up to 6 h post-dosing after administration via intranasal or intravenous route at three bolus doses. In the brain-uptake study, the plasma, whole brain, and cerebrospinal fluid (CSF) were sampled between 15 min and 8 h post-dosing. All samples were analyzed with LC/MS/MS. Plasma, CSF, and brain concentration versus  time profiles were analyzed with nonlinear mixed-effect modeling. Structural model building was performed by NONMEM (version VII, level 2.0). Intranasal administration showed better potential to deliver HIV-1 replication inhibitor DB213 to the brain with 290-fold higher brain to plasma ratio compared with intravenous administration. Based on that, a model with two absorption compartments (nose-to-systemic circulation and nose-to-brain) was developed and demonstrated 72.4% of total absorbed unbound HIV-1 replication inhibitor DB213 after intranasal administration was transported directly into the brain through nose-to-brain pathway.
    Electronic ISSN: 1550-7416
    Topics: Chemistry and Pharmacology
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  • 15
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    Springer
    Publication Date: 2018-03-05
    Description: ABSTRACT The drug of abuse γ-hydroxybutyric acid (GHB) demonstrates complex toxicokinetics with dose-dependent metabolic and renal clearance. GHB is a substrate of monocarboxylate transporters (MCTs) which are responsible for the saturable renal reabsorption of GHB. MCT expression is observed in many tissues and therefore may impact the tissue distribution of GHB. The objective of the present study was to evaluate the tissue distribution kinetics of GHB at supratherapeutic doses. GHB (400, 600, and 800 mg/kg iv) or GHB 600 mg/kg plus l -lactate (330 mg/kg iv bolus followed by 121 mg/kg/h infusion) was administered to rats and blood and tissues were collected for up to 330 min post-dose. K p values for GHB varied in both a tissue- and dose-dependent manner and were less than 0.5 (except in the kidney). Nonlinear partitioning was observed in the liver (0.06 at 400 mg/kg to 0.30 at 800 mg/kg), kidney (0.62 at 400 mg/kg to 0.98 at 800 mg/kg), and heart (0.15 at 400 mg/kg to 0.29 at 800 mg/kg), with K p values increasing with dose consistent with saturation of transporter-mediated efflux. In contrast, lung partitioning decreased in a dose-dependent manner (0.43 at 400 mg/kg to 0.25 at 800 mg/kg) suggesting saturation of active uptake. l -lactate administration decreased K p values in liver, striatum, and hippocampus and increased K p values in lung and spleen. GHB demonstrates tissue-specific nonlinear distribution consistent with the involvement of monocarboxylate transporters. These observed complexities are likely due to the involvement of MCT1 and 4 with different affinities and directionality for GHB transport.
    Electronic ISSN: 1550-7416
    Topics: Chemistry and Pharmacology
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  • 16
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    Springer
    Publication Date: 2018-03-05
    Description: Despite the improvements in drug screening, high levels of drug attrition persist. Although high-throughput screening platforms permit the testing of compound libraries, poor compound efficacy or unexpected organ toxicity are major causes of attrition. Part of the reason for drug failure resides in the models employed, most of which are not representative of normal organ biology. This same problem affects all the major organs during drug development. Hepatotoxicity and cardiotoxicity are two interesting examples of organ disease and can present in the late stages of drug development, resulting in major cost and increased risk to the patient. Currently, cell-based systems used within industry rely on immortalized or primary cell lines from donated tissue. These models possess significant advantages and disadvantages, but in general display limited relevance to the organ of interest. Recently, stem cell technology has shown promise in drug development and has been proposed as an alternative to current industrial systems. These offerings will provide the field with exciting new models to study human organ biology at scale and in detail. We believe that the recent advances in production of stem cell-derived hepatocytes and cardiomyocytes combined with cutting-edge engineering technologies make them an attractive alternative to current screening models for drug discovery. This will lead to fast failing of poor drugs earlier in the process, delivering safer and more efficacious medicines for the patient.
    Electronic ISSN: 1550-7416
    Topics: Chemistry and Pharmacology
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  • 17
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    Springer
    Publication Date: 2018-03-05
    Description: According to the National Center of Health Statistics, cancer was the culprit of nearly 600,000 deaths in 2016 in the USA. It is by far one of the most heterogeneous diseases to treat. Treatment for metastasized cancers remains a challenge despite modern diagnostics and treatment regimens. For this reason, alternative approaches are needed. Chemoprevention using dietary phytochemicals such as triterpenoids, isothiocyanates, and curcumin in the prevention of initiation and/or progression of cancer poses a promising alternative strategy. However, significant challenges exist in the extrapolation of in vitro cell culture data to in vivo efficacy in animal models and to humans. In this review, the dose at which these phytochemicals elicit a response in vitro and in vivo of a multitude of cellular signaling pathways will be reviewed highlighting Nrf2-mediated antioxidative stress, anti-inflammation, epigenetics, cytoprotection, differentiation, and growth inhibition. The in vitro - in vivo dose response of phytochemicals can vary due, in part, to the cell line/animal model used, the assay system of the biomarker used for the readout, chemical structure of the functional analog of the phytochemical, and the source of compounds used for the treatment study. While the dose response varies across different experimental designs, the chemopreventive efficacy appears to remain and demonstrate the therapeutic potential of triterpenoids, isothiocyanates, and curcumin in cancer prevention and in health in general.
    Electronic ISSN: 1550-7416
    Topics: Chemistry and Pharmacology
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  • 18
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    Springer
    Publication Date: 2018-03-05
    Description: Simvastatin (Sim), a lipid-lowering drug has been studied in chronic neuroinflammation associated with degenerative brain disorders due to its potential protective properties against inflammatory reaction, oxidative damage, neuronal dysfunction, and death. Meanwhile, potential application of Sim in neuroinflammation will require a suitable delivery system that can overcome notable challenges pertaining to poor blood–brain barrier (BBB) permeability and side/off-target effects. Herein, we engineered and characterized nano-sized polymersomes loaded with Sim (Sim-Ps) using PEG-PdLLA (methoxy polyethylene glycol-poly( d , l ) lactic acid) diblock co-polymers. Studies in BV2 microglia indicated that Sim-Ps was superior to Sim alone in suppressing nitric oxide (NO) and proinflammatory cytokines (interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) secretion against LPS activation. The effectiveness of Sim-Ps as compared with Sim alone, in attenuating NO and cytokine production by activated BV2 cells can be attributed to (a) colloidal stability of the delivery platform, (b) protracted release of biologically active Sim, and (c) particulate internalization coupled with enhanced Sim exposure to BV2 cells. Intranasal delivery in BALB/c mice demonstrated enhanced brain distribution with increasing time after administration. Overall data demonstrated suitability of PEG-PdLLA polymersomes in Sim delivery for potential application in treating neuroinflammation.
    Electronic ISSN: 1550-7416
    Topics: Chemistry and Pharmacology
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  • 19
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    Springer
    Publication Date: 2018-03-05
    Description: For accurately measuring the volume change of a soil specimen under monotonic and cyclic loading, a new double-cell system is described in this paper. This newly designed double-cell system is equipped with local linear variable differential transformers (LVDTs) and can also accommodate large specimens. Careful calibrations, including the effect of cell pressure change, “creep” of inner cell volume, the effect of temperature fluctuation, and loading ram movement, are presented and discussed by comparing the possible errors with those of other existing apparatuses. This system exhibits superior performances in volume change due to cell pressure, temperature sensitivity, and accuracy of loading ram movement. Three monotonic compression tests under saturated and unsaturated conditions were conducted to evaluate the performance of volume change measurement and local LVDTs. Moreover, six different frequencies were used to verify the workability and accuracy of this system in conducting cyclic testing. The results indicate that the maximum frequency this system can achieve, with a satisfactory precision, is 0.2 Hz, which is four times higher than what the previous systems could achieve. Finally, several suggestions are made on how to improve the system’s performance even better.
    Print ISSN: 1861-1125
    Electronic ISSN: 1861-1133
    Topics: Geosciences
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  • 20
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    Springer
    Publication Date: 2018-03-05
    Description: The increasing importance of performance-based earthquake engineering analysis points out the necessity to assess quantitatively the risk of liquefaction of embankment-type structures. In this extreme scenario of soil liquefaction, devastating consequences are observed, e.g., excessive settlements, lateral spreading and slope instability. The present work discusses the global dynamic response and interaction of an earth structure-foundation system, so as to determine quantitatively the collapse mechanism due to foundation’s soil liquefaction. A levee-foundation system is simulated, and the influence of characteristics of input ground motion, as well as of the position of liquefied layer on the liquefaction-induced failure, is evaluated. For the current levee model, its induced damage level (i.e., induced crest settlements) is strongly related to both liquefaction apparition and dissipation of excess pore water pressure on the foundation. The respective role of input ground motion characteristics is a key component for soil liquefaction apparition, as long duration of mainshock can lead to important nonlinearity and extended soil liquefaction. A circular collapse surface is generated inside the liquefied region and extends toward the crest in both sides of the levee. Even so, when the liquefied layer is situated in depth, no significant effect on the levee response is found. This research work provides a reference case study for seismic assessment of embankment-type structures subjected to earthquake and proposes a high-performance computational framework accessible to engineers.
    Print ISSN: 1861-1125
    Electronic ISSN: 1861-1133
    Topics: Geosciences
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  • 21
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    Springer
    Publication Date: 2018-03-05
    Description: Purpose The purpose of the study was to provide a systematic evaluation of the computed tomography(CT) findings after radiofrequency ablation (RFA) in locally advanced pancreatic cancer(LAPC). Methods Eighteen patients with intra-operative RFA-treated LAPC were included in a prospective case series. All CT-scans performed prior to RFA and 1 week and 3 months of post-RFA, according to standard regimen, were assessed by two radiologists in consensus, using standardized radiological scoring lists. Results 51 CT-scans were assessed. One week after RFA, the ablation zone was visible in all patients as a (partially) sharply defined (83%), heterogeneous area (94%). At 3 months of follow-up, the ablation zone was completely invaded by tumor in 67% of patients and still present, but decreased in 33%. In two patients (11%), local thrombosis and/or occlusion of the superior mesenteric vein occurred. The occlusions persisted without clinical consequences and the thrombosis disappeared. A peripancreatic fluid collection was visible 1 week after RFA in 3 patients, wherein the ablation zone extended ventrally outside of the pancreas. Conclusions Directly after RFA for LAPC, a well-defined ablation zone is visible on CT-imaging. This ablation zone is usually replaced by tumor ingrowth after 3 months. Moreover, the ablation zone regularly included vascular structures, with rare asymptomatic venous occlusion or thrombosis and without adverse effects on arteries.
    Electronic ISSN: 1432-0509
    Topics: Medicine
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  • 22
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    Springer
    Publication Date: 2018-03-05
    Description: Extracellular vesicles (EVs) are cell membrane-derived compartments that regulate physiology and pathology in the body. Naturally secreted EVs have been well studied in their biogenesis and have been exploited in targeted drug delivery. Due to the limitations on production of EVs, nitrogen cavitation has been utilized to efficiently generate EV-like drug delivery systems used in treating inflammatory disorders. In this short review, we will discuss the production and purification of EVs, and we will summarize what technologies are needed to improve their production for translation. We describe the drug-loading processes in EVs and their applications as drug delivery systems for inflammatory therapies, focusing on a new type of EVs made from neutrophil membrane using nitrogen cavitation.
    Electronic ISSN: 1550-7416
    Topics: Chemistry and Pharmacology
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  • 23
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    Springer
    Publication Date: 2018-03-05
    Description: Purpose On computed tomography (CT), intrahepatic cholangiocarcinomas (ICC) are a visibly heterogeneous group of tumors. The purpose of this study was to investigate the associations between CT imaging phenotypes, patient survival, and known genetic markers. Methods A retrospective study was performed with 66 patients with surgically resected ICC. Pre-surgical CT images of ICC were assessed by radiologists blinded to tumor genetics and patient clinical data. Associations between qualitative imaging features and overall survival (OS) and disease-free survival (DFS) were performed with Cox proportional hazards regression and visualized with Kaplan–Meier plots. Associations between radiographic features and genetic pathways (IDH1, Chromatin and RAS-MAPK) were assessed with Fisher’s Exact test and the Wilcoxon Rank sum test where appropriate and corrected for multiple comparisons within each pathway using the False Discovery Rate correction. Results Three imaging features were significantly associated with a higher risk of death: necrosis (hazard ratio (HR) 2.95 95% CI 1.44–6.04, p  = 0.029), satellite nodules (HR 3.29, 95% CI:1.35–8.02, p  = 0.029), and vascular encasement (HR 2.63, 95% CI 1.28–5.41, p  = 0.029). Additionally, with each increase in axial size, the risk of death increased (HR 1.14, 95% CI 1.03–1.26, p  = 0.029). Similar to findings for OS, satellite nodules (HR 3.81, 95% CI 1.88–7.71, p  = 0.002) and vascular encasement (HR 2.25, 95% CI 1.24–4.06, p  = 0.019) were associated with increased risk of recurrence/death. No significant associations were found between radiographic features and genes in the IDH1, Chromatin or RAS-MAPK pathways ( p  = 0.63–84). Conclusion This preliminary analysis of resected ICC suggests associations between CT imaging features and OS and DFS. No association was identified between imaging features and currently known genetic pathways.
    Electronic ISSN: 1432-0509
    Topics: Medicine
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  • 24
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    Springer
    Publication Date: 2018-03-05
    Description: The healing professions have only about four main therapeutic tools at their disposal—surgery, drugs, physical therapy, and psychotherapy. For the general profession of internal medicine, drug therapy is its primary tool. Providing an understanding of the state-of-the-art in therapeutic methods, grounded in solid scientific and mathematical rigor, is therefore of the utmost clinical importance for both physicians and clinical pharmacists. This is particularly true where rapidly evolving scientific changes require an up-to-date education upon which students can rely. Unfortunately, relatively little attention has been paid to training clinical pharmacokineticists and physicians to manage drug therapy optimally for patients under their care in their everyday practice. In this paper, we discuss one of these basic deficiencies from the perspective of the longstanding controversy in pharmacokinetic modeling: whether the volume and clearance approach or the volume and rate constant approach is somehow “better”. We examine this controversy using the mathematical principle of invariance, which to our knowledge has not been done before. The conclusion of this analysis is that both approaches are rigorously proven mathematically to be equally valid. We also discuss some implications of these equally valid approaches from the framework of mechanistic and non-compartmental models. Ultimately, the conclusion is that the choice of one parameterization over the other is based on preference or usefulness for research or clinical practice, but no longer, because of this analysis, on science.
    Electronic ISSN: 1550-7416
    Topics: Chemistry and Pharmacology
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  • 25
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    Springer
    Publication Date: 2018-03-05
    Description: The rapidly increasing number of therapeutic biologics in development has led to a growing recognition of the need for improvements in immunogenicity assessment. Published data are often inadequate to assess the impact of an antidrug antibody (ADA) on pharmacokinetics, safety, and efficacy, and enable a fully informed decision about patient management in the event of ADA development. The recent introduction of detailed regulatory guidance for industry should help address many past inadequacies in immunogenicity assessment. Nonetheless, careful analysis of gathered data and clear reporting of results are critical to a full understanding of the clinical relevance of ADAs, but have not been widely considered in published literature to date. Here, we review visualization and modeling of immunogenicity data. We present several relatively simple visualization techniques that can provide preliminary information about the kinetics and magnitude of ADA responses, and their impact on pharmacokinetics and clinical endpoints for a given therapeutic protein. We focus on individual sample- and patient-level data, which can be used to build a picture of any trends, thereby guiding analysis of the overall study population. We also discuss methods for modeling ADA data to investigate the impact of immunogenicity on pharmacokinetics, efficacy, and safety.
    Electronic ISSN: 1550-7416
    Topics: Chemistry and Pharmacology
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  • 26
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    Springer
    In: 4OR
    Publication Date: 2018-03-05
    Description: In this study, we deal with the problem of short-term transportation outsourcing for transshipment centers. The carrier needs to determine the numbers of outsourced and self-run trips for the different types of transportation tasks. Stochastic demands which are likely to occur in actual operation are considered. Different trip numbers need to be determined in sequence, so a two-stage stochastic programming technique is applied to formulate the problem. Two models are developed based upon practical considerations to help determine the optimal transportation outsourcing plan. A case study regarding the operations of a logistics carrier in Taiwan is performed. Several tests are also performed considering the number of demand scenarios, optimality gaps, variations in demands, outsourcing cost variations, and problem dimensions in order to better understand the performance of the two models.
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  • 27
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    In: 4OR
    Publication Date: 2018-03-05
    Description: Fritz John and Karush–Kuhn–Tucker necessary conditions for local LU-optimal solutions of the constrained interval-valued optimization problems involving inequality, equality and set constraints in Banach spaces in terms of convexificators are established. Under suitable assumptions on the generalized convexity of objective and constraint functions, sufficient conditions for LU-optimal solutions are given. The dual problems of Mond–Weir and Wolfe types are studied together with weak and strong duality theorems for them.
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  • 28
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    Springer
    In: 4OR
    Publication Date: 2018-03-05
    Description: In the context of recreational routing, the problem of finding a route which starts and ends in the same location (while achieving a length between specified upper and lower boundaries) is a common task, especially for tourists or cyclists who want to exercise. The topic of finding a tour between a specified starting and ending location while minimizing one or multiple criteria is well covered in literature. In contrast to this, the route planning task in which a pleasant tour with length between a maximum and a minimum boundary needs to be found is relatively underexplored. In this paper, we provide a formal definition of this problem, taking into account the existing literature on which route attributes influence cyclists in their route choice. We show that the resulting problem is NP-hard and devise a branch-and-bound algorithm that is able to provide a bound on the quality of the best solution in pseudo-polynomial time. Furthermore, we also create an efficient heuristic to tackle the problem and we compare the quality of the solutions that are generated by the heuristic with the bounds provided by the branch-and-bound algorithm. Also, we thoroughly discuss the complexity and running time of the heuristic.
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  • 29
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    Springer
    In: 4OR
    Publication Date: 2018-03-05
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  • 30
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    In: 4OR
    Publication Date: 2018-03-05
    Description: Interior point methods usually rely on iterative methods to solve the linear systems of large scale problems. The paper proposes a hybrid strategy using groups for the preconditioning of these iterative methods. The objective is to solve large scale linear programming problems more efficiently by a faster and robust computation of the preconditioner. In these problems, the coefficient matrix of the linear system becomes ill conditioned during the interior point iterations, causing numerical difficulties to find a solution, mainly with iterative methods. Therefore, the use of preconditioners is a mandatory requirement to achieve successful results. The paper proposes the use of a new columns ordering for the splitting preconditioner computation, exploring the sparsity of the original matrix and the concepts of groups. This new preconditioner is designed specially for the final interior point iterations; a hybrid approach with the controlled Cholesky factorization preconditioner is adopted. Case studies show that the proposed methodology reduces the computational times with the same quality of solutions when compared to previous reference approaches. Furthermore, the benefits are obtained while preserving the sparse structure of the systems. These results highlight the suitability of the proposed approach for large scale problems.
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  • 31
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    In: 4OR
    Publication Date: 2018-03-05
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  • 32
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    Springer
    In: 4OR
    Publication Date: 2018-03-05
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  • 33
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    In: 4OR
    Publication Date: 2018-03-05
    Description: This paper investigates the coordination problem of a supply chain (SC) composed of a manufacturer exhibiting corporate social responsibility (CSR) and a retailer faced with random demand. The random demand is made up of the multiplication of price-dependent demand and random demand factor (RDF), plus the CSR-dependent demand. The centralized decision problem of the SC is an extension of the existing price setting newsvendor problem (PSNP). It is found that the sufficient condition for the quasi-concavity of expected profit (EP) on PSNP can not ensure the quasi-concavity of EP of the SC. Then, the concavity condition of EP related to the CSR effect factor is presented in the case of uniformly distributed RDF and linear demand in price, and the concavity of EP is proven under centralized decision. For decentralized decision under manufacturer’s Stackelberg game, the manufacturer determines wholesale price and its CSR investment, and then the retailer decides the order quantity and the retail price. The standard revenue-sharing (RS) contract is found not able to coordinate the SC, so a modified RS (MRS) contract is proposed to coordinate the SC. Finally, numerical examples illustrate the validity of the theoretical analysis and the coordination effectiveness of the MRS contract via Matlab.
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  • 34
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    In: 4OR
    Publication Date: 2018-03-05
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  • 35
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    In: 4OR
    Publication Date: 2018-03-05
    Description: We introduce and prove new necessary and sufficient conditions to carry out a compact linearization approach for a general class of binary quadratic problems subject to assignment constraints that has been proposed by Liberti (4OR 5(3):231–245, 2007 , https://doi.org/10.1007/s10288-006-0015-3 ). The new conditions resolve inconsistencies that can occur when the original method is used. We also present a mixed-integer linear program to compute a minimally sized linearization. When all the assignment constraints have non-overlapping variable support, this program is shown to have a totally unimodular constraint matrix. Finally, we give a polynomial-time combinatorial algorithm that is exact in this case and can be used as a heuristic otherwise.
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  • 36
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    Publication Date: 2018-03-05
    Description: Advances in multi-material 3D printing technologies have opened a new horizon for design and fabrication of architected multi-materials in multiple length scales from nano-/microscale to meso-/macroscales. In this study, we apply modified couple stress and first-order shear deformation theories for a size-dependent structural analysis of 3D printable functionally graded (FG) doubly-curved panels where their microarchitecture can be engineered to improve their structural performance. This non-classical model incorporates the microstructure-dependent size effects for the structural performance through the introduction of a length scale in the kinematics of deformation. The volume fraction of matrix in the dual-phase (inclusion and matrix) FG size-dependent panels varies continuously through the thickness. The microarchitecture of inclusion and matrix in FG panels is engineered to show its effect on the structural responses. We implement the standard mechanics homogenization technique via finite element simulation to accurately predict the effective mechanical properties of FG materials for different topologies of engineered microarchitecture to show the significance of selecting appropriate micromechanical modeling for analyzing FG structures. Governing equations derived by variational Hamilton’s principle are solved by applying the Galerkin method for different sets of boundary conditions. We investigate the effects of material length scale, material composition, heterogeneous material distribution, particulate topology, length-to-thickness ratio, and panel curvature on the structural performance. It is found that the fundamental frequencies of size-dependent two-phase FG doubly-curved panels with square-shape inclusions are higher than for those with other topologies, which sheds lights on the engineering of the inclusion shape in advanced architected materials to optimize their structural performance.
    Print ISSN: 0001-5970
    Electronic ISSN: 1619-6937
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
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  • 37
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    Publication Date: 2018-03-05
    Description: This paper presents a smoothed FE-Meshfree (SFE-Meshfree) method for solving solid mechanics problems. The system stiffness matrix is calculated via a strain-smoothing technique with the composite shape function, which is based on the partition of unity-based method, combing the classical isoparametric quadrilateral function and radial-polynomial basis function. The corresponding Gauss integration in the element is replaced by line integration along the edges of the smoothing cells, so no derivatives of the composite shape functions are needed during the field gradient estimation process. Several numerical examples including an automobile mechanical component are employed to examine the presented method. Calculation results indicate that SFE-Meshfree can obtain a high convergence rate and accuracy without introducing additional degrees of freedom to the system. In addition, it is also more tolerant with respect to mesh distortion. The volumetric locking problem is also explored in this paper under a selective smoothing integration scheme.
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    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
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  • 38
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    Publication Date: 2018-03-05
    Description: This paper deals with the coupled bending–torsional vibrations of beams carrying an arbitrary number of viscoelastic dampers and attached masses. Exact closed analytical expressions are derived for the frequency response under harmonically varying, arbitrarily placed polynomial loads, making use of coupled bending–torsion theory including warping effects and taking advantage of generalized functions to model response discontinuities at the application points of dampers/masses. In this context, the exact dynamic Green’s functions of the beam are also obtained. The frequency response solutions are the basis to derive the exact dynamic stiffness matrix and load vector of a two-node coupled bending–torsional beam finite element with warping effects, which may include any number of dampers/masses. Remarkably, the size of the dynamic stiffness matrix and load vector is \(8\times 8\) and \(8\times 1\) , respectively, regardless of the number of dampers/masses and loads along the beam finite element.
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    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
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  • 39
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    Publication Date: 2018-03-05
    Description: In this paper, we study buckling of radially FGM circular plates. In a previous study, a fourth-order polynomial expressing the exact solution of a linear elastic problem was used as buckling mode shape. To generalise such investigation, in this contribution the buckling mode is postulated to take the shape of a fifth-order polynomial function of the radial coordinate. The flexural rigidity is consequently sought as a polynomial of suitable order, expressing the functional grading. New solutions in closed form are then obtained by a semi-inverse method. It is found that suitable choices of functional grading may increase the buckling load up to 246% with respect to the homogeneous and uniform cases.
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  • 40
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    Publication Date: 2018-03-05
    Description: The steady-state diagnostic and prognostic simulation for the Xiao Dongkemadi glacier (XD) of the Tibetan Plateau was performed with the thermo-mechanically-coupled-with-Full-Stokes code Elmer ( http://www.csc.fi/elmer/ ). In this paper, some changes of glacial thermodynamic parameters caused by ice thickness and atmospheric temperature variation were simulated in view of different thickness. The purpose of this study was to fill the gap in analyzing the ice dynamic characteristic of a polar continental glacier. The diagnostic simulation revealed the following conclusions: (1) when the thickness change was small, surface velocity, ice temperature, and deviation stress variation in the bedrock showed a tendency to change with thickness, and when the terrain was gentle, the thickness variation dominated the ice velocity. (2) The ice temperature of the bedrock was high in the whole profile and reached the pressure melting point in the terminus, and it was easy to slide at the bottom, which was consistent with the measured ground penetrating radar data near the terminus. (3) The static friction forces decrease with thickness, and they showed a complex nonlinear relationship, which revealed that the deviation stress in the bottom was influenced by thickness and ice temperature at the bedrock. The prognostic simulating from 2007 to 2047 presented: (1) The simulation forecasted a shrinkage of nearly 600 m in the terminus and the longitudinal section, and wound up diminished by nearly 25% by the end of 2047; (2) the change of thickness was small at the region between 5650 and 5700 m.a.s.l, which might be related to lower atmospheric temperature; (3) thickness dominated the deviation stress ( \(\sigma _{xx}\) and \(\sigma _{xz}\) ) in the bottom, and the impact of the terrain was little higher compared to deviation stress ( \(\sigma _{xx}\) ). In other words, the glacial thickness dominated the glacial force and movement to a great extent and the low temperature at high altitude reduced the XD’s sensitivity facing future climate warming.
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    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
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  • 41
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    Publication Date: 2018-03-05
    Description: The sensitivity of tropical cyclone (TC) intensification to the ambient rotation effect under vertical shear is investigated. The results show that the vortices develop more rapidly with intermediate planetary vorticity, which suggests an optimal latitude for the TC development in the presence of vertical shear. This is different from the previous studies in which no mean flow is considered. It is found that the ambient rotation has two main effects. On the one hand, the boundary layer imbalance is largely controlled by the Coriolis parameter. For TCs at lower latitudes, due to the weaker inertial instability, the boundary inflow is promptly established, which results in a stronger moisture convergence and thus greater diabatic heating in the inner core region. On the other hand, the Coriolis parameter modulates the vertical realignment of the vortex with a higher Coriolis parameter, favoring a quicker vertical realignment and thus a greater potential for TC development. The combination of these two effects results in an optimal latitude for TC intensification in the presence of a vertical shear investigated.
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  • 42
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    Publication Date: 2018-03-05
    Description: We used daily maximum temperature data (1986–2100) from the COSMO-CLM (COnsortium for Small-scale MOdeling in CLimate Mode) regional climate model and the population statistics for China in 2010 to determine the frequency, intensity, coverage, and population exposure of extreme maximum temperature events (EMTEs) with the intensity–area–duration method. Between 1986 and 2005 (reference period), the frequency, intensity, and coverage of EMTEs are 1330–1680 times yr –1 , 31.4–33.3°C, and 1.76–3.88 million km 2 , respectively. The center of the most severe EMTEs is located in central China and 179.5–392.8 million people are exposed to EMTEs annually. Relative to 1986–2005, the frequency, intensity, and coverage of EMTEs increase by 1.13–6.84, 0.32–1.50, and 15.98%–30.68%, respectively, under 1.5°C warming; under 2.0°C warming, the increases are 1.73–12.48, 0.64–2.76, and 31.96%–50.00%, respectively. It is possible that both the intensity and coverage of future EMTEs could exceed the most severe EMTEs currently observed. Two new centers of EMTEs are projected to develop under 1.5°C warming, one in North China and the other in Southwest China. Under 2.0°C warming, a fourth EMTE center is projected to develop in Northwest China. Under 1.5 and 2.0°C warming, population exposure is projected to increase by 23.2%–39.2% and 26.6%–48%, respectively. From a regional perspective, population exposure is expected to increase most rapidly in Southwest China. A greater proportion of the population in North, Northeast, and Northwest China will be exposed to EMTEs under 2.0°C warming. The results show that a warming world will lead to increases in the intensity, frequency, and coverage of EMTEs. Warming of 2.0°C will lead to both more severe EMTEs and the exposure of more people to EMTEs. Given the probability of the increased occurrence of more severe EMTEs than in the past, it is vitally important to China that the global temperature increase is limited within 1.5°C.
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  • 43
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    Publication Date: 2018-03-05
    Description: By using idealized numerical simulations, the impact of tropical cyclone size on secondary eyewall formation (SEF) is examined. Both unbalanced boundary layer and balanced processes are examined to reveal the underlying mechanism. The results show that a tropical cyclone (TC) with a larger initial size favors a quicker SEF and a larger outer eyewall. For a TC with a larger initial size, it will lead to a stronger surface entropy flux, and thus more active outer convection. Meanwhile, a greater inertial stability helps the conversion from diabatic heating to kinetic energy. Furthermore, the progressively broadening of the tangential wind field will induce significant boundary layer imbalances. This unbalanced boundary layer process results in a supergradient wind zone that acts as an important mechanism for triggering and maintaining deep convection. In short, different behaviors of balanced and unbalanced processes associated with the initial wind profile lead to different development rates of the secondary eyewall.
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  • 44
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    Publication Date: 2018-03-05
    Description: The available agro-climate resources that can be absorbed and converted into dry matter could directly affect crop growth and yield under climate change. Knowledge of the average amount and stability of available agro-climate resources for maize in the main cropping regions of China under climate change is essential for farmers and advisors to optimize cropping choices and develop adaptation strategies under limited resources. In this study, the three main maize cropping regions in China—the North China spring maize region (NCS), the Huanghuaihai summer maize region (HS), and the Southwest China mountain maize region (SCM)—were selected as study regions. Based on observed solar radiation, temperature, and precipitation data, we analyzed the spatial distributions and temporal trends in the available agro-climate resources for maize during 1981–2010. During this period, significantly prolonged climatological growing seasons for maize [3.3, 2.0, and 4.7 day (10 yr) –1 in NCS, HS, and SCM] were found in all three regions. However, the spatiotemporal patterns of the available agro-climate resources differed among the three regions. The available heating resources for maize increased significantly in the three regions, and the rates of increase were higher in NCS [95.5°C day (10 yr)–1] and SCM [93.5°C day (10 yr) –1 ] than that in HS [57.7°C day (10 yr) –1 ]. Meanwhile, decreasing trends in the available water resources were found in NCS [–5.3 mm (10 yr) –1 ] and SCM [–5.8 mm (10 yr) –1 ], whereas an increasing trend was observed in HS [3.0 mm (10 yr) –1 ]. Increasing trends in the available radiation resources were found in NCS [20.9 MJ m –2 (10 yr) –1 ] and SCM [25.2 MJ m –2 (10 yr) –1 ], whereas a decreasing trend was found in HS [11.6 MJ m –2 (10 yr) –1 ]. Compared with 1981–90, the stability of all three resource types decreased during 1991–2000 and 2001–10 in the three regions. More consideration should be placed on the extreme events caused by more intense climate fluctuations. The results can provide guidance in the development of suitable adaptations to climate change in the main maize cropping regions in China.
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  • 45
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    Publication Date: 2018-03-05
    Description: Statistical methods for category (yes/no) forecasts, such as the Threat Score, are typically used in the verification of precipitation forecasts. However, these standard methods are affected by the so-called “double-penalty” problem caused by slight displacements in either space or time with respect to the observations. Spatial techniques have recently been developed to help solve this problem. The fractions skill score (FSS), a neighborhood spatial verification method, directly compares the fractional coverage of events in windows surrounding the observations and forecasts. We applied the FSS to hourly precipitation verification by taking hourly forecast products from the GRAPES (Global/Regional Assimilation Prediction System) regional model and quantitative precipitation estimation products from the National Meteorological Information Center of China during July and August 2016, and investigated the difference between these results and those obtained with the traditional category score. We found that the model spin-up period affected the assessment of stability. Systematic errors had an insignificant role in the fraction Brier score and could be ignored. The dispersion of observations followed a diurnal cycle and the standard deviation of the forecast had a similar pattern to the reference maximum of the fraction Brier score. The coefficient of the forecasts and the observations is similar to the FSS; that is, the FSS may be a useful index that can be used to indicate correlation. Compared with the traditional skill score, the FSS has obvious advantages in distinguishing differences in precipitation time series, especially in the assessment of heavy rainfall.
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  • 46
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    Publication Date: 2018-03-05
    Description: We traced the adjoint sensitivity of a severe pollution event in December 2016 in Beijing using the adjoint model of the GRAPES–CUACE (Global/Regional Assimilation and Prediction System coupled with the China Meteorological Administration Unified Atmospheric Chemistry Environmental Forecasting System). The key emission sources and periods affecting this severe pollution event are analyzed. For comaprison, we define 2000 Beijing Time 3 December 2016 as the objective time when PM 2.5 reached the maximum concentration in Beijing. It is found that the local hourly sensitivity coefficient amounts to a peak of 9.31 μg m –3 just 1 h before the objective time, suggesting that PM 2.5 concentration responds rapidly to local emissions. The accumulated sensitivity coefficient in Beijing is large during the 20-h period prior to the objective time, showing that local emissions are the most important in this period. The accumulated contribution rates of emissions from Beijing, Tianjin, Hebei, and Shanxi are 34.2%, 3.0%, 49.4%, and 13.4%, respectively, in the 72-h period before the objective time. The evolution of hourly sensitivity coefficient shows that the main contribution from the Tianjin source occurs 1–26 h before the objective time and its peak hourly contribution is 0.59 μg m –3 at 4 h before the objective time. The main contributions of the Hebei and Shanxi emission sources occur 1–54 and 14–53 h, respectively, before the objective time and their hourly sensitivity coefficients both show periodic fluctuations. The Hebei source shows three sensitivity coefficient peaks of 3.45, 4.27, and 0.71 μg m –3 at 4, 16, and 38 h before the objective time, respectively. The sensitivity coefficient of the Shanxi source peaks twice, with values of 1.41 and 0.64 μg m –3 at 24 and 45 h before the objective time, respectively. Overall, the adjoint model is effective in tracking the crucial sources and key periods of emissions for the severe pollution event.
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  • 47
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    Publication Date: 2018-03-05
    Description: We compared the regional synoptic patterns and local meteorological conditions during persistent and non-persistent pollution events in Beijing using US NCEP–Department of Energy reanalysis outputs and observations from meteorological stations. The analysis focused on the impacts of high-frequency (period 〈 90 days) variations in meteorological conditions on persistent pollution events (those lasting for at least 3 days). Persistent pollution events tended to occur in association with slow-moving weather systems producing stagnant weather conditions, whereas rapidly moving weather systems caused a dramatic change in the local weather conditions so that the pollution event was short-lived. Although Beijing was under the influence of anomalous southerly winds in all four seasons during pollution events, notable differences were identified in the regional patterns of sea-level pressure and local anomalies in relative humidity among persistent pollution events in different seasons. A region of lower pressure was present to the north of Beijing in spring, fall, and winter, whereas regions of lower and higher pressures were observed northwest and southeast of Beijing, respectively, in summer. The relative humidity near Beijing was higher in fall and winter, but lower in spring and summer. These differences may explain the seasonal dependence of the relationship between air pollution and the local meteorological variables. Our analysis showed that the temperature inversion in the lower troposphere played an important part in the occurrence of air pollution under stagnant weather conditions. Some results from this study are based on a limited number of events and thus require validation using more data.
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  • 48
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    Publication Date: 2018-03-05
    Description: We analyzed the structure and evolution of turbulent transfer and the wind profile in the atmospheric boundary layer in relation to aerosol concentrations during an episode of heavy haze pollution from 6 December 2016 to 9 January 2017. The turbulence data were recorded at Peking University’s atmospheric science and environment observation station. The results showed a negative correlation between the wind speed and the PM 2.5 concentration. The turbulence kinetic energy was large and showed obvious diurnal variations during unpolluted (clean) weather, but was small during episodes of heavy haze pollution. Under both clean and heavy haze conditions, the relation between the non-dimensional wind components and the stability parameter z / L followed a 1/3 power law, but the normalized standard deviations of the wind speed were smaller during heavy pollution events than during clean periods under near-neutral conditions. Under unstable conditions, the normalized standard deviation of the potential temperature σ θ /| θ * | was related to z / L , roughly following a –1/3 power law, and the ratio during pollution days was greater than that during clean days. The three-dimensional turbulence energy spectra satisfied a –2/3 power exponent rate in the high-frequency band. In the low-frequency band, the wind velocity spectrum curve was related to the stability parameters under clear conditions, but was not related to atmospheric stratification under polluted conditions. In the dissipation stage of the heavy pollution episode, the horizontal wind speed first started to increase at high altitudes and then gradually decreased at lower altitudes. The strong upward motion during this stage was an important dynamic factor in the dissipation of the heavy haze.
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  • 49
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    Publication Date: 2018-03-05
    Description: A humidification system was deployed to measure aerosol hygroscopicity at a rural site of the North China Plain during the haze red-alert period 17–22 December 2016. The aerosol scattering coefficients under dry [relative humidity (RH) 〈 30%] and wet (RH in the range of 40%–85%) conditions were simultaneously measured at wavelengths of 450, 550, and 700 nm. It is found that the aerosol scattering coefficient and backscattering coefficient increased by only 29% and 10%, respectively when RH went up from 40% to 80%, while the hemispheric backscatter fraction went down by 14%, implying that the aerosol hygroscopicity represented by the aerosol scattering enhancement factor f (RH) is relatively low and RH exerted little effects on the aerosol light scattering in this case. The scattering enhancement factors do not show significant differences at the three wavelengths, only with an approximate 2% variation, suggesting that the aerosol hygroscopicity is independent of the wavelength. Aerosol hygroscopicity is highly dependent on the aerosol chemical composition. When there is a large mass fraction of inorganics and a small mass fraction of organic matter, f(RH) reaches a high value. The fraction of NO 3 – was strongly correlated with the aerosol scattering coefficient at RH = 80%, which suggests that NO 3 – played an important role in aerosol hygroscopic growth during the heavy pollution period.
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  • 50
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    Springer
    Publication Date: 2018-03-05
    Description: An extensive field experiment for measurement of physical and chemical properties of aerosols was conducted at an urban site in the Chinese Academy of Meteorological Sciences (CAMS) in Beijing and at a rural site in Gucheng (GC), Hebei Province in December 2016. This paper compares the number size distribution of submicron particle matter (PM1, diameter 〈 1 μm) between the two sites. The results show that the mean PM1 number concentration at GC was twice that at CAMS, and the mass concentration was three times the amount at CAMS. It is found that the accumulation mode (100–850 nm) particles constituted the largest fraction of PM1 at GC, which was significantly correlated with the local coal combustion, as confirmed by a significant relationship between the accumulation mode and the absorption coefficient of soot particles. The high PM1 concentration at GC prevented the occurrence of new particle formation (NPF) events, while eight such events were observed at CAMS. During the NPF events, the mass fraction of sulfate increased significantly, indicating that sulfate played an important role in NPF. The contribution of regional transport to PM1 mass concentration was approximately 50% at both sites, same as that of the local emission. However, during the red-alert period when emission control took place, the contribution of regional transport was notably higher.
    Print ISSN: 0894-0525
    Topics: Geosciences
    Published by Springer on behalf of The Chinese Meteorological Society.
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  • 51
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    Springer
    Publication Date: 2018-03-05
    Description: We investigated the acidity and concentrations of water-soluble ions in PM 2.5 aerosol samples collected from an urban site in Beijing and a rural site in Gucheng, Hebei Province from November 2016 to January 2017 to gain an insight into the formation of secondary inorganic species. The average SO 4 2– , NO 3 – , and NH 4 + concentrations were 8.3, 12.5, and 14.1 μg m –3 , respectively, at the urban site and 14.0, 14.2, and 24.2 μg m –3 , respectively, at the rural site. The nitrogen and sulfur oxidation ratios in urban Beijing were correlated with relative humidity (with correlation coefficient r = 0.79 and 0.67, respectively) and the aerosol loadings. Based on a parameterization model, we found that the rate constant of the heterogeneous reactions for SO 2 on polluted days was about 10 times higher than that on clear days, suggesting that the heterogeneous reactions in the aerosol water played an essential role in haze events. The ISORROPIA II model was used to predict the aerosol pH, which had a mean (range) of 5.0 (4.9–5.2) and 5.3 (4.6–6.3) at the urban and rural site, respectively. Under the conditions with this predicted pH value, oxidation by dissolved NO 2 and the hydrolysis of N 2 O 5 may be the major heterogeneous reactions forming SO 4 2– and NO 3 – in haze. We also analyzed the sensitivity of the aerosol pH to changes in the concentrations of SO 4 2– , NO 3 – , and NH 4 + under haze conditions. The aerosol pH was more sensitive to the SO 4 2– and NH 4 + concentrations with opposing trends, than to the NO 3 – concentrations. The sensitivity of the pH was relatively weak overall, which was attributed to the buffering effect of NH 3 partitioning.
    Print ISSN: 0894-0525
    Topics: Geosciences
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  • 52
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    Springer
    Publication Date: 2018-03-06
    Description: In temperate tree-based intercropping (TBI) systems, good survival and early growth of selected tree species without wood defects is critical, when taking into account both economic considerations and rapidly accruing environmental benefits that are provided by the trees. The establishment success of different tree species that have contrasting growth strategies in Northeastern American TBI systems have not been assessed in a well-documented manner, which is an important influential barrier limiting their adoption by farmers. We analyzed establishment success after five growing seasons of six hardwood species and four hybrid poplar clones in a 50 stems ha −1 , tree-based intercropping system. The hardwood species being evaluated were Carya ovata , Juglans nigra , Quercus bicolor , Quercus macrocarpa , Quercus rubra , and Acer saccharum . The hybrid poplar clones being evaluated were four clones of Populus deltoides  ×  P. nigra  ×  P. maximowiczii . We also compared 3-year-old bareroot (165 cm in height) with tree shelter versus 6-year-old root-balled transplants (370 cm in height) without tree shelter for two hardwood species ( Quercus rubra and Acer saccharum ). Mean survival rate of the six hardwood species originating from 3-year-old transplants was 70% after 5 years. Acer saccharum (33%) and Carya ovata (57%) had the lowest survival rates. Tree height of Quercus bicolor and Quercus macrocarpa was taller than that of Carya ovata, Juglans nigra and Quercus rubra . Tree height of Acer saccharum was intermediate among species. Mean survival rate of hybrid poplar after five growing seasons was 82% and did not differ among the clones. Growth of DN 4813 was lower than that of DN×M 915508, DN 3570 and DN 3585. Tree external defects (forks, frost cracks, trunk inclinations, trunk wind bends, and physical injuries) were observed in 63% of the hardwoods and 55% of the hybrid poplars. Red oak and sugar maple originating from 6-year-old transplants had survival rates of 100%. Over 5 years, height increment of 6-year-old transplants was higher than that of 3-year-old transplants. The 6-year-old transplants of Quercus rubra and Acer saccharum were the most cost-effective stock type. We conclude that tree survival, tree growth and tree external defects in establishment phase of TBI systems may vary considerably across hardwood species, hybrid poplar clones and planting stock type.
    Print ISSN: 0167-4366
    Electronic ISSN: 1572-9680
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
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  • 53
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    Springer
    Publication Date: 2018-03-06
    Description: Spatial pattern (SP) and neighbourhood distance (ND) of trees are crucial for pollination services, in particular for dioecious species. However, land use types through human disturbances may affect the natural SP and ND and possibly have a negative effect on pollination services. Though several studies have focused on the effect of land use types on SP of trees, few have reported on ND. In this study, we compared SP and ND of the dioecious Borassus aethiopum Mart. between two land use types (protected areas vs farmlands) in two contrasting climatic regions (semi-arid vs sub-humid) in Benin. Trees were mapped in twelve plots from six populations. Pair-correlation function was used to generate univariate and bivariate SP and ND. Next, ANOVA was used to compare ND. While supporting the overall trend towards a less aggregated pattern along plant life-cycle, the study showed that the SP of B. aethiopum was altered from aggregated and spatial association in protected areas toward random and independence patterns in farmlands with increased ND among individuals, particularly between adult males and females. In addition, differences in ND between land use types varied across climatic regions, the differences being higher in the drier semi-arid region, thus suggesting more intense human activities in this region and climatic region-specific management. Management actions should mainly aim at reducing or not further increasing ND, particularly between female and male adult populations in farmlands in the semi-arid region through planting new individuals of B. aethiopum trees or limiting their removal but at the same time account for other tree species to maximise diversity of farmlands’ functions and services. Further studies should examine whether the observed increased ND due to human-disturbances in farmlands is detrimental for the species pollination services, fruit production and whether it affects the species spatio-temporal population genetic structuring.
    Print ISSN: 0167-4366
    Electronic ISSN: 1572-9680
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
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  • 54
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    Springer
    Publication Date: 2018-03-06
    Description: NTFPs are often presented as a major contributor to livelihoods, as sources of food and cash, particularly for rural communities. There are few data available in Gabon to confirm this common assertion. This study was conducted on 127 households in 14 villages around two timber concessions in the south-eastern and south-western regions of Gabon for a period of one year. Conventional socio‐economic survey tools such as focus group discussions, census and semi-structured interviews with households were used for gathering the data. Results reveal that rural people depend on various sources of food and income for their livelihoods, but overall, the current contribution of NTFPs obtained from plant sources is insignificant compared to those from other activities. Odika ( Irvingia gabonensis ), ‘atanga sauvage’ ( Dacryodes buettneri ), fungus ( Termitomyces spp.) and Gabon nut ( Coula edulis ) represent the main forest products commonly harvested by rural people. They are used primarily for subsistence, but the surplus is sold. The results of this study suggest that: (1) the main components of decree No. 137/PR/MEFP of February 4, 2009, that prohibits the logging of five multiple-use tree species over a period of 25 years in order to safeguard the sources of NTFPs, should be reviewed; and (2) state authorities and partners should promote projects aimed at increasing public awareness of the NTFP sector. These projects should include a census of NTFPs (for food, for medicine and for services), characterize their uses and identify the markets of target products as well as the development potential of NTFPs. Such projects could help Gabon and other Congo Basin countries to fix norms/standards for sustainable natural resource management and for enhancing the contribution of NTFPs to the national economy. This will be particularly relevant in the wake of dwindling oil revenues and the need to diversify and promote other revenue sources in the country.
    Print ISSN: 0167-4366
    Electronic ISSN: 1572-9680
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
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  • 55
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    Springer
    Publication Date: 2018-03-06
    Description: Grape is a major crop, covering 7.5 M ha worldwide, that is currently being confronted with three main challenges: intensive pesticide use that must be reduced, invasion by new pests/diseases, and climate change. The biological control of pests and vectors would help address these challenges. Here, we review the scientific literature on the biological control of grape moths by macroorganisms (excluding nematodes). Two components, biological control with an active human role, mainly using biocontrol agents through inundation or inoculation, and conservation biological control, are considered. The major points are the following. (1) Tortricid grape moths seriously damage grapes worldwide, causing yield losses and quality reduction. The more geographically widespread species, Lobesia botrana , continues to extend its range, invading South American and, more recently, North American vineyards. (2) Parasitoids and predators (including arthropods, birds, and bats) that can control grape pests are very diverse. (3) Different methods exist to assess pest control efficiency in the field but some of them remain to be developed. (4) Environmental factors, including host plants, landscape, grass or floral covers, and organic practices, affect the natural control of grape moths. (5) Pest resistance to parasitoids strongly depends on their immune system, which is controlled by the host plant. Future climate changes may modify this tritrophic interaction and thus affect biological control strategies. We conclude that biological control has a great deal of potential in viticulture and that addressing these key factors would improve the efficiency levels of biological control strategies. This would help growers and stakeholders to significantly reduce insecticide use in vineyards.
    Print ISSN: 1774-0746
    Electronic ISSN: 1773-0155
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
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  • 56
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    Springer
    Publication Date: 2018-03-06
    Description: Current organic agriculture performs well in several sustainability domains, like animal welfare, farm profitability and low pesticide use, but yields are commonly lower than in conventional farming. There is now a re-vitalized interest in increasing yields in organic agriculture to provide more organic food for a growing, more affluent population and reduce negative impacts per unit produced. However, past yield increases have been accompanied by several negative side-effects. Here, we review risks and opportunities related to a broad range of sustainability domains associated with increasing yields in organic agriculture in the Northern European context. We identify increased N input, weed, disease and pest control, improved livestock feeding, breeding for higher yields and reduced losses as the main measures for yield increases. We review the implications of their implementation for biodiversity, greenhouse gas emissions, nutrient losses, soil fertility, animal health and welfare, human nutrition and health and farm profitability. Our findings from this first-of-its-kind integrated analysis reveal which strategies for increasing yields are unlikely to produce negative side-effects and therefore should be a high priority, and which strategies need to be implemented with great attention to trade-offs. For example, increased N inputs in cropping carry many risks and few opportunities, whereas there are many risk-free opportunities for improved pest control through the management of ecosystem services. For most yield increasing strategies, both risks and opportunities arise, and the actual effect depends on management including active mitigation of side-effects. Our review shows that, to be a driving force for increased food system sustainability, organic agriculture may need to reconsider certain fundamental principles. Novel plant nutrient sources, including increased nutrient recycling in society, and in some cases mineral nitrogen fertilisers from renewable sources, and truly alternative animal production systems may need to be developed and accepted.
    Print ISSN: 1774-0746
    Electronic ISSN: 1773-0155
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
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  • 57
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    Springer
    Publication Date: 2018-03-06
    Description: Spatial ecology includes research into factors responsible for observed distribution patterns of organisms. Moreover, the spatial distribution of an animal at a given spatial scale and in a given landscape may provide valuable insight into its host preference, fitness, evolutionary adaptation potential, and response to resource limitations. In agro-ecology, in-depth understanding of spatial distributions of insects is of particular importance when the goals are to (1) promote establishment and persistence of certain food webs, (2) maximize performance of pollinators and natural enemies, and (3) develop precision-targeted monitoring and detection of emerging outbreaks of herbivorous pests. In this article, we review and discuss a spatial phenomenon that is widespread among insect species across agricultural systems and across spatial scales—they tend to show “edge-biased distributions” (spatial distribution patterns show distinct “edge effects”). In the conservation and biodiversity literature, this phenomenon has been studied and reviewed intensively in the context of how landscape fragmentation affects species diversity. However, possible explanations of, and also implications of, edge-biased distributions of insects in agricultural systems have not received the same attention. Our review suggests that (1) mathematical modeling approaches can partially explain edge-biased distributions and (2) abiotic factors, crop vegetation traits, and environmental parameters are factors that are likely responsible for this phenomenon. However, we argue that more research, especially experimental research, is needed to increase the current understanding of how and why edge-biased distributions of insects are so widespread. We argue that the fact that many insect pests show edge-biased distribution patterns may be used to optimize both pest monitoring practices and precision targeting of pesticide applications and releases of natural enemies.
    Print ISSN: 1774-0746
    Electronic ISSN: 1773-0155
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
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  • 58
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    Springer
    Publication Date: 2018-03-06
    Description: The intensive use of synthetic nitrogen fertilizers over the last century has both increased agricultural productivity and modified biogeochemical cycles in terrestrial ecosystems, causing severe negative environmental impacts. Tea ( Camellia sinensis L.) plantations usually receive high levels of synthetic fertilizers, which strongly affect plant and soil properties. However, there is no quantitative study to assess how synthetic N additions affect soil chemistry and the production and quality of tea shoots. Here, we conducted a comprehensive meta-analysis to evaluate the effects of experimental synthetic N fertilizers. Our main findings are (1) N additions in tea plantations acidify soils (− 0.41 pH unit in average) and produce soil nutrient imbalance. Soil acidification commonly exacerbates the accumulations of toxic aluminum ions. (2) Synthetic N fertilizer additions may strongly increase tea production by almost 70% but alter tea shoot quality by increasing the concentrations of free amino acids (+ 16%), caffeine (+ 14%), and water extracts (+ 5%) while decreasing those of soluble sugars (− 8%) in the tea shoots. The responses of soil chemistry, tea production, and quality to N additions can vary among experimental conditions, tea tree species, and N fertilizer forms. Because there is statistical limitation in this meta-analysis, our findings recommend performing additional field studies to explore the potential mechanisms of nutrient cycling and ecosystem functioning under synthetic N additions. The development of a sustainable N management strategy in tea plantations is also urgently needed to enhance N use efficiency and reduce environmental risks.
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    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
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  • 59
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    Springer
    Publication Date: 2018-03-06
    Description: Arable soils tend to lose total organic carbon, thus contributing to the increase of CO 2 emissions into the atmosphere. This process has been occurring in large areas of Mexico cultivated with maize. Perennial species such as cactus ( Opuntia spp.) and agave are grown in Mexico and other parts of the world, which can contribute to the maintenance of total organic carbon in the soil (TOC). Within this context, a study was designed to compare the patterns of emissions of C–CO 2 and TOC in a highland of central Mexico. The selected management systems were the following: (1) maize monoculture with conventional tillage and fertilization, (2) maize associated with Vicia faba and manure addition, (3, 4) cactus without and with composted manure mulching, (5) soil in oak-pine forest, and (6) maize fields under 4 years of soil fallow and without weed control. Measurements of CO 2 flux pulses and volumetric moisture were performed every 15 days at 5 points of each plot. The soil in oak-pine forest showed stable C–CO 2 emissions throughout the year, while under maize fields, emissions were unstable with several respiration peaks. The soil in cactus crop showed a very close pattern of forest soil respiration. The annual patterns of soil respiration were in agreement with the results of TOC recently reported for the same plots where soil respiration was measured. Here we show, for the first time, that TOC in cactus approached the reference line of soil under forest (6 g 100 g −1 ), while in maize, we found a reduction greater than 50% of this value. Cactus crop represents an option in low-input maize for C–CO 2 -reduced emissions in agricultural zones with declining soil fertility.
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    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
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  • 60
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    Springer
    Publication Date: 2018-03-06
    Description: In addition to changes in land use and cover, changes in land management pattern can also have a significant effect on soil fertility. However, to date, changes in grassland grazing management pattern caused by policies have received less attention in terms of their impact on soil fertility. In this paper, we investigated the influence of two different grazing management patterns: the multi-household grazing management pattern (consisting of pastures managed by two or more households with no fences separating them) and the single-household grazing pattern (with fences between adjacent pastures managed by different households), which were implemented after the enactment of grassland contract policy, on soil fertility in the Qinghai-Tibetan Plateau. Our hypothesis was that soil fertility differed between the two grazing management patterns. We selected five study sites with both grazing management patterns in Maqu County on the eastern Qinghai-Tibetan Plateau and sampled 30 winter grasslands from each grazing management pattern to explore differences in soil organic carbon, soil total nitrogen, and soil total phosphorus. We showed that these indicators of fertility status were significantly greater under the multi-household grazing management pattern (47 g C kg −1 , 4.6 g N kg −1 , and 0.77 g P kg −1 ) compared to the single-household grazing management pattern (43 g C kg −1 , 4.3 g N kg −1 , and 0.73 g P kg −1 ). This is the first study of the effects of grazing management pattern on soil fertility in this environment, and it indicated that the multi-household grazing management pattern could maintain better soil fertility and help to support sustainable use of these grasslands.
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    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
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  • 61
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    Springer
    Publication Date: 2018-03-06
    Description: Characterizing and understanding the complexity of numerous interactions occurring in mixed farming systems is still a methodological challenge. We hypothesize that farm functioning features in terms of crop-livestock integration practices impact the agroecological performance of the system, which will be also affected by the farm context. In order to analyze crop-livestock integration in a holistic way, a set of seventeen mixed farming systems from three contrasting socioeconomic regions of the humid tropics (Guadeloupe, Brazilian Amazonia, and Cuba) was selected in order to cover a wide range of crop-livestock integration situations. The ecological network analysis was applied to each farm in order to study the nutrient flow networks, expressed in nitrogen. The activity and flow organization of crop-livestock integration practices were characterized and the agroecological performance has been evaluated in terms of efficiency, resilience, productivity, and dependency of N flow networks. Here, we show for the first time that the range of crop-livestock integration is well characterized by the activity and organization of flows. Gradients of crop-livestock integration were well detected and described. Some agroecological performances were related to a particular socioeconomic context. Resource endowment influenced efficiency, according to the intensification level. The crop-livestock integration however contributed partially to the productivity of the system, being especially effective in promoting resilience. This study applies a suitable framework to analyze complex farming systems while linking their functioning and performance in an agroecological approach. Thus, comparison of contrasting systems was feasible here with the support of numerical and tangible figures for interpreting complex indicators (e.g., resilience), representing a useful tool for monitoring sustainability of agricultural systems in a dynamic and holistic way.
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    Electronic ISSN: 1773-0155
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
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  • 62
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    Springer
    Publication Date: 2018-03-06
    Description: Sustainable agriculture and agro-ecology justify the need to study and understand the role played by ecological processes, and soil biodiversity in particular, in agro-ecosystem functioning. A large number of studies have focused on earthworms in temperate and humid tropical ecosystems and have demonstrated their importance for improving soil biological, physical, and chemical properties in agro-ecosystems. Their “success” is so essential that earthworms are widely considered key species and relevant indicators of soil health in temperate ecosystems. In arid and sub-arid ecosystems, the role of “soil engineer” is usually attributed to termites, and especially fungus-growing termites in Africa and Asia. However, despite this recognition, significant effort is spent eradicating them in plantations because of their pest status. In this review, we discuss the status of termites (“pests” vs. “soil engineers”) and question whether termites play similar roles to earthworms in arid- and sub-arid agroecosystems, with a focus on their influence on nutrient cycling and water dynamics. We argue that the dream of controlling natural interactions and ridding plantations of termites remains a costly legacy of the green revolution. We review the agricultural practices that have been used to reduce termite damage in plantations by restoring refuges to predators or by reorienting termite foraging activity towards organic amendments. Then, we show that the stimulation of termite activity can be used to improve key ecological functions in agro-ecosystems, such as increasing water availability to plants or producing fertility hot-spots. Finally, we suggest that more research on how termites can be used for improving ecosystem services, as is actually done with earthworms in temperate and humid tropical countries, could lead to a paradigm shift in our understanding of the impact of termites in tropical agro-ecosytems.
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    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
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  • 63
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    Springer
    Publication Date: 2018-03-06
    Description: Enhancing natural enemies for pest management in agriculture is an expanding approach offering new opportunities for pest control and the potential to reduce insecticide use. Numerous studies in a variety of cropping systems clearly have shown that adequate measures can benefit natural enemies. However, although carry-over effects from an increase in natural enemies and a subsequent decrease in pest populations leading to a reduction in crop damage are always assumed, they are rarely proven. We established an insecticide-free apple orchard optimized for the self-regulation of pests by supporting natural enemies with shelter, nectar, alternative prey/hosts, and pollen. For six growing seasons, we focused on the control of the major apple pest Dysaphis plantaginea . While fruit damage after the second fruit drop was not affected by aphidophagous insect guilds, it was negatively related to spider abundance in the previous autumn, when aphids immigrate back to the orchard to establish the next generation. In detail, we found that an increase in spider web area reduced the number of aphid fundatrices in spring and subsequently fruit damage. Our findings indicate the rarely proven carry-over effect of enhanced natural enemies on decreased crop damage and we show for the first time, how the rosy apple aphid can be managed without the use of insecticides.
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    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
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  • 64
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    Springer
    Publication Date: 2018-03-06
    Description: Social mechanisms underpinning collaborative approaches to pest management are as important as the biological control of the pest. To facilitate the success of an area-wide management approach, social factors need to be understood and addressed. This study qualitatively analyses social, psychological and institutional barriers and facilitators for the widespread adoption of area-wide management of Queensland fruit fly, and attitudes towards the use of sterile insect technology. Interviews were conducted ( N  = 35) with fruit growers, industry representatives, agronomists, government representatives and community leaders from across the dominant horticultural regions of southeastern Australia. Transcripts were analysed and compared based on thematic organisations. Growers and stakeholders expressed high acceptance for area-wide management of Queensland fruit fly and the use of sterile insect technology. However, participants reported limited knowledge of both area-wide management and sterile insect technology. Factors found to facilitate acceptance were perceptions of increased market access, increased social awareness, operationalising community champions and value chain actors, as well as dissemination of credible scientific evidence. Trust in those individuals advocating area-wide management and sterile insect technology, and interpersonal trust between neighbours, was also seen as an important factor affecting adoption of area-wide management and sterile insect technology. Barriers to acceptance included perceptions of costs and ongoing funding needs, lack of knowledge, apathy towards control of Queensland fruit fly, compatibility of area-wide management and sterile insect technology with current practices and a lack of social cooperation amongst growers. The data show a need to increase growers’ awareness of costs and benefits associated with Queensland fruit fly control and an understanding of the direct and indirect consequences of their own on-farm behaviours with respect to control. This study is the first to use a psychological lens to explore and distil grower and stakeholder attitudes towards a cooperative management approach for a pest of national significance. Results provide insight into beliefs that guide underlying biosecurity decision-making and can help improve uptake of other area-wide control techniques.
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    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
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  • 65
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    Springer
    Publication Date: 2018-03-06
    Description: We investigate the following greedy approach to attack linear programs of type \(\max \{1^{T} x\mid l\le Ax\le u\}\) where A has entries in \(\{-1,0,1\}\) : The greedy algorithm starts with a feasible solution x and, iteratively, chooses an improving variable and raises it until some constraint becomes tight. In the special case, where A is the edge-path incidence matrix of some digraph \(G=(V,E)\) , and \(l=0\) , this greedy algorithm corresponds to the Ford–Fulkerson algorithm to solve the max ( s ,  t )-flow problem in G w.r.t. edge-capacities u . It is well-known that the Ford–Fulkerson algorithm always terminates with an optimal flow, and that the number of augmentations strongly depends on the choice of paths in each iteration. The Edmonds–Karp rule that prefers paths with fewer arcs leads to a running time of at most \(|E|^2\) augmentations. The paper investigates general types of matrices A and preference rules on the variables that make the greedy algorithm efficient. In this paper, we identify conditions that guarantee for the greedy algorithm not to cycle, and/or optimality of the greedy algorithm, and/or to yield a quadratic (in the number of rows) number of augmentations. We illustrate our approach with flow and circulation problems on regular oriented matroids.
    Print ISSN: 0178-4617
    Electronic ISSN: 1432-0541
    Topics: Computer Science , Mathematics
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  • 66
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    Publication Date: 2018-03-06
    Description: The Alborz mountains in N-Iran at 36° N rise from the Caspian Sea to 5671 m a.s.l., with warm-temperate, winter-deciduous forests in the lower montane belt in northern slopes, and vast treeless terrain at higher elevation. A lack of rainfall (ca. 550 mm at high elevations) cannot explain the absence of trees. Hence, it is an open question, which parts of these mountains belong to the alpine belt. Here we use bioclimatic data to estimate the position of the potential climatic treeline, and thus, define bioclimatologically, what is alpine and what is not. We employed the same miniature data loggers and protocol that had been applied in a Europe-wide assessment of alpine climates and a global survey of treeline temperatures. The data suggest a potential treeline position at ca. 3300 m a.s.l., that is ca. 900 m above the upper edge of the current oak forest, or 450 m above its highest outposts. The alpine terrain above the climatic treeline position shows a temperature regime comparable to sites in the European Alps. At the upper limit of angiosperm life, at 4850 m a.s.l., the growing season lasted 63 days with a seasonal mean root zone temperature of 4.5 °C. We conclude that (1) the absence of trees below 2850 m a.s.l. is clearly due to millennia of land use. The absence of trees between 2850 and 3300 m a.s.l. is either due to the absence of suitable tree taxa, or the only potential regional taxon for those elevations, Juniperus excelsa , had been eradicated by land use as well. (2) These continental mountains provide thermal life conditions in the alpine belt similar to other temperate mountains. (3) Topography and snow melt regimes play a significant role for the structure of the alpine vegetation mosaics.
    Topics: Natural Sciences in General
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    Springer
    Publication Date: 2018-03-06
    Description: The functional diversity and composition of plant traits within communities are tightly linked to important ecosystem functions and processes. Whereas vegetative traits reflecting adaptations to environmental conditions are commonly assessed in community ecology, floral traits are often neglected despite their importance for the plants’ life cycle. The consideration of floral traits covers important aspects such as sexual plant reproduction and pollinator diversity, which remain unobserved in studies focussing on vegetative traits only. To test whether vegetative and floral traits differ in their responses to elevation, we measured morphological and chemical traits of plant species occurring in pastures at seven elevations in the Austrian Alps. Variation in functional composition was examined using the concept of n -dimensional hypervolumes and vector analysis. Our data show that vegetative and floral traits vary differently with the elevational gradient. Whereas vegetative traits changed in a predictable manner with elevation, floral traits did not specifically respond to elevation. Overall variation in vegetative traits mainly resulted from phenotypical differences between plants in different elevations, whereas total variation in floral traits was a result from a high variation within communities. The assessment of functional changes in vegetative and floral traits along mountain slopes thus reveals different patterns in plant responses to elevation and may help to generate testable hypotheses on functional responses to current climate warming.
    Topics: Natural Sciences in General
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  • 68
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    Springer
    Publication Date: 2018-03-06
    Description: Alpine plants growing along wide elevational gradients experience very different abiotic and biotic conditions across elevations. As a result of genetic differentiation and/or plastic response, conspecific plants growing in high elevations, as compared to low elevations, generally have shorter stems and lower number of flowers, but larger flower size. However, most often, detailed models of elevational variations were not examined. To reveal the pattern of elevational changes in a set of fitness-related morphological traits, tests of linear and unimodal models were performed based on measurements of 1047 S olidago minuta plants collected from 47 sites distributed along a 1000 m elevational gradient in the Tatra Mountains. Nearly all of the investigated floral traits, i.e. inflorescence and flower heads size, and number and size of individual flowers, expressed unimodal relationships with elevation having their maxima in the centre of the elevation range. This pattern suggests the existence of a local optimum with respect to sexual reproduction at the centre of the elevational range. Possible explanations of observed elevational variations are discussed in the context of pollinator selection and the ‘resource-cost compromise’ hypothesis. Best floral performance in the centre of the elevational range of S. minuta may also support the idea that the favourability of habitat conditions declines from the centre to the margin of the distribution, and species are expected to be more abundant, increase reproduction and perform better in the centre of the range.
    Topics: Natural Sciences in General
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  • 69
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    Springer
    Publication Date: 2018-03-06
    Description: Despite the strong environmental control of seed dormancy and longevity, their changes along latitudes are poorly understood. The aim of this study was to assess seed dormancy and longevity in different populations across the distribution of the arctic–alpine plant Silene suecica . Seeds of seven populations collected from alpine (Spain, Italy, Scotland) and subarctic (Sweden, Norway) populations were incubated at four temperature regimes and five cold stratification intervals for germination and dormancy testing. Seed longevity was studied by exposing seeds to controlled ageing (45 °C, 60% RH) and regularly sampled for germination. Fresh seeds of S. suecica germinated at warm temperature (20/15 °C) and more in subarctic (80–100%) compared to alpine (20–50%) populations showed a negative correlation with autumn temperature (i.e., post-dispersal period). Seed germination increased after cold stratification in all populations, with different percentages (30–100%). Similarly, there was a large variation of seed longevity (p 50  = 12–32 days), with seeds from the wettest locations showing faster deterioration rate. Subarctic populations of S. suecica were less dormant, showing a warmer suitable temperature range for germination, and a higher germinability than alpine populations. Germination and dormancy were driven by an interplay of geographical and climatic factors, with alpine and warm versus subarctic and cool autumn conditions, eliciting a decrease and an increase of emergence, respectively. Germination and dormancy patterns typically found in alpine habitats may not be found in the arctic.
    Topics: Natural Sciences in General
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  • 70
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    Springer
    Publication Date: 2018-03-06
    Description: Engineering of the yeast Saccharomyces cerevisiae towards efficient d-xylose assimilation has been a major focus over the last decades since d-xylose is the second most abundant sugar in nature, and its conversio...
    Electronic ISSN: 2191-0855
    Topics: Biology
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  • 71
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    Springer
    Publication Date: 2018-03-06
    Description: Bacterial strains were isolated from the sediments of the Baltic Sea using ferulic acid, guaiacol or a lignin-rich softwood waste stream as substrate. In total nine isolates were obtained, five on ferulic acid...
    Electronic ISSN: 2191-0855
    Topics: Biology
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  • 72
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    Springer
    Publication Date: 2018-03-06
    Description: 2-Keto-l-gulonic acid (the precursor of vitamin C) is bio-converted from l-sorbose by mixed fermentation of Ketogulonicigenium vulgare and a helper strain. The helper strain promotes the conversion of 2-KLG by en...
    Electronic ISSN: 2191-0855
    Topics: Biology
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  • 73
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    Springer
    Publication Date: 2018-03-06
    Print ISSN: 0044-7447
    Electronic ISSN: 1654-7209
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Published by Springer on behalf of The Royal Swedish Academy of Sciences.
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  • 74
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    Springer
    Publication Date: 2018-03-06
    Description: The Minamata Convention on Mercury, with its objective to protect human health and the environment from the dangers of mercury (Hg), entered into force in 2017. The Convention outlines a life-cycle approach to the production, use, emissions, releases, handling, and disposal of Hg. As it moves into the implementation phase, scientific work and information are critically needed to support decision-making and management. This paper synthesizes existing knowledge and examines three areas in which researchers across the natural sciences, engineering, and social sciences can mobilize and disseminate knowledge in support of Hg abatement and the realization of the Convention’s objective: (1) uses, emissions, and releases; (2) support, awareness raising, and education; and (3) impacts and effectiveness. The paper ends with a discussion of the future of Hg science and policy.
    Print ISSN: 0044-7447
    Electronic ISSN: 1654-7209
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Published by Springer on behalf of The Royal Swedish Academy of Sciences.
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  • 75
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    Springer
    Publication Date: 2018-03-06
    Description: China’s largest-ever resettlement program is underway, aiming to restore ecosystems and lift ecosystem service providers out of the poverty trap and into sustainable livelihoods. We examine the impact of the relocation and settlement program (RSP) to date, reporting on an ecosystem services (ES) assessment and a 1400-household survey. The RSP generally achieves the goals of ES increase and livelihood restore. In biophysical terms, the RSP improves water quality, sediment retention, and carbon sequestration. In social terms, resettled households so far report transformation of livelihoods activities from traditional inefficient agricultural and forest production to non-farm activities. Increased income contributes to decrease the poverty rate and improve resettled households’ living condition and standard. Meanwhile, the RSP decreases households’ dependence on ES in terms of provisioning services. Difficulty and challenge also showed up subsequently after relocation. A major current challenge is to enable poorer households to move, while providing greater follow-up support to relocated households. While the program is unique to China, it illuminates widespread opportunities for addressing environmental and poverty-related concerns in a rapidly changing world.
    Print ISSN: 0044-7447
    Electronic ISSN: 1654-7209
    Topics: Energy, Environment Protection, Nuclear Power Engineering
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  • 76
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    Springer
    Publication Date: 2018-03-05
    Description: Mitochondrial complex I deficiency occurs in the substantia nigra of individuals with Parkinson’s disease. It is generally believed that this phenomenon is caused by accumulating mitochondrial DNA damage in neurons and that it contributes to the process of neurodegeneration. We hypothesized that if these theories are correct, complex I deficiency should extend beyond the substantia nigra to other affected brain regions in Parkinson’s disease and correlate tightly with neuronal mitochondrial DNA damage. To test our hypothesis, we employed a combination of semiquantitative immunohistochemical analyses, Western blot and activity measurements, to assess complex I quantity and function in multiple brain regions from an extensively characterized population-based cohort of idiopathic Parkinson’s disease ( n  = 18) and gender and age matched healthy controls ( n  = 11). Mitochondrial DNA was assessed in single neurons from the same areas by real-time PCR. Immunohistochemistry showed that neuronal complex I deficiency occurs throughout the Parkinson’s disease brain, including areas spared by the neurodegenerative process such as the cerebellum. Activity measurements in brain homogenate confirmed a moderate decrease of complex I function, whereas Western blot was less sensitive, detecting only a mild reduction, which did not reach statistical significance at the group level. With the exception of the substantia nigra, neuronal complex I loss showed no correlation with the load of somatic mitochondrial DNA damage. Interestingly, α-synuclein aggregation was less common in complex I deficient neurons in the substantia nigra. We show that neuronal complex I deficiency is a widespread phenomenon in the Parkinson’s disease brain which, contrary to mainstream theory, does not follow the anatomical distribution of neurodegeneration and is not associated with the neuronal load of mitochondrial DNA mutation. Our findings suggest that complex I deficiency in Parkinson’s disease can occur independently of mitochondrial DNA damage and may not have a pathogenic role in the neurodegenerative process.
    Print ISSN: 0001-6322
    Electronic ISSN: 1432-0533
    Topics: Medicine
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  • 77
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    Springer
    Publication Date: 2018-03-05
    Description: The adult quiescent blood–brain barrier (BBB), a structure organised by endothelial cells through interactions with pericytes, astrocytes, neurons and microglia in the neurovascular unit, is highly regulated but fragile at the same time. In the past decade, there has been considerable progress in understanding not only the molecular pathways involved in BBB development, but also BBB breakdown in neurological diseases. Specifically, the Wnt/β-catenin, retinoic acid and sonic hedgehog pathways moved into the focus of BBB research. Moreover, angiopoietin/Tie2 signalling that is linked to angiogenic processes has gained attention in the BBB field. Blood vessels play an essential role in initiation and progression of many diseases, including inflammation outside the central nervous system (CNS). Therefore, the potential influence of CNS blood vessels in neurological diseases associated with BBB alterations or neuroinflammation has become a major focus of current research to understand their contribution to pathogenesis. Moreover, the BBB remains a major obstacle to pharmaceutical intervention in the CNS. The complications may either be expressed by inadequate therapeutic delivery like in brain tumours, or by poor delivery of the drug across the BBB and ineffective bioavailability. In this review, we initially describe the cellular and molecular components that contribute to the steady state of the healthy BBB. We then discuss BBB alterations in ischaemic stroke, primary and metastatic brain tumour, chronic inflammation and Alzheimer’s disease. Throughout the review, we highlight common mechanisms of BBB abnormalities among these diseases, in particular the contribution of neuroinflammation to BBB dysfunction and disease progression, and emphasise unique aspects of BBB alteration in certain diseases such as brain tumours. Moreover, this review highlights novel strategies to monitor BBB function by non-invasive imaging techniques focussing on ischaemic stroke, as well as novel ways to modulate BBB permeability and function to promote treatment of brain tumours, inflammation and Alzheimer’s disease. In conclusion, a deep understanding of signals that maintain the healthy BBB and promote fluctuations in BBB permeability in disease states will be key to elucidate disease mechanisms and to identify potential targets for diagnostics and therapeutic modulation of the BBB.
    Print ISSN: 0001-6322
    Electronic ISSN: 1432-0533
    Topics: Medicine
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  • 78
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    Springer
    Publication Date: 2018-03-05
    Description: A GGGGCC hexanucleotide repeat expansion in the C9orf72 gene is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. Neurodegeneration may occur via transcription of the repeats into inherently toxic repetitive sense and antisense RNA species, or via repeat-associated non-ATG initiated translation (RANT) of sense and antisense RNA into toxic dipeptide repeat proteins. We have previously demonstrated that regular interspersion of repeat RNA with stop codons prevents RANT (RNA-only models), allowing us to study the role of repeat RNA in isolation. Here we have created novel RNA-only Drosophila models, including the first models of antisense repeat toxicity, and flies expressing extremely large repeats, within the range observed in patients. We generated flies expressing ~ 100 repeat sense or antisense RNA either as part of a processed polyadenylated transcript or intronic sequence. We additionally created Drosophila expressing 〉 1000 RNA-only repeats in the sense direction. When expressed in adult Drosophila neurons polyadenylated repeat RNA is largely cytoplasmic in localisation, whilst intronic repeat RNA forms intranuclear RNA foci, as does 〉 1000 repeat RNA, thus allowing us to investigate both nuclear and cytoplasmic RNA toxicity. We confirmed that these RNA foci are capable of sequestering endogenous Drosophila RNA-binding proteins, and that the production of dipeptide proteins (poly-glycine–proline, and poly-glycine–arginine) is suppressed in our models. We find that neither cytoplasmic nor nuclear sense or antisense RNA are toxic when expressed in adult Drosophila neurons, suggesting they have a limited role in disease pathogenesis.
    Print ISSN: 0001-6322
    Electronic ISSN: 1432-0533
    Topics: Medicine
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  • 79
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    Springer
    Publication Date: 2018-03-05
    Description: The barrier between the blood and the ventricular cerebrospinal fluid (CSF) is located at the choroid plexuses. At the interface between two circulating fluids, these richly vascularized veil-like structures display a peculiar morphology explained by their developmental origin, and fulfill several functions essential for CNS homeostasis. They form a neuroprotective barrier preventing the accumulation of noxious compounds into the CSF and brain, and secrete CSF, which participates in the maintenance of a stable CNS internal environment. The CSF circulation plays an important role in volume transmission within the developing and adult brain, and CSF compartments are key to the immune surveillance of the CNS. In these contexts, the choroid plexuses are an important source of biologically active molecules involved in brain development, stem cell proliferation and differentiation, and brain repair. By sensing both physiological changes in brain homeostasis and peripheral or central insults such as inflammation, they also act as sentinels for the CNS. Finally, their role in the control of immune cell traffic between the blood and the CSF confers on the choroid plexuses a function in neuroimmune regulation and implicates them in neuroinflammation. The choroid plexuses, therefore, deserve more attention while investigating the pathophysiology of CNS diseases and related comorbidities.
    Print ISSN: 0001-6322
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    Topics: Medicine
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  • 80
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    Springer
    Publication Date: 2018-03-05
    Description: The exact mechanism underlying amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) associated with the GGGGCC repeat expansion in C9orf72 is still unclear. Two gain-of-function mechanisms are possible: repeat RNA toxicity and dipeptide repeat protein (DPR) toxicity. We here dissected both possibilities using a zebrafish model for ALS. Expression of two DPRs, glycine–arginine and proline–arginine, induced a motor axonopathy. Similarly, expanded sense and antisense repeat RNA also induced a motor axonopathy and formed mainly cytoplasmic RNA foci. However, DPRs were not detected in these conditions. Moreover, stop codon-interrupted repeat RNA still induced a motor axonopathy and a synergistic role of low levels of DPRs was excluded. Altogether, these results show that repeat RNA toxicity is independent of DPR formation. This RNA toxicity, but not the DPR toxicity, was attenuated by the RNA-binding protein Pur-alpha and the autophagy-related protein p62. Our findings demonstrate that RNA toxicity, independent of DPR toxicity, can contribute to the pathogenesis of C9orf72 -associated ALS/FTD.
    Print ISSN: 0001-6322
    Electronic ISSN: 1432-0533
    Topics: Medicine
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  • 81
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    Springer
    Publication Date: 2018-03-05
    Description: Meninges that surround the CNS consist of an outer fibrous sheet of dura mater (pachymeninx) that is also the inner periosteum of the skull. Underlying the dura are the arachnoid and pia mater (leptomeninges) that form the boundaries of the subarachnoid space. In this review we (1) examine the development of leptomeninges and their role as barriers and facilitators in the foetal CNS. There are two separate CSF systems during early foetal life, inner CSF in the ventricles and outer CSF in the subarachnoid space. As the foramina of Magendi and Luschka develop, one continuous CSF system evolves. Due to the lack of arachnoid granulations during foetal life, it is most likely that CSF is eliminated by lymphatic drainage pathways passing through the cribriform plate and nasal submucosa. (2) We then review the fine structure of the adult human and rodent leptomeninges to establish their roles as barriers and facilitators for the movement of fluid, cells and pathogens. Leptomeningeal cells line CSF spaces, including arachnoid granulations and lymphatic drainage pathways, and separate elements of extracellular matrix from the CSF. The leptomeningeal lining facilitates the traffic of inflammatory cells within CSF but also allows attachment of bacteria such as Neisseria meningitidis and of tumour cells as CSF metastases. Single layers of leptomeningeal cells extend into the brain closely associated with the walls of arteries so that there are no perivascular spaces around arteries in the cerebral cortex. Perivascular spaces surrounding arteries in the white matter and basal ganglia relate to their two encompassing layers of leptomeninges. (3) Finally we examine the roles of ligands expressed by leptomeningeal cells for the attachment of inflammatory cells, bacteria and tumour cells as understanding these roles may aid the design of therapeutic strategies to manage developmental, autoimmune, infectious and neoplastic diseases relating to the CSF, the leptomeninges and the associated CNS.
    Print ISSN: 0001-6322
    Electronic ISSN: 1432-0533
    Topics: Medicine
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  • 82
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    Springer
    Publication Date: 2018-03-06
    Description: A novel and simple method utilizing a chromogenic reaction on filter paper is introduced for the rapid screening of banned aromatic amines released from azo dyes. The proposed method involves the sample preparation protocols outlined by the current standard method and the chromogenic reaction of extracted aromatic amines on filter paper. Based on the principle of the reaction between primary amines and aldehydes, p -dimethylaminobenzaldehyde (DMAB) was used as the chromogenic reagent for the rapid screening of 24 carcinogenic aromatic amines and aniline without any chromatographic instruments under optimized experimental conditions. The detection limit for all the aromatic amines in this study was less than 15 mg/kg. A total of 727 dyed textile samples were analyzed using both the present standard method and the proposed method simultaneously. Using the proposed method, a total of 471 samples did not require further instrumental analysis, which can dramatically save instrumental detection time (61.2%), can decrease instrumental detection costs, and can avoid the use of large amounts of toxic reagents. The proposed method has been applied to detect banned aromatic amines in some inspection institutions and dye factories and has large social and economic benefits. Graphical abstract Chromogenic reaction methods
    Print ISSN: 1618-2642
    Topics: Chemistry and Pharmacology
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  • 83
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    Springer
    Publication Date: 2018-03-06
    Description: One of the major difficulties that arises when selecting aptamers containing a G-quadruplex is the correct amplification of the ssDNA sequence. Can aptamers containing a G-quadruplex be selected from a degenerate library using non-equilibrium capillary electrophoresis (CE) of equilibrium mixtures (NECEEM) along with high-throughput Illumina sequencing? In this article, we present some mismatches of the G-quadruplex T29 aptamer specific to thrombin, which was PCR amplified and sequenced by Illumina sequencing. Then, we show the proportionality between the number of sequenced molecules of T29 added to the library and the number of sequences obtained in Illumina sequencing, and we find that T29 sequences from this aptamer can be detected in a random library of ssDNA after the sample is fractionated by NECEEM, amplified by PCR, and sequenced. Treatment of the data by the counting of double-stranded DNA T29 sequences containing a maximum of two mismatches reveals a good correlation with the enrichment factor ( f E ). This factor is the ratio of the number of aptamer sequences found in the collected complex sample divided by the total number of sequencing reads (aptamer and non-aptamer) plus the quantity of T29 molecules (spiked into a DNA library) injected into CE.
    Print ISSN: 1618-2642
    Topics: Chemistry and Pharmacology
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  • 84
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    Springer
    Publication Date: 2018-03-06
    Description: Galectin-9 consists of two peptide-linked carbohydrate recognition domains (CRDs), but alternative splicing and proteolytic processing can give rise to multiple galectin-9 isoforms. Some of these consist of a single CRD and can exert different functions in cell biology. Here, we explored the role of these galectin-9 isoforms in endothelial cell function and angiogenesis. For this, we compared the effects of the two separate CRDs (Gal-9N and Gal-9C) with the tandem repeat galectin-9M on endothelial cell proliferation, migration, sprouting and tube formation in vitro as well as on angiogenesis in vivo using the chicken chorioallantoic membrane (CAM) assay. Galectin-9 isoforms significantly affected proliferation in quiescent endothelial cells and migration in activated endothelial cells. Interestingly, both monovalent gal-9 CRDs displayed opposite effects compared to gal-9M on proliferation and migration. Sprouting was significantly inhibited by gal-9C, while all isoforms appeared to stimulate tube formation. Angiogenesis in vivo was hampered by all three isoforms with predominant effects on vessel length. In general, the isoforms induced only subtle concentration-dependent effects in vitro as well as in vivo. Collectively, the effects of different galectin-9 isoforms in endothelial cell biology depend on the cellular activation status. While opposing effects can be observed on a cellular level in vitro, all galectin-9 isoforms hamper angiogenesis in vivo. This warrants further investigation of the regulatory mechanisms that underlie the diverging roles of galectin-9 isoforms in endothelial cell biology since this could provide therapeutic opportunities.
    Print ISSN: 0969-6970
    Electronic ISSN: 1573-7209
    Topics: Medicine
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  • 85
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    Springer
    Publication Date: 2018-03-06
    Description: High-density lipoprotein (HDL) has previously been shown to promote angiogenesis. However, the mechanisms by which HDL enhances the formation of blood vessels remain to be defined. To address this, the effects of HDL on the proliferation, transwell migration and tube formation of human umbilical vein endothelial cells were investigated. By examining the abundance and phosphorylation (i.e., activation) of the vascular endothelial growth factor receptor VEGFR2 and modulating the activity of the sphingosine-1 phosphate receptors S1P1–3 and VEGFR2, we characterized mechanisms controlling angiogenic responses in response to HDL exposure. Here, we report that HDL dose-dependently increased endothelial proliferation, migration and tube formation. These events were in association with increased VEGFR2 abundance and rapid VEGFR2 phosphorylation at Tyr1054/Tyr1059 and Tyr1175 residues in response to HDL. Blockade of VEGFR2 activation by the VEGFR2 inhibitor SU1498 markedly abrogated the pro-angiogenic capacity of HDL. Moreover, the S1P3 inhibitor suramin prevented VEGFR2 expression and abolished endothelial migration and tube formation, while the S1P1 agonist CYM-5442 and the S1P2 inhibitor JTE-013 had no effect. Last, the role of S1P3 was further confirmed in regulation of S1P-induced endothelial proliferation, migration and tube formation via up-regulation and activation of VEGFR2. Together, these findings argue that HDL promotes angiogenesis via S1P3-dependent up-regulation and activation of VEGFR2 and also suggest that the S1P–S1P3–VEGFR2 signaling cascades as a novel target for HDL-modulating therapy implicated in vascular remodeling and functional recovery in atherosclerotic diseases such as myocardial infarction and ischemic stroke.
    Print ISSN: 0969-6970
    Electronic ISSN: 1573-7209
    Topics: Medicine
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  • 86
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    Springer
    Publication Date: 2018-03-06
    Description: Inflammation in the normally immune-privileged cornea can initiate a pathologic angiogenic response causing vision-threatening corneal neovascularization. Inflammatory pathways, however, are numerous, complex and are activated in a time-dependent manner. Effective resolution of inflammation and associated angiogenesis in the cornea requires knowledge of these pathways and their time dependence, which has, to date, remained largely unexplored. Here, using a m