bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of in-vivo pharmacokinetic profile for immediate and modified release oral dosage forms of furosemide using an in-vitro–in-silico–in-vivo approach
Authors: Otsuka Keiichi , Wagner Christian , Selen Arzu , Dressman Jennifer 
Published: February 2015

Abstract

Objectives
To develop a physiologically based pharmacokinetic (PBPK) model for furosemide immediate release (IR) tablets and modified release (MR) capsules by coupling biorelevant dissolution testing results with pharmacokinetic (PK) and physiologic parameters, and to investigate the key factors influencing furosemide absorption using simulation approaches and the PBPK model.

Methods
Using solubility, dissolution kinetics, gastrointestinal (GI) parameters and disposition parameters, a PBPK model for furosemide was developed with STELLA software. Solubility and dissolution profiles for both formulations were evaluated in biorelevant and compendial media. The simulated plasma profiles were compared with in-vivo profiles using point estimates of area under plasma concentration-time curve, maximal concentration after the dose and time to maximal concentration after the dose.

Key findings
Simulated plasma profiles of both furosemide IR tablets and MR capsules were similar to the observed in-vivo profile in terms of PK parameters. Sensitivity analysis of the IR tablet model indicated that both the gastric emptying and absorption rate have an influence on the plasma profile. For the MR capsules, the sensitivity analysis suggested that the release rate in the small intestine, gastric emptying and the absorption rate all have an influence on the plasma profile.

Conclusions
A predictive model to describe both IR and MR dosage forms containing furosemide was attained. Because sensitivity analysis of the model is able to identify key factors influencing the plasma profile, this in-vitro–in-silico–in-vivo approach could be a useful tool for facilitating formulation development of drug products.
Danshen (S
alvia miltiorrhiza) water extract inhibits paracetamol-induced toxicity in primary rat hepatocytes via reducing CYP2E1 activity and oxidative stress
Authors: Zhou Xuelin , Cheung Ching Mei , Yang Jia-ming , Or Penelope M Y , Lee Wayne Y W , Yeung John H K 
Published: February 2015

Abstract

Objectives
This study aimed to investigate the protective effects of Danshen (Salvia miltiorrhiza) water extract (DSE) and its major phenolic acid components against CYP2E1-mediated paracetamol (APAP)-induced hepatic toxicity.

Methods
The protection and underlying mechanisms were detected in CYP2E1 overexpression primary rat hepatocytes by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, alamar blue assay, CYP2E1 inhibition assay and glutathione assay.

Key findings
After APAP treatment, DSE (0.06–1 mg/ml) significantly increased cell viability in MTT assay. Two major components danshensu (8.2–130.5 μm) and salvianolic acid B (Sal B; 3.3–53.5 μm) mainly contributed to this protection, but rosmarinic acid, protocatechuic aldehyde and Sal A did not. Alamar blue assay showed that DSE, danshensu and Sal B maintained mitochondrial metabolic activity. DSE inhibited CYP2E1 (Ki = 1.46 mg/ml) in a mixed mode in rat liver microsomes in vitro; DSE decreased APAP-induced total glutathione depletion and preserved redox status (GSH/GSSG ratio) in hepatocytes. Danshensu and Sal B did not inhibit CYP2E1 or decrease total glutathione depletion, but preserved redox status.

Conclusions
DSE protected hepatocytes against APAP-induced injury via maintenance of mitochondrial metabolic activity, CYP2E1 inhibition, reduction of total glutathione depletion and preservation of redox status. Danshensu and Sal B were mainly responsible for this protection.
Genetic variability and taxonomic revision of the genus Auxenochlorella (Shihira et Krauss) Kalina et Puncocharova (Trebouxiophyceae, Chlorophyta)
Authors: Darienko Tatyana , Pröschold Thomas 
Published: February 2015

The monotypic genus Auxenochlorella with its type species A. protothecoides is so far only known from specific habitats such as the sap of several tree species. Several varieties were described according to physiological performances in culture on different organic substrates. However, two strains designated as Auxenochlorella were isolated from other habitats (an endosymbiont of Hydra viridis and an aquatic strain from an acidic volcano stream). We studied those isolates and compared them with six strains of Auxenochlorella belonging to different varieties. The integrative approach used in this study revealed that all strains showed similar morphology but differed in their SSU and ITS rDNA sequences. The Hydra endosymbiont formed a sister taxon to A. protothecoides, which included the varieties protothecoides, galactophila, and communis. The variety acidicola is not closely related to Auxenochlorella and represented its own lineage within the Trebouxiophyceae. In view of these results, we propose a new species of Auxenochlorella, A. symbiontica, for the Hydra symbiont, and a new genus Pumiliosphaera, with its type species, P. acidophila, for acidophilic strain. These results are supported by several compensatory base changes in the conserved region of ITS‐2 and ITS‐2 DNA barcodes.
Biofilm and capsule formation of the diatom Achnanthidium minutissimum are affected by a bacterium
Authors: Windler Miriam , Leinweber Katrin , Bartulos Carolina Rio , Philipp Bodo , Kroth Peter G. 
Published: February 2015

Photoautotrophic biofilms play an important role in various aquatic habitats and are composed of prokaryotic and/or eukaryotic organisms embedded in extracellular polymeric substances (EPS). We have isolated diatoms as well as bacteria from freshwater biofilms to study organismal interactions between representative isolates. We found that bacteria have a strong impact on the biofilm formation of the pennate diatom Achnanthidium minutissimum. This alga produces extracellular capsules of insoluble EPS, mostly carbohydrates (CHO), only in the presence of bacteria (xenic culture). The EPS themselves also have a strong impact on the aggregation and attachment of the algae. In the absence of bacteria (axenic culture), A. minutissimum did not form capsules and the cells grew completely suspended. Fractionation and quantification of CHO revealed that the diatom in axenic culture produces large amounts of soluble CHO, whereas in the xenic culture mainly insoluble CHO were detected. For investigation of biofilm formation by A. minutissimum, a bioassay was established using a diatom satellite Bacteroidetes bacterium that had been shown to induce capsule formation of A. minutissimum. Interestingly, capsule and biofilm induction can be achieved by addition of bacterial spent medium, indicating that soluble hydrophobic molecules produced by the bacterium may mediate the diatom/bacteria interaction. With the designed bioassay, a reliable tool is now available to study the chemical interactions between diatoms and bacteria with consequences for biofilm formation.
Phylogeny of Gracilariaceae (Rhodophyta): evidence from plastid and mitochondrial nucleotide sequences
Authors: Lyra Goia de M. , Costa Emmanuelle da S. , de Jesus Priscila B. , de Matos João Carlos G. , Caires Taiara A. , Oliveira Mariana C. , Oliveira Eurico C. , Xi Zhenxiang , Nunes José Marcos de C. , Davis Charles C. 
Published: February 2015

Gracilariaceae are mostly pantropical red algae and include ~230 species in seven genera. Infrafamilial classification of the group has long been based on reproductive characters, but previous phylogenies have shown that traditionally circumscribed groups are not monophyletic. We performed phylogenetic analyses using two plastid (universal plastid amplicon and rbcL) and one mitochondrial (cox1) loci from a greatly expanded number of taxa to better assess generic relationships and understand patterns of character distributions. Our analyses produce the most well‐supported phylogeny of the family to date, and indicate that key characteristics of spermatangia and cystocarp type do not delineate genera as commonly suggested. Our results further indicate that Hydropuntia is not monophyletic. Given their morphological overlap with closely related members of Gracilaria, we propose that Hydropuntia be synonymized with the former. Our results additionally expand the known ranges of several Gracilariaceae species to include Brazil. Lastly, we demonstrate that the recently described Gracilaria yoneshigueana should be synonymized as G. domingensis based on morphological and molecular characters. These results demonstrate the utility of DNA barcoding for understanding poorly known and fragmentary materials of cryptic red algae.
Physical Parameter Identification of Structural Systems with Hysteretic Pinching
Authors: Zhou Cong , Chase* J. Geoffrey , Rodgers Geoffrey W. , Tomlinson Hamish , Xu Chao 
Published: February 2015

AbstractThis research investigates the physical parameter identification of a nonlinear hysteretic structure with pinching behavior for real‐time or rapid structural health monitoring (SHM) after a major seismic event. The identification procedure is based on the overall least squares linear regression and hypothesis testing. It is applied to a general, nonlinear slip‐lock (SL) pinching model. In particular, the hysteresis loop is reconstructed using data available from current sensor technologies. The path dependent hysteresis response is first divided into different loading and unloading subhalf cycles with a single valued function. These subhalf cycles are then assumed to be piecewise linear, and the number of segments for each subhalf cycle is identified using the sup F type test. The overall least squares linear regression is finally applied to the identified subhalf cycles to compute the regression coefficients and breakpoints that yield the elastic stiffness, plastic stiffness, and cumulative plastic deformation. The performance and robustness of the proposed method is illustrated using a single degree of freedom shear‐type reinforced concrete structure with 10% added root mean square noise and variable pinching behavior. The proposed method is shown to be computationally efficient and accurate in identifying the damage parameters within 10% of true values. These results indicate that the system is able to capture nonlinear behavior and structural parameters, such as preyielding stiffness, postyielding stiffness and cumulative plastic deformation, directly relevant to damage and performance using a computationally efficient and simple method. Finally, the method requires no user input and could thus be automated and performed in real time for each half cycle, with results available effectively immediately after an event, as well as during an event, if required.
Centrally targeted pharmacotherapy for chronic abdominal pain
Authors: Törnblom H. , Drossman D. A. 
Published: February 2015

AbstractBackgroundChronic abdominal pain in the context of the functional gastrointestinal disorders departs from a more traditional approach to treating gastrointestinal symptoms. Chronic abdominal pain involves a dysregulation of brain‐gut modulation of afferent signaling, so treatments directed toward the gut are not usually sufficient to achieve a clinical response. Rather the methods of treatment depend on re‐establishing central pain regulation.PurposeA conceptual model of predisposing, precipitating, and perpetuating factors is used to explain how a situation of chronic pain develops and it provides the evidence for central neuron degeneration as relevant to this chain of events. The rationale for centrally targeted medications, in particular antidepressants, is discussed with regard to effects independent of their role in treating psychiatric disorders: with regard to downregulation of afferent pain signals and their potential role in neuron proliferation. Finally, guiding examples of which drug to use and treatment combinations involving multiple drugs, augmentation treatment, are outlined and some brief clinical cases of centrally targeted pharmacotherapy.
Factors Associated with Unintentional Injury among University Students in 26 Countries
Authors: Peltzer Karl , Pengpid Supa 
Published: February 2015

AbstractObjectiveThe aim of this study was to determine estimates of the incidence and social correlates of nonfatal injury among university students in 26 low‐, middle‐, and high‐income countries.Design and SampleUsing anonymous questionnaires, data were collected in a cross‐sectional survey of 19,111 undergraduate university students (mean age 20.8, SD = 2.8) from 27 universities in 26 countries across Asia, Africa, and the Americas.MeasuresQuestionnaire on health risk behaviors, psychological distress, personality, social variables, and injury requiring medical treatment or missing at least one day of usual activities.ResultsThe percentage of university students reporting one or more serious injuries within the past 12 months was 25.2% for all countries, in men 28.8% and women 21.1%. In multivariate logistic regression among men, socio‐demographic variables, health risk behaviors, posttraumatic stress (PTSD) symptoms, lack of personal control and lack of social support, and among women, residing on campus, health risk behaviors, PTSD symptoms, lack of personal control, and lack of social support were associated with injury incidence.ConclusionsSeveral risk factors were identified which will increase the understanding of public health nurses of injuries in university communities to design programs for injury prevention programs specifically targeting university students, staff, and university health center professionals.
Effectiveness of triploidy as a management tool for reproductive containment of farmed fish: Atlantic salmon (Salmo salar) as a case study
Authors: Benfey Tillmann J. 
Published: February 2015

AbstractAtlantic salmon (Salmo salar) dominates aquaculture production in its native North Atlantic range, raising concerns about the impacts of escaped farmed fish on wild populations. While physical confinement and operational management practices have improved steadily with the development of this industry, some escapes are inevitable. In the absence of effective measures for the rapid recapture of escaped fish, the only practical method currently available to minimize their impacts on wild populations is to ensure that they are female triploids and therefore reproductively sterile. The technology for producing all‐female triploid populations of Atlantic salmon is simple and easily applied on a commercial scale, and routinely results in populations that are entirely female and >98% triploid. Aside from sterility, there are no population‐wide phenotypic effects of triploidy, although triploids do tend to perform less well than diploids with respect to commercial culture characteristics and are also less likely than escaped diploids to outcompete or displace native salmon. Some uncertainties exist with respect to their disease resistance and their potential to become reservoirs for the spread of pathogens to wild populations. If the spawning potential of escaped farmed Atlantic salmon is deemed to pose an unacceptable risk to native populations, then all‐female triploid populations could be used as an alternative to reduce risk. Research should continue to focus on improving triploid performance through breeding programmes and optimization of husbandry conditions (including nutrition, environmental conditions and fish health), with the goal of making triploids an attractive option for fish farmers.
Respiratory disease and respiratory physiology: Putting lung function into perspective: Paediatric asthma
Authors: van den Wijngaart Lara S. , Roukema Jolt , Merkus Peter J.F.M. 
Published: February 2015

AbstractDealing with paediatric asthma in daily practice, we are mostly interested in the airway function: the hallmark of asthma is the variability of airway patency. Various pulmonary function tests (PFT) can be used to quantify airway caliber in asthmatic children. The choice of the test is based on the developmental age of the child, knowledge of the diagnosis/underlying pathophysiology, clinical questions and reasoning, and treatment. PFT is performed to monitor the severity of asthma and the response to therapy, but can also be used as a diagnostic tool, and to study growth and development of the lungs and airways. This review aims to provide clinicians an overview of the differences in assessing PFT in infants and preschool children compared with older cooperative children, which tests are feasible in infants and young children, the limitations of and usefulness of these tests, and of their interpretation in these age groups.
Does Preferential Trade Benefit Poor Countries? A General Equilibrium Assessment with Nonhomothetic Preferences
Authors: Stibora Joachim , de Vaal Albert 
Published: February 2015

AbstractWe develop a Ricardian model of trade with nonhomothetic preferences to analyze preferential trade agreements (PTAs) among countries of different stages of economic development. The richer a country is, the more likely will PTAs improve its terms of trade, also when it is a non‐member. Rich non‐member countries are also less likely to incur welfare losses from PTAs. PTA membership only guarantees welfare gains for countries that are too poor to import the goods rich countries produce. For all other countries, the welfare effects of joining PTAs depend on the world income distribution and on the strength of comparative advantages.
Spillovers in Sports Leagues with Promotion and Relegation
Authors: Dietl Helmut , Grossmann Martin , Hefti Andreas , Lang Markus 
Published: February 2015

AbstractThis paper analyzes spillover effects in sports leagues that are embedded in a system of promotion and relegation. Based on a contest model of a professional sports league with a top division and a second division, we show that league prizes and club efficiencies have opposing effects; while a stronger second division that offers a higher league prize leads to a more balanced top division, the opposite is true for a stronger second division whose clubs become more cost efficient. Moreover, we demonstrate that a higher second‐division prize induces a lower investment level, but higher profits in the top division, while higher club efficiency in the second division leads to both a lower investment level and lower profits in the top division. These results have important policy implications for the organization of sports leagues.
The Economics of Long‐term Contracts in the Footballers' Labour Market
Authors: Buraimo Babatunde , Frick Bernd , Hickfang Michael , Simmons Rob 
Published: February 2015

AbstractPeter Sloane's seminal article in this journal on the objectives of football clubs argued that utility maximising clubs would seek out player talent more aggressively than profit maximising clubs and that this accumulation of player talent by larger teams might need to be checked by redistribution of revenues. We suggest in this article that, in a context of rising revenues and high rewards, the pressures to acquire more and better talent so as to out‐perform other teams on the football pitch leads to a requirement for teams to practise effective contract management. Using a large dataset from the German Bundesliga, we find that players with longer term contracts perform better, ceteris paribus. Hence, selection effects in the award of long‐term contracts dominate moral hazard (shirking) effects in the Bundesliga.
Sportsman Leagues
Authors: Vrooman John 
Published: February 2015

AbstractThis paper compares duopsony profit‐maximization and sportsman leagues and analyzes the effects of revenue sharing in both leagues. This involves formulation of a duopsony model that compares game‐theoretic approaches and price‐taking models. This duopsony game is played in open and closed talent markets with a supply function that approaches perfect inelasticity in the limit. The analysis explores welfare optimality of competitive balance, fan preference and revenue sharing. Revenue sharing minimizes payrolls and reduces overall talent in profit‐max leagues. This leads to the conclusion that a sportsman league with optimal revenue sharing is welfare superior.
Structural contribution from the Oman ophiolite to processes of crustal accretion at the East Pacific Rise
Authors: Nicolas Adolphe , Boudier Françoise 
Published: February 2015

AbstractA comprehensive model for the activity of the elementary accretion segment at fast‐spreading ridges relies on integration of structural data from the Oman ophiolite and geophysical results from the East Pacific Rise (EPR) around 9°N, which are of comparable size and spreading rates. The axial melt lens at shallow crustal level provides a link between Deval segmentation at the seafloor and a lower melt sill at Moho level, imaged at the EPR as a crustal melt zone (CMZ) and mapped in Oman as the Moho transition zone (MTZ). Both are attached to a mantle upwelling at the EPR, and to a frozen diapir in Oman. The physical link between diapiric mantle uprising at the Moho and Devals segmentation at the seafloor is the melt being injected from the mantle into the lower MTZ, ponding there, and then being released by powerful injections into the upper melt lens. The magma chamber covers the diapir at a distance of 5 km from the ridge axis.
Self‐consistent subduction initiation induced by mantle flow
Authors: Lu Gang , Kaus Boris J.P. , Zhao Liang , Zheng Tianyu 
Published: February 2015

AbstractMantle circulation in planets with strongly temperature‐dependent viscosity results in stagnant‐lid convection. It is fundamental to understand how this stagnant‐lid regime can change into a plate‐like convection regime as on the present‐day Earth. Here, we use 2D numerical models to study subduction initiation from an initial stagnant lid with laboratory‐consistent parameters and without pre‐existing weak zones or kinematic boundary conditions. Our results show that subduction can be initiated dynamically as a result of a thermal localization instability. The lithosphere may deform in a stagnant‐lid mode, an un‐necking mode, a symmetric‐subduction mode or an asymmetric‐subduction mode. The asymmetric‐subduction mode occurs only for relatively large friction angles and moderate thermal ages, and the presence of heterogeneities increases the parameter space of this mode. The limited parameter space might explain why only the present‐day Earth has plate tectonics, and suggests that the initiation of plate tectonics is more difficult than previously anticipated.
Does subduction polarity control metallogeny? The Mediterranean case
Authors: Nimis Paolo , Omenetto Paolo 
Published: February 2015

AbstractThe distribution of ore‐deposit types in different sectors of the circum‐Mediterranean realm that have been affected by subduction processes since the Cretaceous varies in space and time. Sectors involved in W‐directed subduction (Sardinia, Apennines–Maghrebides, Internal Betics, Tyrrhenian, Western–Eastern Carpathians) are dominated by relatively low‐sulphidation epithermal (±VMS) deposits. Orogens formed by NE‐directed subduction (Dinarides–Hellenides–Pontides–Anatolides–Taurides; DHPAT) were initially dominated by pluton‐related porphyry–skarn–high‐sulphidation epithermal associations. These distinct metallogenic styles can be related to the systematic tectono‐magmatic asymmetry of E–NE‐ and W‐directed subduction systems and are analogous to the relationship observed in circum‐Pacific belts. Exceptions to this simple pattern occurred in the DHPAT in the Cenozoic, when deposit associations typical of both E‐directed and W‐directed systems were formed. Such exceptions are interpreted to reflect superimposition of contrasting subduction trends and inheritance from earlier metallogenic stages (Apuseni) or the interference of subduction processes with subduction‐unrelated extension (Hellenides, West Anatolia).