bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Food, Antacid, and Age on the Pharmacokinetics of the Oral Thrombin Receptor Antagonist Vorapaxar (SCH 530348) in Healthy Volunteers
Authors: Kosoglou Teddy , Reyderman Larisa , Tseng Jack , Kumar Bharath , Xuan Fengjuan , Schiller James , Meehan Alan G. , Kim Kenneth , Cutler David L. 
Published: May 2013

AbstractThis randomized, open‐label, parallel group study examined the effects of food, antacid, and age on the pharmacokinetics of vorapaxar. In total, 101 subjects were enrolled including 83 young adults (18–45 years) and 18 elderly subjects (>65 years). Subjects received single‐dose vorapaxar 40 mg after a 10‐hour fast (young and elderly) or with extra‐strength antacid, food, or 1 or 2 hours after food (young only). Vorapaxar 40 mg was rapidly absorbed after a fast (median Tmax: 1 hour). Administration with food or 1 or 2 hours post‐meal modestly increased vorapaxar mean area under the curve (AUC) and Cmax and prolonged median Tmax by 1 hour. Concomitant food modestly increased vorapaxar AUC from time zero to infinity [AUC(I)] and Cmax 43% and 31%, respectively. Antacid modestly decreased vorapaxar AUC(I) by 15% and Cmax by 38%, and increased median Tmax by 1 hour. Vorapaxar AUC(I) and Cmax were 41% and 29% higher, respectively, in elderly versus young subjects. Concomitant food and older age were associated with modest increases, and antacid was associated with a small decrease in vorapaxar exposure, which are not expected to affect the drug's safety or efficacy.
Patterns of ecological specialization among microbial populations in the Red Sea and diverse oligotrophic marine environments
Authors: Thompson Luke R. , Field Chris , Romanuk Tamara , Kamanda Ngugi David , Siam Rania , El Dorry Hamza , Stingl Ulrich 
Published: May 2013

AbstractLarge swaths of the nutrient‐poor surface ocean are dominated numerically by cyanobacteria (Prochlorococcus), cyanobacterial viruses (cyanophage), and alphaproteobacteria (SAR11). How these groups thrive in the diverse physicochemical environments of different oceanic regions remains poorly understood. Comparative metagenomics can reveal adaptive responses linked to ecosystem‐specific selective pressures. The Red Sea is well‐suited for studying adaptation of pelagic‐microbes, with salinities, temperatures, and light levels at the extreme end for the surface ocean, and low nutrient concentrations, yet no metagenomic studies have been done there. The Red Sea (high salinity, high light, low N and P) compares favorably with the Mediterranean Sea (high salinity, low P), Sargasso Sea (low P), and North Pacific Subtropical Gyre (high light, low N). We quantified the relative abundance of genetic functions among Prochlorococcus, cyanophage, and SAR11 from these four regions. Gene frequencies indicate selection for phosphorus acquisition (Mediterranean/Sargasso), DNA repair and high‐light responses (Red Sea/Pacific Prochlorococcus), and osmolyte C1 oxidation (Red Sea/Mediterranean SAR11). The unexpected connection between salinity‐dependent osmolyte production and SAR11 C1 metabolism represents a potentially major coevolutionary adaptation and biogeochemical flux. Among Prochlorococcus and cyanophage, genes enriched in specific environments had ecotype distributions similar to nonenriched genes, suggesting that inter‐ecotype gene transfer is not a major source of environment‐specific adaptation. Clustering of metagenomes using gene frequencies shows similarities in populations (Red Sea with Pacific, Mediterranean with Sargasso) that belie their geographic distances. Taken together, the genetic functions enriched in specific environments indicate competitive strategies for maintaining carrying capacity in the face of physical stressors and low nutrient availability.
Estimating streambed parameters for a disconnected river
Authors: Wang Wenke , Li Junting , Wang Wenming , Chen Xunhong , Cheng Donghui , Jia Jia 
Published: May 2013

AbstractEvaluation of stream–aquifer interaction and water balance for a catchment often requires specific information on streambed parameters, such as streambed hydraulic conductivity, seepage flux across the streambed and so on. This paper describes a simple, inexpensive instrument that is used to measure these streambed parameters under the condition of a stream disconnected from groundwater. Our method includes a seepage cylinder for simulation of river water depth. The proposed method was applied to estimate the vertical hydraulic conductivity of a streambed and the changes in vertical seepage rate from stream to groundwater with varied stream water depth in the Manasi River of Xinjiang Uygur Autonomous Region, China. The vertical hydraulic conductivities of the streambed determined from 12 sites along the Manasi River vary from 1.01 to 29.m/day where the stream disconnects from the groundwater. The experimental results suggest that there are two kinds of relations between the vertical seepage rate and the simulated stream water depth. One is a linear relation between the two variables with low Reynolds numbers (less than 10); the other is a nonlinear relation (exponential relation) between the two variables with larger Reynolds numbers (greater than 10). This second relationship is quite different from the traditional model that usually calculates the vertical seepage rate from stream to groundwater under the condition of disconnection using a linear relation (Darcy's Law). Our results suggest that a linear relation can only be used for a limited range of river water depth. This method gives a convenient tool for rapidly estimating the streambed hydraulic conductivity and the changes in the vertical seepage rate across streambed with varied stream water depths for the case of a stream disconnected from groundwater. Copyright © 2013 John Wiley & Sons, Ltd.
Pharmacokinetics and Pharmacodynamics of Canagliflozin, a Sodium Glucose Co‐Transporter 2 Inhibitor, in Subjects With Type 2 Diabetes Mellitus
Authors: Devineni Damayanthi , Curtin Christopher R. , Polidori David , Gutierrez Maria J. , Murphy Joseph , Rusch Sarah , Rothenberg Paul L. 
Published: May 2013

AbstractThis study characterized single‐ and multiple‐dose pharmacokinetics of canagliflozin and its O‐glucuronide metabolites (M5 and M7) and pharmacodynamics (renal threshold for glucose [RTG], urinary glucose excretion [UGE0–24h], and 24‐hour mean plasma glucose [MPG0–24h]) of canagliflozin in subjects with type 2 diabetes. Thirty‐six randomized subjects received canagliflozin 50, 100, or 300 mg/day or placebo for 7 days. On Days 1 and 7, area under the plasma concentration‐time curve and maximum observed plasma concentration (Cmax) for canagliflozin and its metabolites increased dose‐dependently. Half‐life and time at which Cmax was observed were dose‐independent. Systemic molar M5 exposure was half that of canagliflozin; M7 exposure was similar to canagliflozin. Steady‐state plasma canagliflozin concentrations were reached by Day 4 in all active treatment groups. Pharmacodynamic effects were dose‐ and exposure‐dependent. All canagliflozin doses decreased RTG, increased UGE0–24h, and reduced MPG0–24h versus placebo on Days 1 and 7. On Day 7, placebo‐subtracted least‐squares mean decreases in MPG0–24h ranged from 42–57 mg/dL with canagliflozin treatment. Adverse events (AEs) were balanced between treatments; no treatment‐related serious AEs, AE‐related discontinuations, or clinically meaningful adverse changes in routine safety evaluations occurred. The observed pharmacokinetic/pharmacodynamic profile of canagliflozin in subjects with type 2 diabetes supports a once‐daily dosing regimen.
Potential of fibrous adsorbents for the binding and characterization of Porphyridium purpureum bioactive polysaccharides
Authors: Rwehumbiza Vincent M. , Vennapusa Rami Reddy , Gavara Poondi R. , Fernández‐Lahore Héctor M. , Al‐Karablieh Nehaya , Ullrich Matthias S. , Thomsen Claudia 
Published: May 2013

AbstractBACKGROUNDComplex polysaccharides are important in the pharmaceutical industry, yet, due to their large molecular weight and reduced charges, their purification is a highly demanding process that requires binding matrices with unique properties. This work demonstrates for the first time that complex polysaccharides biosynthesized by microalga Porphyridium purpureum can be adsorbed onto Q fibrous anion exchangers.RESULTSWhen the polysaccharides were characterized, the extent of sulfation was higher in native polysaccharides than in ethanol‐ or alkali‐extracts. The zeta potentials increased with increasing pH and the highest charge was observed at pH 8, while the Z‐average diameters of the polysaccharide at pH 6 were highest for alkali‐extracts. Instead of pellicular resins, Q fibrous adsorbents were used to determine Langmuir thermodynamic properties and dynamic binding capacities. The parameters included static binding capacity and dissociation constant of 13.47 ± 1.02 mg g‐1 and 0.141 ± 0.027 mg mL‐1, and 10 and 50% breakthrough capacities of 4.46 ± 0.22 and 5.51 ± 0.28 mg g‐1, respectively. The antiviral activity of the polysaccharides was demonstrated by minimizing bacteriophage lysis of Streptococcus thermophilus.CONCLUSIONThis work demonstrates that polysaccharide extraction can be optimized and the adsorption and desorption of a complex polysaccharide onto Q fibrous matrix is feasible. These parameters could be exploited for up‐scaling of polysaccharides for nutraceutical and pharmaceutical applications. © 2013 Society of Chemical Industry
Substrate versus inhibitor dynamics of P‐glycoprotein
Authors: Ma Jerome , Biggin Philip C. 
Published: May 2013

ABSTRACTBy far the most studied multidrug resistance protein is P‐glycoprotein. Despite recent structural data, key questions about its function remain. P‐glycoprotein (P‐gp) is flexible and undergoes large conformational changes as part of its function and in this respect, details not only of the export cycle, but also the recognition stage are currently lacking. Given the flexibility, molecular dynamics (MD) simulations provide an ideal tool to examine this aspect in detail. We have performed MD simulations to examine the behaviour of P‐gp. In agreement with previous reports, we found that P‐gp undergoes large conformational changes which tended to result in the nucleotide‐binding domains coming closer together. In all simulations, the approach of the NBDs was asymmetrical in agreement with previous observations for other ABC transporter proteins. To validate the simulations, we make extensive comparison to previous cross‐linking data. Our results show very good agreement with the available data. We then went on to compare the influence of inhibitor compounds bound with simulations of a substrate (daunorubicin) bound. Our results suggest that inhibitors may work by keeping the NBDs apart, thus preventing ATP‐hydrolysis. On the other hand, repeat simulations of daunorubicin (substrate) in one particular binding pose suggest that the approach of the NBDs is not impaired and that the structure would be still be competent to perform ATP hydrolysis, thus providing a model for inhibition or substrate transport. Finally we compare the latter to earlier QSAR data to provide a model for the first part of substrate transport within P‐gp. Proteins 2013. © 2013 Wiley Periodicals, Inc.
Vector control and foliar nutrition to maintain economic sustainability of bearing citrus in Florida groves affected by huanglongbing
Authors: Stansly Philip A , Arevalo H Alejandro , Qureshi Jawwad A , Jones Moneen M , Hendricks Katherine , Roberts Pamela D , Roka Fritz M 
Published: May 2013

AbstractBACKGROUNDHuanglongbing (HLB) or citrus greening is a bacterial disease vectored by the Asian citrus psyllid (ACP) causing tree decline, and yield loss. Vector control and foliar nutrition are used in Florida to slow the spread of HLB and mitigate debilitating effects of the disease.A four year replicated field study was initiated February 2008 in a 5.2‐ha commercial block of young ‘Valencia’ orange trees employing a factorial design to evaluate individual and compound effects of vector management and foliar nutrition. Insecticides were sprayed during tree dormancy and when psyllid populations exceeded a nominal threshold. A mixture consisting primarily of micro‐ and macro‐nutrients was applied three times a year corresponding to the principal foliar flushes.RESULTSDifferences in ACP numbers from five‐ to 13‐fold were maintained in insecticide treated and untreated plots. Incidence of HLB estimated by polymerase chain reaction (PCR), rose from 30% at the beginning of the study to 95% in only 18 months. Highest yields all four years were seen from trees receiving both foliar nutrition and vector control. Production for these trees in the fourth year was close to the pre‐HLB regional average for 10 year old ‘Valencia’ on ‘Swingle’. Nevertheless, at current juice prices, the extra revenue generated from the combined insecticide and nutritional treatment did not cover the added treatment costs.CONCLUSIONSThis experiment demonstrated that vector control, especially when combined with enhanced foliar nutrition, could significantly increase yields in a citrus orchard with high incidence of HLB. Economic thresholds for both insecticide and nutrient applications are needed under different market and environmental conditions.
Validation of PREDICCS using LRO/CRaTER observations during three major solar events in 2012
Authors: Joyce C. J. , Schwadron N. A. , Wilson J. K. , Spence H. E. , Kasper J. C. , Golightly M. , Blake J. B. , Mazur J. , Townsend L. W. , Case A. W. , Semones E. , Smith S. , Zeitlin C. J. 
Published: May 2013

AbstractPREDICCS (Predictions of Radiation from Release, EMMREM, and Data Incorporating the CRaTER, COSTEP and other SEP measurements, prediccs.sr.unh.edu) is an online system designed to provide a near real‐time characterization of the radiation environment of the inner heliosphere. PREDICCS utilizes data from various satellites in conjunction with numerical models such as the Earth‐Moon‐Mars Radiation Environment Module (EMMREM) to produce dose rate and particle flux data at the Earth, Moon and Mars. The Cosmic Ray Telescope for the Effects of Radiation (CRaTER) instrument launched aboard the Lunar Reconnaissance Orbiter (LRO) spacecraft in 2009 and designed to measure energetic particle radiation, offers an opportunity to test the capability of PREDICCS to accurately describe the lunar radiation environment. We provide comparisons between dose rates produced by PREDICCS with those measured by CRaTER during three major solar energetic particle (SEP) events that occurred in 2012. In addition, using EMMREM data products together with our archive of measured CRaTER dose rates, we compute the modulation potential at the Moon throughout the LRO mission and, using this, compute the background GCR dose rate during each event. We demonstrate reasonable agreement between PREDICCS and CRaTER dose rates and come to the conclusion that PREDICCS provides credible characterization of the lunar radiation environment. This study represents the first multi‐event validation, via in situ measurement, of radiation models such as EMMREM, which should prove to be valuable in future efforts in risk assessment and in the study of radiation in the inner heliosphere.
Robot‐assisted Gastrectomy for Gastric Cancer: Current Status and Technical Considerations
Authors: Coratti Andrea , Annecchiarico Mario , Di Marino Michele , Gentile Edoardo , Coratti Francesco , Giulianotti Pier Cristoforo 
Published: May 2013

AbstractBackgroundRobot‐assisted gastrectomy has been reported as a safe alternative to the conventional laparoscopy or open approach for treating early gastric carcinoma. To date, however, there are a limited number of published reports available in the literature.MethodsWe assess the current status of robotic surgery in the treatment of gastric cancer, focusing on the technical details and oncological considerations.ResultsIn gastric surgery, the biggest advantage of robotic surgery is the ease and reproducibility of D2‐lymphadenectomy. Reports show that even the intracorporeal digestive restoration is facilitated by use of the robotic approach, particularly following total gastrectomy. Additionally, the accuracy of robotic dissection is confirmed by decreased blood loss, as reported in series comparing robot‐assisted with laparoscopic gastrectomy. The learning curve and technical reproducibility also appear to be shorter with robotic surgery and, consequently, robotics can help to standardize and diffuse minimally invasive surgery in the treatment of gastric cancer, even in the later stages. This is important because the application of minimally invasive surgery is limited by the complexity of performing a D2‐lymphadenectomy. The potential to reproduce D2‐lymphadenectomy, enlarged resections, and complex reconstructions provides robotic surgery with an important role in the therapeutic strategy of advanced gastric cancer.ConclusionsWhile published reports have shown no significant differences in surgical morbidity, mortality, or oncological adequacy between robot‐assisted and conventional laparoscopic gastrectomy, more studies are needed to assess the indications and oncological effectiveness of robotic use in the treatment of gastric carcinoma. Herein, the authors assess the current status of robotic surgery in the treatment of gastric cancer, focusing on the technical details and oncological considerations.
Positional Variations in Mammary Gland Development and Cancer
Authors: Veltmaat Jacqueline M. , Ramsdell Ann F. , Sterneck Esta 
Published: May 2013

Abstract
Most mammals develop their mammary glands in pairs of which the two counterparts are symmetrically displaced away from the ventral midline. Based on this symmetry and the same functional outcome as a milk-producing organ, the mammary glands are easily presumed to be mere copies of one another. Based on our analysis of published data with inclusion of new results related to mammary development and pathology in mice, we argue that this presumption is incorrect: Between and within pairs, mammary glands differ from one another, and tumor incidence and biology depend on the position along the anterior-posterior and the left-right axis as well. This insight has implications for experimental designs with mouse models and for data extrapolation between mammary glands within and between species. We suggest that improved documentation of location-specific mammary gland features will lead to more insights into the molecular mechanisms of mammary gland development and cancer biology in both mice and humans.
A statistical framework for power calculations in ChIP-seq experiments
Authors: Zuo Chandler , Keleş Sündüz 
Published: May 2013

AbstractMotivation: ChIP-seq technology enables investigators to study genome-wide binding of transcription factors and mapping of epigenomic marks. Although the availability of basic analysis tools for ChIP-seq data is rapidly increasing, there has not been much progress on the related design issues. A challenging question for designing a ChIP-seq experiment is how deeply should the ChIP and the control samples be sequenced? The answer depends on multiple factors some of which can be set by the experimenter based on pilot/preliminary data. The sequencing depth of a ChIP-seq experiment is one of the key factors that determine whether all the underlying targets (e.g. binding locations or epigenomic profiles) can be identified with a targeted power.Results: We developed a statistical framework named CSSP (ChIP-seq Statistical Power) for power calculations in ChIP-seq experiments by considering a local Poisson model, which is commonly adopted by many peak callers. Evaluations with simulations and data-driven computational experiments demonstrate that this framework can reliably estimate the power of a ChIP-seq experiment at different sequencing depths based on pilot data. Furthermore, it provides an analytical approach for calculating the required depth for a targeted power while controlling the false discovery rate at a user-specified level. Hence, our results enable researchers to use their own or publicly available data for determining required sequencing depths of their ChIP-seq experiments and potentially make better use of the multiplexing functionality of the sequencers. Evaluation of power for multiple public ChIP-seq datasets indicate that, currently, typical ChIP-seq studies are powered well for detecting large fold changes of ChIP enrichment over the control sample, but they have considerably less power for detecting smaller fold changes.Availability: Available at www.stat.wisc.edu/∼zuo/CSSP.Contact: keles@stat.wisc.eduSupplementary information: Supplementary data are available at Bioinformatics online.
GAGE-B: an evaluation of genome assemblers for bacterial organisms
Authors: Magoc Tanja , Pabinger Stephan , Canzar Stefan , Liu Xinyue , Su Qi , Puiu Daniela , Tallon Luke J. , Salzberg Steven L. 
Published: May 2013

Abstract
Motivation: A large and rapidly growing number of bacterial organisms have been sequenced by the newest sequencing technologies. Cheaper and faster sequencing technologies make it easy to generate very high coverage of bacterial genomes, but these advances mean that DNA preparation costs can exceed the cost of sequencing for small genomes. The need to contain costs often results in the creation of only a single sequencing library, which in turn introduces new challenges for genome assembly methods.
Results: We evaluated the ability of multiple genome assembly programs to assemble bacterial genomes from a single, deep-coverage library. For our comparison, we chose bacterial species spanning a wide range of GC content and measured the contiguity and accuracy of the resulting assemblies. We compared the assemblies produced by this very high-coverage, one-library strategy to the best assemblies created by two-library sequencing, and we found that remarkably good bacterial assemblies are possible with just one library. We also measured the effect of read length and depth of coverage on assembly quality and determined the values that provide the best results with current algorithms.
Contact: salzberg@jhu.edu
Supplementary information: Supplementary data are available at Bioinformatics online.