bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a high‐throughput mass spectrometry based analytical method to support an in vitro OATP1B1 inhibition screening assay
Authors: Wagner Andrew D. , Elkin Lisa , Mosure Kathy , Gallagher Lizbeth , Stavola Lindsey K. , Soars Matthew G. , Shou Wilson 
Published: July 2016

RationaleIt is well known that the organic anion transporting polypeptide 1B1 (OATP1B1) plays a major role in the hepatic uptake of a range of drugs. To this end, it is pivotal that the potential for new molecular entities (NMEs) to inhibit OATP1B1 activity be assessed during early drug discovery. The work reported herein describes the development of a high‐throughput analytical method to measure the clinically relevant probe substrate, pitavastatin, for the in vitro assessment of OATP1B1 inhibition.MethodsDevelopment of an analytical method capable of very fast throughput was crucial for the success of this assay and was accomplished using a system which combines direct, on‐line solid‐phase extraction (SPE) with highly sensitive, label‐free tandem mass spectrometry (MS/MS)‐based detection. Mass spectrometry analysis of pitavastatin, along with the stable isotopically labeled internal standard d5‐pitavastatin, was conducted using positive electrospray ionization (ESI) in selected reaction monitoring (SRM) mode.ResultsThe on‐line SPE‐MS/MS platform demonstrated similar sensitivity, selectivity, reproducibility, linearity and robustness to existing methodologies while achieving analytical cycle times of 10.4 seconds per well. Sensitivity exceeded what was necessary for our assay conditions, with a determined lower limit of quantification (LLOQ) for pitavastatin of 10 pM (picomolar) in assay matrix. Furthermore, the potency of multiple reference compounds was shown to be within 2‐fold of IC50 values generated from liquid chromatography (LC)/MS/MS‐based literature values.ConclusionsA very fast and robust analytical method was successfully developed for the measurement of the clinically relevant OATP1B1 substrate, pitavastatin. The successful development and implementation of this very important early liability screen has helped to facilitate judicious lead candidate progression and will ultimately help build a greater understanding of OATP1B1‐NME interactions, in general. Copyright © 2016 John Wiley & Sons, Ltd.
A Comparison of Main and Side Channel Physical and Water Quality Metrics and Habitat Complexity in the Middle Mississippi River
Authors: Sobotka M. J. , Phelps Q. E. 
Published: July 2016

AbstractWorldwide large rivers have been severely modified by human intervention. Many modifications result in disconnection of the river from floodplain and off‐channel habitats generally characterized by lower velocities and Copyright © 2016 John Wiley & Sons, Ltd. shallower depths relative to the main channel, conditions vital to many organisms. Extensive levees on the Middle Mississippi River (MMR) have cut off backwater systems and disconnected the river from 80% of its floodplain. However, the system is characterized by large side channels associated with islands. We examined a long term data set for differences in physical (e.g. depth and velocity) and water quality metrics (e.g. temperature, suspended solids, dissolved oxygen, chlorophyll, % organic matter) between the main and side channels of a 128‐km reach of the MMR. We compared variability between main and side channels using the coefficient of variation (COV). All metrics differed between habitats. Side channels were shallower with lower velocities and had greater mean and COV of % organic matter and more variable dissolved oxygen concentrations. Velocity, temperature, and suspended solids were similar in the spring. COVs were lowest in both habitats during the spring for all metrics except temperature and DO. Resource management in the MMR tends to focus on maintaining existing side channels because of the difficulty of working in the heavily used navigation channel. This study shows that these actions protect areas that function differently than the main channel for most of the year. However, our results also highlight the need for restoration activities aimed at restoring floodplain connectivity, especially during the spring. Copyright © 2016 John Wiley & Sons, Ltd.
Structural study on the interactions of oxaliplatin and linear DNA
Authors: Zou Yongpeng , Biao Linhai , Xu Fengjie , Liu Ruisi , Liu Zhiguo , Fu Yujie 
Published: July 2016

SummaryDamage to cellular DNA is believed to determine the cytotoxicity of oxaliplatin. However, high resolution structures formed by oxaliplatin and different linear DNA remain unclear. This study characterized, the key structures of different linear DNA in the platination process by UV absorption spectra and atomic force microscopy (AFM). Bathochromic shift and hyperchromicity in UV spectra after addition of oxaliplatin revealed that it can disrupt base stacking of DNA in the platination process. AFM results of different linear DNA indicated that, the platination process can induce DNA change from an extended conformation to the network structure with many kinks and finally to the compact particles, or toroids with increasing the incubation time. All AFM results confirmed that, platination of different linear DNA by oxaliplatin is a time depended process. The present AFM results provide, structural evidence about the interactions between oxaliplatin and different linear DNA containing multiple targets. SCANNING 38:880–888, 2016. © 2016 Wiley Periodicals, Inc.
How Do Undergraduate Students Conceptualize Acid–Base Chemistry? Measurement of a Concept Progression
Authors: ROMINE WILLIAM L. , TODD AMBER N. , CLARK TRAVIS B. 
Published: July 2016

ABSTRACTWe developed and validated a new instrument, calledMeasuring Concept progressions in Acid–Base chemistry(MCAB) and used it to better understand the progression of undergraduate students’ understandings about acid–base chemistry. Items were developed based on an existing learning progression for acid–base chemistry. We used the Rasch rating scale model for validation and to gain understanding of how students at different ability levels conceptualize the topic. We then used latent class analysis (LCA) to place students into concept classes. We found that three concept classes were sufficient to describe students’ various response patterns and that these concept classes described a progression of understanding related to acid–base chemistry. All items fit well with the Rasch model. The final 33‐item instrument measured students along a continuous scale with a reliability of 0.74 and categorized students with a precision of 0.89. All students possessed nonscientific understandings of pH and the pH scale. However, even the most novice students displayed basic scientific understandings about how acid–base indicators work and the Arrhenius model of acids and bases. We discuss the utility of Rasch and LCA procedures for analysis of learning progression‐based assessments and suggest a simple algorithm that can be used to help chemistry instructors diagnose students’ misconceptions.
Participant perceptions of Range Rider Programs operating to mitigate wolf–livestock conflicts in the western United States
Authors: Parks Molly , Messmer Terry 
Published: July 2016

ABSTRACTAs gray wolf (Canis lupus) populations have expanded in the western United States, wolf depredation of domestic livestock has increased. Concomitantly, wildlife managers are seeking management tools to mitigate wolf–livestock conflicts and enhance stakeholder support for conservation efforts. Range Rider Programs (RRPs) have emerged as a nonlethal management strategy that advocates the use of increased human surveillance of livestock herds in areas occupied by wolves to reduce wolf–livestock conflicts. However, little information is available about the scope of contemporary northern Rocky Mountain (NRM) RRPs or participant perceptions about the potential for the programs to mitigate these conflicts. We conducted semistructured phone and personal interviews with 51 participants from 17 RRPs in Montana, Oregon, and Washington during January to April 2014 and October 2014 to January 2015 to develop a typology of NRM RRPs and assess participant perceptions of current programs. Although the RRPs we studied varied in context, program focus, and scale, they shared similar organizational components that included a sponsor; collaboration among several organizations; a funding mechanism; a structure that included a supervisor, the landowner(s), and the range rider(s); and a mechanism for stakeholder feedback. We identified 3 unique RRP versions based on the primary focus of the programs: 1) livestock monitoring, 2) wolf surveillance, and 3) livestock herding. Although participants identified a number of benefits (e.g., increased information about wolf activity, extra herd supervision, rapid carcass identification), they also identified challenges that affected program sustainability. Challenges pertaining to trust and open communication were inherent in several programs; however, the lack of stable funding was viewed as a major threat to program sustainability. The final challenge to RRPs’ sustainability was the largely unproven success of this strategy. © 2016 The Wildlife Society.
Addressing variability in estuarine food density for American black ducks
Authors: Goldstein Marissa , Williams Christopher K. , Castelli Paul. M. , Duren Kenneth R. 
Published: July 2016

ABSTRACTHabitat limitation and availability of food energy may be the cause of decline in American black duck (Anas rubripes) populations. Estimating food availability is a critical step in developing winter carrying‐capacity estimates for black ducks. Recent research has estimated the biomass and energy supply of winter black duck foods in coastal marshes using a single‐core sampling method, but estimates had large variability. We tested whether taking bulk core samples (i.e., homogenizing multiple core samples and subsampling a single core from it) at the same location (vs. a single core sample) would alter the mean and variance in food estimates in 7 different landscape–vegetation types (hereafter, habitat types: mudflat, subtidal, low marsh, high marsh, quasi‐tidal pools, a tidal impoundment, and a freshwater impoundment) in coastal New Jersey, USA, during 2011. In all but one habitat type, there were no differences in the mean biomass or the mean energy density estimates for the single core samples and the bulk core samples, across all food types. Variance was reduced in subtidal and quasi‐tidal pool habitats, but variance increased in tidal impoundments. Assessing time and cost‐efficiency of bulk samples over single samples, cost per sample increased 4–12%/core. Because we observed little difference in food biomass, energy, and their respective variance estimates between single and bulk methods, while recording a slightly greater cost, we recommend researchers use the single‐core sampling method to save both time and money. Further reductions in variance will likely need to be achieved through increased sample sizes. © 2016 The Wildlife Society.
Does operative fixation affect outcomes of displaced medial epicondyle fractures?
Authors: Stepanovich Matthew , Bastrom Tracey P. , Munch John , Roocroft Joanna H. , Edmonds Eric W. , Pennock Andrew T. 
Published: July 2016

Purpose Long-term functional results remain equivocal between operative fixation and closed management of displaced humeral medial epicondyle fractures. The purpose of this study was to determine whether a functional difference exists between treatment types. Methods One hundred and forty patients with a displaced medial epicondyle fracture between 2007 and 2014 met the inclusion criteria. Of this large cohort, only 12 patients agreed to return to clinic at a mean follow-up of 3 years for prospective evaluation. Data collection included radiographs, physical examination, validated outcome tools, and grip strength testing with a Jamar dynamometer. Results Both groups were comparable with regard to age, dominant side injured, length of follow-up, preinjury sports involvement, and initial displacement (10 mm operative vs. 9 mm nonoperative); however, half of the surgical group presented with an associated unreduced elbow dislocation versus 0 % in the nonoperative group. Both treatment methods resulted in high patient satisfaction and elbow function scores. There were four osseous nonunions (67 %) and one malunion (17 %) in the nonoperative group versus none in the operative group ( p = 0.015). Patients treated nonoperatively had a nonsignificant decrease in grip strength (9 ± 6 lbs) as compared to operative patients (6 ± 5 lbs, medium effect size eta = 0.25, p = 0.25). Conclusions In this small cohort, operative management of displaced medial epicondyle fractures resulted in a higher rate of fracture union and return to sports. Other objective and subjective measures were similar between the two treatment groups.
An empirical application of the EVA® framework to business cycles
Authors: Cachanosky Nicolás , Lewin Peter 
Published: July 2016

AbstractFollowing financial concepts like duration and economic value added (EVA®) we estimate the impact of interest rate movements on firms that are more and less roundabout. We find that firms that are more roundabout, that is, work with expected cash‐flows with higher duration, are more sensitive to interest rate movements. To the extent that monetary policy is able to move the discount rate used by investors, monetary policy changes the relative present value of any investment project and therefore affects resource allocation. We show evidence that this effect is present in the U.S. in the years prior to the subprime crisis.
Can the International Criminal Court Deter Atrocity?
Authors: Jo Hyeran , Simmons Beth A. 
Published: July 2016

AbstractWhether and how violence can be controlled to spare innocent lives is a central issue in international relations. The most ambitious effort to date has been the International Criminal Court (ICC), designed to enhance security and safety by preventing egregious human rights abuses and deterring international crimes. We offer the first systematic assessment of the ICC's deterrent effects for both state and nonstate actors. Although no institution can deter all actors, the ICC can deter some governments and those rebel groups that seek legitimacy. We find support for this conditional impact of the ICC cross-nationally. Our work has implications for the study of international relations and institutions, and supports the violence-reducing role of pursuing justice in international affairs.
Another look at Hume's treatment of the argument from design in theNatural History of Religion
Authors: KELAHAN EMILY 
Published: July 2016

AbstractThis article argues that Hume's seemingly peculiar treatment of the argument from design in hisNatural History of Religionis not indicative of a radical, or even modest, shift in his overall epistemic evaluation of it. His focus is on the argument's impact on the psychology of religious believers, and not its rational acceptability. Hume never strays far from his stated intention for the work, to engage in a socio-psychological analysis of the nature of religious belief, including a thorough assessment of the role of the argument from design. Hume concludes that the argument is inconsequential to religious belief formation.
‘POSITIVELY HOMOGENEOUS LATTICE HOMOMORPHISMS BETWEEN RIESZ SPACES NEED NOT BE LINEAR’
Authors: BEN AMOR FETHI 
Published: July 2016

This note furnishes an example showing that the main result (Theorem 4) in Toumi [‘When lattice homomorphisms of Archimedean vector lattices are Riesz homomorphisms’, J. Aust. Math. Soc. 87 (2009), 263–273] is false.
Assessing genetic variation for heat stress tolerance in Indian bread wheat genotypes using morpho-physiological traits and molecular markers
Authors: Sharma P. , Sareen S. , Saini M. , Shefali  
Published: July 2016

AbstractHeat stress greatly limits the productivity of wheat in many regions. Knowledge on the degree of genetic diversity of wheat varieties along with their selective traits will facilitate the development of high yielding, stress-tolerant wheat cultivar. The objective of this study were to determine genetic variation in morpho-physiological traits associated with heat tolerance in 30 diverse wheat genotypes and to examine genetic diversity and relationship among the genotypes varying heat tolerance using molecular markers. Phenotypic data of 15 traits were evaluated for heat tolerance under non-stress and stress conditions for two consecutive years. A positive and significant correlation among cell membrane stability, canopy temperature depression, biomass, susceptibility index and grain yield was shown. Genetic diversity assessed by 41 polymorphic simple sequence repeat (SSR) markers was compared with diversity evaluated for 15 phenotypic traits averaged over stress and non-stress field conditions. The mean polymorphic information content for SSR value was 0.38 with range of 0.12–0.75. Based on morpho-physiological traits and genotypic data, three groups were obtained based on their tolerance (HHT, MHT and LHT) levels. Analysis of molecular variance explained 91.7% of the total variation could be due to variance within the heat tolerance genotypes. Genetic diversity among HHT was higher than LHT genotypes and HHT genotypes were distributed among all cluster implied that genetic basis of heat tolerance in these genotypes was different thereby enabling the wheat breeders to combine these diverse sources of genetic variation to improve heat tolerance in wheat breeding programme.
Islam's Political Disadvantage: Corruption and Religiosity in Quetta, Pakistan
Authors: Kalin Michael , Siddiqui Niloufer 
Published: July 2016

AbstractReligion is often seen as important to voting behavior, particularly in the Islamic world, where personal piety may serve as an informational shortcut to voters otherwise unclear about candidate quality. But how do voters react when nominally pious candidates are alleged to be corrupt? Are pious candidates evaluated differently according to their sectarian affiliations? To investigate the impact of candidate piety and sectarian identity on voter choice, we conducted a survey experiment in Quetta, Balochistan, a region of Pakistan, which has experienced high levels of Sunni-Shia violence. Our results suggest that voters are significantly more punitive of corrupt behavior committed by candidates from sectarian out-groups than those belonging to their religious in-group. Further, we demonstrate that respondents react negatively to information about candidate religiosity, and uncover the existence of a “hypocrisy effect” whereby voters disproportionately punish corrupt candidates purporting to be pious compared to candidates who make no such claims.
Next-generation sequencing with a myeloid gene panel in core-binding factor AML showed KIT activation loop and TET2 mutations predictive of outcome
Authors: Cher C Y , Leung G M K , Au C H , Chan T L , Ma E S K , Sim J P Y , Gill H , Lie A K W , Liang R , Wong K F , Siu L L P , Tsui C S P , So C C , Wong H W W , Yip S F , Lee H K K , Liu H S Y , Lau J S M , Luk T H , Lau C K , Lin S Y , Kwong Y L , Leung A Y H ,   on behalf of the Hong Kong AML Study Group
Published: July 2016

AbstractClinical outcome and mutations of 96 core-binding factor acute myeloid leukemia (AML) patients 18–60 years old were examined. Complete remission (CR) after induction was 94.6%. There was no significant difference in CR, leukemia-free-survival (LFS) and overall survival (OS) between t(8;21) (N=67) and inv(16) patients (N=29). Univariate analysis showed hematopoietic stem cell transplantation at CR1 as the only clinical parameter associated with superior LFS. Next-generation sequencing based on a myeloid gene panel was performed in 72 patients. Mutations in genes involved in cell signaling were associated with inferior LFS and OS, whereas those in genes involved in DNA methylation were associated with inferior LFS. KIT activation loop (AL) mutations occurred in 25 patients, and were associated with inferior LFS (P=0.003) and OS (P=0.001). TET2 mutations occurred in 8 patients, and were associated with significantly shorter LFS (P=0.015) but not OS. Patients negative for KIT-AL and TET2 mutations (N=41) had significantly better LFS (P<0.001) and OS (P=0.012) than those positive for both or either mutation. Multivariate analysis showed that KIT-AL and TET2 mutations were associated with inferior LFS, whereas age ⩾40 years and marrow blast ⩾70% were associated with inferior OS. These observations provide new insights that may guide better treatment for this AML subtype.
Frizzled 7 and PIP2 binding by syntenin PDZ2 domain supports Frizzled 7 trafficking and signalling
Authors: Egea-Jimenez Antonio Luis , Gallardo Rodrigo , Garcia-Pino Abel , Ivarsson Ylva , Wawrzyniak Anna Maria , Kashyap Rudra , Loris Remy , Schymkowitz Joost , Rousseau Frederic , Zimmermann Pascale 
Published: July 2016

AbstractPDZ domain-containing proteins work as intracellular scaffolds to control spatio-temporal aspects of cell signalling. This function is supported by the ability of their PDZ domains to bind other proteins such as receptors, but also phosphoinositide lipids important for membrane trafficking. Here we report a crystal structure of the syntenin PDZ tandem in complex with the carboxy-terminal fragment of Frizzled 7 and phosphatidylinositol 4,5-bisphosphate (PIP2). The crystal structure reveals a tripartite interaction formed via the second PDZ domain of syntenin. Biophysical and biochemical experiments establish co-operative binding of the tripartite complex and identify residues crucial for membrane PIP2-specific recognition. Experiments with cells support the importance of the syntenin–PIP2 interaction for plasma membrane targeting of Frizzled 7 and c-jun phosphorylation. This study contributes to our understanding of the biology of PDZ proteins as key players in membrane compartmentalization and dynamics.
A heavy metal P-type ATPase OsHMA4 prevents copper accumulation in rice grain
Authors: Huang Xin-Yuan , Deng Fenglin , Yamaji Naoki , Pinson Shannon R.M. , Fujii-Kashino Miho , Danku John , Douglas Alex , Guerinot Mary Lou , Salt David E. , Ma Jian Feng 
Published: July 2016

AbstractRice is a major source of calories and mineral nutrients for over half the world’s human population. However, little is known in rice about the genetic basis of variation in accumulation of copper (Cu), an essential but potentially toxic nutrient. Here we identify OsHMA4 as the likely causal gene of a quantitative trait locus controlling Cu accumulation in rice grain. We provide evidence that OsHMA4 functions to sequester Cu into root vacuoles, limiting Cu accumulation in the grain. The difference in grain Cu accumulation is most likely attributed to a single amino acid substitution that leads to different OsHMA4 transport activity. The allele associated with low grain Cu was found in 67 of the 1,367 rice accessions investigated. Identification of natural allelic variation in OsHMA4 may facilitate the development of rice varieties with grain Cu concentrations tuned to both the concentration of Cu in the soil and dietary needs.