bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics, biodistribution and toxicology following intravenous and oral administration of DSM-RX78 and EFB-1, two new 2-(2-fluorobenzamido)benzoate-based PDE4 inhibitors, to rats
Authors: Fang Jia-You , Liu Yi-Ting , Huang Yaw-Bin , Pan Tai-Long , Wang Han-Hsiang , Hsieh Pei-Wen 
Published: November 2012

Abstract

Objectives
The aim of this study was to determine the pharmacokinetic profile, biodistribution and toxicity of ethyl 2-(2-fluorobenzamido)benzoate (EFB-1) and methyl 2-(2-fluorobenzamido)benzoate (DSM-RX 78), two phosphodiesterase IV inhibitors, which potently attenuate haemorrhagic shock-induced lung injury in rat.

Methods
Quantification of DSM-RX78, EFB-1 and 2-(2-fluorobenzamido)benzoate (SMP-3) in plasma was carried out by HPLC. Furthermore, the pharmacokinetics and biodistribution of intravenously (1.0 and 3.0 mg/kg) and orally (40.0 mg/kg) administered DSM-RX78, EFB-1, and SMP-3 were determined in Sprague–Dawley rats. Toxicity and histological analyses were also evaluated herein.

Key findings
A liquid chromatography method has been developed for the quanification of EFB-1, DSM-RX78 and SMP-3 in rat plasma. The method was sensitive with good linearity (r2 = 0.9990) over a range of 1.56–0.0975 μg/ml. The mean kinetic parameters of DSM-RX 78 and EFB-1 following intravenous administration were as follows: elimination half-life (t½) 8.98 and 8.77 min; clearance (Cl) 24.57 and 22.31 ml/min/kg; AUC0-∞ 41.76 and 48.03 min mg/l.

Conclusions
The pharmacokinetics, toxicity and biodistribution of DSM-RX78 and EFB-1 were determined for the first time. The results showed that the pharmacokinetic profiles of DSM-RX78 and EFB-1 were similar, and that EFB-1 had a better safety profile than DSM-RX78. Therefore, EFB-1 was suitable as a lead compound for the development of new agents in the treatment of neutrophilic inflammatory diseases.
Low‐Temperature Relaxations Associated with Mixed‐Valent Structure in Sr2TiMnO6
Authors: Sun Xiaohong , Wang Chunchang , Wang Guojing , Lei Changmei , Teng Li  , Liu Lina 
Published: November 2012

The dielectric properties of Sr2TiMnO6 ceramic samples were investigated as functions of temperature (100 K ≤ T ≤ 320 K) and frequency (100 Hz ≤ f ≤ 10 MHz). Two thermally activated dielectric relaxations were observed. The sample was confirmed to possess multivalent states of Mn and Ti ions and the coexistence of electron holes and electrons. Our results revealed that both relaxations are bulk effect related to localized carriers hopping inside grains. It was suggested that the low‐temperature relaxation (LTR) can be related to dipolar effect due to electron holes, and the high‐temperature relaxation (HTR) was associated with the electrons hopping between Ti3+ and Ti4+ ions.
Biogeographical diversification of Mentzelia section Bartonia in western North America
Authors: Schenk John J. 
Published: November 2012

AbstractAimAridification of western North America from the Miocene to the Recent has spurred plant migrations, as species invaded and/or diversified into newly formed floristic regions. The 51 species of Mentzelia section Bartonia (Loasaceae) inhabit most of these regions, providing an opportunity to investigate lineage‐specific diversification among the western floras. Lineage‐specific formation of the modern western North American flora was investigated by applying statistical phylogenetic methods to molecular data.LocationWestern North America, including the intermountain region, south‐western deserts, Rocky Mountains and North American Prairies Province.MethodsInternal and external transcribed spacer region data for all taxa in section Bartonia and outgroups were analysed with maximum likelihood and Bayesian inference methods for phylogenetic relationships. Distribution and phylogenetic data were then analysed by Bayesian, maximum likelihood, parsimony, and stochastic mapping optimization methods for inference of biogeographical transitions among floristic regions. Model fitting was used to assess the symmetry of transitions from mesic to arid environments.ResultsMultiple transitions were inferred, especially those associated with the Colorado Plateau and the Rocky Mountains. The ancestral area for section Bartonia was estimated equivocally to be all regions except the Great Basin in parsimony reconstructions, but to be the Colorado Plateau with highest probability with the Bayesian approach. Throughout these regions, transitions between mesic to arid habitats were consistent with expectations under a null model, suggesting no directional bias in transitions. In section Bartonia, within‐region diversification occurred in all areas except the Great Basin and Sonoran Desert, the diversity of which is explained as the result of movement into these regions.Main conclusionsThe floristic regions of western North America have exchanged numerous migrants throughout their history. Among them, the Colorado Plateau, Great Basin and Rocky Mountains were particularly important floristic sources and recipients of migrants. Although previous studies have revealed a strong association among the south‐western deserts, these results suggest that the plant diversities in these deserts can be influenced more by adjacent provinces than by each other.
Historical biogeography and phylogeny of Typhlatya cave shrimps (Decapoda: Atyidae) based on mitochondrial and nuclear data
Authors: Botello Alejandro , Iliffe Thomas M. , Alvarez Fernando , Juan Carlos , Pons Joan , Jaume Damià 
Published: November 2012

AbstractAimOur aim was to produce a dated phylogeny of Typhlatya, a stygobiont shrimp genus with an extremely disjunct localized distribution across the Mediterranean, the central Atlantic and eastern Pacific. Using phylogenetic analyses, we examine the role of dispersal and plate tectonics in determining its distribution.LocationWestern Mediterranean, Ascension Island, Bermuda, Bahamas, Yucatán, Caribbean, Galápagos, Western Australia.MethodsThirteen of the 17 species of Typhlatya were analysed, using Stygiocaris, Halocaridina and Antecaridina as outgroups. Fragments of three mitochondrial and three nuclear genes were combined into a data set of 2449 mitochondrial and 1374 nuclear base pairs.ResultsPhylogenetic trees clearly showed Typhlatya to be paraphyletic, with the Galápagos species clustering with Antecaridina. Only the phylogenetic position of Typhlatya monae (Hispaniola and Puerto Rico) showed some uncertainty, appearing as the sister group to the Australian genus Stygiocaris on the most likely topology. We estimated an average age of 45 Myr (30.6–61.1 Myr) for the most recent common ancestor of Typhlatya + Stygiocaris + Antecaridina + Halocaridina. All Typhlatya (except Typhlatya galapagensis) + Stygiocaris derived from a node dated to 35.7 Ma (25.7–47.0 Ma), whereas the ancestor of all Typhlatya species (excluding T. monae and T. galapagensis) lived 30.7 Ma (21.9–40.4 Ma).Main conclusionsTyphlatya is paraphyletic and apparently absent from the eastern Pacific, with T. galapagensis clustering with Antecaridina. The remaining Typhlatya species form a robust monophyletic group with Stygiocaris, and both molecular and morphological evidence support the recognition of three sublineages: (1) Typhlatya s. str., Atlantic–Mediterranean, embracing all Typhlatya species minus T. monae; (2) Stygiocaris, limited to north‐western Australia; and (3) T. monae (Caribbean), for which a new genus could be erected. No congruence was found between temporal and geographical projections of cladogenetic events within Typhlatya/Stygiocaris and the major plate tectonic events underlying Tethyan history.
Study of early flood warning dissemination system in Bangladesh
Authors: Rahman M.M. , Goel N.K. , Arya D.S. 
Published: November 2012

AbstractA study has been conducted with the objective to assess the existing early flood warning dissemination system (EFWDS) in Bangladesh and to suggest the suitable improvements in the same system based on review of literature, interaction with stakeholders of various organisations involved in flood forecasting and dissemination, and analysis of feedback from the flood‐affected people of Dhobaura and Shibalaya subdistricts in Bangladesh. The existing set‐up has been studied to assess the present activities and future expectations. The recommendation for active participation by all related organisations has been made in this study. Two studies have been conducted by surveying the opinion of flood vulnerable communities so that all elements of the EFWDS would provide useful flood warnings to all potential users.
The spatial and temporal arrangement of the radial glial scaffold suggests a role in axon tract formation in the developing spinal cord
Authors: Barry Denis S. , Pakan Janelle M. P. , O'Keeffe Gerard W. , McDermott Kieran W. 
Published: November 2012

AbstractRadial glial cells serve diverse roles during the development of the central nervous system (CNS). In the embryonic brain, they are recognised as guidance conduits for migrating neuroblasts and as multipotent stem cells, generating both neurons and glia. While their stem cell capacities in the developing spinal cord are as yet not fully clarified, they are classically seen as a population of astrocytes precursors, before gradually disappearing as the spinal cord matures. Although the origins and lineages of CNS radial glial cells are being more clearly understood, the relationships between radial glial cells and growing white matter (WM) tracts are largely unknown. Here, we provide an in‐depth description of the distribution and organisation of radial glial cell processes during the peak periods of axonogenesis in the rat spinal cord. We show that radial glial cell distribution is highly ordered in the WM from E14 to E18, when the initial patterning of axon tracts is taking place. We report that the density of radial glial cell processes is tightly conserved throughout development in the dorsal, lateral and ventral WM funiculi along the rostrocaudal axis of the spinal cord. We provide evidence that from E16 the dorsal funiculi grow within and are segregated by fascicles of processes emanating from the dorsomedial septum. The density of radial glial cells declines with the maturation of axon tracts and coincides with the onset of the radial glial cell–astrocyte transformation. As such, we propose that radial glial cells act as structural scaffolds by compartmentalising and supporting WM patterning in the spinal cord during embryonic development.
Students’ experiences of implementing clinical skills in the real world of practice
Authors: Houghton Catherine E , Casey Dympna , Shaw David , Murphy Kathy 
Published: November 2012

Aims and objectivesTo examine the factors that impact on students' implementation of clinical skills in the practice setting. This was a part of a larger exploration into the role of the Clinical Skills Laboratory in preparing student nurses for clinical practice.BackgroundIt is already known that students can experience reality shock on clinical placement and that staff support is crucial for their adaptation to the environment. This process is similar to socialisation theory whereby the newcomer adapts to the workplace.DesignA multiple case study design (n = 5) was used.MethodsData were collected using semi‐structured interviews (n = 43) and non‐participant observation of students implementing skills in clinical practice.ResultsFindings revealed the factors that could facilitate students' implementation of clinical skills were as follows: provision of learning opportunities, staff support and supervision, and students' confidence. Factors that hindered students were reality shock, ‘the gap’ in how skills were taught in the higher education institutions and the clinical setting, and missed learning opportunities. Support from peers in the clinical area and having previous experience of working as a health care assistant, or similar, were the factors that could either positively or negatively impact on students.ConclusionsStudents need to be adequately prepared for the real‐life clinical environment. Understanding, through socialisation theory, how students adapt to the workplace can facilitate this process. Facilitating students' learning includes supporting them, developing their confidence and ensuring that they have prior exposure to undertaking clinical skills.Relevance to practiceStaff working with students in clinical practice can help facilitate students’ learning and implementing of clinical skills through an understanding of how students adapt and ‘fit in’ to their working environment.
Altered Expression of MicroRNAs and Target mRNAs in Tomato Root and Stem Tissues upon Different Viral Infection
Authors: Feng Junli , Wang Yuwei , Lin Ruohong , Chen Jishuang 
Published: November 2012

AbstractMicroRNAs (miRNAs) are post‐transcriptional regulators that are involved in numerous biological processes in both plants and animals. In plants, root and stem tissues play essential roles in their anchorage to soil as well as in nutrient and water uptake and transfer. We have quantified the expression alterations of eleven miRNAs and their target mRNAs in tomato root and stem tissues after infection with Cucumber mosaic virus (CMV)‐Fny, CMV‐FnyΔ2b (a CMV‐Fny 2b‐deletion mutant), CMV‐Fny‐satT1 (CMV‐Fny plus an aggressive satellite (sat) RNA variant satT1) and Tomato aspermy virus (TAV)‐Bj. From 21 days postinoculation onwards, we found the stem tissues were ‘hollow’ in CMV‐Fny‐satT1 infected tomatoes, and a ‘fibrosis’ phenotype was observed in stems of TAV‐Bj infected plants. In addition, this phenotype was associated with the decreasing of tomato lateral root numbers upon the two infections. Consistence with these phenotypic alterations, tomato miRNA/mRNA levels upon different viral infections were changed by different degrees. Based on our results, the interference of different viral infections with tomato miRNA pathways were analysed and the correlations between miRNAs/mRNAs expression alterations and tomato symptoms were discussed.
Characterization of the nutritive value of tropical legume grains as alternative ingredients for small‐scale pork producers using in vitro enzymatic hydrolysis and fermentation*
Authors: Torres J. , Muñoz L. S. , Peters M. , Montoya C. A. 
Published: November 2012

SummaryIn the tropic, the small‐scale pork production is negatively influenced by the low availability of high protein ingredients. The study aimed to compare the protein and starch hydrolysis as well as fibre fermentation of five tropical legume grains (Canavalia brasiliensis, CB; Lablab purpureus, LP; Vigna unguiculata, white WVU; pink PVU and red RVU) and a control (extruded full‐fat soybean (SB)), using an in vitro model that simulated digestion in the gastrointestinal tract of pigs. A sequential in vitro hydrolysis was carried out with pepsin (120 min) and pancreatin (240 min) to determine the degree of hydrolysis (DH) of protein and starch. The indigestible residue was fermented in vitro with pig faecal inoculum to compare the modelled kinetics of gas production over 72 h and the production of short‐chain fatty acids (SCFA). After 360 min of pepsin–pancreatin hydrolysis, SB and WVU had the highest protein hydrolysis (76% and 66%) and PVU and WVU the highest starch hydrolysis (70% and 64%) (p < 0.01). The in vitro fermentation of the indigestible residue of WVU resulted in the highest (482 ml/g DM; p < 0.001) and CB the lowest (335 ml/g DM) gas production. These data were consistent with the SCFA production. Butyrate, propionate and total SCFA were higher (or tended) for RVU and WVU when compared with CB and SB (p = 0.015–0.085). In conclusion, the high DH of protein and starch as well as the high gas and SCFA production obtained with raw WVU makes it an interesting alternative to SB as a feedstuff for swine nutrition in the tropic. Other legume grains (LP and CB) cannot be used by pigs in their raw form.
Activation of FoxO3a/Bim axis in patients with Primary Biliary Cirrhosis
Authors: Kopycinska Justyna , Kempińska‐Podhorodecka Agnieszka , Haas Tara , Elias Elwyn , DePinho Ronald A. , Paik Jihye , Milkiewicz Piotr , Milkiewicz Malgorzata 
Published: November 2012

AbstractBackground/AimsImpaired regulation of apoptosis has been suggested to play a role in the pathogenesis of Primary Biliary Cirrhosis (PBC). In this study, we analysed a signalling pathway that comprises the transcription factor FoxO3a and its downstream target Bim, a Bcl‐2 interacting mediator of apoptosis.Materials & MethodsThe tissues examined included livers explanted from patients with cirrhotic PBC, primary sclerosing cholangitis (PSC), alcoholic liver disease (ALD) and liver biopsies from patients with non‐cirrhotic PBC. Large margin resections of hepatocellular carcinoma were used as controls.ResultsExpression of FoxO3a and Bim mRNA was significantly enhanced in both non‐cirrhotic and end‐stage PBC (2.2‐fold and 4.3‐fold increases, respectively), but not in the other disorders. Similarly, FOXO3a protein level was increased in end‐stage PBC (P < 0.05 vs. control). A significant increase in Bim mRNA in non‐cirrhotic and cirrhotic PBC was observed (2.2‐fold and 8.2‐fold respectively). In addition, the most pro‐apoptotic isoform of Bim dominated in livers of PBC patients (2.5‐ fold increase vs. control; P < 0.05). Enhanced FoxO3a and Bim expression was associated with a substantial activation of caspase‐3 in PBC (2‐fold increase vs. controls; P < 0.0001), whereas it was decreased in both ALD and PSC (46% and 67% reductions respectively).The relationship between FoxO3a and Bim was further investigated in the livers of FoxO‐deficient mice. The somatic deletion of FoxO3a caused a significant decrease in Bim, but not caspase‐3 protein expression confirming the crucial role of FoxO3a in induction of Bim gene transcription.ConclusionsOur results imply that the FoxO3/Bim signalling pathway can be of importance in the livers of patients with PBC.
AN ONLINE PORTFOLIO SELECTION ALGORITHM WITH REGRET LOGARITHMIC IN PRICE VARIATION
Authors: Hazan Elad , Kale Satyen 
Published: November 2012

We present a novel efficient algorithm for portfolio selection which theoretically attains two desirable properties:

Worst‐case guarantee: the algorithm is universal in the sense that it asymptotically performs almost as well as the best constant rebalanced portfolio determined in hindsight from the realized market prices. Furthermore, it attains the tightest known bounds on the regret, or the log‐wealth difference relative to the best constant rebalanced portfolio. We prove that the regret of the algorithm is bounded by O(log Q), where Q is the quadratic variation of the stock prices. This is the first improvement upon Cover's (1991) seminal work that attains a regret bound of O(log T), where T is the number of trading iterations.
Average‐case guarantee: in the Geometric Brownian Motion (GBM) model of stock prices, our algorithm attains tighter regret bounds, which are provably impossible in the worst‐case. Hence, when the GBM model is a good approximation of the behavior of market, the new algorithm has an advantage over previous ones, albeit retaining worst‐case guarantees.
We derive this algorithm as a special case of a novel and more general method for online convex optimization with exp‐concave loss functions.
Genomic conflict drives patterns of X‐linked population structure in Drosophila neotestacea
Authors: Dyer Kelly A. , Bray Michael J. , Lopez S. Jeese 
Published: November 2012

AbstractIntragenomic conflict has the potential to cause widespread changes in patterns of genetic diversity and genome evolution. In this study, we investigate the consequences of sex‐ratio (SR) drive on the population genetic patterns of the X‐chromosome in Drosophila neotestacea. An SR X‐chromosome prevents the maturation of Y‐bearing sperm during male spermatogenesis and thus is transmitted to ~100% of the offspring, nearly all of which are daughters. Selection on the rest of the genome to suppress SR can be strong, and the resulting conflict over the offspring sex ratio can result in the accumulation of multiple loci on the X‐chromosome that are necessary for the expression of drive. We surveyed variation at 12 random X‐linked microsatellites across 16 populations of D. neotestacea that range in SR frequency from 0% to 30%. First, every locus was differentiated between SR and wild‐type chromosomes, and this drives genetic structure at the X‐chromosome. Once the association with SR is accounted for, the patterns of differentiation among populations are similar to the autosomes. Second, within wild‐type chromosomes, the relative heterozygosity is reduced in populations with an increased prevalence of drive, and the heterozygosity of SR chromosomes is higher than expected based on its prevalence. The combination of the relatively high prevalence of SR drive and the structuring of polymorphism between the SR and wild‐type chromosomes suggests that genetic conflict because of SR drive has had significant consequences on the patterns of X‐linked polymorphism and thus also probably affects the tempo of X‐chromosome evolution in D. neotestacea.
Population genetic correlates of declining transmission in a human pathogen
Authors: Nkhoma Standwell C. , Nair Shalini , Al‐Saai Salma , Ashley Elizabeth , McGready Rose , Phyo Aung P. , Nosten François , Anderson Tim J. C. 
Published: November 2012

AbstractPathogen control programs provide a valuable, but rarely exploited, opportunity to directly examine the relationship between population decline and population genetics. We investigated the impact of an ~12‐fold decline in transmission on the population genetics of Plasmodium falciparum infections (n = 1731) sampled from four clinics on the Thai–Burma border over 10 years and genotyped using 96 genome‐wide SNPs. The most striking associated genetic change was a reduction in the frequency of infections containing multiple parasite genotypes from 63% in 2001 to 14% in 2010 (P = 3 × 10−15). Two measures of the clonal composition of populations (genotypic richness and the β‐parameter of the Pareto distribution) declined over time as more people were infected by parasites with identical multilocus genotypes, consistent with increased selfing and a reduction in the rate at which multilocus genotypes are broken apart by recombination. We predicted that the reduction in transmission, multiple clone carriage and outbreeding would be mirrored by an increased influence of genetic drift. However, geographical differentiation and expected heterozygosity remained stable across the sampling period. Furthermore, Ne estimates derived from allele frequencies fluctuation between years remained high (582 to ∞) and showed no downward trend. These results demonstrate how genetic data can compliment epidemiological assessments of infectious disease control programs. The temporal changes in a single declining population parallel to those seen in comparisons of parasite genetics in regions of differing endemicity, strongly supporting the notion that reduced opportunity for outbreeding is the key driver of these patterns.