bluuebunny/crossref_metadata_2025_split huggingface dataset:
Network Measures for Chemical Library Design
Authors: Sukumar Nagamani , Krein Michael P. , Prabhu Ganesh , Bhattacharya Sudeepto , Sen Subhabrata 
Published: September 2014

Abstract

Preclinical Research

In this overview, we examine recent developments in network approaches to drug design. A brief overview of networks is followed by a discussion of how chemical similarity networks and their properties address challenges in drug design. Multiple methods used to assess or enhance chemical diversity for early‐stage drug discovery are discussed, as well as methods that can be used for drug repositioning and ligand polypharmacology.
Computational Approaches for Drug Discovery
Authors: Hung Che‐Lun , Chen Chi‐Chun 
Published: September 2014

Abstract

Preclinical Research

Cellular proteins are the mediators of multiple organism functions being involved in physiological mechanisms and disease. By discovering lead compounds that affect the function of target proteins, the target diseases or physiological mechanisms can be modulated. Based on knowledge of the ligand–receptor interaction, the chemical structures of leads can be modified to improve efficacy, selectivity and reduce side effects. One rational drug design technology, which enables drug discovery based on knowledge of target structures, functional properties and mechanisms, is computer‐aided drug design (CADD). The application of CADD can be cost‐effective using experiments to compare predicted and actual drug activity, the results from which can used iteratively to improve compound properties. The two major CADD‐based approaches are structure‐based drug design, where protein structures are required, and ligand‐based drug design, where ligand and ligand activities can be used to design compounds interacting with the protein structure. Approaches in structure‐based drug design include docking, de novo design, fragment‐based drug discovery and structure‐based pharmacophore modeling. Approaches in ligand‐based drug design include quantitative structure–affinity relationship and pharmacophore modeling based on ligand properties. Based on whether the structure of the receptor and its interaction with the ligand are known, different design strategies can be seed. After lead compounds are generated, the rule of five can be used to assess whether these have drug‐like properties. Several quality validation methods, such as cost function analysis, Fisher's cross‐validation analysis and goodness of hit test, can be used to estimate the metrics of different drug design strategies. To further improve CADD performance, multi‐computers and graphics processing units may be applied to reduce costs.
The benefits of using semi‐continuous and continuous models to analyze binge eating data: A Monte Carlo investigation
Authors: Grotzinger Andrew , Hildebrandt Tom , Yu Jessica 
Published: September 2014

ABSTRACTObjectiveChange in binge eating is typically a primary outcome for interventions targeting individuals with eating pathology. A range of statistical models exist to handle these types of frequency distributions, but little empirical evidence exists to guide the appropriate choice of statistical model.MethodMonte Carlo simulations were used to investigate the utility of semi‐continuous models relative to continuous models in various situations relevant to binge eating treatment studies.ResultsSemi‐continuous models yielded more accurate estimates of the population, while continuous models were higher powered when higher levels of missing data were present.DiscussionThe present findings generally support the use of semi‐continuous models applied to binge eating data, with total sample sizes of roughly 200 being adequately powered to detect moderate treatment effects. However, models with a significant amount of missing data yielded more favorable power estimates for continuous models. © 2014 Wiley Periodicals, Inc. (Int J Eat Disord 2015; 48:746–758)
A trait‐based trade‐off between growth and mortality: evidence from 15 tropical tree species using size‐specific relative growth rates
Authors: Philipson Christopher D. , Dent Daisy H. , O'Brien Michael J. , Chamagne Juliette , Dzulkifli Dzaeman , Nilus Reuben , Philips Sam , Reynolds Glen , Saner Philippe , Hector Andy 
Published: September 2014

AbstractA life‐history trade‐off between low mortality in the dark and rapid growth in the light is one of the most widely accepted mechanisms underlying plant ecological strategies in tropical forests. Differences in plant functional traits are thought to underlie these distinct ecological strategies; however, very few studies have shown relationships between functional traits and demographic rates within a functional group. We present 8 years of growth and mortality data from saplings of 15 species of Dipterocarpaceae planted into logged‐over forest in Malaysian Borneo, and the relationships between these demographic rates and four key functional traits: wood density, specific leaf area (SLA), seed mass, and leaf C:N ratio. Species‐specific differences in growth rates were separated from seedling size effects by fitting nonlinear mixed‐effects models, to repeated measurements taken on individuals at multiple time points. Mortality data were analyzed using binary logistic regressions in a mixed‐effects models framework. Growth increased and mortality decreased with increasing light availability. Species differed in both their growth and mortality rates, yet there was little evidence for a statistical interaction between species and light for either response. There was a positive relationship between growth rate and the predicted probability of mortality regardless of light environment, suggesting that this relationship may be driven by a general trade‐off between traits that maximize growth and traits that minimize mortality, rather than through differential species responses to light. Our results indicate that wood density is an important trait that indicates both the ability of species to grow and resistance to mortality, but no other trait was correlated with either growth or mortality. Therefore, the growth mortality trade‐off among species of dipterocarp appears to be general in being independent of species crossovers in performance in different light environments.
Pakistan's Flood Challenges: An assessment through the lens of learning and adaptive governance
Authors: Mian Saima 
Published: September 2014

ABSTRACTExtreme events such as floods present major challenges for water governance in many parts of the world. Following two rounds of disastrous floods in 2010 and 2011, the need for a change in Pakistan's approach to dealing with floods has been highlighted in the literature. However, scant attention has been given to the nature of an alternative framework and the mechanism for driving a change towards it. This research aims to provide a better understanding of how Pakistan can cope with future flood challenges by examining the role of learning processes in facilitating a change towards an adaptive governance framework that is considered useful for dealing with complex issues in an uncertain environment. Key informant interviews and document analysis are used to examine characteristics of the current regime, analyse the influence of learning processes on flood governance dynamics, and identify barriers and bridges to change. Study findings show that state actors continue to dominate flood governance. However, the actor network in emergency flood management has broadened, with increasing participation by non‐state actors. Single‐loop learning, limited to routine improvements, is predominant among state actors in preventive management. A few state and non‐state actors in emergency management exhibit double‐loop learning reflected by their reframing of problems and incorporation of new information. However, in the absence of any triple‐loop learning associated with a paradigm change, the overall impact of learning processes in facilitating a transition towards more adaptive approaches to flood governance has been limited. Copyright © 2014 John Wiley & Sons, Ltd and ERP Environment
Synthesis of Indole‐Derived Allocolchicine Congeners through Pd‐Catalyzed Intramolecular C‐H Arylation Reaction
Authors: Sitnikov Nikolay S. , Kokisheva Antonina S. , Fukin Georgy K. , Neudörfl Jörg‐Martin , Sutorius Hannah , Prokop Aram , Fokin Valery V. , Schmalz Hans‐Günther , Fedorov Alexey Yu. 
Published: September 2014

AbstractThe synthesis of several new heterocyclic structural analogs of the natural antimitotic agent allocolchicine is reported. As a key step an intramolecular Pd‐catalyzed C–H arylation reaction was used to close the seven‐membered ring fused with two electron‐rich aryl fragments. The stereostructure of the target compounds was determined by X‐ray crystal analysis. The primary biological assessment of the synthesized compounds was carried out on human lymphoma cells. Several allocolchicinoids were determined to possess antiproliferative and apoptosis‐inducing activity in the micromolar concentration range.
A model to predict stream water temperature across the conterminous USA
Authors: Segura Catalina , Caldwell Peter , Sun Ge , McNulty Steve , Zhang Yang 
Published: September 2014

AbstractStream water temperature (ts) is a critical water quality parameter for aquatic ecosystems. However, ts records are sparse or nonexistent in many river systems. In this work, we present an empirical model to predict ts at the site scale across the USA. The model, derived using data from 171 reference sites selected from the Geospatial Attributes of Gages for Evaluating Streamflow database, describes the linear relationship between monthly mean air temperature (ta) and ts. Multiple linear regression models are used to predict the slope (m) and intercept (b) of the ta–ts linear relation as a function of climatic, hydrologic and land cover characteristics. Model performance to predict ts resulted in a mean Nash–Sutcliffe efficiency coefficient of 0.78 across all sites. Application of the model to predict ts at additional 89 nonreference sites with a higher human alteration yielded a mean Nash–Sutcliffe value of 0.45. We also analysed seasonal thermal sensitivity (m) and found strong hysteresis in the ta–ts relation. Drainage area exerts a strong control on m in all seasons, whereas the cooling effect of groundwater was only evident for the spring and fall seasons. However, groundwater contributions are negatively related to mean ts in all seasons. Finally, we found that elevation and mean basin slope are negatively related to mean ts in all seasons, indicating that steep basins tend to stay cooler because of shorter residence times to gain heat from their surroundings. This model can potentially be used to predict climate change impacts on ts across the USA. Copyright © 2014 John Wiley & Sons, Ltd.
Efficient Generation of Electricity from Methane using High Temperature Fuel Cells – Status, Challenges and Prospects
Authors: Manohar Aswin K. , Narayanan S. R. 
Published: September 2014

AbstractHigh temperature fuel cells (HTFCs), comprising solid oxide fuel cells and molten carbonate fuel cells, present efficient means for generating electricity from methane and natural gas. The high quality heat generated by HTFCs allows operation in the combined heat and power mode (CHP) to further enhance efficiency. The overall fuel‐to‐electricity conversion efficiency of an HTFC system operating in CHP mode can approach up to 80 %. Despite the high operating efficiency of HTFCs, high capital costs and durability issues have hindered their widespread commercialization. This article provides an overview of the operating principles, technical challenges, commercialization status of HTFCs, and outlines the strategies being adopted to lower capital costs and increase durability.
Diagnostic and predictive performance and standardized threshold of traditional biomarkers for drug‐induced liver injury in rats
Authors: Tonomura Yutaka , Kato Yuki , Hanafusa Hiroyuki , Morikawa Yuji , Matsuyama Keigo , Uehara Takeki , Ueno Motonobu , Torii Mikinori 
Published: September 2014

ABSTRACTTraditional biomarkers such as alanine and aspartate aminotransferase (ALT, AST) and total bilirubin (TBIL) have been widely used for detecting drug‐induced liver injury (DILI). Although the Food and Drug Administration (FDA) proposed standardized thresholds for human as Hy's law, those for animals have not been determined, and predictability of these biomarkers for future onset of hepatic lesions remains unclear. In this study, we investigated these diagnostic and predictive performance of 10 traditional biomarkers for liver injury by receiver‐operating characteristic (ROC) curve, using a free‐access database where 142 hepatotoxic or non‐hepatotoxic compounds were administrated to male rats (n = 5253). Standardization of each biomarker value was achieved by calculating the ratio to control mean value, and the thresholds were determined under the condition of permitting 5% false positive. Of these 10 biomarkers, AST showed the best diagnostic performance. Furthermore, ALT and TBIL also showed high performance under the situation of hepatocellular necrosis and bile duct injury, respectively. Additionally, the availability of the diagnostic thresholds in difference testing facility was confirmed by the application of these thresholds to in‐house prepared dataset. Meanwhile, incorrect diagnosis by the thresholds was also observed. Regarding prediction, all 10 biomarkers showed insufficient performance for future onset of hepatic lesions. In conclusion, the standardized diagnostic thresholds enable consistent evaluation of traditional biomarkers among different facilities, whereas it was suggested that novel biomarker is required for more accurate diagnosis and prediction of DILI. Copyright © 2014 John Wiley & Sons, Ltd.
mTORC2 Signaling Promotes Skeletal Growth and Bone Formation in Mice
Authors: Chen Jianquan , Holguin Nilsson , Shi Yu , Silva Matthew J. , Long Fanxin 
Published: September 2014

ABSTRACT

Mammalian target of rapamycin (mTOR) is an evolutionarily conserved serine/threonine kinase controlling many physiological processes in mammals. mTOR functions in two distinct protein complexes, namely mTORC1 and mTORC2. Compared to mTORC1, the specific roles of mTORC2 are less well understood. To investigate the potential contribution of mTORC2 to skeletal development and homeostasis, we have genetically deleted Rictor, an essential component of mTORC2, in the limb skeletogenic mesenchyme of the mouse embryo. Loss of Rictor leads to shorter and narrower skeletal elements in both embryos and postnatal mice. In the embryo, Rictor deletion reduces the width but not the length of the initial cartilage anlage. Subsequently, the embryonic skeletal elements are shortened due to a delay in chondrocyte hypertrophy, with no change in proliferation, apoptosis, cell size, or matrix production. Postnatally, Rictor-deficient mice exhibit impaired bone formation, resulting in thinner cortical bone, but the trabecular bone mass is relatively normal thanks to a concurrent decrease in bone resorption. Moreover, Rictor-deficient bones exhibit a lesser anabolic response to mechanical loading. Thus, mTORC2 signaling is necessary for optimal skeletal growth and bone anabolism. © 2014 American Society for Bone and Mineral Research.
Enzyme Kinetics of an Alternative Splicing Isoform of Mitochondrial 8‐Oxoguanine DNA Glycosylase, OGG1‐1b, and Compared with the Nuclear OGG1‐1a
Authors: Ogawa Akira , Watanabe Takashi , Shoji Sayaka , Furihata Chie 
Published: September 2014

ABSTRACTEight alternatively spliced isoforms of human 8‐oxoguanine DNA glycosylase (OGG1) (OGG1‐1a to ‐1c and ‐2a to ‐2e) are registered in the National Center for Biotechnology Information. OGG1(s) in mitochondria have not yet been fully characterized biochemically. In this study, we purified mitochondrial recombinant OGG1‐1b protein and compared its activity with nuclear OGG1‐1a protein. The reaction rate constant (kg) of the 7,8‐dihydro‐8‐oxoguanine (8‐oxoG) glycosylase activity of OGG1‐1b was 8‐oxoG:C >> 8‐oxoG:T >> 8‐oxoG:G > 8‐oxoG:A (7.96, 0.805, 0.070, and 0.015 min−1, respectively) and that of the N‐glycosylase/DNA lyase activity (kgl) of OGG1‐1b was 8‐oxoG:C > 8‐oxoG:T ≃8‐oxoG:G >> 8‐oxoG:A (0.286, 0.079, 0.040, and negligible min−1, respectively). These reaction rate constants were similar to those of OGG1‐1a except for kgl against 8‐oxoG:A. APEX nuclease 1 was required to promote DNA strand breakage by OGG1‐1b. These results suggest that OGG1‐1b is associated with 8‐oxoG cleavage in human mitochondria and that the mechanism of this repair is similar to that of nuclear OGG1‐1a.
Surgical treatment of intrahepatic cholangiocarcinoma in the USA
Authors: Lubezky Nir , Facciuto Marcelo , Harimoto Norifumi , Schwartz Myron E. , Florman Sander S. 
Published: September 2014

AbstractCholangiocarcinoma (CC) is a malignancy that arises from the epithelial cells of the biliary system (ductules as well as large ducts, and likely from progenitor cells, as well). Intrahepatic CC (ICC) is the second most common primary hepatic malignancy after hepatocellular carcinoma (HCC), and accounts for 10–15% of primary liver cancers. ICC differs from both extrahepatic and CC and HCC and has unique risk factors, histological features, genetic alterations and clinical outcomes. The natural history and results of surgical intervention are not well described as ICC is a relatively uncommon tumor, especially in the USA. This article reviews the literature relevant to the surgical management and outcome of patients with ICC in the USA.
Characterization of chemical constituents in Zhi–Zi–Da–Huang decoction by ultra high performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry
Authors: Zhu Heyun , Yin Ran , Han Fei , Guan Jiao , Zhang Xiaoshu , Mao Xinjuan , Zhao Longshan , Li Qing , Hou Xiaohong , Bi Kaishun 
Published: September 2014

A sensitive and reliable ultra high performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry method was established to separate and identify the chemical constituents of Zhi–Zi–Da–Huang decoction, a classic traditional Chinese medicine formula. The chromatographic separation was achieved on a Shim‐pack XR‐ODS C18 column (75 × 3.0 mm, 2.2 μm) using a gradient elution program. The detection was performed on a Waters Xevo G2 Q‐TOF mass spectrometer equipped with electrospray ionization source in both positive and negative modes. With the optimized conditions, a total of 82 compounds were identified or tentatively characterized. Of the 82 compounds, 21 compounds were identified by comparing the retention time and MS data with reference standards, the rest were characterized by analyzing MS data and retrieving the reference literature. In addition, 31 compounds were identified from Gardenia jasminoides Ellis, ten compounds were identified from Rheum palmatum L., 33 compounds were identified from Citrus aurantium L., and eight compounds were identified from Sojae Semen Praeparatum. Results indicated that iridoids, anthraquinones, flavonoids, isoflavonoids, coumarins, glycosides of crocetin, monoterpenoids, and organic acids were major constituents in Zhi–Zi–Da–Huang decoction. It is concluded that the developed ultra high performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry method with high sensitivity and resolution is suitable for identifying and characterizing the chemical constituents of Zhi–Zi–Da–Huang decoction, and the analysis provides a helpful chemical basis for further research on Zhi–Zi–Da–Huang decoction.
Improved Thin‐Film Transistor Performance Through a Melt of Poly(para‐phenyleneethynylene)
Authors: Schmid Stefanie , Kast Anne K. , Schröder Rasmus R. , Bunz Uwe H. F. , Melzer Christian 
Published: September 2014

The performance of polymer field‐effect transistors (PFETs) based on short rigid rod semiconducting poly(2,5‐didodecyloxy‐p‐phenyleneethynylene) (D‐OPPE) is highlighted. The controlled heating and cooling of thin films of D‐OPPE allows for a recrystallization from the melt, boosting the performance of D‐OPPE‐based transistors. The improved film properties induced by controlled annealing lead to a hole field‐effect mobility around 0.014 cm2 V−1 s−1, an on/off ratio of 106, a sub‐threshold swing of 3 V dec−1 and a threshold voltage of −35 V, employing a poly(methyl methacrylate) (PMMA) gate dielectric. Thus, PFETs out of D‐OPPE compete now with spin‐coated, polycrystalline poly(3‐hexylthiophene)‐based PFETs.
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Enantiomeric Determination of Four Diastereoisomeric Oxyneolignans from Bambusa tuldoides Munro
Authors: Sun Jia , Yu Jin , Zhang Pei‐Cheng , Yue Yong‐De 
Published: September 2014

ABSTRACTIntroductionBambusa tuldoides Munro, a bamboo species, is used as a health food, dietary supplement and folk medicine in China, and produces lignans that can be used to supplement other natural sources.ObjectiveTo simultaneously separate eight stereoisomers of a particular type of oxyneolignan by chiral chromatography.MethodsNinety‐five per cent ethanol extracts of B. tuldoides Munro were analysed using HPLC/UV with a chiral column. The structures and configurations of isolated compounds were elucidated using NMR and circular dichroism (CD).ResultsFour diastereoisomers were characterised and given the names oxyneolignans A, B, C and D. Furthermore, each oxyneolignan occurred as a pair of enantiomers. The oxyneolignans A–D consisted of the erythro‐diastereoisomer of oxyneolignan at C7 and C8.ConclusionThe chiral chromatography combined with the analysis techniques of NMR and CD reported here were reliable methods for discovering and separating the enantiomers. Copyright © 2014 John Wiley & Sons, Ltd.
The relationship between expressed emotion and wellbeing for families and carers of a relative with Borderline Personality Disorder
Authors: Bailey Rachel C. , Grenyer Brin F.S. 
Published: September 2014

AbstractBackgroundPrevious research has found that family environments high in expressed emotion, in particular emotional overinvolvement, are beneficial to the clinical outcome of patients with Borderline Personality Disorder (BPD).AimThis study aims to investigate the relationship between expressed emotion, carer burden and carer wellbeing.MethodA total of 280 carers of a relative with BPD were administered the McLean Screening Instrument for BPD – Carer Version, The Family Questionnaire, Burden Assessment Scale and Mental Health Inventory.ResultsCarers reported family environments high in expressed emotion, particularly criticism (82.9% of carers) and emotional overinvolvement (69.6%). Elevated emotional overinvolvement was correlated with higher burden and mental health problems.ConclusionsElevated criticism and emotional overinvolvement in family environments represent a dynamic involving high conflict, anxious concern, overprotection and emotional closeness. The findings suggest that carers may benefit from intervention and support options considering the challenged interpersonal dynamic, burden and impaired carer wellbeing reported in this study. Copyright © 2014 John Wiley & Sons, Ltd.