bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bioactivation and Reactive Metabolite Assays
Authors: Tang Wei , Zhang Zhoupeng 
Published: May 2012

Abstract

A number of small‐molecule drugs that cause severe adverse effects (AEs) undergo metabolism to form reactive species capable of covalently modifying proteins and/or nucleic acids. This has led to a working hypothesis that eliminating compounds susceptible to bioactivation in drug discovery should eventually produce safer medicines. A technical challenge associated with this strategy is to identify reactive metabolites that are often short lived either in biological systems or during sample preparation. Current bioanalytical options include capture of reactive metabolites with various trapping agents, such as glutathione (GSH) derivatives, synthetic peptides, cyanide, and nucleobase derivatives. These agents “trap” different types of reactive species, presenting the first hint on the mechanism of bioactivation.
In vitro
incubations usually are carried out in the presence of an appropriate trapping agent, with liver microsomes or hepatocytes serving as the source of enzymes responsible for bioactivation. The resulting samples are subjected to chromatographic separations and mass spectrometry (MS)‐based detection of the trapped stable products. Similar procedures are applicable to specimens from preclinical species and humans for identification of GSH‐related adducts formed
in vivo
via the mercapturic acid pathway. Sample analyses by triple quadrupole or ion trap mass spectrometers follow primarily a stepwise manner from neutral loss and/or parent ion scans to multiple‐stage mass fragmentations in order to acquire sufficient data for metabolite structural assignment. Recent developments in instrumentation have centered on coupling ultraperformance liquid chromatography (UPLC) and high resolution MS; this combination is able to achieve a superior separation of analytes and acquisition of accurate mass spectra, hence a significant increase in sample throughput and improvement of metabolite detection. Use of accurate mass‐based data‐processing software further simplifies data interpretation, enabling quick structural assignment of the trapped products from which reactive species and bioactivation mechanisms are deduced. From a bioanalytical perspective, these experiments often require minimal sample preparation and method development, with a throughput usually satisfying the need of medicinal chemistry to construct a structure–activity relationship (SAR) with respect to the formation of reactive metabolites. The database accumulated, together with preclinical and clinical safety information, should also lead to better understanding of drug treatment‐related adverse effects (AEs).
Oral Chemotherapeutic Agents
Authors: Ogita Shin , LoRusso Patricia , Li Jing 
Published: May 2012

AbstractOral chemotherapeutic agents have been available for decades, and there has been an accelerated expansion in their development during the recent decade. Oral chemotherapeutic agents offer obvious advantages in terms of convenient and noninvasive administration, flexibility and adaptability of dosing, as well as financial and staff time savings. Compared to intravenous agents, oral chemotherapeutic agents generally exhibit substantial interindividual pharmacokinetic variability. Many factors contribute to this variability, including physiological, pathological, environmental, and genetic factors. Unique to oral agents, poor and variable bioavailability is one important source of the interindividual pharmacokinetic variability. This chapter discusses the factors influencing bioavailability of oral chemotherapeutic agents, with focus on the first‐pass metabolism by cytochrome P450 3A4 (CYP3A4), intestinal efflux by ABCB1 transporter, and other factors such as concomitant administration of antiacid medications, food effect, and surgery. Oral chemotherapeutic agents can be classified as traditional cytotoxic agents and novel molecularly targeted agents, hormonal agents, and immune‐modulating agents. Each class of agents is unique with regard to its mechanisms of action, pharmacokinetics, mechanisms of drug resistance, and clinical use. This chapter provides an overview of the major classes of oral chemotherapeutic agents, particularly highlighting examples whereby genetic variations in the genes involved in the drug disposition or drug–target interaction influence the pharmacokinetics and/or response.
Clinical Pharmacology in Drug Labeling. The Impact of Drug Metabolism and Clinical Pharmacology on Recommended Dose of Drugs
Authors: Dombey Stuart 
Published: May 2012

Abstract
Drugs have extensive investigation of clinical pharmacology during development, leading to comprehensive drug labels. However, modification of the dose of a drug in different metabolic states or in the presence of concomitant disease is not clearly labeled. Most drugs seem robust enough to be used with minimal dose modification.
Losing Your Car in the Parking Lot: Spatial Memory in the Real World
Authors: Postma Albert , van Oers Marijn , Back Florinda , Plukaard Sarah 
Published: May 2012

SummaryThe present study investigated qualitative aspects of spatial memory for the parking place of one's car during an incidental visit to a shopping mall. A total of 115 participants (59 men, age range: 19–85 years) performed a number of short tests, designed to measure several aspects of applied spatial memory, prior to leaving a shopping mall in order to return to their car. Gender differences were observed on two aspects of spatial memory. First, women reported more landmarks in their route descriptions than men, whereas men used metric terms more often than women. Second, men outperformed women with respect to estimating the distance to their car. A main effect of age was observed for map location reconstruction: Older participants had more difficulty in relocating their car on a map. Overall, participants were fairly good in finding back their car. Only 14% made a substantial detour, most of them women. This searching behaviour appeared to depend on sense of direction as well as on map relocation ability. Participants employed a variety of strategies, but the number of strategies used was not related to the measured aspects of spatial memory. The current results give further insight into spatial memory usage in the real world. Copyright © 2012 John Wiley & Sons, Ltd.
Practicing Safe Text: the Impact of Texting on Walking Behavior
Authors: Lopresti‐Goodman Stacy M. , Rivera Ana , Dressel Christen 
Published: May 2012

SummarySending and receiving text messages on cell phones is increasingly common. Texting while walking or driving, however, increases the likelihood of accidents. One possible cause is that distracted individuals are unable to detect safe opportunities for action. To investigate this, we asked participants to walk through doorways of differing widths while holding or texting on their phone. We measured walking speed, doorway‐to‐shoulder‐width ratio, and the number of bumps into the doorframes. Our results revealed that texters were more cautious than non‐texters; they walked slower and rotated their body through doorways they could have safely walked straight through. There were no significant differences, however, in the number of bumps into the doorframes. If texters in the real world behave like those in our laboratory, then the number of texting‐related accidents reported in other studies might suggest that being overcautious while texting does not actually decrease the likelihood of accidents. Copyright © 2012 John Wiley & Sons, Ltd.
Multiple loci influencing hippocampal degeneration identified by genome scan
Authors: Melville Scott A. , Buros Jacqueline , Parrado Antonio R. , Vardarajan Badri , Logue Mark W. , Shen Li , Risacher Shannon L. , Kim Sungeun , Jun Gyungah , DeCarli Charles , Lunetta Kathryn L. , Baldwin Clinton T. , Saykin Andrew J. , Farrer Lindsay A. ,   the Alzheimer's Disease Neuroimaging Initiative
Published: May 2012

AbstractObjective:Large genome‐wide association studies (GWASs) have identified many novel genes influencing Alzheimer disease (AD) risk, but most of the genetic variance remains unexplained. We conducted a 2‐stage GWAS for AD‐related quantitative measures of hippocampal volume (HV), total cerebral volume (TCV), and white matter hyperintensities (WMH).Methods:Brain magnetic resonance imaging measures of HV, TCV, and WMH were obtained from 981 Caucasian and 419 African American AD cases and their cognitively normal siblings in the MIRAGE (Multi Institutional Research in Alzheimer's Genetic Epidemiology) Study, and from 168 AD cases, 336 individuals with mild cognitive impairment, and 188 controls in the Alzheimer's Disease Neuroimaging Initiative Study. A GWAS for each trait was conducted in the 2 Caucasian data sets in stage 1. Results from the 2 data sets were combined by meta‐analysis. In stage 2, 1 single nucleotide polymorphism (SNP) from each region that was nominally significant in each data set (p < 0.05) and strongly associated in both data sets (p < 1.0 × 10−5) was evaluated in the African American data set.Results:Twenty‐two markers (14 for HV, 3 for TCV, and 5 for WMH) from distinct regions met criteria for evaluation in stage 2. Novel genome‐wide significant associations (p < 5.0 × 10−8) were attained for HV with SNPs in the APOE, F5/SELP, LHFP, and GCFC2 gene regions. All of these associations were supported by evidence in each data set. Associations with different SNPs in the same gene (p < 1 × 10−5 in Caucasians and p < 2.2 × 10−4 in African Americans) were also observed for PICALM with HV, SYNPR with TCV, and TTC27 with WMH.Interpretation:Our study demonstrates the efficacy of endophenotypes for broadening our understanding of the genetic basis of AD. ANN NEUROL 2012;
Functional Organic Materials Based on Polymerized Liquid‐Crystal Monomers: Supramolecular Hydrogen‐Bonded Systems
Authors: Broer Dirk J. , Bastiaansen Cees M. W. , Debije Michael G. , Schenning Albertus P. H. J. 
Published: May 2012

AbstractFunctional organic materials are of great interest for a variety of applications. To obtain precise functional properties, well‐defined hierarchically ordered supramolecular materials are crucial. The self‐assembly of liquid crystals has proven to be an extremely useful tool in the development of well‐defined nanostructured materials. We have chosen the illustrative example of photopolymerizable hydrogen‐bonding mesogens to show that a wide variety of functional materials can be made from a relatively simple set of building blocks. Upon mixing these compounds with other reactive mesogens, nematic, chiral nematic, and smectic or columnar liquid‐crystalline phases can be formed that can be applied as actuators, sensors and responsive reflectors, and nanoporous membranes, respectively.
Improved adsorption and separation of palladium(II) and platinum(IV) in strong hydrochloric acid solutions using thiocyanate‐retaining tannin gel
Authors: Morisada Shintaro , Kim Yoen‐Ho , Yakuwa Shinpei , Ogata Takeshi , Nakano Yoshio 
Published: May 2012

AbstractA tannin gel (TG) synthesized from condensed tannin molecules has a remarkable ability to adsorb various metal ions in aqueous solutions. In the present study, we have investigated the adsorption behaviors of palladium and platinum ions, Pd(II) and Pt(IV), in strong HCl solutions using the thiocyanate‐retaining tannin gel (SCN‐TG) prepared by adsorption of thiocyanate ion (SCN−) onto the TG in acidic thiocyanate solutions as reported previously (Ind Eng Chem Res 2011, 50, 12366). Although the adsorption rate of Pt(IV) is slow compared to that of Pd(II), the SCN‐TG was able to adsorb both Pd(II) and Pt(IV) in a 1 M HCl solution, where the TG can never adsorb them. Besides, we have succeeded in the selective adsorption of Pd(II) from the mixture solution of Pd(II) and Pt(IV) at a temperature somewhat lower than room temperature using the SCN‐TG. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
Why More Intelligent Individuals Like Classical Music
Authors: Kanazawa Satoshi , Perina Kaja 
Published: May 2012

ABSTRACTThe origin of values and preferences is an unresolved theoretical problem in social and behavioral sciences. The Savanna‐IQ Interaction Hypothesis, derived from the Savanna Principle and a theory of the evolution of general intelligence, suggests that more intelligent individuals are more likely to acquire and espouse evolutionarily novel values and preferences than less intelligent individuals but that general intelligence has no effect on the acquisition and espousal of evolutionarily familiar values and preferences. Recent work on the evolution of music suggests that music in its evolutionary origin was always vocal and that purely instrumental music is evolutionarily novel. The Savanna‐IQ Interaction Hypothesis would then imply that more intelligent individuals are more likely to prefer purely instrumental music than less intelligent individuals, but general intelligence has no effect on the preference for vocal music. The analyses of American (General Social Surveys) and British (British Cohort Study) data are consistent with this hypothesis. Additional analyses suggest that the effect of intelligence on musical preference is not a function of the cognitive complexity of music. Copyright © 2011 John Wiley & Sons, Ltd.
Interactive buildup of animation sequences with captured motion data
Authors: Lee Sang Won , Lee Kang Hoon 
Published: May 2012

ABSTRACTWe present a new approach to interactive resequencing of captured motion data that allows the user to progressively extend his or her animations such that each extension can best fit user requirements with respect to space, time, and pose. In the preprocessing phase, captured frames are clustered into pose groups and interconnected into a transition graph. For each step in building an animation sequence at runtime, the user is allowed to browse through motion paths in the graph that are connectable to the existing sequence by specifying the desired locations and poses at path ends and to select one of those paths to extend the animation. Instead of using graph search algorithms, our path browser unrolls the graph locally into spatial search trees and employs an efficient nearest‐neighbor search method to quickly find the optimal paths that satisfy user inputs. We demonstrate the usefulness of our approach by creating animation examples in scenarios involving spatial, temporal, and postural requirements simultaneously. Copyright © 2012 John Wiley & Sons, Ltd.
Adaptive surface splatting for facial rendering
Authors: Kim Hyeon‐Joong , Cengiz Öztireli A. , Gross Markus , Choi Soo‐Mi 
Published: May 2012

ABSTRACTRecent advances in facial scanning technology provide highly detailed faces, including fine wrinkles. However, because of the increasing complexity of the resulting models, it is necessary to reduce the amount of data while preserving small‐scale facial features. In this paper, we propose a new adaptive surface splatting method to reduce the number of splats by optimizing the size and shape of splats using geometric and color information. Using the optimized splats, we can improve the rendering quality, especially in the visually sensitive feature areas. Our adaptive surface splatting is very effective to render massive facial data on tablet PCs or smartphones. Copyright © 2012 John Wiley & Sons, Ltd.
Ligand Conformation Dictates Membrane and Endosomal Trafficking of Arginine‐Glycine‐Aspartate (RGD)‐Functionalized Mesoporous Silica Nanoparticles
Authors: Fang I‐Ju , Slowing Igor I. , Wu Kevin C.‐W. , Lin Victor S.‐Y. , Trewyn Brian G. 
Published: May 2012

AbstractRecent breakthrough research on mesoporous silica nanoparticle (MSN) materials has illustrated their significant potential in biological applications due to their excellent drug delivery and endocytotic behavior. We set out to determine if MSN, covalently functionalized with conformation specific bioactive molecules (either linear or cyclic RGD ligands), behave towards mammalian cells in a similar manner as the free ligands. We discovered that RGD immobilized on the MSN surface did not influence the integrity of the porous matrix and improved the endocytosis efficiency of the MSN materials. Through competition experiments with free RGD ligands, we also discovered a conformation specific receptor–integrin association. The interaction between RGD immobilized on the MSN surface and integrins plays an important role in endosome trafficking, specifically dictating the kinetics of endosomal escape. Thus, covalent functionalization of biomolecules on MSN assists in the design of a system for controlling the interface with cancer cells.
Ionic‐Liquid‐Mediated Active‐Site Control of MoS2 for the Electrocatalytic Hydrogen Evolution Reaction
Authors: Lau Vincent Wing‐hei , Masters Anthony F. , Bond Alan M. , Maschmeyer Thomas 
Published: May 2012

AbstractThe layered crystal MoS2 has been proposed as an alternative to noble metals as the electrocatalyst for the hydrogen evolution reaction (HER). However, the activity of this catalyst is limited by the number of available edge sites. It was previously shown that, by using an imidazolium ionic liquid as synthesis medium, nanometre‐size crystal layers of MoS2 can be prepared which exhibit a very high number of active edge sites as well as a de‐layered morphology, both of which contribute to HER electrocatalytic activity. Herein, it is examined how to control these features synthetically by using a range of ionic liquids as synthesis media. Non‐coordinating ILs with a planar heterocyclic cation produced MoS2 with the de‐layered morphology, which was subsequently shown to be highly advantageous for HER electrocatalytic activity. The results furthermore suggest that the crystallinity, and in turn the catalytic activity, of the MoS2 layers can be improved by employing an IL with specific solvation properties. These results provide the basis for a synthetic strategy for increasing the HER electrocatalytic activity of MoS2 by tuning its crystal properties, and thus improving its potential for use in hydrogen production technologies.
Gold(I)‐Catalysed Cycloisomerisation of 1,6‐Cyclopropene‐enes
Authors: Miege Frédéric , Meyer Christophe , Cossy Janine 
Published: May 2012

AbstractThe gold(I)‐catalysed cycloisomerisation of appropriately substituted 1,6‐cyclopropene‐enes proceeds through regioselective electrophilic ring opening of the three‐membered ring to generate an alkenyl gold carbenoid that achieves the intramolecular cyclopropanation of the remote olefin. This strategy allows straightforward, highly efficient and diastereoselective access to a variety of substituted 3‐oxa‐ and 3‐azabicyclo[4.1.0]heptanes, as well as to bicyclo[4.1.0]heptan‐3‐ol derivatives. Since the isopropylidene group in the resulting cycloisomerisation products can be subjected to ozonolysis, 3,3‐dimethylcyclopropenes behave as interesting surrogates for α‐diazoketones.
Genetics of Coronary Artery Disease in the 21st Century
Authors: Roberts Robert , Stewart Alexandre F. R. 
Published: May 2012

AbstractCoronary artery disease (CAD) is still the number‐one killer in the world, and clinical trials indicate that it is preventable. Mortality and morbidity can be reduced by at least 30% to 40% by treating known risk factors. Genetic susceptibility is claimed to account for 50% of predisposition. The challenge of preventing CAD in this century, as claimed by some investigators, will require a more comprehensive prevention and treatment of environmental and genetic risk factors. Part of that challenge has been met by genome‐wide association studies, which have identified 36 genetic variants with increased risk for CAD. All of these genetic variants have reached genome‐wide significance (5×10−8) and replicate in independent populations with large sample sizes. More than 50% of these variants occur in >50% of the population, with 10 occurring in >75% of the population. The challenge and the opportunity lie in the observation that >66% of these risk variants do not mediate their risk through known conventional risk factors. These results suggest that genetic predisposition for CAD is conferred by common DNA variants and many factors contributing to the pathogenesis of CAD are yet to be determined. Comprehensive prevention of CAD will most likely require combating genetic and environmental risk factors. We are on the cusp of genetic screening, and new therapeutic targets are becoming available to manage both genetic and environmental risk factors for CAD.The authors are supported by grants from the Canadian Institutes of Health Research, nos. MOP82810 (RR) and MOP77682 (AFRS), and the Canada Foundation for Innovation, no. 11966 (RR). The authors have no other funding, financial relationships, or conflicts of interest to disclose.
Treatment and Outcomes of Acute Coronary Syndrome in the Cancer Population
Authors: Yusuf Syed Wamique , Daraban Nicoleta , Abbasi Nadia , Lei Xiudong , Durand Jean‐Bernard , Daher Iyad N. 
Published: May 2012

AbstractBackground:Randomized trials have established the benefit of medical therapy and revascularization in the treatment of acute myocardial infarction (MI). Cancer and cardiovascular disease are the 2 most common diseases worldwide. In clinical practice, cancer patients are frequently afflicted with MI. The benefit of medical and/or revascularization therapy in the cancer population with MI is less well known.Hypothesis:Medical and revascularization therapy reduces mortality in cancer patients with MI.Methods:After approval by the institutional review board, we retrospectively reviewed all patients with a discharge diagnosis of acute MI who were admitted to the University of Texas MD Anderson Cancer Center between December 2000 and October 2006 and evaluated the association between cardiac treatments with survival outcomes.Results:A total of 456 patients with a discharge diagnosis of acute MI were identified and included in the study, of which 386 had non–ST‐segment elevation MI (NSTEMI) and 70 had ST‐segment elevation MI (STEMI). Compared with patients with NSTEMI, patients who had STEMI were more often prescribed aspirin (66% vs 43%; P = 0.004), β‐blockers (61% vs 46%; P = 0.018), and thrombolytic therapy (9% vs 0.3%; P = 0.0001). In the multivariable analysis, aspirin use was associated with a 23% decreased risk of death (hazard ratio [HR]: 0.77, 95% confidence interval [CI]: 0.60‐0.98, P = 0.033) and β‐blocker use was associated with a 36% decreased risk of death (HR: 0.64, 95% CI: 0.51–0.81, P = 0.0002). Statins (HR: 0.82, P = 0.18) and catheter‐based revascularization (HR: 0.57, P = 0.09) did not have an impact on the risk of death. Compared with patients with limited cancer, advanced cancer patients were twice as likely to die (HR: 2.12, 95 CI: 1.47–3.04, P < 0.0001). Previous chemotherapy (P = 0.005) and chest radiotherapy (P = 0.017) were associated with increased 1‐year mortality, whereas hyperlipidemia (P = 0.018) was protective.Conclusions:In this study of cancer patients with MI, medical therapy with aspirin and β‐blockers was associated with improved survival.The authors have no funding, financial relationships, or conflicts of interest to disclose.