bluuebunny/crossref_metadata_2025 huggingface dataset:
Hominid paleoecology: The competitive exclusion principle and determinants of niche relationships
Authors: Winterhalder Bruce
Published: October 2012

Some paleonanthropologists invoke the competitive exclusion principle programmatically in support of a single‐species (or lineage) hypothesis of hominid evolution. Others apparently accept the association between competitive exclusion and a single species view, and develop multi‐species interpretations using only taxonomic concepts. This paper demonstrates that the competitive exclusion principle itself is too assumption‐bound to be appropriate for analyzing questions of hominid coexistence. Especially, the principle does not establish the ecological validity of the single‐species hypothesis. Contrary to its immediate appearances, the principle has developed historically and analytically to predict and explain the evolution and maintenance of diversity in communities. Used in this manner it constitutes an important basis for the study of hominid paleoecology. Niche concepts necessary to demonstrate this are introduced, and competition and other factors that may have influenced the realized niches of sympatric hominid species are discussed. Nearly all modifications of the competitive exclusion principle that make it more realistic also illuminate factors that generate stable coexistence among competing species. These factors and their organizing theory establish the relevance of a broad data base to the analysis of hominid paleoecology; they should help to guide research on the ecology of early homonid species and their interrelationships.
Hominid brain evolution: The approach from paleoneurology
Authors: Falk Dean
Published: October 2012

The recent literature on hominid paleoneurology is reviewed and critically assessed. Two theoretical approaches for interpreting hominid paleoneurological data are discussed: (1) identifying cerebral “rubicons” that theoretically distinguish hominids from other primates and (2) analyzing brain evolution in terms of “residual” encephalization factors that remain after body size factors have been accounted for. Although these two approaches are scientific, much of the literature on human brain evolution is speculative—i.e., based on efforts to identify “prime movers,” such as hunting or warfare, that theoretically were responsible for the marked increase in both absolute and relative brain size that occurred during hominid evolution. The search for rubicons has been unfruitful. Features that distinguish hominid from pongid brains seem to be the result of allometry (i.e., determined by brain size) rather than the result of selection for qualitatively different neurological features. However, this finding may simply reflect the crude nature of the paleoneurological evidence. Thus, the field of comparative neurology is more likely than paleoneurology to contribute to our knowledge of the details of human brain evolution.
Nutritional status and physical work capacity
Authors: Spurr G. B.
Published: October 2012

The functional consequences of nutritional intake and resulting nutritional status are reviewed in terms of maximal oxygen consumption, physical work capacity, heart rate response to exercise, work productivity, and endurance at submaximal work loads. The results of both acute “laboratory” and chronic “naturally occurring” malnutrition are considered as well as the effects of dietary supplementation and recovery from previously existing undernutrition. Obesity and anemia are also treated as separate but related nutritional entities.
Genetic and familial factors in essential hypertension and related traits
Authors: Siervogel Roger M.
Published: October 2012

The health significance of essential hypertension “high blood pressure of undefined origin” is well established. It is a major factor contributing to coronary heart disease, stroke, and kidney failure. It directly affects about one in five Americans. Factors which are known to be associated with blood pressure include: body composition as it relates to overall mass and fat mass; physiological variables involving the sympathetic and parasympathetic nervous systems; biochemical variables such as renin, aldosterone, kallikrein, lipids, and lipoproteins, etc.; environmental variables such as sodium intake, heavy metals, and noise; and psychological variables involving personality type and mental stress.

There is a definite, well‐established genetic involvement in hypertension, but specific genetic mechanisms remain a mystery. Familial aggregation occurs for many of the associated traits listed above. For some, specific polymorphic major genes have been identified, but for others genetic factors are unidentified. Essential hypertension is undoubtedly a heterogeneous group of diseases with the common end result of elevated blood pressure. Because of its health significance, there is considerable interest in identifying genetic mechanisms resulting in essential hypertension. One area that currently shows some potential for the identification of a specific genetic mechanism is related to the transmembrane transport of sodium and potassium cations.
Fetal growth as measured by ultrasound
Authors: Cronk Christine E.
Published: October 2012

Until the last decade, investigation of fetal growth has been based on data from premature births and abortuses. Advances in ultrasound scanning have expanded the precision and uses of this technology in studies of fetal growth. Most ultrasound studies of fetal growth are based on clinical populations and are reported in clinical journals. The present paper reviews features of ultrasound technology relating to fetal measurement. The most commonly measured dimensions and their associated measurement errors, distributions and uses are detailed. Ultrasound studies of intrauterine growth retardation and in utero fetal weight estimation are critically reviewed. Finally, a comparison between the fetal growth curve based on ultrasound measurement and on data from preterm or aborted fetuses is compared. Critical comments on sample design and statistical treatment of the data from ultrasound studies is included in each of the areas discussed.
Dominance and reproductive success in primates
Authors: Fedigan Linda Marie
Published: October 2012

Theoretical models of the relationship between competition and differential reproduction in primates share the premise that agonistic dominance hierarchies determine differential access to those limited resources which are essential to reproduction. In particular, the priority‐of‐access‐to‐estrous‐female model is based on the postulate that high rank in males enhances reproductive success. Tests for a correlation between rank and reproductive success in males have produced mixed results. Problems in measuring male reproductive success and in conceptualizing dominance systems are implicated in the diversity of conclusions reached. Other attributes which affect reproductive success have been proposed, and alternative models of mating systems, based on the concepts of reproductive strategies, social skills, and life histories have also been developed.

Studies of differential reproduction in female primates are fewer, but have the advantage over male studies of directly measuring infant production and offspring survival. Research on the relationship between rank and reproductive success in females has shown that under conditions of low resource availability, subordinate females sometimes suffer reduced fecundity and infant survival as a result of restricted access to food and water. Under conditions of social stress, low‐ranking females may suffer from disruption of their reproductive cycles, resulting in lowered fecundity. Dominant females may also incur reproductive costs as well as benefits for their social position.

Better insights into the relationship between dominance and reproduction are potentially offered by improved genetic paternity measures, new models of social and demographic processes, and the recent availability of life history data from field studies.
The genetics of human fatness
Authors: Mueller William H.
Published: October 2012

Studies on the quantitative genetics of fatness are reviewed in the framework of the twin, adoption‐cohabitation, and familial aggregation methodologies. Low to moderate heritability of adult static fatness is evident. Somewhat less than one‐third of the variation appears ascribable to genetic causes. Genetic factors may play a greater role in childhood fatness, especially during adolescence. Comparison of studies is made difficult by many methodological shortcomings. These include a rarity of studies of adult first‐degree relatives “adulthood being the period in which fatness has the greatest health consequences”, different criteria of body fatness among studies, a lack of a full variety of genetic and adoptive relationships, inadequate sample sizes “especially in twin studies”, and unreported precision of fatness variables. Fatness change in the life cycle and the anatomical placement of fat are important modifiers of the health effects of obesity. Yet the genetics of these characteristics are little understood. Innovative statistical methods and study designs including path analysis, the family set method, and families of monozygous twins need wider application to the genetics of human fatness.
Thermal decomposition studies of Schiff‐base‐substitute polyphenol–metal complexes
Authors: Doğan Fatih , Kaya İsmet
Published: October 2012

The thermal behaviors of 2,3‐bis[(2‐hydroxyphenyl)methylene] diaminopyridine, oligo‐2,3‐bis[(2‐hydroxyphenyl)methylene] diaminopyridine, and some oligo‐2,3‐bis[(2‐hydroxyphenyl) methylene] diaminopyridine–metal complexes were studied in a nitrogen atmosphere with thermogravimetric analysis, derivative thermogravimetric analysis, and differential thermal analysis techniques. The decompositions of oligo‐2,3‐bis[(2‐hydroxyphenyl) methylene] diamino pyridine–metal complexes occurred in multiple steps. The values of the activation energy (E) and reaction order of the thermal decomposition were calculated by means of several methods, including Coats–Redfern, Horowitz–Metzger, Madhusudanan–Krishnan–Ninan, van Krevelen, Wanjun–Yuwen–Hen–Cunxin, and MacCallum–Tanner on the basis of a single heating rate. The most appropriate method was determined for each decomposition step according to a least‐squares linear regression. The E values obtained by each method were in good agreement with each other. It was found that the E values of the complexes for the first decomposition stage followed the order EOHPMDAP–Ni > EOHPMDAP–Cd > EOHPMDAP–Cu > EOHPMDAP–Fe > EOHPMDAP–Zn > EOHPMDAP–Co > EOHPMDAP–Cr > EHPMDAP > EOHPMDAP. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Mechanical properties of silane‐treated silica particle‐filled polyisoprene composites: Influence of the alkoxy group mixing ratio in silane coupling agent containing mercapto group
Authors: Nakamura Yoshinobu , Nishida Yuji , Fukuda Tomoyoshi , Fujii Syuji , Sasaki Mariko
Published: October 2012

Spherical silica particles were treated with a mixture of silane coupling agents with mercapto functional groups and dialkoxy or trialkoxy groups. The surface coverage, which indicates the number of layers covering the silica surface, was in the range from 1.6 to 6.0. The molecular mobility of the treated layer was analyzed with 1H‐NMR spectroscopy. The silane chain became more flexible with increasing dialkoxy structures in the mixture and with increasing surface coverage. The stress–strain behavior was measured for a composite consisting of the treated silica and vulcanized polyisoprene rubber (PIR). There was no influence of the dialkoxy and trialkoxy mixing ratio for near monolayer coverage. In the case of the pure dialkoxy and low trialkoxy contents, a higher stress was observed at the same strain for surface coverages of 2.4–3.8. However, a longer length flexible silane chain, that is, with a surface coverage of 6.0, was disadvantageous for the reinforcement effect. The results of pulse NMR analysis of the unextracted PIR on the particle surface and swelling test indicate that the reinforcement effect was strongly affected both by entanglement and the crosslinking reaction between the silane chain and PIR at the interfacial region. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Gas permeation and separation properties of polyimide/ZSM‐5 zeolite composite membranes containing liquid sulfolane
Authors: Kanehashi Shinji , Gu Hua , Shindo Ryohei , Sato Shuichi , Miyakoshi Tetsuo , Nagai Kazukiyo
Published: October 2012

The preparation, characterization, and gas permeation properties of novel composite membranes containing polyimide (PI), liquid sulfolane (SF), and zeolite (ZSM‐5) were investigated to address the interface defects between the PI and the zeolite. The free‐standing composite membranes were prepared by the solvent casting method. The gas permeability of the PI+ZSM‐5 membrane was higher than that of PI, whereas its gas selectivity was significantly reduced, suggesting that these results are attributed to the interface defects. The CO2 selectivity of PI+ZSM‐5+SF was higher than those of the PI+ZSM‐5 membranes because of the introduction of liquid SF into the interface defects. Furthermore, liquid SF enhanced the CO2/H2 selectivity near the recent upper bound. Therefore, the use of liquid SF could be an effective approach to preventing interface defects and increasing the CO2 selectivity, particularly for CO2/H2. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
A new method for stabilizing softwood kraft lignin fibers for carbon fiber production
Authors: Norberg Ida , Nordström Ylva , Drougge Rickard , Gellerstedt Göran , Sjöholm Elisabeth
Published: October 2012

Renewable resources, such as kraft lignin, have shown great potential as precursors for carbon fiber production. This manuscript reports an investigation into the stabilization of softwood kraft lignin (SKL) fibers and the determination of the difference in stabilization between hardwood‐ and softwood‐based kraft lignin fibers. The stabilization was achieved either thermally by using only heat or oxidatively in the presence of air, at various heating rates. A heating rate of 4°C min−1 and a holding time of 30 min at 250°C were successfully used for the thermal stabilization experiments. Faster stabilization was achieved using oxidative conditions at a heating rate of 15°C min−1 and 30 min holding time at 250°C. Furthermore, stabilization and carbonization in a one‐step process was performed on SKL fibers, which show great potential to reduce both production time and costs. The stabilized and carbonized fibers were evaluated using thermal, spectroscopic, and microscopic methods. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Lanolin‐based organogels as a matrix for topical drug delivery
Authors: Sagiri Sai Sateesh , Behera Beauty , Pal Kunal , Basak Piyali
Published: October 2012

The current study deals with the development of lanolin‐based emulsion gels by hot emulsification method. Bright‐field, phase contrast, and fluorescent micrographs of the gels have shown the uniform distribution of circular water droplets in the formulations. Coalescence of water droplets was observed in gels containing higher proportion of water. Fourier transform infrared spectrophotometric studies indicated absence of Ln‐drug chemical interactions. X‐ray diffraction studies suggested an increase in amorphousness of the gels with the incorporation of water into the gel structure. The salicylic acid (SA), model drug, release from the gels was found to follow Higuchi kinetics. Krossmeyer–Peppas model fitting indicated non‐Fickian release of the drug. As the water content of the gels increased, there was a corresponding increase in the rate of release of the drug. The gels showed non‐Newtonian and thixotropic flow behavior. The gel to sol transition and melting temperatures of the gels were identified by differential scanning calorimetric (DSC) thermal analysis and falling ball method. DSC thermograms indicated an increase in thermal stability with the increase of water content in the gels. The gels showed sufficient spreadability and biocompatibility characteristics to be used as topical formulations. SA loaded gels showed good antimicrobial efficacy against Bacillus subtilis, a Gram‐positive bacterium. Based on the preliminary studies, the developed gels may be regarded as carriers in topical drug delivery. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Electrical properties of sorbitol‐doped poly(vinyl alcohol)–poly(acrylamide‐co‐acrylic acid) polymer membranes
Authors: Josh Vinitha , Haik Mohammad Y. , Ayesh Ahmad I. , Mohsin Mahmoud A. , Haik Yousef
Published: October 2012

Solid polymer membranes from poly(vinyl alcohol) (PVA) and poly(acrylamide‐co‐acrylic acid) (PAA) with varying doping ratios of sorbitol were prepared using the solution casting method. The films were examined with Fourier transform infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, and AC impedance spectroscopy. The impedance measurements showed that the ionic conductivity of PVA–PAA polymer membrane can be controlled by controlled doping of sorbitol within the polymer blends. The PVA–PAA–sorbitol membranes were found to exhibit excellent thermal properties and were stable for a wide temperature range (398–563K), which creates a possibility of using them as suitable polymers for device applications. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Effect of polymer matrix/montmorillonite compatibility on morphology and melt rheology of polypropylene nanocomposites
Authors: Zhu Shipeng , Chen Jinyao , Li Huilin , Cao Ya
Published: October 2012

In this study, Ca2+‐montmorillonite (Ca2+‐MMT) and organo‐montmorillonite (OMMT) were modified by three compatibilizers with different degrees of polarity [poly(ethylene glycol) (PEG), alkyl‐PEG, and polypropylene (PP)‐g‐PEG]. PP/MMT nanocomposites were prepared by melt blending and characterized using X‐ray diffraction and transmission electron microscopy. The results showed the degree of dispersion of OMMT in the PP/PP‐g‐PEG/OMMT (PMOM) nanocomposite was considerably higher than those in the PP/PEG/OMMT and PP/alkyl‐PEG/OMMT nanocomposites, which indicated that the dispersion was relative to the compatibility between modified OMMT and PP matrix. Linear viscoelasticity of PP/MMT nanocomposites in melt states was investigated by small amplitude dynamic rheology measurements. With the addition of the modified MMT, the shear viscosities and storage modulus of all the PP/MMT nanocomposites decreased. It can be attributed to the plasticization effect of PEG segments in the three modifiers. This rheological behavior was different from most surfactant modified MMT nanocomposites which typically showed an increase in dynamic modulus and viscosity relative to the polymer matrix. The unusual rheological observations were explained in terms of the compatibility between the polymer matrix and MMT. In addition, the mechanical properties of PP/MMT nanocomposites were improved. A simultaneous increase in the tensile strength and toughness was observed in PP/PMOM nanocomposites. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
The role of lateral connectivity in the maintenance of macrophyte diversity and production in large rivers
Authors: Keruzoré Antoine A. , Willby Nigel J. , Gilvear David J.
Published: October 2012

Large European river floodplains have been intensively reduced through human activities over several millennia. Ecological assessments of natural large river systems remain rare and potentially flawed since they typically omit either the main channel of the river or, more commonly, aquatic habitats that occur naturally in the floodplain of dynamic systems.

Surveys were conducted over a longitudinal and lateral gradient to assess distribution, richness and production of macrophytes along two little‐disturbed large upland rivers in Scotland.

Lateral dynamics, through the creation of backwaters, underpinned the occurrence, abundance and production of macrophytes in these rivers. Indeed, backwaters, despite representing only 5% of the total area of aquatic habitat, supported a significantly higher concentration of species (65% of species recorded at the riverscape scale were unique to backwaters) than the main channel.

The frequency with which backwaters were connected to the main channel during flood flows influenced their species richness. Highest species richness in backwaters was typically found at low connectivity. Standing crop in backwaters was 150 times higher per unit area than in the main channel, while at the riverscape scale backwaters accounted for an average 89% of aquatic plant biomass. The highest plant biomass was found at low and medium connectivity with the main channel.

Backwaters appear to be crucial habitats in maintaining macrophyte diversity and production in large river ecosystems. These results emphasize the importance of river hydrodynamics and lateral connectivity in maintaining macrophyte community diversity along large rivers. The results illustrate also the potentially very significant role of backwaters as source habitats supplying propagules and organic matter to downstream reaches.

It is argued that the entire riverscape (floodplain plus main channel) must be considered in the holistic assessment of such systems, while protection of this resource requires greater recognition of linkages within and across habitats, both aquatic and terrestrial, to be effective.

Copyright © 2012 John Wiley & Sons, Ltd.
Comparing Performance of Centerline Algorithms for Quantitative Assessment of Brain Vascular Anatomy
Authors: Diedrich Karl T. , Roberts John A. , Schmidt Richard H. , Parker Dennis L.
Published: October 2012

Attributes like length, diameter, and tortuosity of tubular anatomical structures such as blood vessels in medical images can be measured from centerlines. This study develops methods for comparing the accuracy and stability of centerline algorithms. Sample data included numeric phantoms simulating arteries and clinical human brain artery images. Centerlines were calculated from segmented phantoms and arteries with shortest paths centerline algorithms developed with different cost functions. The cost functions were the inverse modified distance from edge (MDFEi), the center of mass (COM), the binary‐thinned (BT)‐MDFEi, and the BT‐COM. The accuracy of the centerline algorithms were measured by the root mean square error from known centerlines of phantoms. The stability of the centerlines was measured by starting the centerline tree from different points and measuring the differences between trees. The accuracy and stability of the centerlines were visualized by overlaying centerlines on vasculature images. The BT‐COM cost function centerline was the most stable in numeric phantoms and human brain arteries. The MDFEi‐based centerline was most accurate in the numeric phantoms. The COM‐based centerline correctly handled the “kissing” artery in 16 of 16 arteries in eight subjects whereas the BT‐COM was correct in 10 of 16 and MDFEi was correct in 6 of 16. The COM‐based centerline algorithm was selected for future use based on the ability to handle arteries where the initial binary vessels segmentation exhibits closed loops. The selected COM centerline was found to measure numerical phantoms to within 2% of the known length. Anat Rec, 2012. © 2012 Wiley Periodicals, Inc.
Five examples of assessment and expression of measurement uncertainty
Authors: Possolo Antonio
Published: October 2012

It is a long‐accepted tenet of scientific practice that every measurement result ought to include a statement of uncertainty associated with the measured value. Such uncertainty should also be propagated to functions of the measured values. It is also widely recognized that probability distributions are well suited to express measurement uncertainty and that statistical methods are the choice vehicles to produce uncertainty assessments incorporating information in empirical data as well as other relevant information, either about the quantity that is the object of measurement or about the techniques or apparatuses used in measurement.

Statistical models and methods of statistical inference provide the technical machinery necessary to evaluate and propagate measurement uncertainty. Some of these models and methods are illustrated in five examples: (i) measurement of the refractive index of a glass prism (employing a venerable formula due to Gauss, as well as contemporary Monte Carlo methods); (ii) measurement of the mass fraction of arsenic in oyster tissue using data from an inter‐laboratory study (introducing a Bayesian hierarchical model with adaptive tail heaviness); (iii) measurement of the relative viscosity increment of a solution of sucrose in water (using a copula); (iv) mapping measurements of radioactivity in the area of Fukushima, Japan (via both local regression and kriging, and explaining how model uncertainty may be evaluated); and (v) combining expert opinions about the flow rate of oil during the Deepwater Horizon oil spill into the Gulf of Mexico (via linear or logarithmic pooling). Copyright © 2012 John Wiley & Sons, Ltd.
Hierarchical Bayesian autoregressive models for large space–time data with applications to ozone concentration modelling
Authors: Sahu Sujit Kumar , Bakar Khandoker Shuvo
Published: October 2012

Increasingly large volumes of space–time data are collected everywhere by mobile computing applications, and in many of these cases, temporal data are obtained by registering events, for example, telecommunication or Web traffic data. Having both the spatial and temporal dimensions adds substantial complexity to data analysis and inference tasks. The computational complexity increases rapidly for fitting Bayesian hierarchical models, as such a task involves repeated inversion of large matrices. The primary focus of this paper is on developing space–time autoregressive models under the hierarchical Bayesian setup. To handle large data sets, a recently developed Gaussian predictive process approximation method is extended to include autoregressive terms of latent space–time processes. Specifically, a space–time autoregressive process, supported on a set of a smaller number of knot locations, is spatially interpolated to approximate the original space–time process. The resulting model is specified within a hierarchical Bayesian framework, and Markov chain Monte Carlo techniques are used to make inference. The proposed model is applied for analysing the daily maximum 8‐h average ground level ozone concentration data from 1997 to 2006 from a large study region in the Eastern United States. The developed methods allow accurate spatial prediction of a temporally aggregated ozone summary, known as the primary ozone standard, along with its uncertainty, at any unmonitored location during the study period. Trends in spatial patterns of many features of the posterior predictive distribution of the primary standard, such as the probability of noncompliance with respect to the standard, are obtained and illustrated. Copyright © 2012 John Wiley & Sons, Ltd.
Understanding pharmacokinetic food effects using molecular dynamics simulation coupled with physiologically based pharmacokinetic modeling
Authors: Turner David C. , Yin Fuchang , Kindt James T. , Zhang Hailing
Published: October 2012

In this study, a molecular dynamics (MD) method is assessed as a new front‐end tool for deriving relevant drug‐micelle partitioning rates for use in conjunction with a compartmental‐style gastrointestinal absorption model. A refined mechanistic approach for handling micelle‐associated vs unbound drug is presented and examined in terms of its utility for projecting human oral pharmacokinetic food/formulation effects. Similar to predecessor oral absorption models, the intestinal drug absorption rate is formulated as a function of the combined permeability through the unstirred water layer and the epithelial membrane, however, an additional diffusion coefficient adjustment is applied to account for the viscosity changes of the postprandial small intestine. Bulk passage of drug particles through the GI tract is simulated by compartmental transit through a network of nine compartments comprising the stomach, small intestine and colon. The tandem MD simulation/compartmental absorption algorithm is applied to identify factors influencing the fed vs fasted absorption ratios of a structurally diverse set of orally administered drugs. The data illustrate the interplay and apparent compromise between micelle solubilization and permeability. Copyright © 2012 John Wiley & Sons, Ltd.
Development of oral extended release formulations of 6‐hydroxybuspirone
Authors: Nicholson Sarah J. , Timmins Peter , Dockens Randy C. , Connor Alyson , Croop Robert , Ferrie Peter , Zeng Jianing , Dennis Andrew B. , Wilding Ian
Published: October 2012

Reducing the maximum plasma concentration whilst maintaining the exposure was shown to ameliorate adverse events following the oral administration of 6‐hydroxybuspirone. This observation, along with a desire to provide for once daily dosing of this compound, provided the basis for the development of an extended release formulation. Hydrophilic matrix tablets based on hydroxypropyl methylcellulose and containing citric acid to provide for an acid microenvironment were prepared and evaluated by in vitro drug release studies and in vivo pharmacokinetic and scintigraphic studies using samarium oxide (153Sm) labelled dosage forms. The dosage forms were found to release the contained drug by a predominantly diffusion mechanism and the release rate was relatively independent of environmental pH. Following administration of the extended release formulations to volunteers, comparative pharmacokinetic data indicated that the extended release formulations provided for a reduction in the maximum plasma concentration of 64–70% relative to that provided by the same dose given as an oral solution, whilst maintaining exposure relative to the oral solution. By examination of absorption curves derived by Wagner‐Nelson analysis of pharmacokinetic data it was noted that drug release in vivo correlated well with drug release observed in vitro and no marked change in rate of absorption was noted when dosage forms were located in and releasing drug in the colon. The robust control of drug release seen in vitro translated to a good in vivo performance. Copyright © 2012 John Wiley & Sons, Ltd.
Nonparametric inference on cause‐specific quantile residual life
Authors: Jeong Jong‐Hyeon , Fine Jason P.
Published: October 2012

In medical research, investigators are often interested in inferring time‐to‐event distributions under competing risks. It is well known, however, that the naive approach based on the Kaplan–Meier method to estimate the proportion of cause‐specific events overestimates the true quantity. In this paper, we show that the quantile residual life function, a natural and popular summary measure of survival data, could be also seriously affected by the competing events. An existing two‐sample test statistic for inference on median residual life is modified for competing risks data, which does not involve estimation of the improper probability density function of the subdistribution of cause‐specific events under censoring. Simulation results demonstrate that the test statistic controls the type 1 error probabilities reasonably well. The proposed method is applied to a real data example from a large‐scale phase III breast cancer study.
Development and validation of a liquid chromatography–tandem mass spectrometry method for quantitation of indomethacin in rat plasma and its application to a pharmacokinetic study in rats
Authors: S Suresh P , Dixit Abhishek , Giri Sanjeev , Rajagopal Sriram , Mullangi Ramesh
Published: October 2012

A highly sensitive and rapid bioanalytical method has been developed and validated for the estimation of indomethacin in rat plasma with liquid chromatography coupled to tandem mass spectrometry with electrospray ionization in the positive‐ion mode. The assay procedure involves a simple liquid–liquid extraction of indomethacin and phenacetin (internal standard, IS) from rat plasma with acetonitrile. Chromatographic separation was achieved with 0.2% formic acid–acetonitrile (25:75, v/v) at a flow rate of 0.60 mL/min on an Atlantis dC18 column with a total run time 3.0 min. The MS/MS ion transitions monitored were 357.7 → 139.1 for indomethacin and 180.20 → 110.10 for IS. Method validation and pharmacokinetic study plasma analysis were performed as per FDA guidelines and the results met the acceptance criteria. The lower limit of quantitation achieved was 0.51 ng/mL and the linearity was observed from 0.51 to 25.5 ng/mL. The intra‐ and inter‐day precisions were in the range of 1.00–10.2 and 5.88–9.80%, respectively. This novel method has been applied to an oral pharmacokinetic study in rats. Copyright © 2012 John Wiley & Sons, Ltd.
Meta‐stereotypes, Social Image and Help Seeking: Dependency‐Related Meta‐stereotypes Reduce Help‐Seeking Behaviour
Authors: Wakefield Juliet R. H. , Hopkins Nick , Greenwood Ronni Michelle
Published: October 2012

People who need help can be reluctant to seek it. This can be due to social image concerns. Here, we investigate if these concerns may be prompted by a salient negative meta‐stereotype: the belief that one's group is judged negatively by another group. Specifically, we researched group members' help‐seeking behaviour in the context of a dependency‐related meta‐stereotype. In a two‐condition study (N = 45), we manipulated participants' belief that their national group was judged dependent by a significant out‐group. We then examined their subsequent help‐seeking behaviour on a real‐world task. Participants whose social identity as a group member was salient showed greater reluctance to seek help when the meta‐stereotype was made prominent compared with when it was not. This suggests that, in a context where social image and social identity concerns are relevant, group members are willing to sacrifice the possibility of accessing needed help in order to avoid confirming a negative stereotype of their group. The implications of these results for helping transactions and community development are discussed. Copyright © 2012 John Wiley & Sons, Ltd.
The Influence of the Internet on the Psychosocial Predictors of Collective Action
Authors: Alberici Augusta Isabella , Milesi Patrizia
Published: October 2012

The Internet has emerged as an important communication platform for the support of collective action, but little is known about how it influences the psychosocial motives for participation. Two quantitative studies were conducted within two different mobilizing contexts, in which offline collective actions were launched through computer‐mediated communication. We examined whether and how the frequency with which people participated in online political discussions moderated the effects of the psychosocial predictors of collective action, specifically politicized identity, anger, collective efficacy, and morality. Results showed that collective action intention was predicted by politicized identity only when participants reported a higher versus lower frequency of online discussion. However, anger did not predict collective action when people had the chance to express this emotion through a higher versus lower frequency of online discussion. Moreover, collective efficacy and morality supported collective action intention in participants who reported a higher versus lower frequency of online discussion. We theorize on how computer‐mediated communication, and its specific features, can be studied as a mobilizing context that influences the psychosocial motives to participate in collective action. Copyright © 2012 John Wiley & Sons, Ltd.
One‐Pot Conversion of Inulin to Furan Derivatives Catalyzed by Sulfated TiO2/Mordenite Solid Acid
Authors: Shen X. , Wang Y. X. , Hu C. W. , Qian K. , Ji Z. , Jin M.
Published: October 2012

We prepared a sulfated TiO2/mordenite solid acid for the heterogeneous catalytic conversion of inulin (polysaccharide) to 5‐hydroxymethylfurfural and 2,5‐furancarboxaldehyde. The hydrolysis of inulin and the dehydration of fructose were performed by using a one‐pot method in a water/2‐butanol biphasic system. With an inulin conversion rate of 82.3 %, a high 5‐hydroxymethylfurfural yield of 61.5 % was obtained, which represents moderate catalytic reactivity and selectivity but facilitates the separation process comprehensively. The catalytic performance was attributed to the SO42− groups and the Lewis acid sites on the titania surfaces. A delicate loading rate of titania over mordenite was critical to maintain sufficient active sites, whereas an appropriate porosity of the complex system was reserved for the diffusion of reactants and products.
Selective Catalytic Oxidation of CH Bonds with Molecular Oxygen
Authors: Roduner Emil , Kaim Wolfgang , Sarkar Biprajit , Urlacher Vlada B. , Pleiss Jürgen , Gläser Roger , Einicke Wolf‐Dietrich , Sprenger Georg A. , Beifuß Uwe , Klemm Elias , Liebner Christian , Hieronymus Hartmut , Hsu Shih‐Fan , Plietker Bernd , Laschat Sabine
Published: October 2012

Although catalytic reductions, cross‐couplings, metathesis, and oxidation of CC double bonds are well established, the corresponding catalytic hydroxylations of CH bonds in alkanes, arenes, or benzylic (allylic) positions, particularly with O2, the cheapest, “greenest”, and most abundant oxidant, are severely lacking. Certainly, some promising examples in homogenous and heterogenous catalysis exist, as well as enzymes that can perform catalytic aerobic oxidations on various substrates, but these have never achieved an industrial‐scale, owing to a low space‐time‐yield and poor stability. This review illustrates recent advances in aerobic oxidation catalysis by discussing selected examples, and aims to stimulate further exciting work in this area. Theoretical work on catalyst precursors, resting states, and elementary steps, as well as model reactions complemented by spectroscopic studies provide detailed insight into the molecular mechanisms of oxidation catalyses and pave the way for preparative applications. However, O2 also poses a safety hazard, especially when used for large scale reactions, therefore sophisticated methodologies have been developed to minimize these risks and to allow convenient transfer onto industrial scale.
Organic Dye‐Photocatalyzed Acylnitroso Ene Reaction
Authors: Teo Yew Chin , Pan Yuanhang , Tan Choon Hong
Published: October 2012

Rose bengal, an inexpensive and readily available organic dye, is demonstrated to be a photoredox catalyst for the formation of transient acylnitroso intermediates under visible light irradiation. This method is operationally simple and uses air as the terminal oxidant. Reactions of acylnitroso with a range of functionalized alkenes give intermolecular acylnitroso ene products in moderate to good yields. This is an environmentally friendly allylic amination methodology that avoids the use of metal catalysts and stoichiometric amount of oxidants. A plausible reaction mechanism is proposed on the basis of singlet oxygen and fluorescence quenching studies.
Phosphine Organocatalysis in the Synthesis of Natural Products and Bioactive Compounds
Authors: Gomez Catherine , Betzer Jean‐François , Voituriez Arnaud , Marinetti Angela
Published: October 2012

During the last few years, synthetic methods based on phosphine organocatalysis have experienced extremely fast developments. This short overview is intended to demonstrate that these methods can afford suitable tools for the constitution of either focused or diversity‐oriented‐synthesis (DOS) inspired libraries of small molecules for biological screening. It also reports selected examples where these organocatalytic methods have been used conveniently as key steps in the formal or total synthesis of complex natural products. Especially, synthetic applications of the inter‐ and intramolecular cyclizations of unsaturated substrates have been considered in this review.
Quaternary Chiral β2,2‐Amino Acids with Pyridinium and Imidazolium Substituents
Authors: Mata Lara , Avenoza Alberto , Busto Jesús H. , Corzana Francisco , Peregrina Jesús M.
Published: October 2012

The reactions of cyclic sulfamidates as electrophiles with a variety of nitrogen‐containing aromatic heterocycle nucleophiles, such as pyridines, N‐alkylimidazoles and N‐methylbenzimidazol, was explored. In all cases, although the nucleophilic substitution reactions occurred on quaternary centres, elimination products were not detected. The inversion of configuration at this quaternary centre was determined by X‐ray diffraction analysis and the enantiomeric excess of the reactions was checked by chiral HPLC. This synthetic approach allowed us to obtain a new family of chiral charged β2,2‐amino acids, including a new bisamino acid that incorporates an imidazolium salt as a cross‐linker. In this context, the treatment of these chiral imidazolium salts with Ag2O opens the way to new chiral N‐heterocyclic carbenes, which are important substrates in the fields of organometallic and organocatalytic chemistry. Additionally, we have done a thorough conformational analysis of these β‐amino acid derivatives, both in the solid state and in solution. The most important conformational feature of these acyclic systems is the rigidity of the N‐CH2‐C‐N+ dihedral angle, which is essentially due to the gauche effect.
Thermodynamic and Mechanistic Insights into Translesion DNA Synthesis Catalyzed by Y‐Family DNA Polymerase Across a Bulky Double‐Base Lesion of an Antitumor Platinum Drug
Authors: Brabec Viktor , Malina Jaroslav , Margiotta Nicola , Natile Giovanni , Kasparkova Jana
Published: October 2012

To determine how the Y‐family translesion DNA polymerase η (Polη) processes lesions remains fundamental to understanding the molecular origins of the mutagenic translesion bypass. We utilized model systems employing a DNA double‐base lesion derived from 1,2‐GG intrastrand cross‐links of a new antitumor PtII complex containing a bulky carrier ligand, namely [PtCl2(cis‐1,4‐dach)] (DACH=diaminocyclohexane). The catalytic efficiency of Polη for the insertion of correct dCTP, with respect to the other incorrect nucleotides, opposite the 1,2‐GG cross‐link was markedly reduced by the DACH carrier ligand. This reduced efficiency of Polη to incorporate the correct dCTP could be due to a more extensive DNA unstacking and deformation of the minor groove induced in the DNA by the cross‐link of bulky [PtCl2(cis‐1,4‐dach)]. The major products of the bypass of this double‐base lesion produced by [PtCl2(cis‐1,4‐dach)] by Polη resulted from misincorporation of dATP opposite the platinated G residues. The results of the present work support the thesis that this misincorporation could be due to sterical effects of the bulkier 1,4‐DACH ligand hindering the formation of the Polη–DNA–incoming nucleotide complex. Calorimetric analysis suggested that thermodynamic factors may contribute to the forces that governed enhanced incorporation of the incorrect dATP by Polη as well.
Enantiomerization Mechanism of Thalidomide and the Role of Water and Hydroxide Ions
Authors: Tian Chuanjin , Xiu Peng , Meng Yan , Zhao Wenyan , Wang Zhigang , Zhou Ruhong
Published: October 2012

The significance of the molecular chirality of drugs has been widely recognized due to the thalidomide tragedy. Most of the new drugs reaching the market today are single enantiomers, rather than racemic mixtures. However, many optically pure drugs, including thalidomide, undergo enantiomerization in vivo, thus negating the single enantiomers’ benefits or inducing unexpected effects. A detailed atomic level understanding of chiral conversion, which is still largely lacking, is thus critical for drug development. Herein, we use first‐principle density function theory (DFT) to explore the mechanism of enantiomerization of thalidomide. We have identified the two most plausible interconversion pathways for isolated thalidomide: 1) proton transfer from the chiral carbon center to an adjacent carbonyl oxygen atom, followed by isomerization and rotation of the glutarimide ring (before the proton hops back to the chiral carbon atom); and 2) a pathway that is the same as “1”, but with the isomerization of the glutarimide ring occurring ahead of the initial proton transfer reaction. There are two remarkable energy barriers, 73.29 and 23.59 kcal mol−1, corresponding to the proton transfer and the rotation of the glutarimide ring, respectively. Furthermore, we found that water effectively catalyzes the interconversion by facilitating the proton transfer with the highest energy barrier falling to approximately 30 kcal mol−1, which, to our knowledge, is the first time that this important role of water in chiral conversion has been demonstrated. Finally, we show that the hydroxide ion can further lower the enantiomerization energy barrier to approximately 24 kcal mol−1 by facilitating proton abstraction, which agrees well with recent experimental data under basic conditions. Our current findings highlight the importance of water and hydroxide ions in the enantiomerization of thalidomide and also provide new insights into the mechanism of enantiomerization at an atomic level.
Percutaneous image‐guided cryoablation of painful metastases involving bone
Authors: Callstrom Matthew R. , Dupuy Damian E. , Solomon Stephen B. , Beres Robert A. , Littrup Peter J. , Davis Kirkland W. , Paz‐Fumagalli Ricardo , Hoffman Cheryl , Atwell Thomas D. , Charboneau J. William , Schmit Grant D. , Goetz Matthew P. , Rubin Joseph , Brown Kathy J. , Novotny Paul J. , Sloan Jeff A.
Published: October 2012

BACKGROUND:

This study sought to describe the results of a single‐arm multicenter clinical trial using image‐guided percutaneous cryoablation for the palliation of painful metastatic tumors involving bone.

METHODS:

Over a 44‐month period, 61 adult patients with 1 or 2 painful bone metastases with a score of 4 or more on a scale of 0 to 10 (≥4/10) worst pain in a 24‐hour period who had failed or refused conventional treatment were treated with percutaneous image‐guided cryoablation. Patient pain and quality of life was measured using the Brief Pain Inventory prior to treatment, 1 and 4 days after the procedure, weekly for 4 weeks, and every 2 weeks thereafter for a total of 6 months. Patient analgesic use was also recorded at these same follow‐up intervals. Complications were monitored. Analysis of the primary endpoint was undertaken via paired comparison procedures.

RESULTS:

A total of 69 treated tumors ranged in size from 1 to 11 cm. Prior to cryoablation, the mean score for worst pain in a 24‐hour period was 7.1/10 with a range of 4/10 to 10/10. At 1, 4, 8, and 24 weeks after treatment, the mean score for worst pain in a 24‐hour period decreased to 5.1/10 (P < .0001), 4.0/10 (P < .0001), 3.6/10 (P < .0001), and 1.4/10 (P < .0001), respectively. One of 61 (2%) patients had a major complication with osteomyelitis at the site of ablation.

CONCLUSIONS:

Percutaneous cryoablation is a safe, effective, and durable method for palliation of pain due to metastatic disease involving bone. Cancer 2013. © 2012 American Cancer Society.