bluuebunny/crossref_metadata_2025 huggingface dataset:
Modification of polystyrene properties by CO2: Experimental study and correlation
Authors: Gutiérrez Cristina , Rodríguez Juan Francisco , Gracia Ignacio , de Lucas Antonio , García M. Teresa
Published: November 2014

The sorption of CO2 in polymers entails their swelling and plasticization whose study is crucial for the design of processes and further applications. The operating conditions during foaming, purification, or impregnation of polymers in CO2 are mainly determined by the mentioned binary system. In this work, the modification of polystyrene's physical properties (glass transition temperature and viscosity) has been experimentally studied. Since plasticization phenomena are very valuable for the processing of polymers, the amount of CO2 absorbed into the polymer is related with the changes in the described properties. Furthermore, interfacial tension is also correlated with the sorption of CO2 from literature data. The proposed correlation fits pretty well the properties shifts in the studied working conditions. Finally, the influence of pressure and temperature on the diffusivity of the CO2 in the polystyrene is calculated through the measurement of viscosity along time. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41696.
Stress relaxation behavior of starch powder‐epoxy resin composites
Authors: Papanicolaou George C. , Kontaxis Lykourgos C. , Koutsomitopoulou Anastasia F. , Zaoutsos Stephanos P.
Published: November 2014

The purpose of the present study is to investigate the quasi‐static and the viscoelastic behavior of epoxy resin reinforced with starch powder. An increase in the elastic modulus on the order of 42% was achieved; a behavior that was predicted by the modulus prediction model (MPM). Next, the composite was subjected to flexural relaxation experiments, in order to determine the relaxation modulus, at different filler‐weight fractions and flexural deflections imposed. The viscoelastic models of the standard linear solid, the power law model and the residual property model (RPM) were applied in order to simulate/predict the stress relaxation curves. Predicted values derived from the application of the above models were compared to each‐other as well as to respective experimental findings. From the above comparison it was proved the superiority of the RPM model in predicting both the linear and the nonlinear viscoelastic response of the materials investigated. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41697.
Proteins as supramolecular building blocks: Nterm‐Lsr2 as a new protein tecton
Authors: Ashmead Helen M. , Negron Leonardo , Webster Kyle , Arcus Vic , Gerrard Juliet A.
Published: November 2014

Proteins hold great promise in forming complex nanoscale structures which could be used in the development of new nanomaterials, devices, biosensors, electronics, and pharmaceuticals. The potential to produce nanomaterials from proteins is well supported by the numerous examples of self‐assembling proteins found in nature. We have explored self‐assembling proteins for use as supramolecular building blocks, or tectons, specifically the N‐terminal domain of Lsr2, Nterm‐Lsr2. A key feature of this protein is that it undergoes self‐assembly via proteolytic cleavage, thereby allowing us to generate supramolecular assemblies in response to a specific trigger. Herein, we report the effects of pH and protein concentration on the oligomerization of Nterm‐Lsr2. Furthermore, via protein engineering, we have introduced a new trigger for oligomerization via enteropeptidase cleavage. The new construct of Nterm‐Lsr2 can be activated and assembled in a controlled fashion and provides some ability to alter the ratio of higher ordered structures formed. © 2014 Wiley Periodicals, Inc. Biopolymers 103: 260–270, 2015.
Nanofibrous nonmulberry silk/PVA scaffold for osteoinduction and osseointegration
Authors: Bhattacharjee Promita , Kundu Banani , Naskar Deboki , Maiti Tapas K. , Bhattacharya Debasis , Kundu Subhas C.
Published: November 2014

Poly‐vinyl alcohol and nonmulberry tasar silk fibroin of Antheraea mylitta are blended to fabricate nanofibrous scaffolds for bone regeneration. Nanofibrous matrices are prepared by electrospinning the equal volume ratio blends of silk fibroin (2 and 4 wt%) with poly‐vinyl alcohol solution (10 wt%) and designated as 2SF/PVA and 4SF/PVA, respectively with average nanofiber diameters of 177 ± 13 nm (2SF/PVA) and 193 ± 17 nm (4SF/PVA). Fourier transform infrared spectroscopy confirms retention of the secondary structure of fibroin in blends indicating the structural stability of neo‐matrix. Both thermal stability and contact angle of the blends decrease with increasing fibroin percentage. Conversely, fibroin imparts mechanical stability to the blends; greater tensile strength is observed with increasing fibroin concentration. Blended scaffolds are biodegradable and support well the neo‐bone matrix synthesis by human osteoblast like cells. The findings indicate the potentiality of nanofibrous scaffolds of nonmulberry fibroin as bone scaffolding material. © 2014 Wiley Periodicals, Inc. Biopolymers 103: 271–284, 2015.
Development and analysis of an instrument to assess student understanding of GOB chemistry knowledge relevant to clinical nursing practice
Authors: Brown Corina E. , Hyslop Richard M. , Barbera Jack
Published: November 2014

The General, Organic, and Biological Chemistry Knowledge Assessment (GOB‐CKA) is a multiple‐choice instrument designed to assess students' understanding of the chemistry topics deemed important to clinical nursing practice. This manuscript describes the development process of the individual items along with a psychometric evaluation of the final version of the items and instrument. In developing items for the GOB‐CKA, essential topics were identified through a series of expert interviews (with practicing nurses, nurse educators, and GOB chemistry instructors) and confirmed through a national survey. Individual items were tested in qualitative studies with students from the target population for clarity and wording. Data from pilot and beta studies were used to evaluate each item and narrow the total item count to 45. A psychometric analysis performed on data from the 45‐item final version was used to provide evidence of validity and reliability. The final version of the instrument has a Cronbach's alpha value of 0.76. Feedback from an expert panel provided evidence of face and content validity. Convergent validity was estimated by comparing the results from the GOB‐CKA with the General‐Organic‐Biochemistry Exam (Form 2007) of the American Chemical Society. Instructors who wish to use the GOB‐CKA for teaching and research may contact the corresponding author for a copy of the instrument. © 2014 by The International Union of Biochemistry and Molecular Biology, 43(1):13–19, 2015.
Detection by near‐infrared spectroscopy of large lipid cores at culprit sites in patients with non‐st‐segment elevation myocardial infarction and unstable angina
Authors: Madder Ryan D. , Husaini Mustafa , Davis Alan T. , Van Oosterhout Stacie , Harnek Jan , Götberg Matthias , Erlinge David
Published: November 2014

Objective

This study was performed to assess the lipid burden of culprit lesions in non‐ST‐segment elevation myocardial infarction (non‐STEMI) and unstable angina (UA).

Background

A recent intracoronary near‐infrared spectroscopy (NIRS) study showed 85% of STEMI culprit lesions have a maximum lipid core burden index in 4‐mm (maxLCBI4mm) ≥ 400. Whether culprit lesions in non‐STEMI and UA are characterized by a similarly large lipid burden is unknown.

Methods

We studied 81 non‐STEMI and UA patients undergoing culprit vessel NIRS imaging before stenting. Culprit segments were compared to all nonoverlapping 10‐mm nonculprit segments for maxLCBI4mm. Culprit segments in non‐STEMI and UA were compared for the frequency of maxLCBI4mm ≥ 400.

Results

Among 81 patients (53.1% non‐STEMI, 46.9% UA), non‐STEMI culprit segments had a 3.4‐fold greater maxLCBI4mm than nonculprits (448 ± 229 vs 132 ± 154, P < 0.001) and UA culprit segments had a 2.6‐fold higher maxLCBI4mm than nonculprits (381 ± 239 vs 146 ± 175, P < 0.001). NIRS detected a maxLCBI4mm ≥ 400 in 63.6% of culprit segments in NSTEMI and in 38.5% of culprit segments in UA (P = 0.02). Against a background of nonculprit segments, maxLCBI4mm ≥ 400 had a sensitivity of 63.6% and specificity of 94.0% for culprit segments in NSTEMI and a sensitivity of 38.5% and specificity of 89.8% for culprit segments in UA.

Conclusions

Large lipid cores similar to those recently detected by NIRS at STEMI culprit sites were frequently observed at culprit sites in patients with non‐STEMI and UA. These findings support ongoing prospective trials designed to determine if NIRS can provide site‐specific prediction of future acute coronary events. © 2014 Wiley Periodicals, Inc.
Multimodality image guidance with Dyna‐CT for transcatheter treatment of paravalvular leak of a stentless valve
Authors: Van Leer‐Greenberg Brett , Martinez Claudia A. , Heldman Alan W.
Published: November 2014

The transcatheter treatment of paravalvular leaks (PVL) are technically challenging procedures; they pose increasing difficulty in cases where there is a stentless valve, without the usual fluoroscopic landmarks. Hence, there is limited experience in treating this defect percutaneously. We present a case of a patient with an aortic PVL of a stentless valve and how the integrated use of multi‐imaging modalities (transesophageal echocardiography, computed tomography and rotational angiography) allowed the demarcation of landmarks onto live fluoroscopy and guided the transcatheter occlusion of the PVL. © 2014 Wiley Periodicals, Inc.
Left atrial intramural hematoma after percutaneous coronary intervention
Authors: Franks Russell J. , de Souza Anthony , Di Mario Carlo
Published: November 2014

We describe a rare complication of a complex chronic total occlusion recanalization procedure. Perforation of a distal right coronary artery collateral results in a left atrial intramural hematoma with consequent circulatory collapse. Access to prompt transoesophageal echocardiography and urgent surgical intervention were lifesaving and the case highlights possible implications on the planning of complex chronic total occlusion recanalization procedures. © 2015 Wiley Periodicals, Inc.
Indirect Chiral Separation of New Recreational Drugs by Gas Chromatography‐Mass Spectrometry Using Trifluoroacetyl‐L‐Prolyl Chloride as Chiral Derivatization Reagent
Authors: Weiß Jennifer A. , Mohr Stefan , Schmid Martin G.
Published: November 2014

New recreational drugs such as amphetamine‐, cathinone, and benzofury derivatives gained high popularity on the drug market in recent years. They can be purchased via the Internet from different providers and online portals. Most of these compounds are chiral, which makes the development of chiral separation methods necessary. Besides this, it is useful to find out if the compounds were sold as racemic mixtures. Also, it is important to check whether the new psychoactive compounds contain further ingredients or impurities. The aim of this research was the continuation of the application of a method for indirect chiral separation of 24 new psychoactive compounds recently purchased via the Internet. After derivatization with the chiral derivatization reagent trifluoroacetyl‐L‐prolyl chloride, chromatographic separation of diastereomers was achieved using a 30 m HP5‐MS capillary column. As carrier gas, helium was used with a constant flow of 1.0 ml/min. Three different column temperature programs were tested. Under optimum conditions 13 out of 24 compounds were successfully resolved into their enantiomers obtaining Rs values up to 7.0. The use of a single quadrupole mass spectrometer as the detector allowed the identification of the compounds in multicomponent samples. Chirality 27:211–215, 2015. © 2014 Wiley Periodicals, Inc.
Image analysis of heavy oil liberation from host rocks/sands
Authors: He Lin , Zhang Yile , Lin Feng , Xu Zhenghe , Li Xingang , Sui Hong
Published: November 2014

An essential requirement for efficient heavy oil production is liberation of heavy oil from host rocks, which is determined by the wettability of the rocks, and the interfacial tension and viscosity of heavy oil. Recent progress on the design of an online visualization flow cell allows capture of dynamic heavy oil liberation processes from the surfaces of sand grains in real time under a water flooding environment. However, the accurate assessment of heavy oil liberation remains a challenge, due to uncertainties in defining oil‐free areas of heavy oil contaminated rock surfaces. In this study, three new image‐processing algorithms of modified empirical, Gridding, and Edge‐covering methods were applied to image transformation for heavy oil liberation analysis. These methods were found to be more accurate and robust in determining the threshold value distinguishing liberated from unliberated sand surfaces. The use of wavelet transform theory in the Gridding and Edge‐covering methods led to faster calculations with a typical error of less than 2 % in the quantitative analysis on the threshold value determination and the degree of heavy oil liberation. Among these three methods, the Gridding method with a sound theoretical foundation was shown to be the most reliable. The results showed that the threshold value determined was highly dependent on the types of ores and the image capture settings such as lighting conditions, exposure time, and microscope magnification.
Impacts of elevated glycaemic haemoglobin and disease duration on the sensorimotor control of hands in diabetes patients
Authors: Hsu Hsiu‐Yun , Chiu Haw‐Yen , Lin Hwai‐Ting , Su Fong‐Chin , Lu Chieh‐Hsiang , Kuo Li‐Chieh
Published: November 2014

Background

To understand the impacts of disease chronicity and hyperglycaemia on sensorimotor control of hands of diabetic patients, this study investigated the differences in hand sensation, strength and motor control by applying the pinch‐holding‐up activity test for patients with diabetes mellitus (DM) with different levels of glycaemic control and disease chronicity.

Methods

One hundred and fifty‐nine patients with clinically defined DM were included. Semmes–Weinstein monofilament, static two‐point discrimination and moving two‐point discrimination, maximal pinch strength precision pinch performance tests and nerve conduction studies (NCS) of the subjects were carried out. Forty‐seven (29.6%) patients were in the HbA1c < 7% category, and 112 (70.4%) patients were in the >7% group. There were 87 (54.7%) patients with the disease duration <10 years, and 72 (45.3%) patients with disease duration ≧10 years.

Results

The severity of hyperglycaemia significantly impacts the results for Semmes–Weinstein monofilament, precision pinch force control, sensory and motor NCS tests (p < 0.05). In addition, the chronicity of disease influences the motor control of precision pinch performance and the amplitude of motor NCS (p < 0.05) for the diabetes patients.

Conclusions

The evidence suggests that disease chronicity and hyperglycaemia have impacts on sensorimotor control in the hands of DM patients. In addition, the efficiency of prehensile forces of hand‐to‐object interactions in the pinch‐holding‐up activity test could be significant for identifying hand function, as well as pathologic changes in median nerve function, for patients with DM. Copyright © 2014 John Wiley & Sons, Ltd.
Ceftaroline fosamil for treatment of diabetic foot infections: the CAPTURE study experience
Authors: Lipsky Benjamin A. , Cannon Chad M. , Ramani Ananthakrishnan , Jandourek Alena , Calmaggi Anibal , Friedland H. D. , Goldstein Ellie J. C.
Published: November 2014

Background

To ascertain which demographic, clinical, and microbiological factors might affect clinical outcomes of patients with diabetic foot infections, excluding known osteomyelitis, by analysing Clinical Assessment Program and Teflaro® Utilization Registry study data of patients treated with ceftaroline fosamil.

Methods

At participating study centres, we collected data by randomized selection and chart review, including patient demographics, co‐morbidities, infecting pathogens, antibiotic use, surgical interventions, and clinical response. Evaluable patients were those with data sufficient to determine clinical outcome. Clinical success was defined as clinical cure with no use of other antibiotics or clinical improvement with a switch to oral antibiotic therapy at the end of intravenous ceftaroline fosamil treatment.

Results

Among 201 patients (mean age 61.7 years, mean body mass index 33.2 and 57% male patients), 40% had peripheral vascular disease. Prior antibiotic therapy had been given to 161 (80%) of the patients, most commonly with vancomycin and/or piperacillin–tazobactam. Patients received ceftaroline fosamil for mean duration of 6.1 days (range 1–30), as monotherapy in 130 (65%) patients and concurrently with other antibiotics in 71 (35%). Bacterial pathogens were identified in 114 (57%) of the patients; methicillin‐resistant Staphylococcus aureus and methicillin‐sensitive S. aureus were isolated from 56 (49%) and 28 (25%) of culture‐positive patients respectively. Clinical success was noted in 81% of patients and was not significantly associated with co‐morbidities, pathogen type, or need for surgical intervention.

Conclusions

Ceftaroline fosamil treatment of diabetic foot infections was associated with high clinical success, including inpatients with obesity, co‐morbidities, or methicillin‐resistant Staphylococcus aureus or mixed infections or requiring surgical intervention. Copyright © 2014 John Wiley & Sons, Ltd.
Herbivory drives large‐scale spatial variation in reef fish trophic interactions
Authors: Longo Guilherme O. , Ferreira Carlos Eduardo L. , Floeter Sergio R.
Published: November 2014

Trophic interactions play a critical role in the structure and function of ecosystems. Given the widespread loss of biodiversity due to anthropogenic activities, understanding how trophic interactions respond to natural gradients (e.g., abiotic conditions, species richness) through large‐scale comparisons can provide a broader understanding of their importance in changing ecosystems and support informed conservation actions. We explored large‐scale variation in reef fish trophic interactions, encompassing tropical and subtropical reefs with different abiotic conditions and trophic structure of reef fish community. Reef fish feeding pressure on the benthos was determined combining bite rates on the substrate and the individual biomass per unit of time and area, using video recordings in three sites between latitudes 17°S and 27°S on the Brazilian Coast. Total feeding pressure decreased 10‐fold and the composition of functional groups and species shifted from the northern to the southernmost sites. Both patterns were driven by the decline in the feeding pressure of roving herbivores, particularly scrapers, while the feeding pressure of invertebrate feeders and omnivores remained similar. The differential contribution to the feeding pressure across trophic categories, with roving herbivores being more important in the northernmost and southeastern reefs, determined changes in the intensity and composition of fish feeding pressure on the benthos among sites. It also determined the distribution of trophic interactions across different trophic categories, altering the evenness of interactions. Feeding pressure was more evenly distributed at the southernmost than in the southeastern and northernmost sites, where it was dominated by few herbivores. Species and functional groups that performed higher feeding pressure than predicted by their biomass were identified as critical for their potential to remove benthic biomass. Fishing pressure unlikely drove the large‐scale pattern; however, it affected the contribution of some groups on a local scale (e.g., large‐bodied parrotfish) highlighting the need to incorporate critical functions into conservation strategies.
Assessment of the physical environment of epigean invertebrates in a unique habitat: the case of a karst sulfidic spring, Slovenia
Authors: Mulec Janez , Oarga Andreea , Schiller Edmund K. , Perşoiu Aurel , Holko Ladislav , Šebela Stanka
Published: November 2014

A well‐fissured and faulted karst area at the Žveplenica sulfidic spring created suitable conditions for epigean copepods. Their presence in sulfidic water is a rare phenomenon. To understand the conditions related to sulfidic habitats in the region, two additional springs were analysed: the Studenec karst spring and the Sovra artesian borehole, which contains dissolved sulfide. Water temperature, chemistry and the stable isotopes of oxygen and hydrogen show that the Sovra borehole water has a different origin and history to that of the Žveplenica and Studenec springs water, which is derived from local precipitation. The low slope of the δ18O–δ2H regression line for the Žveplenica spring indicates a mixing of local precipitation water with geothermal sulfidic water that may explain the presence of live copepods. These harpacticoid and cyclopoid copepods must have survived anoxia and high sulfide for some time. The mean transit time for Žveplenica spring cannot be defined precisely from the available data, although the degree of attenuation of the isotopic signal indicates mean transit times of about 1·0 to 1·5 years. Sites similar to Žveplenica spring should be carefully analysed because not only do they provide insights into biodiversity but they also represent an ecotone between the anoxic/oxic and high/low sulfide of these karst waters. Copepods in similar geological settings can be used as additional parameters to evaluate conditions in subsurface sulfidic habitats and their spatial connectivity and responses to hydrological events. Copyright © 2014 John Wiley & Sons, Ltd.
Characterizing instability of aeolian environments using analytical reasoning
Authors: Houser Chris , Bishop Michael P. , Barrineau Patrick
Published: November 2014

This short communication describes the development and application of analytical reasoning to quantify instability of an aeolian environment using scale‐dependent information coupled with conceptual knowledge of process and feedback mechanisms. Specifically, a simple Fuzzy Cognitive Map (FCM) for aeolian landscape instability was developed that represents conceptual knowledge of key biophysical processes and feedbacks. Model inputs include satellite‐derived surface biophysical and geomorphometric parameters. FCMs are a knowledge‐based artificial intelligence (AI) technique that merges fuzzy logic and neural computing in which knowledge or concepts are structured as a web of relationships that is similar to both human reasoning and the human decision‐making process. Given simple process–form relationships, the analytical reasoning model is able to map the influence of land management practices and the geomorphology of the inherited surface on aeolian instability within the South Texas Sand Sheet. Results suggest that FCMs can be used to formalize process–form relationships and information integration analogous to human cognition with future iterations accounting for the spatial interactions and temporal lags across the sand sheets. Copyright © 2014 John Wiley & Sons, Ltd.
Alluvial floodplain classification by multivariate clustering and discriminant analysis for low‐relief glacially conditioned river catchments
Authors: Phillips Roger T. J. , Desloges Joseph R.
Published: November 2014

River classifications provide useful frameworks to understand complex fluvial landscapes and to manage freshwater ecosystems. Alluvial floodplains for rivers in low‐relief glacially conditioned catchments of southern Ontario (Canada) are classified and tested using a sequence of multivariate statistical analyses. An original dataset of 109 floodplain sites is investigated using k‐means clustering, principal component analysis, and discriminant analysis statistical approaches. Four primary floodplain types are proposed representing basic morphological, stratigraphical, and sedimentological characteristics. Classifications are successfully discriminated by two principal dimensions: (1) stream power‐resistance; and (2) floodplain sedimentology. The latter is most efficiently represented by the availability of alluvial sand, and specifically a new variable defined as floodplain sand equivalent (FSE). Floodplain types are generally consistent with previous river classifications, however the glacial legacy requires refined classifications which account for inherited cobble bed materials and patterns of sand supply. Representing the residual variability of stream power‐resistance correlations, a third explanatory dimension of sediment transport is suggested, and may explain some within‐class variability in channel morphology. Balancing the opposing concepts of fluvial process domains and landform continuums, the potential for transitional floodplain types is also explored. The proposed first‐order alluvial floodplain classifications provide a basis from which to further investigate geomorphological diversity within the context of complex glacial legacy effects in low‐relief settings. Future research to reveal the spatial arrangement and linkages of distinct morphological groups within a regional landscape mosaic is expected to provide insights into patterns of post‐glacial fluvial adjustment. Copyright © 2014 John Wiley & Sons, Ltd.
A proprietary blend of quail egg for the attenuation of nasal provocation with a standardized allergenic challenge: a randomized, double‐blind, placebo‐controlled study
Authors: Benichou Annie‐Claude , Armanet Marion , Bussière Anthony , Chevreau Nathalie , Cardot Jean‐Michel , Tétard Jan
Published: November 2014

Occasional rhinitis symptoms caused by exposure to pollution or allergens is a growing concern. Based first on empirical observation of a lesser occurrence of allergies in quail farmers and then scientific works on ovomucoids properties, we developed a dietary supplement for the relief of such occasional rhinitis symptoms. The objective of the study was to determine whether one acute oral dose of the study product attenuates nasal provocation and other allergy‐related symptoms after exposure to a standardized allergenic challenge as compared to placebo. Healthy subjects were recruited to participate in a randomized, double‐blind, two‐arm crossover, placebo‐controlled, clinical trial. One acute dose of either the active study product (proprietary blend of quail egg) or placebo was given concomitantly to the standardized allergenic challenge. The primary endpoint was peak nasal inspiratory flow (PNIF) measurement and the secondary endpoints were subjects' perceived feelings of well‐being based on Visual Analog Scale (VAS) scores for allergy‐related symptoms, as well as immunoglobulin E count. Forty‐three healthy subjects were enrolled and evaluable in a per protocol analysis. A gradual increase in PNIF from nadir up to Time 120 reflected the normal, gradual recovery from nasal obstruction induced by allergenic challenge for both the active and the placebo groups. At all postchallenge time points, the active group had higher PNIF values compared to the placebo group, indicating that the active product was associated with fewer symptoms and reduced intensity of these symptoms. The active product resulted also in statistically significant improvements of most of the subjects' perceived feelings of well‐being based on VAS scores. No adverse events occurred during the study. In conclusion, the dietary supplement consisting of proprietary blend made of quail eggs provides fast and efficient relief of allergic rhinitis symptoms caused by the most common outdoor and indoor allergens, without adverse events.
Population Genetic Simulations of Complex Phenotypes with Implications for Rare Variant Association Tests
Authors: Uricchio Lawrence H. , Torres Raul , Witte John S. , Hernandez Ryan D.
Published: November 2014

Demographic events and natural selection alter patterns of genetic variation within populations and may play a substantial role in shaping the genetic architecture of complex phenotypes and disease. However, the joint impact of these basic evolutionary forces is often ignored in the assessment of statistical tests of association. Here, we provide a simulation‐based framework for generating DNA sequences that incorporates selection and demography with flexible models for simulating phenotypic variation (sfs_coder). This tool also allows the user to perform locus‐specific simulations by automatically querying annotated genomic functional elements and genetic maps. We demonstrate the effects of evolutionary forces on patterns of genetic variation by simulating recently inferred models of human selection and demography. We use these simulations to show that the demographic model and locus‐specific features, such as the proportion of sites under selection, may have practical implications for estimating the statistical power of sequencing‐based rare variant association tests. In particular, for some phenotype models, there may be higher power to detect rare variant associations in African populations compared to non‐Africans, but power is considerably reduced in regions of the genome with rampant negative selection. Furthermore, we show that existing methods for simulating large samples based on resampling from a small set of observed haplotypes fail to recapitulate the distribution of rare variants in the presence of rapid population growth (as has been observed in several human populations).
Fine‐Mapping Additive and Dominant SNP Effects Using Group‐LASSO and Fractional Resample Model Averaging
Authors: Sabourin Jeremy , Nobel Andrew B. , Valdar William
Published: November 2014

Genomewide association studies (GWAS) sometimes identify loci at which both the number and identities of the underlying causal variants are ambiguous. In such cases, statistical methods that model effects of multiple single‐nucleotide polymorphisms (SNPs) simultaneously can help disentangle the observed patterns of association and provide information about how those SNPs could be prioritized for follow‐up studies. Current multi‐SNP methods, however, tend to assume that SNP effects are well captured by additive genetics; yet when genetic dominance is present, this assumption translates to reduced power and faulty prioritizations. We describe a statistical procedure for prioritizing SNPs at GWAS loci that efficiently models both additive and dominance effects. Our method, LLARRMA‐dawg, combines a group LASSO procedure for sparse modeling of multiple SNP effects with a resampling procedure based on fractional observation weights. It estimates for each SNP the robustness of association with the phenotype both to sampling variation and to competing explanations from other SNPs. In producing an SNP prioritization that best identifies underlying true signals, we show the following: our method easily outperforms a single‐marker analysis; when additive‐only signals are present, our joint model for additive and dominance is equivalent to or only slightly less powerful than modeling additive‐only effects; and when dominance signals are present, even in combination with substantial additive effects, our joint model is unequivocally more powerful than a model assuming additivity. We also describe how performance can be improved through calibrated randomized penalization, and discuss how dominance in ungenotyped SNPs can be incorporated through either heterozygote dosage or multiple imputation.
Prevention of hepatitis C virus infection and spread in human liver chimeric mice by an anti‐CD81 monoclonal antibody
Authors: Ji Changhua , Liu Yang , Pamulapati Chandra , Bohini Sandhya , Fertig Georg , Schraeml Michael , Rubas Werner , Brandt Michael , Ries Stefan , Ma Han , Klumpp Klaus
Published: November 2014

CD81 is a required receptor for hepatitis C virus (HCV) infection of human hepatocytes in vitro. We generated several high‐affinity anti‐human CD81 monoclonal antibodies (mAbs) that demonstrated potent, specific, and cross‐genotype inhibition of HCV entry. One of these mAbs, K04, was administered to human liver chimeric mice before or after HCV infection to determine its ability to prevent HCV infection or spread of HCV infection, respectively. All vehicle control mice established HCV infection, reaching steady‐state levels of serum HCV RNA by day 21. Pretreatment of mice with K04 prevented HCV infection in all mice (n = 5). Treatment of mice with mAb K04 every 3 days for 21 days, starting at 6 hours postinfection, resulted in effective inhibition of virus spread. In 3 mice that were sacrificed on day 24, serum HCV levels remained detectable, below the limit of quantification (LOQ), indicating that infection was established, but virus spread was blocked, by the anti‐CD81 mAb. In 5 additional mice that were followed for a longer time, virus remained detectable, below LOQ, until days 24 and 30 in 4 of 5 mice. In the fifth mouse, viral load was quantifiable, but reduced to 64‐fold below the mean viral load in vehicle control at day 24. In addition, 2 of 5 mice cleared the infection by day 30 and 1 mouse had undetectable virus load from day 6 onward. Conclusion: These results demonstrate that CD81 is required for HCV infection and virus spread in vivo, and that anti‐CD81 antibodies such as K04 may have potential as broad‐spectrum antiviral agents for prevention and treatment of HCV infection. (Hepatology 2015;61:1136–1144)
Seeing the climate through the trees: observing climate and forestry impacts on streamflow using a 60‐year record
Authors: Burt T. P. , Howden N. J. K. , McDonnell J. J. , Jones J. A. , Hancock G. R.
Published: November 2014

Paired watershed experiments involving the removal or manipulation of forest cover in one of the watersheds have been conducted for more than a century to quantify the impact of forestry operations on streamflow. Because climate variability is expected to be large, forestry treatment effects would be undetectable without the treatment–control comparison. New understanding of climate variability provides an opportunity to examine whether climate variability interacts with forestry treatments, in a predictable manner. Here, we use data from the H. J. Andrews Experimental Forest, Oregon, USA, to examine the impact of the El Niño‐Southern Oscillation on streamflow linked to forest harvesting. Our results show that the contrast between El Niño and La Niña events is so large that, whatever the state of the treated watershed in terms of regrowth of the forest canopy, extreme climatic variability related to El Niño‐Southern Oscillation remains the more dominant driver of streamflow response at this location. Improvements in forecasting interannual variation in climate might be used to minimize the impact of forestry treatments on streamflow by avoiding initial operations in La Niña years. Copyright © 2014 John Wiley & Sons, Ltd.
Screening outcome and surgical treatment during and after the transition from screen‐film to digital screening mammography in the south of The Netherlands
Authors: Weber Roy J.P. , Nederend Joost , Voogd Adri C. , Strobbe Luc J. , Duijm Lucien E.M.
Published: November 2014

We determined screening outcome of subsequent screens during and after the transition from screen‐film mammography (SFM) to full‐field digital mammography (FFDM). A consecutive series of 102,863 subsequent (SFM screens with a prior SFM screen (SFM‐SFM cohort), 91,941 FFDM screens with a prior SFM screen (FFDM‐SFM cohort) and 90,407 FFDM screens with a prior FFDM screen (FFDM‐FFDM cohort) were obtained between January 2006 and July 2013. The referral rate and cancer detection rate (CDR) per 1,000 screens were higher at FFDM‐SFM than at SFM–SFM (2.7% vs. 1.2% (p < 0.001) and 7.0 vs. 4.9, p < 0.001), at the expense of a lower positive predictive value (PPV) of referral (25.8% vs. 39.6%, p < 0.001). These parameters were comparable for FFDM‐SFM and FFDM–FFDM. Ductal carcinoma in situ (DCIS) and invasive cancer rates increased during transition and remained stable after transition. The rate of DCIS of intermediate grade increased during the transition from 0.2 per 1,000 screened women at SFM‐SFM to 0.6 at FFDM‐SFM (p < 0.001) and 0.5 at FFDM‐FFDM (p = 0.001). Compared to SFM‐SFM, a significantly higher rate of invasive cancers were stage T1a‐b at FFDM‐SFM (p < 0.001) and FFDM‐FFDM (p < 0.001). Breast conserving surgery rates increased during transition (p < 0.001) and remained stable afterwards. The CDR and referral rate remained significantly higher at FFDM than at SFM, at the expense of a decreased PPV of referral. During transition, DCIS was more often of intermediate grade and invasive cancers were of smaller size.
Adjuvant chemotherapy in rectal cancer: Defining subgroups who may benefit after neoadjuvant chemoradiation and resection: A pooled analysis of 3,313 patients
Authors: Maas Monique , Nelemans Patty J , Valentini Vincenzo , Crane Christopher H. , Capirci Carlo , Rödel Claus , Nash Garrett M. , Kuo Li‐Jen , Glynne‐Jones Rob , García‐Aguilar Julio , Suárez Javier , Calvo Felipe A. , Pucciarelli Salvatore , Biondo Sebastiano , Theodoropoulos George , Lambregts Doenja M.J. , Beets‐Tan Regina G.H. , Beets Geerard L.
Published: November 2014

Recent literature suggests that the benefit of adjuvant chemotherapy (aCT) for rectal cancer patients might depend on the response to neoadjuvant chemoradiation (CRT). Aim was to evaluate whether the effect of aCT in rectal cancer is modified by response to CRT and to identify which patients benefit from aCT after CRT, by means of a pooled analysis of individual patient data from 13 datasets. Patients were categorized into three groups: pCR (ypT0N0), ypT1‐2 tumour and ypT3‐4 tumour. Hazard ratios (HR) for the effect of aCT were derived from multivariable Cox regression analyses. Primary outcome measure was recurrence‐free survival (RFS). One thousand seven hundred and twenty three (1723) (52%) of 3,313 included patients received aCT. Eight hundred and ninety eight (898) patients had a pCR, 966 had a ypT1‐2 tumour and 1,302 had a ypT3‐4 tumour. For 122 patients response, category was missing and 25 patients had ypT0N+. Median follow‐up for all patients was 51 (0–219) months. HR for RFS with 95% CI for patients treated with aCT were 1.25(0.68–2.29), 0.58(0.37–0.89) and 0.83(0.66–1.10) for patients with pCR, ypT1‐2 and ypT3‐4 tumours, respectively. The effect of aCT in rectal cancer patients treated with CRT differs between subgroups. Patients with a pCR after CRT may not benefit from aCT, whereas patients with residual tumour had superior outcomes when aCT was administered. The test for interaction did not reach statistical significance, but the results support further investigation of a more individualized approach to administer aCT after CRT and surgery based on pathologic staging.
Coping and defence mechanisms: What are we assessing?
Authors: Maricutoiu Laurentiu P. , Crasovan Danut I.
Published: November 2014

The present research study addresses the disparity between theoretical considerations and empirical evidence regarding the relationships between coping strategies and defence mechanisms. Self‐reported measures of coping and defences were administered to a Romanian adult sample (N = 542; 74.53% female, mean age = 31.28). Using structural equation modelling, models that assumed independence between coping and defences were compared with models that assumed the existence of relationships between the two concepts. Findings identified strong relationships between coping and defences, indicating large common variance between the two concepts. Furthermore, results suggested that coping and defences can be classified into two independent types of adaptation processes. Results of this research study suggested that coping and defences are facets of common adaptation processes.
An Investigation of the Mineral in Ductile and Brittle Cortical Mouse Bone
Authors: Rodriguez-Florez Naiara , Garcia-Tunon Esther , Mukadam Quresh , Saiz Eduardo , Oldknow Karla J , Farquharson Colin , Millán José Luis , Boyde Alan , Shefelbine Sandra J
Published: November 2014

Bone is a strong and tough material composed of apatite mineral, organic matter, and water. Changes in composition and organization of these building blocks affect bone's mechanical integrity. Skeletal disorders often affect bone's mineral phase, either by variations in the collagen or directly altering mineralization. The aim of the current study was to explore the differences in the mineral of brittle and ductile cortical bone at the mineral (nm) and tissue (µm) levels using two mouse phenotypes. Osteogenesis imperfecta model, oim-/-, mice have a defect in the collagen, which leads to brittle bone; PHOSPHO1 mutants, Phospho1-/-, have ductile bone resulting from altered mineralization. Oim-/- and Phospho1-/- were compared with their respective wild-type controls. Femora were defatted and ground to powder to measure average mineral crystal size using X-ray diffraction (XRD) and to monitor the bulk mineral to matrix ratio via thermogravimetric analysis (TGA). XRD scans were run after TGA for phase identification to assess the fractions of hydroxyapatite and β-tricalcium phosphate. Tibiae were embedded to measure elastic properties with nanoindentation and the extent of mineralization with backscattered electron microscopy (BSE SEM). Results revealed that although both pathology models had extremely different whole-bone mechanics, they both had smaller apatite crystals, lower bulk mineral to matrix ratio, and showed more thermal conversion to β-tricalcium phosphate than their wild types, indicating deviations from stoichiometric hydroxyapatite in the original mineral. In contrast, the degree of mineralization of bone matrix was different for each strain: brittle oim-/- were hypermineralized, whereas ductile Phospho1-/- were hypomineralized. Despite differences in the mineralization, nanoscale alterations in the mineral were associated with reduced tissue elastic moduli in both pathologies. Results indicated that alterations from normal crystal size, composition, and structure are correlated with reduced mechanical integrity of bone. © 2014 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.
Myelosuppressive Therapies Significantly Increase Pro-Inflammatory Cytokines and Directly Cause Bone Loss
Authors: Quach Julie M , Askmyr Maria , Jovic Tanja , Baker Emma K , Walsh Nicole C , Harrison Simon J , Neeson Paul , Ritchie David , Ebeling Peter R , Purton Louise E
Published: November 2014

Skeletal-related events resulting from accelerated bone loss are common complications in patients treated for a range of cancers. However, the mechanisms and rate of bone loss after myelosuppression are unclear. We, therefore, investigated this in mice and humans. We treated mice with different myelosuppressive therapies (chemotherapy or irradiation with or without transplantation) and studied their effects on bone structure. Myelosuppression of mice rapidly caused an increase in bone resorption that was not matched by bone formation. The resultant significant and persistent bone loss early after therapy was associated with increased inflammatory cytokines, in particular, monocyte chemoattractant protein 1 (MCP1). Therapy-induced bone loss was prevented with a single dose of the bisphosphonate zoledronic acid (ZA), administered before myelosuppression. Importantly, ZA treatment of mice did not impair hematopoiesis, including hematopoietic stem cell function. Furthermore, examination of serum from patients before and after autologous or allogeneic stem cell transplantion (SCT) revealed altered levels of bone turnover markers and elevated inflammatory cytokines. MCP1 levels in serum obtained between days 7 and 14 post-SCT positively correlated with bone loss observed at 100 days after allogeneic SCT. Similar to that observed in our studies in mice, the bone loss was long term, persisting at 12 months post-SCT. Furthermore, patients who received chemotherapy less than 100 days before SCT had significantly more bone loss at the hip. In these patients, serum levels of MCP1, but not routine biomarkers of bone turnover, including C-terminal cross-linking telopeptide of type-1 collagen (β-CTx), positively correlated with their bone loss. Hence, myelosuppressive therapies increase inflammation and directly contribute to bone loss. Administration of an osteoclast inhibitor before the initiation of cancer therapy is likely to have the best outcome in preventing bone loss in patients with cancer. © 2014 American Society for Bone and Mineral Research.
Investigation of the Effects of Some Drugs and Phenolic Compounds on Human Dihydrofolate Reductase Activity
Authors: Aslan Erdem , Adem Sevki
Published: November 2014

Dihydrofolate reductase (DHFR) plays a fundamental role in cellular metabolism and cell growth. Inhibition of this enzyme will cause a decrease in the amount of folate that occurs in many metabolic processes, and the deficiency of which may cause various diseases. This study investigated the effects of some drugs and phenolic compounds on DHFR activity in vitro. To determine the inhibitory effect of compounds, enzyme activity was measured with a final concentration of an inhibitor ranging from 10 μM to 51 mM. DHFR was inhibited effectively by naringin, ferulic acid, and levofloxacin with IC50 values under 660 μM. Syringic acid, cefepime, ceftizoxime, cefazolin, ceftriaxone, and ceftazidime exhibited inhibitory effects on the enzyme activity with IC50 values in the range of 3.840–30.224 mM. Ki constants were calculated using the Cheng–Prusoff equation. Ki constants calculated in the range of 0.009–2.024 mM with respect to nicotinamide adenine dinucleotide phosphate oxidase (NADPH) and in the range of 0.060–5.830 mM about FH2.
Prevention of Nephrotoxicity Induced by Cyclosporine‐A: Role of Antioxidants
Authors: Damiano Sara , Ciarcia Roberto , Montagnaro Serena , Pagnini Ugo , Garofano Tiziana , Capasso Giovambattista , Florio Salvatore , Giordano Antonio
Published: November 2014

Cyclosporine A (CsA) is a powerful immunosuppressive drug used to prevent allograft rejection after organ transplantation as well as in human and veterinary medicine. Unfortunately, its use is hampered by its nephrotoxic effects. The mechanisms of CsA‐induced hypertension and nephrotoxicity are not clear, but several studies suggest the possible involvement of free radicals. In this review we have summarized the effect of some antioxidants that we have used in the recent years, in combination with CsA, to better understand the exact mechanism of action of CsA and to try to open new perspectives in the treatment of CsA nephrotoxicity. J. Cell. Biochem. 116: 364–369, 2015. © 2014 Wiley Periodicals, Inc.
A Carboxy Terminal BMP/TGF‐β Binding Site in Secreted Phosphoprotein 24 kD Independently Affects BMP‐2 Activity
Authors: Tian Haijun , Li Chen‐Shuang , Zhao Ke‐Wei , Wang Jeffrey C. , Duarte M. Eugenia L. , David Cynthia L. , Phan Kevin , Atti Elisa , Brochmann Elsa J. , Murray Samuel S.
Published: November 2014

Secreted phosphoprotein 24 kD (spp24) is a bone matrix protein isolated during attempts to identify osteogenic proteins. It is not osteogenic but performs other important roles in the regulation of bone metabolism, at least in part, by binding to and affecting the activity of members of the BMP/TGF‐β family of cytokines. Spp24 exists in a number of forms that preserve the N‐terminus and are truncated at the C‐terminus. The hypothesized cytokine binding domain is present within the cystatin domain which is preserved in all of the N‐terminal products. In this report, we describe a C‐terminal fragment that is distinct from the cystatin domain and which independently binds to BMP‐2 and TGF‐β. This fragment inhibited BMP‐2 activity in an ectopic bone forming assay. A shorter C‐terminal product did not inhibit BMP‐2 activity but improved bone quality induced by BMP‐2 and produced increased calcium deposition outside of bone. Spp24 has been used to develop several potential therapeutic proteins. These results provide more information on the function of spp24 and provide other materials that can be exploited for clinical interventions. J. Cell. Biochem. 116: 667–676, 2015. © 2014 Wiley Periodicals, Inc.