bluuebunny/crossref_metadata_2025 huggingface dataset:
Branched Terthiophenes in Organic Electronics: From Small Molecules to Polymers
Authors: Scheuble Martin , Goll Miriam , Ludwigs Sabine
Published: November 2014

A zoo of chemical structures is accessible when the branched unit 2,2′:3',2″‐terthiophene (3T) is included both in structurally well‐defined small molecules and polymer‐like architectures. The first part of this review article highlights literature on all‐thiophene based branched oligomers including dendrimers as well as combinations of 3T‐units with functional moieties for light‐harvesting systems. Motivated by the perfectly branched macromolecular dendrimers both electropoly­merization as well as chemical approaches are presented as methods for the preparation of branched polythiophenes with different branching densities. Structure‐function relationships between the molecular architecture and optical and electronic properties are discussed throughout the article.

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Should firms conceal information when dealing with common suppliers?
Authors: Jain Aditya , Sohoni Milind
Published: November 2014

A firm making quantity decision under uncertainty loses profit if its private information is leaked to competitors. Outsourcing increases this risk as a third party supplier may leak information for its own benefit. The firm may choose to conceal information from the competitors by entering in a confidentiality agreement with the supplier. This, however, diminishes the firm's ability to dampen competition by signaling a higher quantity commitment. We examine this trade‐off in a stylized supply chain in which two firms, endowed with private demand information, order sequentially from a common supplier, and engage in differentiated quantity competition. In our model, the supplier can set different wholesale prices for firms, and the second‐mover firm could be better informed. Contrary to what is expected, information concealment is not always beneficial to the first mover. We characterize conditions under which the first mover firm will not prefer concealing information. We show that this depends on the relative informativeness of the second mover and is moderated by competition intensity. We examine the supplier's incentive in participating in information concealment, and develop a contract that enables it for wider set of parameter values. We extend our analysis to examine firms' incentive to improve information. © 2014 Wiley Periodicals, Inc. 62:1–15, 2015
A dietary phytochemical blend prevents liver damage associated with adipose tissue mobilization in ovariectomized rats
Authors: Miller Colette N. , Yang Jeong‐Yeh , Avra Tucker , Ambati Suresh , Della‐Fera Mary Anne , Rayalam Srujana , Baile Clifton A.
Published: November 2014

Objective

Menopausal reduction in estrogen causes increased adipose accumulation, leading many to turn to dietary supplements to prevent and treat such changes. Enhanced adipose mobilization stimulated by some supplements can increase the risk of non‐alcoholic fatty liver disease (NAFLD). Cytoprotective and anti‐obesity compounds may prevent the lipotoxicity associated with mobilization.

Methods

A phytochemical blend was tested in aged, ovariectomized rats. Rats were given the AIN‐93M basal diet or a diet containing varying doses of phytochemicals with 2.4 IU/g vitamin D [diet 1: 1000 mg/kg genistein (G); diet 2: 500 mg/kg (G), 200 mg/kg resveratrol (R), and 1000 mg/kg quercetin (Q); diet 3: 1000 mg/kg (G), 400 mg/kg (R), and 2000 mg/kg (Q)].

Results

Serum free fatty acids and hepatic triglycerides were elevated with diets 2 and 3. Despite this increase, the phytochemical blends did not increase apoptotic, cell repair, or remodeling gene expression. The highest phytochemical dose prevented increases in serum alanine aminotransferase.

Conclusions

Adverse hepatic effects secondary to ovariectomy were mitigated through the inclusion of a dietary phytochemical blend in aged ovariectomized rats. The use of such compounds may not only help with weight management and disease risk in menopausal women, but may also prevent the lipotoxicity in NAFLD.
A long‐term intensive lifestyle intervention and physical function: The look AHEAD Movement and Memory Study
Authors: Houston Denise K. , Leng Xiaoyan , Bray George A. , Hergenroeder Andrea L. , Hill James O. , Jakicic John M. , Johnson Karen C. , Neiberg Rebecca H. , Marsh Anthony P. , Rejeski W. Jack , Kritchevsky Stephen B. ,   for the Action for Health In Diabetes (Look AHEAD) Movement and Memory Ancillary Study Research Group
Published: November 2014

Objective

To assess the long‐term effects of an intensive lifestyle intervention on physical function using a randomized post‐test design in the Look AHEAD trial.

Methods

Overweight and obese (BMI ≥ 25 kg m−2) middle‐aged and older adults (aged 45‐76 years at enrollment) with type 2 diabetes (n = 964) at four clinics in Look AHEAD, a trial evaluating an intensive lifestyle intervention (ILI) designed to achieve weight loss through caloric restriction and increased physical activity compared to diabetes support and education (DSE), underwent standardized assessments of performance‐based physical function including an expanded short physical performance battery (SPPBexp), 20‐m and 400‐m walk, and grip and knee extensor strength 8 years post‐randomization, during the trial's weight maintenance phase.

Results

Eight years post‐randomization, individuals randomized to ILI had better SPPBexp scores [adjusted mean (SE) difference: 0.055 (0.022), P = 0.01] and faster 20‐m and 400‐m walk speeds [0.032 (0.012) m s−1, P = 0.01, and 0.025 (0.011) m s−1, P = 0.02, respectively] compared to those randomized to DSE. Achieved weight loss greatly attenuated the group differences in physical function, and the intervention effect was no longer significant.

Conclusions

An intensive lifestyle intervention has long‐term benefits for mobility function in overweight and obese middle‐aged and older individuals with type 2 diabetes.
Preparation, characterization, and mechanical/tribological properties of polyamide 11/Titanium dioxide nanocomposites
Authors: Ambrósio José Donato , Balarim Caio Vinicius Morisco , de Carvalho Gustavo Baldi
Published: November 2014

In this study, the effects of the surface chemical modification of titanium dioxide (TiO2) nanoparticles and their addition into polyamide 11 (PA11) on the mechanical, dynamic‐mechanical, and tribological properties of PA11/TiO2 nanocomposites were investigated. To improve the interfacial adhesion between the nanoparticles and the polymeric matrix, the surface of TiO2 nanoparticles was modified with 3‐aminopropyl trimethoxysilane (ATPMS). Nuclear magnetic resonance (NMR), infrared spectroscopy (IR), and thermogravimetric analysis (TG) were used to evaluate the efficiency of the surface chemical modification of TiO2 nanoxide. PA11/TiO2 nanocomposites with 2 and 4 wt% of TiO2 were prepared in an internal mixer. The interfacial adhesion between the matrix and the TiO2 was evaluated by dynamic‐mechanical analysis (DMA), and the dispersion of nanoparticles was analyzed by scanning electron microscopy (SEM). The NMR spectrum of the modified TiO2 exhibited peaks in the region between −55 ppm and −70 ppm, indicating disubstituted and trisubstituted chemical structures between alkoxysilano structures and TiO2. Nanocomposites with modified TiO2 exhibited the lowest tan δ peak values, which provide evidence that the chemical modification of the TiO2 facilitated energy dissipation at the interface of TiO2 with the PA11 matrix. Surface modification of the TiO2 nanoparticles with ATPMS caused a greater reduction of the mass loss by abrasion when compared with nonmodified PA11/TiO2 nanocomposites; this reduction reached approximately 70% in comparison with the mass loss of neat PA11. POLYM. COMPOS., 37:1415–1424, 2016. © 2014 Society of Plastics Engineers
Processing and failure behavior of carbon‐nanotube composites in sheet forms
Authors: Kuo Wen‐Shyong , Lai Hung‐Chih , Chang Ting‐Wei , Wen Chan‐Chao
Published: November 2014

In their original forms, carbon nanotubes (CNT) are spatially entangled. To make CNT papers (CNTPs), the CNT agglomerates must be dispersed and re‐entangled into a planar sheet. The processing characteristics are very different from those of traditional buck‐form nanocomposites. This article examines the processing, micro‐structures, and failure behavior of the CNTP composites. The CNTPs were first made by a dispersion and filtering process. Then, an epoxy resin was added into the CNTP by using a vacuum bag method. Different CNT weights were employed to make the CNTPs with different thicknesses and areal weights. The CNTP allows direct resin impregnation along the thickness direction and avoids the difficulty of dispersing CNTs in the viscous resin. The CNT content can be much higher than that attainable in traditional bulk CNT composites. Both tensile and tearing tests were conducted, and the fracture behaviors were examined. POLYM. COMPOS., 37:1564–1571, 2016. © 2014 Society of Plastics Engineers
Effects of fiber extraction, morphology, and surface modification on the mechanical properties and water absorption of bamboo fibers‐unsaturated polyester composites
Authors: Liu Wendi , Qiu Renhui , Li Kaichang
Published: November 2014

Bamboo fibers reinforced unsaturated polyester (UPE) composites were prepared by compression molding. Effects of fiber extraction, morphology, and chemical modification on the mechanical properties and water absorption of the bamboo fibers‐UPE composites were investigated. Results showed that the unidirectional original bamboo fibers resulting composites demonstrated the highest tensile strength, flexural strength, and flexural modulus; the 30–40 mesh bamboo particles resulting composites had the lowest tensile strength and flexural strength, but had comparable flexural modulus with that of chemical pulp fibers. The treatment of bamboo fibers with 1,6‐diisocyanatohexane (DIH) and 2‐hydroxyethyl acrylate (HEA) significantly increased the tensile strength, flexural strength and flexural modulus, and water resistance of the resulting composites. Fourier Transform Infrared and X‐ray photoelectron spectroscopy analyses showed that DIH and HEA were covalently bonded onto bamboo fibers. Scanning electron microscopic images of the fractured surfaces of the composites showed that the treatment of bamboo fibers greatly improved the interfacial adhesion between the fibers and UPE resins. The water absorption kinetics of the composites was also investigated; and the results showed that the water absorption of the composites fitted Fickian behavior well. POLYM. COMPOS., 37:1612–1619, 2016. © 2014 Society of Plastics Engineers
Crystalline structure and thermodynamic analysis of ultra‐low diameter VGCF‐polypropylene nanocomposite monofilaments
Authors: Tanami Golan A. , Wachtel Ellen , Marom Gad
Published: November 2014

Nanocomposites of VGCF reinforced polypropylene monofilaments were created using melt compounding extrusion. The monofilament diameter and VGCF loading were varied to characterize the effects of spinline stress and imposed confinement on material properties, including crystalline structure and thermodynamic behavior. A correlation was found between spinline stress, degree of confinement, depression of the melting temperature, and changes in crystallite dimensions and orientation. POLYM. COMPOS., 37:1641–1649, 2016. © 2014 Society of Plastics Engineers
Photovoltaics literature survey (No. 114)
Authors: Shrestha Santosh , Hameiri Ziv
Published: November 2014

In order to help keep readers up‐to‐date in the field each issue of Progress in Photovoltaics will contain a list of recently published journal articles most relevant to its aims and scope. This list is drawn from an extremely wide range of journals, including IEEE Transactions on Electron Devices, Journal of Applied Physics, Applied Physics Letters, Progress in Photovoltaics and Solar Energy Materials and Solar Cells. To assist the reader, the list is separated into broad categories, but please note that these classifications are by no means strict. Also note that inclusion in the list is not an endorsement of a paper's quality. If you have any suggestions please email Santosh Shrestha at s.shrestha@unsw.edu.au.
Multiple Emulsion Templating of Hybrid Ag/SiO2 Capsules for Antibacterial Applications
Authors: Sousa Filipa L. , Almeida Adelaide , Girão Ana V. , Fateixa Sara , Trindade Tito
Published: November 2014

Silver nanoparticles (NPs) encapsulated in amorphous silica shells are synthesized and evaluated for their antibacterial action using the Gram‐negative Escherichia coli bacterium. These inorganic capsules are synthesized using a new approach that comprises the use of oil‐in‐water‐in‐oil (O/W/O) multiple emulsions to fabricate SiO2 capsules incorporating organically capped Ag NPs. This strategy is explored as a mean to promote the bioadhesion of the microorganisms to the silica rough surfaces while still keeping the system with a high surface area for the active metal. The results have shown that the hybrid capsules enable a slow release of cationic silver from the interior of the silica microsphere to the external medium probably through the pore channels in the shell. The antibacterial activity against E. coli is mainly determined by the Ag+ ion release rate, suggesting that these particulates can be employed as a robust system for prolonged used as an antimicrobial material.
Recent Advances in Graphene Quantum Dots for Fluorescence Bioimaging from Cells through Tissues to Animals
Authors: Wang Dan , Chen Jian‐Feng , Dai Liming
Published: November 2014

Graphene quantum dots (GQDs) have attracted tremendous attention in recent years. In this review, the recent developments are summarized in the synthesis, edge functionalization, and cyctotoxicity of GQDs, followed by presenting a focused overview on their current applications for in vitro fluorescence imaging in cells and tissues as well as in vivo macroscopic and microscopic imaging in animals. Challenges and opportunities in the development of GQDs for bioimaging are also discussed.
Capillary‐channeled polymer (C‐CP) fibers for the rapid extraction of proteins from urine matrices prior to detection with MALDI‐MS
Authors: Manard Benjamin T. , Jones Sarah M. H. , Marcus R. Kenneth
Published: November 2014

Purpose

While MS is a powerful tool for biomarker determinations, the high salt content and the small molecules present in urine poses incredible challenges. Separation/extraction methods must be employed for the isolation of target species at relevant concentrations. Micropipette tips packed with capillary‐channeled polymer (C‐CP) fibers are employed for the SPE of proteins from a synthetic and a certified urine matrix.

Experimental design

Extractions are performed utilizing a very simple centrifugation method to spin‐down species through the C‐CP fiber tips. Proteins adsorb to the hydrophobic polypropylene fibers and are eluted in a solvent suitable for MALDI‐MS analysis. Figures of merit are determined for representative compounds β2‐microglobulin, retinol binding protein, and transferrin.

Results

The optimum protein processing included a 100 μL aqueous rinse and an elution solvent composition was 10 μL of 55:45 ACN:water (with triflouroacetic acid). MALDI‐MS responses for the target proteins are improved from nondetectable levels to eventually yield LOD ranging from 5 to 180 nM in 1 μL aliquots.

Conclusion and clinical relevance

C‐CP fiber tips offer a plethora of advantages including low materials costs, high throughput, microvolume processing, and the determination of sub‐nanogram quantities of analyte; allowing determination of biomarkers that are otherwise undetectable in urine matrices.
Network of long‐range concerted chemical shift displacements upon ligand binding to human angiogenin
Authors: Gagné Donald , Narayanan Chitra , Doucet Nicolas
Published: November 2014

Molecular recognition models of both induced fit and conformational selection rely on coupled networks of flexible residues and/or structural rearrangements to promote protein function. While the atomic details of these motional events still remain elusive, members of the pancreatic ribonuclease superfamily were previously shown to depend on subtle conformational heterogeneity for optimal catalytic function. Human angiogenin, a structural homologue of bovine pancreatic RNase A, induces blood vessel formation and relies on a weak yet functionally mandatory ribonucleolytic activity to promote neovascularization. Here, we use the NMR chemical shift projection analysis (CHESPA) to clarify the mechanism of ligand binding in human angiogenin, further providing information on long‐range intramolecular residue networks potentially involved in the function of this enzyme. We identify two main clusters of residue networks displaying correlated linear chemical shift trajectories upon binding of substrate fragments to the purine‐ and pyrimidine‐specific subsites of the catalytic cleft. A large correlated residue network clusters in the region corresponding to the V1 domain, a site generally associated with the angiogenic response and structural stability of the enzyme. Another correlated network (residues 40–42) negatively affects the catalytic activity but also increases the angiogenic activity. 15N‐CPMG relaxation dispersion experiments could not reveal the existence of millisecond timescale conformational exchange in this enzyme, a lack of flexibility supported by the very low‐binding affinities and catalytic activity of angiogenin. Altogether, the current report potentially highlights the existence of long‐range dynamic reorganization of the structure upon distinct subsite binding events in human angiogenin.
CD41 Marks the Initial Myelo-Erythroid Lineage Specification in Adult Mouse Hematopoiesis: Redefinition of Murine Common Myeloid Progenitor
Authors: Miyawaki Kohta , Arinobu Yojiro , Iwasaki Hiromi , Kohno Kentaro , Tsuzuki Hirofumi , Iino Tadafumi , Shima Takahiro , Kikushige Yoshikane , Takenaka Katsuto , Miyamoto Toshihiro , Akashi Koichi
Published: November 2014

Previous studies have predicted that reciprocal activation of GATA-1 and PU.1 regulates myelo-erythroid versus myelo-lymphoid lineage commitment in early hematopoiesis. Such PU.1-activating myelo-lymphoid progenitors exist within the lymphoid-primed multipotent progenitor (LMPP) population at the primitive Lineage−Sca-1+c-Kit+ (LSK) stage. We here show that the counterpart of GATA-1-activating myelo-erythroid progenitor resides also at the LSK stage, expressing CD41 at a high level. Purified CD41hi LSK cells showed exceedingly strong and prolonged myelo-erythroid-restricted reconstitution, and primed myelo-erythroid gene expression with a more primitive molecular signature as compared to the original common myeloid progenitor (CMP). The CD41hi LSK cells more strongly contributed to emergent and malignant myelopoiesis than LMPPs, and produced the original CMP by downregulating Sca-1 and CD41, suggesting that they are the earliest CMPs. Thus, the hematopoietic developmental map should be revised by integrating the primary branchpoint comprised of the new, isolatable CD41hi CMP and the LMPP populations. Stem Cells  2015;33:976–987
c‐di‐AMP recognition by Staphylococcus aureus PstA
Authors: Müller Martina , Hopfner Karl-Peter , Witte Gregor
Published: November 2014

Cyclic‐di‐AMP (c‐di‐AMP) is a bacterial secondary messenger involved in various processes, including sensing of DNA‐integrity, cell wall metabolism and potassium transport. A number of c‐di‐AMP receptor proteins have recently been identified in Staphylococcus aureus. One of them ‐ PstA ‐ possesses a ferredoxin‐like fold and is structurally related to the class of PII signal‐transduction proteins. PII proteins are involved in a large number of pathways, most of them associated with nitrogen metabolism. In this study we describe the mode of c‐di‐AMP binding and subsequent structural changes of S. aureus PstA. An altered architecture in PstA compared to canonical PII proteins results in differences in ligand coordination.
The green tea polyphenol (−)‐epigallocatechin gallate prevents the aggregation of tau protein into toxic oligomers at substoichiometric ratios
Authors: Wobst Heike J. , Sharma Apurwa , Diamond Marc I. , Wanker Erich E. , Bieschke Jan
Published: November 2014

The accumulation of amyloid‐beta (Aβ) and tau aggregates is a pathological hallmark of Alzheimer's disease. Both polypeptides form fibrillar deposits, but several lines of evidence indicate that Aβ and tau form toxic oligomeric aggregation intermediates. Depleting such structures could thus be a powerful therapeutic strategy. We generated a fragment of tau (His‐K18ΔK280) that forms stable, toxic, oligomeric tau aggregates in vitro. We show that (−)‐epigallocatechin gallate (EGCG), a green tea polyphenol that was previously found to reduce Aβ aggregation, inhibits the aggregation of tau K18ΔK280 into toxic oligomers at ten‐ to hundred‐fold substoichiometric concentrations, thereby rescuing toxicity in neuronal model cells.
Intrinsically disordered proteins as crucial constituents of cellular aqueous two phase systems and coacervates
Authors: Uversky Vladimir N. , Kuznetsova Irina M. , Turoverov Konstantin K. , Zaslavsky Boris
Published: November 2014

Here, we hypothesize that intrinsically disordered proteins (IDPs) serve as important drivers of the intracellular liquid–liquid phase separations that generate various membrane‐less organelles. This hypothesis is supported by the overwhelming abundance of IDPs in these organelles. Assembly and disassembly of these organelles are controlled by changes in the concentrations of IDPs, their posttranslational modifications, binding of specific partners, and changes in the pH and/or temperature of the solution. Each resulting phase provides a distinct solvent environment for other solutes leading to their unequal distribution within phases. The specificity and efficiency of such partitioning is determined by the nature of the IDP(s) and defines “targeted” enrichment of specific molecules in the resulting membrane‐less organelles that determines their specific activities.
Structural and biochemical characterization of a carbohydrate acetylesterase from Sinorhizobium meliloti 1021
Authors: Kim Kyungmin , Ryu Bum Han , Kim Sung Soo , An Deu Rae , Ngo Tri Duc , Pandian Ramesh , Kim Kyeong Kyu , Kim T. Doohun
Published: November 2014

In many microorganisms, carbohydrate acetylesterases remove the acetyl groups from various types of carbohydrates. Sm23 from Sinorhizobium meliloti is a putative member of carbohydrate esterase family 3 (CE3) in the CAZy classification system. Here, we determined the crystal structure of Sm23 at 1.75 Å resolution and investigated functional properties using biochemical methods. Furthermore, immobilized Sm23 exhibited improved stability compared with soluble Sm23, which can be used for the design of plant cell wall degrading‐systems.
Piperine, a component of black pepper, decreases eugenol‐induced cAMP and calcium levels in non‐chemosensory 3T3‐L1 cells
Authors: Yoon Yeo Cho , Kim Sung-Hee , Kim Min Jung , Yang Hye Jeong , Rhyu Mee-Ra , Park Jae-Ho
Published: November 2014

This study investigated the effects of an ethanol extract of black pepper and its constituent, piperine, on odorant‐induced signal transduction in non‐chemosensory cells. An ethanol extract of black pepper decreased eugenol‐induced cAMP and calcium levels in preadipocyte 3T3‐L1 cells with no toxicity. Phosphorylation of CREB (cAMP response element‐binding protein) was down‐regulated by the black pepper extract. The concentration (133.8 mg/g) and retention time (5.5 min) of piperine in the ethanol extract were quantified using UPLC–MS/MS. Pretreatment with piperine decreased eugenol‐induced cAMP and calcium levels in 3T3‐L1 cells. Piperine also decreased the phosphorylation of CREB, which is up‐regulated by eugenol. These results suggest that piperine inhibits the eugenol‐induced signal transduction pathway through modulation of cAMP and calcium levels and phosphorylation of CREB in non‐chemosensory cells.
A prospective open‐label study of home use of mifepristone for medical abortion in Nepal
Authors: Conkling Kathryn , Karki Chanda , Tuladhar Heera , Bracken Hillary , Winikoff Beverly
Published: November 2014

Objective

To assess the uptake and acceptability of self‐administration of mifepristone at home for medical abortion in Nepal.

Methods

A prospective, comparative, non‐randomized, open‐label study was conducted at two hospitals in Kathmandu, Nepal, between November 11, 2009, and January 15, 2011. All women in good health and aged 18 years or older who sought medical abortion after fewer than 64 days of pregnancy were enrolled. Participants were offered the choice of taking 200 mg mifepristone orally in the clinic or at home; all participants self‐administered 400 μg of sublingual misoprostol at home 24–72 hours later. All participants were scheduled to return to the clinic within 14 days of mifepristone administration for follow‐up.

Results

Among 200 participants, 144 (72.0%) opted to take the mifepristone at home. Medical abortion was successful in 130 (95.6%) of 136 women in the home group who were followed up and 53 (94.6%) of 56 women in the clinic group. Only 4 (2.9%) women in the home group took the mifepristone after the scheduled time. Overall, 133 (97.8%) women in the home group stated that they would recommend home administration of mifepristone if a friend wanted a medical abortion.

Conclusion

Self‐administration of mifepristone outside the clinic should be offered to all women as part of routine medical abortion services in Nepal.

Clinicaltrials.gov: NCT00994734.
Uptake of a women‐only, sex‐work‐specific drop‐in center and links with sexual and reproductive health care for sex workers
Authors: Kim Soyoun Rachel , Goldenberg Shira M. , Duff Putu , Nguyen Paul , Gibson Kate , Shannon Kate
Published: November 2014

Objective

To longitudinally examine female sex workers’ (FSWs’) uptake of a women‐only, sex‐work‐specific drop‐in service and its impact on their access to sexual and reproductive health (SRH) services.

Methods

For the present longitudinal analysis, data were drawn from the AESHA (An Evaluation of Sex Workers’ Health Access) study, a community‐based, open, prospective cohort of FSWs from Vancouver, BC, Canada. Data obtained between January 2010 and February 2013 were analyzed. Participants are followed up on a semi‐annual basis. Multivariable logistic regression using generalized estimating equations was used to identify correlates of service uptake.

Results

Of 547 FSWs included in the present analysis, 330 (60.3%) utilized the services during the 3‐year study period. Service use was independently associated with age (adjusted odds ratio [AOR] 1.04; 95% confidence interval [CI] 1.03–1.06), Aboriginal ancestry (AOR 2.18; 95% CI 1.61–2.95), injection drug use (AOR 1.67; 95% CI 1.29–2.17), exchange of sex for drugs (AOR 1.40; 95%CI 1.15–1.71), and accessing SRH services (AOR 1.65; 95% CI 1.35–2.02).

Conclusion

A sex‐work‐specific drop‐in space for marginalized FSWs had high uptake. Women‐centered and low‐threshold drop‐in services can effectively link marginalized women with SRH services.
Immediate electrical storm of Torsades de Pointes after CRT‐D implantation in an ischemic cardiomyopathy patient
Authors: Kaya Adnan , Sungur Aylin , Tekkesin Ahmet Ilker , Turkkan Ceyhan , Alper Ahmet Taha
Published: November 2014

Cardiac resynchronization therapy with an implantable cardioverter‐defibrillator (CRT‐D) is the preferred treatment for patients with severe heart failure, dyssynchrony, and an increased risk of sudden cardiac death or for primary ventricular arrhythmia survivors. Rarely, left ventricular epicardial pacing can induce ventricular tachyarrhythmia rather than a beneficial effect. We describe an ischemic cardiomyopathy patient who underwent CRT‐D therapy and developed sustained torsades de pointes (TdP) immediately after switching to biventricular pacing (BVP) mode. Here, TdP possibly developed owing to the change in the dispersion of repolarization of the left ventricle myocardium. The diagnosis and management of BVP‐induced ventricular arrhythmia is discussed.
Prediction of clinical outcome in glioblastoma using a biologically relevant nine‐microRNA signature
Authors: Hayes Josie , Thygesen Helene , Tumilson Charlotte , Droop Alastair , Boissinot Marjorie , Hughes Thomas A. , Westhead David , Alder Jane E. , Shaw Lisa , Short Susan C. , Lawler Sean E.
Published: November 2014

Background

Glioblastoma is the most aggressive primary brain tumor, and is associated with a very poor prognosis. In this study we investigated the potential of microRNA expression profiles to predict survival in this challenging disease.

Methods

MicroRNA and mRNA expression data from glioblastoma (n = 475) and grade II and III glioma (n = 178) were accessed from The Cancer Genome Atlas. LASSO regression models were used to identify a prognostic microRNA signature. Functionally relevant targets of microRNAs were determined using microRNA target prediction, experimental validation and correlation of microRNA and mRNA expression data.

Results

A 9‐microRNA prognostic signature was identified which stratified patients into risk groups strongly associated with survival (p = 2.26e−09), significant in all glioblastoma subtypes except the non‐G‐CIMP proneural group. The statistical significance of the microRNA signature was higher than MGMT methylation in temozolomide treated tumors. The 9‐microRNA risk score was validated in an independent dataset (p = 4.50e−02) and also stratified patients into high‐ and low‐risk groups in lower grade glioma (p = 5.20e−03). The majority of the 9 microRNAs have been previously linked to glioblastoma biology or treatment response. Integration of the expression patterns of predicted microRNA targets revealed a number of relevant microRNA/target pairs, which were validated in cell lines.

Conclusions

We have identified a novel, biologically relevant microRNA signature that stratifies high‐ and low‐risk patients in glioblastoma. MicroRNA/mRNA interactions identified within the signature point to novel regulatory networks. This is the first study to formulate a survival risk score for glioblastoma which consists of microRNAs associated with glioblastoma biology and/or treatment response, indicating a functionally relevant signature.
Late Glacial Lake-Level Changes in the Lake Karakul Basin (a Closed Glacierized-Basin), eastern Pamirs, Tajikistan
Authors: Komatsu Tetsuya , Tsukamoto Sumiko
Published: November 2014

The lake-level variations during the Late Glacial in the Lake Karakul basin (a closed glacierized-basin), in the northernmost part of the eastern Pamirs, were reconstructed using geomorphological and sedimentological evidence, with a chronology developed using luminescence ages from sand-sized quartz and K-feldspar in the lake sediments. Lake transgression started before ~ 19 ka, with the peak water level of ~ 35 m above the present elevation occurring at ~ 15 ka. This was synchronous with a significant advance of the glacier in the catchment. Stepwise lake regression, including a rapid lowering of the lake level (~ 13 m at ~ 12 ka), persisted until at least ~ 10 ka. Lake transgression and localized glacier expansion from ~ 19 to ~ 15 ka likely correlate with the more regional Late Glacial glacier advances across the semi-arid western Himalayan–Tibetan orogen and the eastern Pamirs. The longer-term trend of this lake transgression was probably caused by colder and/or wetter climatic conditions, forcing a notable glacier advance.
Use of a Population Pharmacokinetic Approach for the Clinical Development of a Fixed‐Dose Subcutaneous Formulation of Trastuzumab
Authors: Hourcade‐Potelleret F , Lemenuel‐Diot A , McIntyre C , Brewster M , Lum B , Bittner B
Published: November 2014

A new subcutaneous (s.c.) trastuzumab formulation provides savings in terms of time and is preferred by patients and health care professionals relative to standard intravenous (i.v.) administration due to simpler and more rapid administration (2–5 minutes). Selection of the s.c. dose was based on a pharmacokinetic bridging approach that aimed to achieve noninferior trastuzumab serum trough concentrations (Ctrough) vs. reference i.v. administration. Using population modeling and simulation, we showed that a fixed 600‐mg trastuzumab s.c. dose, administered thrice‐weekly (Q3W) without a loading dose, would provide Ctrough (predose Cycle 8) and area under the time–concentration curve (AUC0–21 days, Cycle 7) at least as high as Q3W i.v. administration. The model was retrospectively validated using observed pharmacokinetic data from an independent phase III study of (neo)adjuvant trastuzumab (HannaH). These results provide a strong pharmacokinetic rationale for the trastuzumab s.c. 600‐mg fixed dose, supported by the noninferior efficacy of this regimen vs. reference i.v. administration.

CPT Pharmacometrics Syst. Pharmacol. (2014) 3, e87; doi:10.1038/psp.2013.63; advance online publication 2 January 2014
HealthPathways: creating a pathway for health systems reform
Authors: Robinson Suzanne , Varhol Richard , Bell Colin , Quirk Frances , Durrington Learne
Published: November 2014

Inefficiencies in the co-ordination and integration of primary and secondary care services in Australia, have led to increases in waiting times, unnecessary presentations to emergency departments and issues around poor discharge of patients. HealthPathways is a program developed in Canterbury, New Zealand, that builds relationships between General Practitioners and Specialists and uses information technology so that efficiency is maximised and the right patient is given the right care at the right time. Healthpathways is being implemented by a number of Medicare Locals across Australia however, little is known about the impact HealthPathways may have in Australia. This article provides a short description of HealthPathways and considers what it may offer in the Australian context and some of the barriers and facilitators to implementation.

What is known about the topic?
Early evidence on HealthPathways suggests that the program does seem to be strengthening relationships between GPs and secondary care specialists. In New Zealand advances in efficiency and system integration have been noted. However, there is limited evidence on the effectiveness of HealthPathways in Australia.

What does this paper add?
It is one of the first published papers to provide a perspective around HealthPathways and draws existing evidence and research to explore some of the barriers and facilitators to the development and implementation of HealthPathways in Australia.

What are the implications for practitioners’?
Early evidence suggests HealthPathways could help GPs and other practitioners’ in the delivery of health services, it could also help to strengthen practitioner relationships.
Modelling of Transition State in Grignard Reaction of Rigid N-(Aryl)imino-Acenapthenone (Ar-BIAO): A Combined Experimental and Computational Study
Authors: Anga Srinivas , Das Gupta Sayak , Rej Supriya , Mallik Bhabani S. , Panda Tarun K.
Published: November 2014

We present a combined synthetic and computational study on the addition of Grignard reagents RMgBr/RMgI (R = Me, Et) to various sterically rigid N-(aryl)imino-acenapthenone (Ar-BIAO) (Ar = 2,6-iPr2C6H3 (1), 2,6-Me2C6H3 (2), and 2,4,6-Me3C6H2 (3) ligands). In the experimental method, when compounds 1–3 were treated with RMgBr (R = Me, Et) at room temperature, the corresponding racemic N-(aryl)imino-acenapthylene-1-ol (Ar-BIAOH) compounds (Ar = 2,6- iPr2C6H3, R = Me (1a), Et (1b); Ar = 2,6-Me2C6H3, R = Me (2a), Et (2b); and Ar = 2,4,6-Me3C6H2, R = Me (3a), Et (3b)) were obtained in yields up to 82 %. The Ar-BIAOH compounds were characterized by spectroscopic and combustion analyses. The solid state structures of compounds 1a–3a were established by single-crystal X-ray diffraction analysis. To model the transition state of the Grignard reaction with asymmetrical and sterically rigid Ar-BIAO ligands having three fused rings containing exo-cyclic carbonyl and imine functionalities, we carried out computational analysis. During our study, we have considered the gas phase addition of CH3MgBr to 2 and the model system of 2-(methylimino)pentanone (2′). We have carried out ab initio (HF/3–21G*) and density functional theory calculations with the hybrid density functional B3LYP/6–311+G(2d,p) to probe two major aspects: (1) the stability of an intra-molecular chelation involving magnesium, carbonyl oxygen, and imine nitrogen and (2) to suggest a probable transition state and a mechanistic pathway. The computational investigation suggests the formation of a tetra-coordinated magnesium complex as the transition state for the Grignard reaction.
Faster sequence homology searches by clustering subsequences
Authors: Suzuki Shuji , Kakuta Masanori , Ishida Takashi , Akiyama Yutaka
Published: November 2014

Motivation: Sequence homology searches are used in various fields. New sequencing technologies produce huge amounts of sequence data, which continuously increase the size of sequence databases. As a result, homology searches require large amounts of computational time, especially for metagenomic analysis.

Results: We developed a fast homology search method based on database subsequence clustering, and implemented it as GHOSTZ. This method clusters similar subsequences from a database to perform an efficient seed search and ungapped extension by reducing alignment candidates based on triangle inequality. The database subsequence clustering technique achieved an ∼2-fold increase in speed without a large decrease in search sensitivity. When we measured with metagenomic data, GHOSTZ is ∼2.2–2.8 times faster than RAPSearch and is ∼185–261 times faster than BLASTX.

Availability and implementation: The source code is freely available for download at http://www.bi.cs.titech.ac.jp/ghostz/

Contact:  akiyama@cs.titech.ac.jp

Supplementary information:  Supplementary data are available at Bioinformatics online.
PEASE: predicting B-cell epitopes utilizing antibody sequence
Authors: Sela-Culang Inbal , Ashkenazi Shaul , Peters Bjoern , Ofran Yanay
Published: November 2014

Summary: Antibody epitope mapping is a key step in understanding antibody–antigen recognition and is of particular interest for drug development, diagnostics and vaccine design. Most computational methods for epitope prediction are based on properties of the antigen sequence and/or structure, not taking into account the antibody for which the epitope is predicted. Here, we introduce PEASE, a web server predicting antibody-specific epitopes, utilizing the sequence of the antibody. The predictions are provided both at the residue level and as patches on the antigen structure. The tradeoff between recall and precision can be tuned by the user, by changing the default parameters. The results are provided as text and HTML files as well as a graph, and can be viewed on the antigen 3D structure.

Availability and implementation: PEASE is freely available on the web at www.ofranlab.org/PEASE.

Contact:  yanay@ofranlab.org
Community-associated MRSA strain ST72-SCCmecIV causing bloodstream infections: clinical outcomes and bacterial virulence factors
Authors: Park Ki-Ho , Chong Yong Pil , Kim Sung-Han , Lee Sang-Oh , Choi Sang-Ho , Lee Mi Suk , Jeong Jin-Yong , Woo Jun Hee , Kim Yang Soo
Published: November 2014

Objectives

Community-associated MRSA (CA-MRSA) has emerged in the community and has recently been spreading in healthcare settings. The objectives of this study were to evaluate the clinical outcomes and bacterial virulence factors of the Korean CA-MRSA (ST72-SCCmecIV) strain, which causes bloodstream infections.

Methods

All adult patients with MRSA bacteraemia were prospectively enrolled. Clinical outcomes, microbiological characteristics and 40 bacterial virulence factors were evaluated.

Results

Of the 352 typed MRSA isolates, 342 isolates (97.2%) belonged to three Panton–Valentine leucocidin-negative strains: ST5-SCCmecII (70.2%), ST72-SCCmecIV (22.4%) and ST239-SCCmecIII (4.6%). The remaining 10 (2.8%) isolates from minor strains were excluded from the final analysis. After controlling for several confounding factors, ST72-SCCmecIV was associated with the lowest mortality (compared with ST5-SCCmecII, adjusted OR = 0.26; 95% CI = 0.13–0.54). However, MRSA isolates with vancomycin MICs of ≥1.5 mg/L were more common in ST72-SCCmecIV compared with ST5-SCCmecII (84.8% versus 66.7%; P = 0.002). Reduced vancomycin susceptibility and vancomycin heteroresistance were not associated with mortality. Compared with ST5-SCCmecII isolates, ST72-SCCmecIV isolates were less likely to harbour multiple virulence genes. Of these genes, three staphylococcal superantigen genes were associated with mortality: sec (OR = 2.31; P = 0.002), sel (OR = 2.55; P = 0.003) and tst (OR = 2.76; P < 0.001).

Conclusions

After controlling for confounding factors, ST72-SCCmecIV was independently associated with lower mortality compared with ST5-SCCmecII, suggesting this CA-MRSA strain to be of lower virulence. The lack of virulence genes, including staphylococcal superantigen genes, may play a role in the lower virulence of this strain.
Modeling Latent Information in Voting Data with Dirichlet Process Priors
Authors: Traunmüller Richard , Murr Andreas , Gill Jeff
Published: November 2014

We apply a specialized Bayesian method that helps us deal with the methodological challenge of unobserved heterogeneity among immigrant voters. Our approach is based ongeneralized linear mixed Dirichlet models(GLMDMs) where random effects are specified semiparametrically using a Dirichlet process mixture prior that has been shown to account for unobserved grouping in the data. Such models are drawn from Bayesian nonparametrics to help overcome objections handling latent effects with strongly informed prior distributions. Using 2009 German voting data of immigrants, we show that for difficult problems of missing key covariates and unexplained heterogeneity this approach provides (1) overall improved model fit, (2) smaller standard errors on average, and (3) less bias from omitted variables. As a result, the GLMDM changed our substantive understanding of the factors affecting immigrants' turnout and vote choice. Once we account for unobserved heterogeneity among immigrant voters, whether a voter belongs to the first immigrant generation or not is much less important than the extant literature suggests. When looking at vote choice, we also found that an immigrant's degree of structural integration does not affect the vote in favor of the CDU/CSU, a party that is traditionally associated with restrictive immigration policy.
Generalised empirical Bayesian methods for discovery of differential data in high-throughput biology
Authors: Hardcastle Thomas J
Published: November 2014

Motivation

High-throughput data are now commonplace in biological research. Rapidly changing technologies and application mean that novel methods for detecting differential behaviour that account for a ‘largeP, smalln’ setting are required at an increasing rate. The development of such methods is, in general, being done on anad hocbasis, requiring further development cycles and a lack of standardization between analyses.

Results

We present here a generalised method for identifying differential behaviour within high-throughput biological data through empirical Bayesian methods. This approach is based on ourbaySeqalgorithm for identification of differential expression in RNA-seq data based on a negative binomial distribution, and in paired data based on a beta-binomial distribution. Here we show how the same empirical Bayesian approach can be applied to any parametric distribution, removing the need for lengthy development of novel methods for differently distributed data. Comparisons with existing methods developed to address specific problems in high-throughput biological data show that these generic methods can achieve equivalent or better performance. A number of enhancements to the basic algorithm are also presented to increase flexibility and reduce computational costs.

Availability

The methods are implemented in theRbaySeq(v2) package, available on Bioconductorhttp://www.bioconductor.org/packages/release/bioc/html/baySeq.html.

Contact

tjh48@cam.ac.uk
A diffusive homeostatic signal maintains neural heterogeneity and responsiveness in cortical networks
Authors: Sweeney Yann , Hellgren Kotaleski Jeanette , Hennig Matthias H
Published: November 2014

Gaseous neurotransmitters such as nitric oxide (NO) provide a unique and often overlooked mechanism for neurons to communicate through diffusion within a network, independent of synaptic connectivity. NO provides homeostatic control of intrinsic excitability. Here we conduct a theoretical investigation of the distinguishing roles of NO-mediated diffusive homeostasis in comparison with canonical non-diffusive homeostasis in cortical networks. We find that both forms of homeostasis provide a robust mechanism for maintaining stable activity following perturbations. However, the resulting networks differ, with diffusive homeostasis maintaining substantial heterogeneity in activity levels of individual neurons, a feature disrupted in networks with non-diffusive homeostasis. This results in networks capable of representing input heterogeneity, and linearly responding over a broader range of inputs than those undergoing non-diffusive homeostasis. We further show that these properties are preserved when homeostatic and Hebbian plasticity are combined. These results suggest a mechanism for dynamically maintaining neural heterogeneity, and expose computational advantages of non-local homeostatic processes.
Estimating the effects of water-induced shallow landslides on soil erosion
Authors: Bosco Claudio , Sander Graham
Published: November 2014

Rainfall induced landslides and soil erosion are part of a complex system of multiple interacting processes, and both are capable of significantly affecting sediment budgets. These sediment mass movements also have the potential to significantly impact on a broad network of ecosystems health, functionality and the services they provide. To support the integrated assessment of these processes it is necessary to develop reliable modelling architectures. This paper proposes a semi-quantitative integrated methodology for a robust assessment of soil erosion rates in data poor regions affected by landslide activity. It combines heuristic, empirical and probabilistic approaches. This proposed methodology is based on the geospatial semantic array programming paradigm and has been implemented on a catchment scale methodology using GIS spatial analysis tools and GNU Octave. The integrated data-transformation model relies on a modular architecture, where the information flow among modules is constrained by semantic checks. In order to improve computational reproducibility, the geospatial data transformations implemented in ESRI ArcGis are made available in the free software GRASS GIS. The proposed modelling architecture is flexible enough for future transdisciplinary scenario-analysis to be more easily designed. In particular, the architecture might contribute as a novel component to simplify future integrated analyses of the potential impact of wildfires or vegetation types and distributions, on sediment transport from water induced landslides and erosion.