bluuebunny/crossref_metadata_2025 huggingface dataset:
Periodontitis‐associated pathogens P. gingivalis and A. actinomycetemcomitans activate human CD14+ monocytes leading to enhanced Th17/IL‐17 responses
Authors: Cheng Wan‐Chien , van Asten Saskia D. , Burns Lachrissa A. , Evans Hayley G. , Walter Gina J. , Hashim Ahmed , Hughes Francis J. , Taams Leonie S.
Published: June 2016

The Th17/IL‐17 pathway is implicated in the pathogenesis of periodontitis (PD), however the mechanisms are not fully understood. We investigated the mechanism by which the periodontal pathogens Porphyromonas gingivalis (Pg) and Aggregatibacter actinomycetemcomitans (Aa) promote a Th17/IL‐17 response in vitro, and studied IL‐17+ CD4+ T‐cell frequencies in gingival tissue and peripheral blood from patients with PD versus periodontally healthy controls. Addition of Pg or Aa to monocyte/CD4+ T‐cell co‐cultures promoted a Th17/IL‐17 response in vitro in a dose‐ and time‐dependent manner. Pg or Aa stimulation of monocytes resulted in increased CD40, CD54 and HLA‐DR expression, and enhanced TNF‐α, IL‐1β, IL‐6 and IL‐23 production. Mechanistically, IL‐17 production in Pg‐stimulated co‐cultures was partially dependent on IL‐1β, IL‐23 and TLR2/TLR4 signalling. Increased frequencies of IL‐17+ cells were observed in gingival tissue from patients with PD compared to healthy subjects. No differences were observed in IL‐17+ CD4+ T‐cell frequencies in peripheral blood. In vitro, Pg induced significantly higher IL‐17 production in anti‐CD3 mAb‐stimulated monocyte/CD4+ T‐cell co‐cultures from patients with PD compared to healthy controls. Our data suggest that periodontal pathogens can activate monocytes, resulting in increased IL‐17 production by human CD4+ T cells, a process that appears enhanced in patients with PD.
The effect of the belief in free market ideology on redressing corporate injustice
Authors: Kardos Peter , Leidner Bernhard , Zsolnai Laszlo , Castano Emanuele
Published: June 2016

Many people in the major Western economies (e.g., United States, UK, and Germany) subscribe to free market ideology (FMI), which claims that institutional oversight of the market is unnecessary for public reaction can force corporations to regulate their own behavior. The question then becomes how people's belief in FMI affects their reactions to corporate transgressions. Given its ingroup‐centered values, we hypothesized that FMI beliefs would bias reactions to corporate transgressions. We report results of a pilot study showing that FMI beliefs are predicted by selfishness, tradition, conformity, and lack of universalism. We then report three experiments, which showed that stronger FMI beliefs predict weaker demands to redress corporate injustices committed by ingroup (but not outgroup) corporations (Studies 1–3), especially when victims of corporate wrongdoings belong to an outgroup (rather than the ingroup; Study 3). The findings inform our conceptual understanding of FMI and give insights about its implications for market justice.
Are we going about chemical risk assessment for the aquatic environment the wrong way?
Authors: Johnson Andrew C. , Sumpter John P.
Published: June 2016

The goal of protecting the aquatic environment through testing thousands of chemicals against hundreds of aquatic species with thousands of endpoints while also considering mixtures is impossible given the present resources. Much of the impetus for studies on micropollutants, such as pharmaceuticals, came from the topic of endocrine disruption in wild fish. But despite concern over reductions in fish fertility, there is little evidence that fish populations are in peril. Indeed, fish biologists suggest that many cyprinid populations have been recovering for the past 30 to 40 yr. The central assumption, key to current risk assessment, that effects observed in the laboratory or predicted by models are readily transferrable to the population level, is therefore questionable. The neglect in monitoring wildlife populations is the key weakness in environmental protection strategies. If we do not know whether aquatic wildlife species are declining or increasing, how valuable are our other ecotoxicological activities? Environ Toxicol Chem 2016;35:1609–1616. © 2016 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.
Effects of diluted bitumen exposure on juvenile sockeye salmon: From cells to performance
Authors: Alderman Sarah L. , Lin Feng , Farrell Anthony P. , Kennedy Christopher J. , Gillis Todd E.
Published: June 2016

Diluted bitumen (dilbit; the product of oil sands extraction) is transported through freshwater ecosystems critical to Pacific salmon. This is concerning, because crude oil disrupts cardiac development, morphology, and function in embryonic fish, and cardiac impairment in salmon can have major consequences on migratory success and fitness. The sensitivity of early life-stage salmon to dilbit and its specific cardiotoxic effects are unknown. Sockeye salmon parr were exposed to environmentally relevant concentrations of the water-soluble fraction (WSF) of dilbit for 1 wk and 4 wk, followed by an examination of molecular, morphological, and organismal endpoints related to cardiotoxicity. We show that parr are sensitive to WSF of dilbit, with total polycyclic aromatic hydrocarbon (PAH) concentrations of 3.5 µg/L sufficient to induce a liver biomarker of PAH exposure, and total PAH of 16.4 µg/L and 66.7 µg/L inducing PAH biomarkers in the heart. Furthermore, WSF of dilbit induces concentration–dependent cardiac remodeling coincident with performance effects: fish exposed to 66.7 µg/L total PAH have relatively fewer myocytes and more collagen in the compact myocardium and impaired swimming performance at 4 wk, whereas the opposite changes occur in fish exposed to 3.5 µg/L total PAH. The results demonstrate cardiac sensitivity to dilbit exposure that could directly impact sockeye migratory success. Environ Toxicol Chem 2017;36:354–360. © 2016 SETAC
A Palaeoenvironmental Investigation of Two Prehistoric Burnt Mound Sites in Northern Ireland
Authors: Wheeler J. , Timpany S. , Mighall T. M. , Scott L.
Published: June 2016

This paper provides a summary of the palaeoenvironmental evidence from a spread of late Mesolithic burnt material and two late Neolithic to early Bronze Age burnt mounds. The burnt mounds were up to 10 m diameter, had an amorphous shape, and were consistently less than 0.8 m thick. Monoliths were collected from two sites, Ballygawley and Roughan, in Co. Tyrone, Northern Ireland. This provided an opportunity to use a detailed palaeoecological approach for the first time to investigate the use and function of burnt mounds. Pollen, non‐pollen palynomorphs, micro‐ and macroscopic charcoal were used to place these features within their environmental context, and to establish if such an approach could provide further insights into their function. The palynological results shared similar characteristics: high microscopic charcoal values, repetitive fluctuations in tree and shrub taxa, increased Sphagnum, and the presence of non‐pollen palynomorphs (NPPs) HdV‐114 and HdV‐146, all of which could be diagnostic indicators of burnt mounds in palynological records. While the data do not allow us to ascribe a specific function for the burnt mounds, their environmental setting is discussed. A “see‐saw” pattern of arboreal pollen, combined with the macroscopic charcoal data, indicate possible species selection and management of local woodland for fuelwood.
FARVATX: Family‐Based Rare Variant Association Test for X‐Linked Genes
Authors: Choi Sungkyoung , Lee Sungyoung , Qiao Dandi , Hardin Megan , Cho Michael H. , Silverman Edwin K , Park Taesung , Won Sungho
Published: June 2016

Although the X chromosome has many genes that are functionally related to human diseases, the complicated biological properties of the X chromosome have prevented efficient genetic association analyses, and only a few significantly associated X‐linked variants have been reported for complex traits. For instance, dosage compensation of X‐linked genes is often achieved via the inactivation of one allele in each X‐linked variant in females; however, some X‐linked variants can escape this X chromosome inactivation. Efficient genetic analyses cannot be conducted without prior knowledge about the gene expression process of X‐linked variants, and misspecified information can lead to power loss. In this report, we propose new statistical methods for rare X‐linked variant genetic association analysis of dichotomous phenotypes with family‐based samples. The proposed methods are computationally efficient and can complete X‐linked analyses within a few hours. Simulation studies demonstrate the statistical efficiency of the proposed methods, which were then applied to rare‐variant association analysis of the X chromosome in chronic obstructive pulmonary disease. Some promising significant X‐linked genes were identified, illustrating the practical importance of the proposed methods.
Incarcerated Sex Offenders in Rehabilitation Account for their Offending
Authors: Geiger Brenda , Fischer Michael
Published: June 2016

This research examines the accounts of 10 out of 22 incarcerated sex offenders undergoing therapy in one of the prison‐based sex‐offender rehabilitation units in Israel and their ability to renegotiate reality to reject stigmatisation and maintain a favourable identity. The research participants had been convicted either of child molestation or of date/statutory rape against an acquaintance. This differentiation was maintained when analysing the individual interviews conducted in prison. Prior to the provision of accounts, to establish the soundness of their character, the interviewees resituated themselves within a normative background in terms of setting, routine activities, and interactions preceding and following the offence. Offenders convicted of child molestation attributed their behaviour to a sudden unpredictable shift in the setting and interactions with the child that resulted in an erection and consequent impulsive sexual behaviour of which they could not be held responsible. Offenders convicted of date/statutory rape admitted responsibility for their action, yet minimised its harm by attributing it to the dynamic chain of interactions with the victim whose behaviour had deviated from the ‘good’ girl or ‘macho’ man on a date and thus had precipitated the act. Rather than discounting sex offenders' accounts as cognitive distortions of a sick mind, prevention and education programme are to rely on such accounts to increase youth and young adult awareness to traditional gender‐role schemata and dating scripts espoused by Israeli macho men that facilitate date rape and to the dynamics of interactional and situational factors placing young children at risk of sexual victimisation. Copyright © 2016 John Wiley & Sons, Ltd.
The nematode stoma: Homology of cell architecture with improved understanding by confocal microscopy of labeled cell boundaries
Authors: Jay Burr A. H. , Baldwin James G.
Published: June 2016

Nematode stomas vary widely in the cuticular structures evolved for different feeding strategies, yet the arrangement of the epithelial cell classes that form these structures may be conserved. This article addresses several issues that have impeded the full acceptance of this hypothesis including controversies arising from the structure of the Caenorhabditis elegans stoma. We investigated fluorescent antibody labeling of cell boundaries in conjunction with confocal microscopy as an alternative to transmission electron microscopy (TEM), using MH27 to label apical junctions in C. elegans and two other species. Accurately spaced optical sections collected by the confocal microscope provide a three‐dimensional array of pixels (voxels) that, using image‐processing software, can be rotated and sectioned at accurately chosen thicknesses and locations. Ribbons of fluorescence clearly identify cell boundaries along the luminal cuticle in C. elegans and Zeldia punctata and less clearly in Bunonema sp. The patterns render cell classes and their relationships readily identifiable. In the C. elegans stoma they correct a misreading of serial TEMs that was not congruent with architecture in other nematodes—the row of marginal cells is now seen to be continuous as in other nematodes, rather than being interrupted by encircling pm1 cells. Also impeding understanding, the reference to certain cell classes as ‘epithelial’ and others as “muscle” in the C. elegans literature is at variance with muscle expression in most other taxa. For consistent comparison among species, we propose that these cell class descriptors based on function be replaced by topological terms. With these and other confusing concepts and terminology removed, the homology of the cellular architecture among taxa becomes obvious. We provide a corrected description of the cell architecture of the C. elegans stoma and examples of how it is modified in other taxa with different feeding strategies. J. Morphol. 277:1168–1186, 2016. © 2016 Wiley Periodicals, Inc.
The locomotion of Babakotia radofilai inferred from epiphyseal and diaphyseal morphology of the humerus and femur
Authors: Marchi Damiano , Ruff Christopher B. , Capobianco Alessio , Rafferty Katherine L. , Habib Michael B. , Patel Biren A.
Published: June 2016

Palaeopropithecids, or “sloth lemurs,” are a diverse clade of large‐bodied Malagasy subfossil primates characterized by their inferred suspensory positional behavior. The most recently discovered genus of the palaeopropithecids is Babakotia, and it has been described as more arboreal than Mesopropithecus, but less than Palaeopropithecus. In this article, the within‐bone and between‐bones articular and cross‐sectional diaphyseal proportions of the humerus and femur of Babakotia were compared to extant lemurs, Mesopropithecus and Palaeopropithecus in order to further understand its arboreal adaptations. Additionally, a sample of apes and sloths (Choloepus and Bradypus) are included as functional outgroups composed of suspensory adapted primates and non‐primates. Results show that Babakotia and Mesopropithecus both have high humeral/femoral shaft strength proportions, similar to extant great apes and sloths and indicative of forelimb suspensory behavior, with Babakotia more extreme in this regard. All three subfossil taxa have relatively large femoral heads, also associated with suspension in modern taxa. However, Babakotia and Mesopropithecus (but not Palaeopropithecus) have relatively small femoral head surface area to shaft strength proportions suggesting that hind‐limb positioning in these taxa during climbing and other behaviors was different than in extant great apes, involving less mobility. Knee and humeral articular dimensions relative to shaft strengths are small in Babakotia and Mesopropithecus, similar to those found in modern sloths and divergent from those in extant great apes and lemurs, suggesting more sloth‐like use of these joints during locomotion. Mesopropithecus and Babakotia are more similar to Choloepus in humerofemoral head and length proportions while Palaeopropithecus is more similar to Bradypus. These results provide further evidence of the suspensory adaptations of Babakotia and further highlight similarities to both extant suspensory primates and non‐primate slow arboreal climbers and hangers. J. Morphol. 277:1199–1218, 2016. © 2016 Wiley Periodicals, Inc.
Different HIV‐1 env frames: gp120 and ASP (antisense protein) biosynthesis, and theirs co‐variation tropic amino acid signatures in X4‐ and R5‐viruses
Authors: Dimonte Salvatore
Published: June 2016

Antisense protein (ASP) is the new actor of viral life of Human Immunodeficiency Virus type 1 (HIV‐1) although proposed above 20 years ago. The asp ORF is into complementary strand of the gp120/gp41 junction of env gene. The ASP biological role remains little known. Knowing the Env markers of viral tropism, a dataset of sequences (660 strains) was used to analyze the hypothetical ASP involvement in CCR5 (R5) and/or CXCR4 (X4) co‐receptor interaction. Preliminarily, prevalence of ASP and gp120V3 mutations was performed; following association among mutations were elaborate. The classical V3 tropic‐signatures were confirmed, and 36 R5‐ and 22 X4‐tropic ASP mutations were found. Moreover, by analyzing the ASP sequences, 36 out of 179 amino acid positions significantly associated with different co‐receptor usage were found. Several statistically significant associations between gp120V3 and ASP mutations were observed. The dendrogram showed the existence of a cluster associated with R5‐usage and a large cluster associated with X4‐usage. These results show that gp120V3 and specific amino acid changes in ASP are associated together with CXCR4 and/or CCR5‐usage. These findings implement previous observations on unclear ASP functions. J. Med. Virol. 89:112–122, 2017. © 2016 Wiley Periodicals, Inc.
Effects of Curcuma longa rhizome powder on egg quality, performance and some physiological indices of laying hens fed different levels of metabolizable energy
Authors: Mirbod Mahsa , Mahdavi Amir Hossein , Samie Abdol‐Hossein , Mehri Mehran
Published: June 2016

BACKGROUND

High‐energy diets of laying hens may improve roductive performance, although some negative effects may also appear with respect to egg quality and physiological parameters. Curcuma longa rhizome powder (CRP) has beneficial effects on health indices of the birds through antioxidant and antimicrobial properties, especially when the birds experience nutritional stress.

RESULTS

Increasing dietary CRP enhanced egg quality by improving eggshell thickness and hardness but decreasing yolk cholesterol content (P < 0.05). The best feed conversion ratio was obtained in birds fed high‐apparent metabolizable energy (AME) diets supplemented with 2.0 g kg−1 CRP (P < 0.05). Although increasing dietary AME elevated the serum concentration of triglycerides (P < 0.05) and enzymatic activities of alanine aminotransferase and aspartate aminotransferase (P < 0.05), dietary inclusion of CRP alleviates the blood levels of these enzymes (P < 0.01). Low level of dietary CRP boosted the immune responses to Newcastle virus (P < 0.01) and sheep red blood cells (P < 0.05) antigens but decreased the heterophil to lymphocyte ratio (P < 0.05). Inclusion of at least 2.0 g kg−1 CRP in the diet of laying decreased Escherichia coli enumerations in the ileal content (P < 0.01) and improved villus height, crypt depth and goblet cell numbers (P < 0.05).

CONCLUSION

An improvement in the productive performance of laying hens fed high‐energy diets might be associated with decreasing health indices and product quality, which could potentially be amended by nutritional modifications such as incorporating medicinal herbs in the feed. © 2016 Society of Chemical Industry
Spatio‐temporal variability of methane (CH4) concentrations and diffusive fluxes from a tropical coastal embayment surrounded by a large urban area (Guanabara Bay, Rio de Janeiro, Brazil)
Authors: Cotovicz Luiz C. , Knoppers Bastiaan A. , Brandini Nilva , Poirier Dominique , Costa Santos Suzan J. , Abril Gwenaël
Published: June 2016

The increasing concentrations of methane (CH4) in the atmosphere stress the importance of monitoring and quantifying the fluxes from coastal environments. In nine sampling campaigns between 2013 and 2014, we measured the spatial CH4 concentrations, identified major sources and calculated the fluxes at the air‐water interface in an eutrophic tropical embayment, Guanabara Bay, Rio de Janeiro, Brazil. The bay presented high spatial variability of CH4 concentrations, without a significant trend with salinity, but observed the influence of the urban areas at its watershed. Although the more polluted sector of the bay accounts for about 10% of the sampled surface area, it contributed to one half of the bay's total CH4 emissions. In most cases, high CH4 concentrations seemed be sustained by allochtonous sources such as the sewage network and polluted rivers, especially under high accumulated precipitation conditions. In the most stratified area, at the inner and centre of the Bay, CH4 concentrations were not significantly higher in bottom hypoxic waters than in surface waters, suggesting that CH4 diffusion from these sediments was modest, due to the prevalence of sulphate reduction over methanogenesis. Our calculated annual air‐sea fluxes (565–980 μmol m−2 d−1) are well above those of most estuaries worldwide, showing that urban pollution can be an important source of CH4 to the coastal waters and even more significant than the presence of organic‐rich environments, like salt marshes and mangroves. Comparing the greenhouse gas emissions in terms of CO2‐equivalent, CH4 emissions reduced the net CO2 sink in Guanabara Bay by 16%.
One‐Pot Polymerization Syntheses: Incorporating Bioactives into Poly(anhydride‐esters)
Authors: Faig Jonathan J. , Smith Kervin , Moretti Alysha , Yu Weiling , Uhrich Kathryn E.
Published: June 2016

To reduce raw material consumption and increase synthetic efficiency, bioactive‐based poly(anhydride‐esters) containing aliphatic dicarboxylic acid‐linkages and bioactives, salicylic and p‐hydroxybenzyl acid, are synthesized via one‐pot melt‐condensation polymerizations. One‐pot poly(anhydride‐esters) physicochemical characteristics, molecular weight, and thermal properties are analyzed and compared. One‐pot salicylic acid‐based poly(anhydride‐esters) are further evaluated against analogous polymers synthesized via established methods, possessing statistically similar polymer and thermal properties while drastically reducing reaction time and solvent usage. Interestingly, p‐hydroxybenzyl acid‐based poly(anhydride‐ester) synthesis is temperature‐dependent, as higher reaction temperatures facilitate polyester formation. Compared to their poly(anhydride‐ester) analogs, these are found to possess improved thermal properties and higher molecular weight while. Accelerated hydrolytic degradation studies confirm complete bioactive release and polymer degradation. Furthermore, polymer cytotoxicity studies using 3T3 mouse fibroblasts show all polymers to be cytocompatible above therapeutically relevant concentrations. This method demonstrates that the synthesis of high‐yielding monomers can be followed by melt‐condensation polymerization in situ for the synthesis of polyanhydrides and their derivatives.

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Does epicatechin contribute to the acute vascular function effects of dark chocolate? A randomized, crossover study
Authors: Dower James I. , Geleijnse Johanna M. , Kroon Paul A. , Philo Mark , Mensink Marco , Kromhout Daan , Hollman Peter C. H.
Published: June 2016

Scope

Cocoa, rich in flavan‐3‐ols, improves vascular function, but the contribution of specific flavan‐3‐ols is unknown. We compared the effects of pure epicatechin, a major cocoa flavan‐3‐ol, and chocolate.

Methods and results

In a randomized crossover study, twenty healthy men (40–80 years) were supplemented with: (1) 70g dark chocolate (150 mg epicatechin) with placebo capsules; (2) pure epicatechin capsules (2 × 50 mg epicatechin) with 75g white chocolate; and (3) placebo capsules with 75 g white chocolate (0 mg epicatechin). Vascular function (flow‐mediated dilation (FMD) and augmentation index (AIx)) were measured before and 2 hours after interventions. Epicatechin metabolites time‐profiles were measured in blood to calculate the bioavailability. Pure epicatechin did not significantly improve FMD (+0.75%; p = 0.10) or AIx (–2.2%; p = 0.23) compared to placebo. Dark chocolate significantly improved FMD (+0.96%; p = 0.04) and AIx (–4.6%; p = 0.02). Differences in improvements in FMD (+ 0.21%; p = 0.65) or Aix (–2.4%; p = 0.20) between pure epicatechin and dark chocolate were not significant. The bioavailability of epicatechin did not differ between pure epicatechin and dark chocolate (p = 0.14).

Conclusions

Despite differences in epicatechin dose, improvements in vascular function after pure epicatechin and chocolate were similar and the bioavailability did not differ, suggesting a role for epicatechin.
Genealogy of hypoplasticity and barodesy
Authors: Kolymbas Dimitrios , Medicus Gertraud
Published: June 2016

This article is an attempt at providing an insight into the development of hypoplasticity (including barodesy, which is a recent development of hypoplasticity) as a theory elaborated since 1977, when the first version was published by the first author, until present. The multiplicity of the many versions published since then is hard to overlook. This article presents a review and insight into the evolution of a theory and the struggle to formulate a satisfactory constitutive law. Among the many proposed versions, we focus on those ones that can be seen as changes of paradigm. Copyright © 2016 John Wiley & Sons, Ltd.
Single‐step quantitative susceptibility mapping with variational penalties
Authors: Chatnuntawech Itthi , McDaniel Patrick , Cauley Stephen F. , Gagoski Borjan A. , Langkammer Christian , Martin Adrian , Grant P. Ellen , Wald Lawrence L. , Setsompop Kawin , Adalsteinsson Elfar , Bilgic Berkin
Published: June 2016

Quantitative susceptibility mapping (QSM) estimates the underlying tissue magnetic susceptibility from the gradient echo (GRE) phase signal through background phase removal and dipole inversion steps. Each of these steps typically requires the solution of an ill‐posed inverse problem and thus necessitates additional regularization. Recently developed single‐step QSM algorithms directly relate the unprocessed GRE phase to the unknown susceptibility distribution, thereby requiring the solution of a single inverse problem. In this work, we show that such a holistic approach provides susceptibility estimation with artifact mitigation and develop efficient algorithms that involve simple analytical solutions for all of the optimization steps. Our methods employ total variation (TV) and total generalized variation (TGV) to jointly perform the background removal and dipole inversion in a single step. Using multiple spherical mean value (SMV) kernels of varying radii permits high‐fidelity background removal whilst retaining the phase information in the cortex. Using numerical simulations, we demonstrate that the proposed single‐step methods reduce the reconstruction error by up to 66% relative to the multi‐step methods that involve SMV background filtering with the same number of SMV kernels, followed by TV‐ or TGV‐regularized dipole inversion. In vivo single‐step experiments demonstrate a dramatic reduction in dipole streaking artifacts and improved homogeneity of image contrast. These acquisitions employ the rapid three‐dimensional echo planar imaging (3D EPI) and Wave‐CAIPI (controlled aliasing in parallel imaging) trajectories for signal‐to‐noise ratio‐efficient whole‐brain imaging. Herein, we also demonstrate the multi‐echo capability of the Wave‐CAIPI sequence for the first time, and introduce an automated, phase‐sensitive coil sensitivity estimation scheme based on a 4‐s calibration acquisition. Copyright © 2016 John Wiley & Sons, Ltd.
A novel donor–donor polymeric dyad of Poly(3‐hexylthiophene‐block‐oligo(anthracene‐9,10‐diyl): Synthesis, solid‐state packing, and electronic properties
Authors: Ananthakrishnan Soundaram Jeevarathinam , Strain Jacob , Neerudu Sreeramulu Niharika , Mitul Abu , McNamara Louis E. , Iefanova Anastasiia , Hammer Nathan I. , Qiao Qiquan , Rathnayake Hemali
Published: June 2016

A new polymeric dyad of oligo‐anthracene‐block‐poly(3‐hexylthiophene) (Oligo‐ANT‐b‐P3HT) has been synthesized as a donor–donor dyad building block for organic photovoltaics. The polymer dyad and oligomer of anthracene‐9,10‐diyl (Oligo‐ANT) are prepared by Grignard Metathesis. The higher order of crystallinity and molecular chains ordering at solid phase reveal the intrinsic optical and electrical properties of polymeric dyad resulting in relatively higher light harvesting ability compared to the oligo(anthracene‐9,10‐diyl). The UV‐visible spectrum of (Oligo‐ANT‐b‐P3HT) in solution shows broad absorption with two sets of absorption from both anthracene and thiophene core units, covering a wide range of the visible spectrum. The test devices of the blends of polymeric dyad with fullerene C61 (PCBM) show improved photovoltaic performance with a power conversion efficiency of 3.26% upon subjecting to pre‐fabrication thermal treatments. With optimized morphology of the interpenetrating network and the shorter fluorescence lifetime of the annealed dyad/PCBM blends, the effective charge transfer from the donor dyad to PCBM has evidenced. Thus, these studies will allow further synthetic advances to make potential high crystalline polymeric dyads with significantly improved light harvesting capability. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 3032–3045
Interdomain salt‐bridges in the Ebola virus protein VP40 and their role in domain association and plasma membrane localization
Authors: GC Jeevan B. , Johnson Kristen A. , Husby Monica L. , Frick Cary T. , Gerstman Bernard S. , Stahelin Robert V. , Chapagain Prem P.
Published: June 2016

The Ebola virus protein VP40 is a transformer protein that possesses an extraordinary ability to accomplish multiple functions by transforming into various oligomeric conformations. The disengagement of the C‐terminal domain (CTD) from the N‐terminal domain (NTD) is a crucial step in the conformational transformations of VP40 from the dimeric form to the hexameric form or octameric ring structure. Here, we use various molecular dynamics (MD) simulations to investigate the dynamics of the VP40 protein and the roles of interdomain interactions that are important for the domain–domain association and dissociation, and report on experimental results of the behavior of mutant variants of VP40. The MD studies find that various salt‐bridge interactions modulate the VP40 domain dynamics by providing conformational specificity through interdomain interactions. The MD simulations reveal a novel salt‐bridge between D45‐K326 when the CTD participates in a latch‐like interaction with the NTD. The D45‐K326 salt‐bridge interaction is proposed to help domain–domain association, whereas the E76‐K291 interaction is important for stabilizing the closed‐form structure. The effects of the removal of important VP40 salt‐bridges on plasma membrane (PM) localization, VP40 oligomerization, and virus like particle (VLP) budding assays were investigated experimentally by live cell imaging using an EGFP‐tagged VP40 system. It is found that the mutations K291E and D45K show enhanced PM localization but D45K significantly reduced VLP formation.
Phase I Trial of Anti‐PSMA Designer CAR‐T Cells in Prostate Cancer: Possible Role for Interacting Interleukin 2‐T Cell Pharmacodynamics as a Determinant of Clinical Response
Authors: Junghans Richard P. , Ma Qiangzhong , Rathore Ritesh , Gomes Erica M. , Bais Anthony J. , Lo Agnes S.Y. , Abedi Mehrdad , Davies Robin A. , Cabral Howard J. , Al‐Homsi A. Samer , Cohen Stephen I.
Published: June 2016

BACKGROUND

Chimeric antigen receptor (CAR)‐modified “designer” T cells (dTc, CAR‐T) against PSMA selectively target antigen‐expressing cells in vitro and eliminate tumors in vivo. Interleukin 2 (IL2), widely used in adoptive therapies, was proven essential in animal models for dTc to eradicate established solid tumors.

METHODS

Patients under­went chemotherapy condi­tion­ing, followed by dTc dosing under a Phase I escalation with continuous infusion low dose IL2 (LDI). A target of dTc escalation was to achieve ≥20% engraftment of infused activated T cells.

RESULTS

Six patients enrolled with doses prepared of whom five were treated. Patients received 109 or 1010 autologous T cells, achieving expansions of 20–560‐fold over 2 weeks and engraftments of 5–56%. Pharmacokinetic and pharmacodynamic analyses established the impact of conditioning to promote expansion and engraftment of the infused T cells. Unexpectedly, administered IL2 was depleted up to 20‐fold with high engraftments of activated T cells (aTc) in an inverse correlation (P < 0.01). Clinically, no anti‐PSMA toxicities were noted, and no anti‐CAR reactivities were detected post‐treatment. Two‐of‐five patients achieved clinical partial responses (PR), with PSA declines of 50% and 70% and PSA delays of 78 and 150 days, plus a minor response in a third patient. Responses were unrelated to dose size (P = 0.6), instead correlating inversely with engraftment (P = 0.06) and directly with plasma IL2 (P = 0.03), suggesting insufficient IL2 with our LDI protocol to support dTc anti‐tumor activity under optimal (high) dTc engraftments.

CONCLUSIONS

Under a Phase I dose escalation in prostate cancer, a 20% engraftment target was met or exceeded in three subjects with adequate safety, leading to study conclusion. Clinical responses were obtained but were suggested to be restrained by low plasma IL2 when depleted by high levels of engrafted activated T cells. This report presents a unique example of how the pharmaco­dynamics of “drug–drug” interactions may have a critical impact on the efficacy of their co‐application. A new Pilot/Phase II trial is planned to test moderate dose IL2 (MDI) together with high dTc engraftments for anticipated improved therapeutic efficacy. Prostate 76:1257–1270, 2016. © 2016 Wiley Periodicals, Inc.
Bacterial response to nanodiamonds and graphene oxide sheets
Authors: Kromka Alexander , Jira Jaroslav , Stenclova Pavla , Kriha Vitezslav , Kozak Halyna , Beranova Jana , Vretenar Viliam , Skakalova Viera , Rezek Bohuslav
Published: June 2016

Carbon nanomaterials such as nanodiamond (ND) and graphene oxide (GO) attract increasing attention for biomedical applications due their unique and adjustable properties. Here we report on antibacterial activity of NDs and GO as evaluated by bacterial colony counting. ND and GO were used in oxidized (O‐ND, GO) or reduced (H‐ND, rGO) forms. ND or GO are mixed in Mueller–Hinton (MH) broth with Escherichia coli at the concentration of 1 mg ml−1. The resulting suspensions were cultivated for 5 and 24 h at 37 °C in a shaker. After each period, a sample of the suspension was spread on the MH agar and cultivated for 24 h at 37° C. The effect of nanomaterials on colony forming ability (CFA) of E. coli was evaluated and compared with the negative control sample. The most noticeable effect was that after 5 h H‐ND decreased the CFA of E. coli in the MH broth by 60% and GO by 50%. After 24 h, H‐ND decreased CFA by 50%. Other nanomaterials had no statistically significant antibacterial effect. Factors influencing ND and GO antibacterial activity against the E. coli and possibly against other bacteria are discussed.
Synthesis of Multisubstituted Olefins through Regio‐ and Stereoselective Addition of Interelement Compounds Having B–Si, B–B, and Cl–S Bonds to Alkynes, and Subsequent Cross‐Couplings
Authors: Iwasaki Masayuki , Nishihara Yasushi
Published: June 2016

Multisubstituted olefins are fundamental motifs in organic compounds. In this account, we describe the synthesis of organic molecules bearing an olefinic moiety by the transition‐metal‐catalyzed regio‐ and stereoselective addition of a variety of interelement compounds to alkynes. Regio‐ and stereoselective silaboration, diborylation, and chlorothiolation have been achieved by using the transition‐metal catalysts. The subsequent cross‐coupling reactions of the boron‐containing alkenes to install various aryl groups afforded the corresponding tri‐ and tetraarylated olefins. This account describes our research on the highly regio‐ and stereoselective synthesis of multifunctionalized olefins such as tetraarylethenes with four different aryl groups.

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An Integrated Perspective on Foreign Ethical Divestment
Authors: Nyuur Richard B. , Amankwah‐Amoah Joseph , Osabutey Ellis L. C.
Published: June 2016

Much of the existing literature on foreign ethical divestment has been developed in isolation and scattered across multiple disciplines. This article reviews the existing literature on foreign ethical divestment to extract emerging themes and outline new directions for future research. Our review uncovered that foreign ethical divestment decisions can be attributed to macro‐, firm‐, and individual‐level factors. We therefore develop an integrated model to link the dynamics of ethical foreign divestment. The study identified a number of unanswered questions and implications for future research. © 2016 Wiley Periodicals, Inc.
Detection of t(8;14) c-myc/IgH gene rearrangement by long-distance polymerase chain reaction in patients with diffuse large B-cell lymphoma
Authors: Kiaei Arezoo , Onsori Habib , Alijani Aylar , Andalib Sasan , Ghorbian Saeid , Sakhinia Ebrahim
Published: June 2016

Objective/background:

Specific chromosomal translocations are found in human leukemias and lymphomas. These translocations are closely related to particular histological and immunological phenotypes. In Burkitt's lymphoma, translocation t(8;14)(q24;q32), which involves the c-myc gene (8q24) and the immunoglobulin heavy-chain (IgH) locus (14q32), accounts for 90-95% of all chromosomal translocations. This translocation can be found in 2-5% of diffuse large B-cell lymphoma (DLBCL). Long-distance polymerase chain reaction (LD-PCR) assays, which can identify oncogene/Ig gene rearrangement, can detect these fusion genes. The objective of this study was to detect t(8;14) c-myc/IgH gene rearrangement by LD-PCR in patients with DLBCL.

Methods:

In this study, 54 DLBCL cases were tested by LD-PCR with specific primers. LD-PCR was used for two breakpoints in both the IgH gene (joining region and γ switch region) and the myc gene (Exons 2 and 3).

Results:

As much as 1.85% of the samples were positive for the γ constant region and Exon 2 of the myc gene.

Conclusion:

LD-PCR can be used for the detection of t(8;14) c-myc/IgH gene rearrangement in patients with DLBCL.
Heat and mass transfer of a second grade magnetohydrodynamic fluid over a convectively heated stretching sheet
Authors: Das Kalidas , Sharma Ram Prakash , Sarkar Amit
Published: June 2016

The present work is concerned with heat and mass transfer of an electrically conducting second grade MHD fluid past a semi-infinite stretching sheet with convective surface heat flux. The analysis accounts for thermophoresis and thermal radiation. A similarity transformations is used to reduce the governing equations into a dimensionless form. The local similarity equations are derived and solved using Nachtsheim-Swigert shooting iteration technique together with Runge–Kutta sixth order integration scheme. Results for various flow characteristics are presented through graphs and tables delineating the effect of various parameters characterizing the flow. Our analysis explores that the rate of heat transfer enhances with increasing the values of the surface convection parameter. Also the fluid velocity and temperature in the boundary layer region rise significantly for increasing the values of thermal radiation parameter.

Highlights Effect of thermal radiation on second grade fluid in the presence of thermophoresis is studied. The rate of mass transfer increases with the increase of thermophoretic parameter. The rate of heat transfer increases for increasing the values of the surface convection parameter. The temperature profile enhances with increase in the thermal radiation parameter.
The ASEAN Human Rights System: A Critical Analysis
Authors: BUI Hien
Published: June 2016

This article offers a critical analysis of the human rights system established by ASEAN. It first investigates concrete evidence of the system’s ineffectiveness by comparing the cases of Myanmar and Thailand, which illustrate ASEAN’s failure to address human rights violations both before and after the creation of the ASEAN system. It then examines the substantive and procedural limitations of the ASEAN human rights instruments and mechanisms. Specifically, while restrictions on rights and freedoms contained in the instruments undermine the universality of human rights, ASEAN’s mechanisms lack independence and offer only weak protection mandates to address rights violations. In addition, the absence of a judicial body to hear complaints and issue binding remedies makes the system incomplete. The article recommends the creation of an ASEAN court of human rights and suggests changes to the existing instruments and mechanisms that might accommodate the new court.
A Simple Stated Preference Tool for Estimating the Value of Travel Time in Rural Africa
Authors: Cook Joseph , Kimuyu Peter , Blum Annalise G. , Gatua Josephine
Published: June 2016

Despite its importance in benefit-cost analyses in the water supply, transportation, and health care sectors, there are relatively few empirical estimates of the value of travel time savings (VTT) in low-income countries, particularly in rural areas. Analysts instead often rely on a textbook “rule of thumb” of valuing time at 50% of prevailing unskilled wage rates, though these benchmarks have little empirical support in these settings. We estimate the value of travel time through the use of a repeated discrete choice stated preference exercise. We asked 325 rural households in Meru County, Kenya to rank two new hypothetical water sources against their current water source. The two new hypothetical sources were described as safe and reliable to use, but varied only in their distance from the household and the price charged per water container. Results from random-parameters logit models imply an average value of travel time of 18 Ksh/hr, and generally support the 50% rule. These models produce the first individual-level VTT estimates reported in a low-income setting, and indicate statistically-significant heterogeneity in VTTs, though the heterogeneity is not well correlated with observables. A latent-class approach identifies four classes of respondents: one class (about one third of respondents) values time very highly (49 Ksh/hr), one poorer group values time hardly at all (less than 1 Ksh/hr), and two groups value time at approximately 9 Ksh/hr.
Script Generation and Executive Dysfunction in Patients with Anterior and Posterior Brain Lesions
Authors: Emmanouel Anna , Boelen Danielle , Mouza Eirini , Allain Phillipe , Kessels Roy P.C. , Fasotti Luciano
Published: June 2016

Introduction: Studies on script processing have shown inconsistent relations between deficits in script action generation and frontal lobe pathology. Therefore, we investigated which difficulties in script action generation are linked to anterior lesions. Moreover, we explored whether verbal script generation can be predicted by specific executive processes.

Methods: Fifty-two patients with acquired brain injury (mean age: 44.23 years, 30 male/22 female) were included, of whom 30 had anterior and 22 had posterior lesions. Several indices of the Everyday Description Task were investigated: relevant central actions (RCAs); relevant trivial actions (RTAs); relevant and irrelevant intrusions (RI & IRI); sequencing (SEs) and perseverative (PEs) errors. Additionally, fivez-composite scores representing planning, response generation, working memory, inhibition and shifting were calculated. Correlations and multiple linear regression analyses were computed.

Results: Anteriorly lesioned patients produced significantly less RCAs and more PEs and SEs compared to posteriorly damaged patients. No differences were found with RTAs, RI and IRI. RCAs were predicted by planning, response generation and working memory, RI by response generation and working memory, IRI by inhibition, PEs and SEs by response generation and shifting. None of these executive processes predicted RTAs.

Conclusions: Difficulties in RCAs, PEs and SEs are sensitive indicators of anterior brain damage and script generation demands various executive abilities.
Convection at an isothermal wall in an enclosure and establishment of stratification
Authors: Caudwell T. , Flór J.-B. , Negretti M. E.
Published: June 2016

In this experimental–theoretical investigation, we consider a turbulent plume generated by an isothermal wall in a closed cavity and the formation of heat stratification in the interior. The buoyancy of the plume near the wall and the temperature stratification are measured across a vertical plane with the temperature laser induced fluorescence method, which is shown to be accurate and efficient (precision of $0.2\,^{\circ }$C) for experimental studies on convection. The simultaneous measurement of the velocity field with particle image velocimetry allows for the calculation of the flow characteristics such as the Richardson number and Reynolds stress. This enables us to give a refined description of the wall plume, as well as the circulation and evolution of the stratification in the interior. The wall plume is found to have an inner layer close to the heated boundary with a laminar transport of hardly mixed fluid which causes a relatively warm top layer and an outer layer with a transition from laminar to turbulent at a considerable height. The measured entrainment coefficient is found to be dramatically influenced by the increase in stratification of the ambient fluid. To model the flow, the entrainment model of Morton, Taylor & Turner (Proc. R. Soc. Lond. A, vol. 234 (1196), 1956, pp. 1–23) has first been adapted to the case of an isothermal wall. Differences due to their boundary condition of a constant buoyancy flux, modelled with salt by Cooper & Hunt (J. Fluid Mech., vol. 646, 2010, pp. 39–58), turn out to be small. Next, to include the laminar–turbulent transition of the boundary layer, a hybrid model is constructed which is based on the similarity solutions reported by Worster & Leitch (J. Fluid Mech., vol. 156, 1985, pp. 301–319) for the laminar part and the entrainment model for the turbulent part. Finally, the observed variation of the global entrainment coefficient, which is due to the increased presence of an upper stratified layer with a relatively low entrainment coefficient, is incorporated into both models. All models show reasonable agreement with experimental measurements for the volume, momentum and buoyancy fluxes as well as for the evolution of the stratification in the interior. In particular, the introduction of the variable entrainment coefficient improves all models significantly.
Spectral modelling for passive scalar dynamics in homogeneous anisotropic turbulence
Authors: Briard A. , Gomez T. , Cambon C.
Published: June 2016

The present work aims at developing a spectral model for a passive scalar field and its associated scalar flux in homogeneous anisotropic turbulence. This is achieved using the paradigm of eddy-damped quasi-normal Markovian (EDQNM) closure extended to anisotropic flows. In order to assess the validity of this approach, the model is compared to several detailed direct numerical simulations (DNS) and experiments of shear-driven flows and isotropic turbulence with a mean scalar gradient at moderate Reynolds numbers. This anisotropic modelling is then used to investigate the passive scalar dynamics at very high Reynolds numbers. In the framework of homogeneous isotropic turbulence submitted to a mean scalar gradient, decay and growth exponents for the cospectrum and scalar energies are obtained analytically and assessed numerically thanks to EDQNM closure. With the additional presence of a mean shear, the scaling of the scalar flux and passive scalar spectra in the inertial range are investigated and confirm recent theoretical predictions. Finally, it is found that, in shear-driven flows, the small scales of the scalar second-order moments progressively return to isotropy when the Reynolds number increases.