bluuebunny/crossref_metadata_2025 huggingface dataset:
Sensitivity of net thermal flux to the abundance of trace gases in the lower atmosphere of Venus
Authors: Lee Yeon Joo , Sagawa Hideo , Haus Rainer , Stefani Stefania , Imamura Takeshi , Titov Dmitrij V. , Piccioni Giuseppe
Published: August 2016

We calculated the net thermal flux in the atmosphere of Venus from the surface to 100 km altitude. Our atmospheric model was carefully constructed especially for altitudes below the clouds (<48 km), using recent CO2 absorption data. It includes updated collision‐induced absorptions in the <250 cm−1, 1200–1500 cm−1, and 2650–3130 cm−1 wave number ranges. We studied sensitivity of the net thermal flux below the clouds on the abundances of trace gases that were varied within the range reported by observations. Our results reveal a considerable effect of trace gases on radiative budget. We successfully simulate net thermal flux profiles measured in situ by the Night and North probes of Pioneer Venus using 20–50 ppmv H2O, suggesting that the high H2O abundance of 200 ppmv derived in the earlier analysis is not required. Our sensitivity study shows that the trace gases SO2, H2O, and OCS are effective thermal agents, while CO and HCl influences are rather weak. We suggest that the influence of the former three gases should be taken into account to estimate the net radiative energy in the deep atmosphere.
Influence of ionic liquid composition on the stability of polyvinyl chloride‐based ionic liquid inclusion membranes in aqueous solution
Authors: Tomás‐Alonso Francisca , Rubio Aurora M. , Giménez Alfonso , de los Ríos Antonia P. , Salar‐García Maria J. , Ortiz‐Martínez Victor M. , Hernández‐Fernández Francisco J.
Published: August 2016

Membrane technology has gained significant importance with the incorporation of ionic liquids into their structure. This work shows the influence of ionic liquid composition on the stability of PVC‐based polymer ionic liquid inclusion membranes (PILIMs) in aqueous solution. Among the ILs investigated, those membranes which contain between 20 and 30%w/w of the least soluble, [OMIM+][PF6−] and [OMIM+][Ntf2−], exhibit losses of IL lower than 10%. For both ILs, the amount immobilized was maximum for the membranes with 30%w/w of IL (0.0838 and 0.0832 g, respectively). On the contrary, the ionic liquid loss increases as its solubility in water increase, reaching 99.52% when PILIMs are prepared with 70%w/w of [OMIM+][BF4−]. The results demonstrate that the stability of PILIMs depends on the solubility of the IL in the surrounding phase and the specific interaction between the IL and the polymeric support for PVC‐to‐IL ratios higher than 30%w/w. © 2016 American Institute of Chemical Engineers AIChE J, 63: 770–780, 2017
Rapidly progressive acute chest syndrome in individuals with sickle cell anemia: a distinct acute chest syndrome phenotype
Authors: Chaturvedi Shruti , Ghafuri Djamila L. , Glassberg Jeffrey , Kassim Adetola A. , Rodeghier Mark , DeBaun Michael R.
Published: August 2016

Current definitions of acute chest syndrome (ACS) in sickle cell anemia (SCA) do not account for rapid progression of respiratory compromise. In this two‐center retrospective cohort study, we tested the hypothesis that in children and adults with ACS and respiratory failure (≤24 hours after onset of respiratory symptoms) have a distinct ACS phenotype associated with multiorgan failure when compared to those with ACS that have a more subacute and protracted course. We identified 173 individuals (97 children <20 years and 76 adults ≥20 years) with SCA and at least one episode of ACS. Only one ACS episode was considered per individual. Rapidly progressive ACS occurred in 21% (n = 16) of adults, but only 2.1% (n = 2) of children. Compared to adults without rapidly progressive ACS, adults with rapidly progressive ACS more frequently developed acute kidney injury (68.8% vs. 3.3%, P < 0.001), hepatic dysfunction (75.0% vs. 15.0%, P < 0.001), altered mental status (43.8% vs. 11.7%, P < 0.001), multiorgan failure (93.8% vs. 10%, P < 0.001), and death (6.3% vs. 0%, P = 0.05). Clinical and laboratory covariates that were evaluable on the first day of respiratory symptoms were evaluated to identify predictors of rapidly progressive ACS. On multivariable analysis, decline in platelet count at presentation was the only predictor of rapidly progressive ACS [odds ratio 4.82 (95% CI 1.20–19.39), P = 0.027]. In conclusion, rapidly progressive ACS is a distinct phenotype that occurs more frequently in adults, is preceded by thrombocytopenia, and is associated with multiorgan failure. Am. J. Hematol. 91:1185–1190, 2016. © 2016 Wiley Periodicals, Inc.
Morphology modulation of gas‐foamed, micrometric, hollow polystyrene particles
Authors: Contaldi Vincenzo , Imperato Luigi , Orsi Silvia , Di Maio Ernesto , Netti Paolo Antonio , Iannace Salvatore
Published: August 2016

In this article, we reports the effects of the processing conditions on the morphological and hollow attributes of polystyrene micrometric hollow particles produced by the use of a recently developed technique based on the gas foaming of spherical, dense particles. By modulating the foaming temperature and saturation pressure, we produced hollow particles with different attributes in terms of hollow dimensions, eccentricity, and open–close features. The results from these small systems were compared, and we found agreement with what is typically observed in bulk polymeric foaming, for example, an increase in the foaming efficiency with saturation pressure and the nonmonotonic effect of temperature. Furthermore, we observed an increase in the hollow number when using nucleating agents with respect to the neat polymer and when using nitrogen with respect to carbon dioxide as the blowing agent. The effects of particle manipulation before foaming to achieve hollow elongated or distorted particles are also reported. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 44236.
Evaluation of mechanical properties of Al2O3 and TiO2 nano filled enhanced glass fiber reinforced polymer composites
Authors: Nayak Ramesh Kumar , Mahato K. K. , Routara B. C. , Ray Bankim Chandra
Published: August 2016

The present investigation has emphasized the implication of nano fillers (Al2O3 and TiO2) combined additions in glass fiber reinforced polymer composite on the variation of interlaminar shear strength (ILSS). The experiment has also investigated the effect of crosshead speed during testing and subsequent fracture surface analysis to find out the possible failure modes by scanning electron micrograph examinations. Loss and storage modulus have been experimentally evaluated to support the new findings in the present experimental design. It has been observed that the concurrent presence of nano Al2O3 and TiO2 fillers improves the ILSS. Dynamic mechanical thermal analysis indicated that, the addition of nano fillers reduces the storage and loss modulus of the composites. However, glass transition temperature has not been altered by the nano fillers addition. Box–Behnken design of experiment of surface response methodology has been adopted to optimize the filler content and crosshead speed. A second order mathematical model has been developed and the predicted optimum input parameters are 0.3 wt % Al2O3, 0.15 wt %TiO2, and 500 mm/min crosshead speed. Furthermore, the model predicted results are compared with experimental one and found a close agreement between them. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 44274.
Utilization of tall oil to enhance natural fibers for composite applications and production of a bioplastic
Authors: George Michael , Mussone Paolo G. , Bressler David C.
Published: August 2016

Tall oil is one of the side products from the kraft pulping process of lignocellulosic material. The most abundant acid found in this crude viscous material is abietic acid. Strangely, in the past, the utilization of tall oil has been limited to incineration for cogeneration of power. In this study, tall oil rosin acids (TORAs) were used in two different applications. First, it was used to enhance the hydrophobicity and thermal properties of hemp fibers. Second, TORAs were used to supplement epoxy for the production of a polymeric material. The reaction conditions from a model study were mimicked using a crude tall oil rosin acid mixture to enhance hemp fibers. Treated hemp fibers were characterized with increased surface hydrophobicity and improved thermal properties. Also, IR and X‐ray photoelectron spectroscopy confirmed successful chemical modification and grafting of carbon rich moieties onto the surface of the fibers, respectively. Furthermore, TORAs were used to supplement epoxy resin and produced plastics with comparable properties to pure epoxy based plastics. Specifically, 25% (w/w) replacement exhibited little difference in thermal stability and curing when compared to virgin epoxy plastics. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 44327.
Real‐time monitoring and control of the load phase of a protein A capture step
Authors: Rüdt Matthias , Brestrich Nina , Rolinger Laura , Hubbuch Jürgen
Published: August 2016

The load phase in preparative Protein A capture steps is commonly not controlled in real‐time. The load volume is generally based on an offline quantification of the monoclonal antibody (mAb) prior to loading and on a conservative column capacity determined by resin‐life time studies. While this results in a reduced productivity in batch mode, the bottleneck of suitable real‐time analytics has to be overcome in order to enable continuous mAb purification. In this study, Partial Least Squares Regression (PLS) modeling on UV/Vis absorption spectra was applied to quantify mAb in the effluent of a Protein A capture step during the load phase. A PLS model based on several breakthrough curves with variable mAb titers in the HCCF was successfully calibrated. The PLS model predicted the mAb concentrations in the effluent of a validation experiment with a root mean square error (RMSE) of 0.06 mg/mL. The information was applied to automatically terminate the load phase, when a product breakthrough of 1.5 mg/mL was reached. In a second part of the study, the sensitivity of the method was further increased by only considering small mAb concentrations in the calibration and by subtracting an impurity background signal. The resulting PLS model exhibited a RMSE of prediction of 0.01 mg/mL and was successfully applied to terminate the load phase, when a product breakthrough of 0.15 mg/mL was achieved. The proposed method has hence potential for the real‐time monitoring and control of capture steps at large scale production. This might enhance the resin capacity utilization, eliminate time‐consuming offline analytics, and contribute to the realization of continuous processing. Biotechnol. Bioeng. 2017;114: 368–373. © 2016 The Authors. Biotechnology and Bioengineering published by Wiley Periodicals, Inc.
Non‐chromatographic bioprocess engineering of a recombinant mineralizing protein for the synthesis of silica nanocapsules
Authors: Wibowo David , Yang Guang‐Ze , Middelberg Anton P.J. , Zhao Chun‐Xia
Published: August 2016

Inspired by nature, synthetic mineralizing proteins have been developed to synthesize various structures of silica‐based nanomaterials under environmentally friendly conditions. However, the development of bioprocesses able to assist in the translation of these new materials has lagged the development of the materials themselves. The development of cost‐effective and scalable bioprocesses which minimize reliance on chromatography to recover biomolecules from microbial cell factories remains a significant challenge. This paper reports a simplified purification process for a recently reported recombinant catalytic modular (D4S2) protein (M(DPSMKQLADS‐LHQLARQ‐VSRLEHA)4EPSRKKRKKRKKRKKGGGY; M 13.3 kDa; pI 10.9), which combines a variant of the established designer biosurfactant protein DAMP4 with a new biomimetic sequence (RKKRKKRKKRKKGGGY), providing for a bi‐modular functionality (emulsification and biosilicification). The four‐helix bundle structure of the protein has been demonstrated to remain stable and soluble under high temperature and high salt conditions, which confers simplified bioprocessing character. However, the high positive charge on the biosilification sequence necessitates removal of DNA contaminants from crude cell‐extract at an early stage in the process by adding poly(ethyleneimine) (PEI). In this process, cellular protein contaminants were selectively precipitated by adding Na2SO4 to the protein mixture up to a high concentration (1 M) and mixed at high temperature (90°C, 5 min) where D4S2 remained stable and soluble due to its four‐helix bundle structure. Further increase of the Na2SO4 concentration to 1.8 M precipitated, thus separated, D4S2 from residual PEI. The overall yield of the protein D4S2 was 28.8 mg per 800 mL cells (final cultivation OD600 ∼2) which gives an approximate 79% D4S2‐protein yield. In comparison with the previously reported chromatographic purification of D4S2 protein (Wibowo et al., 2015), the final yield of D4S2 protein is increased fourfold in this study. The bio‐produced protein D4S2 was proved to retain it emulsification and biosilicification functionalities enabling the formation of oil‐core silica‐shell nanocapsules at near‐neutral pH and room temperature without the use of any toxic organic solvents, confirming no adverse effects due to bioprocess simplification. This work demonstrates that, through proper bioprocess engineering including the removal of critical contaminants such as DNA, a more efficient, simple, and scalable purification process can be used for the high‐yield bio‐production of a recombinant templating protein useful in the synthesis of bio‐inspired nanomaterials. This simplified process is expected to be easily adapted to recover other mineralizing helix bundle‐based functional proteins from microbial cell factories. Biotechnol. Bioeng. 2017;114: 335–343. © 2016 Wiley Periodicals, Inc.
Constructing “quantized quorums” to guide emergent phenotypes through quorum quenching capsules
Authors: Zargar Amin , Quan David N. , Abutaleb Nadia , Choi Erica , Terrell Jessica L. , Payne Gregory F. , Bentley William E.
Published: August 2016

Microbial cells have for many years been engineered to facilitate
efficient production of biologics, chemicals, and other compounds. As
the “metabolic” burden of synthetic genetic components can impair cell performance, microbial consortia are being developed to piece together specialized subpopulations that collectively produce desired products. Their use, however, has been limited by the inability to control their composition and function. One approach to leverage advantages of the division of labor within consortia is to link microbial subpopulations together through quorum sensing (QS) molecules. Previously, we directed the assembly of “quantized quorums,” microbial subpopulations that are parsed through QS activation, by the exogenous addition of QS signal molecules to QS synthase mutants. In this work, we develop a more facile and general platform for creating “quantized quorums.” Moreover, the methodology is not restricted to QS‐mutant populations. We constructed quorum quenching capsules that partition QS‐mediated phenotypes into discrete subpopulations. This compartmentalization guides QS subpopulations in a dose‐dependent manner, parsing cell populations into activated or deactivated groups. The capsular “devices” consist of polyelectrolyte alginate–chitosan beads that encapsulate high‐efficiency (HE) “controller cells” that, in turn, provide rapid uptake of the QS signal molecule AI‐2 from culture fluids. In this methodology, instead of adding AI‐2 to parse QS‐mutants into subpopulations, we engineered cells to encapsulate them into compartments, and they serve to deplete AI‐2 from wild‐type populations. These encapsulated bacteria therefore, provide orthogonal control of population composition while allowing only minimal interaction with the product‐producing cell population or consortia. We envision that compartmentalized control of QS should have applications in both metabolic engineering and human disease. Biotechnol. Bioeng. 2017;114: 407–415. © 2016 Wiley Periodicals, Inc.
Enhanced itaconic acid production by self‐assembly of two biosynthetic enzymes in Escherichia coli
Authors: Yang Zhongwei , Gao Xin , Xie Hui , Wang Fengqing , Ren Yuhong , Wei Dongzhi
Published: August 2016

Here, we described a novel strategy for the production of itaconic acid in Escherichia coli by self‐assembly of aconitase (ACO) and cis‐aconitate decarboxylase (CAD) existing in the metabolic pathway of itaconic acid via the protein–peptide interactions of PDZ domain and PDZ ligand. Co‐expression of ACO and CAD in E. coli (uCA) resulted in low levels of itaconate (117.25 mg/L) after 48 h fermentation while the itaconate titre was significantly improved up to 222.15 mg/L by self‐assembly of ACO‐PDZ (APd) and CAD‐PDZlig (CPl) in E. coli (sPP) under the same conditions. To further confirm the effect of self‐assembly, the itaconate catalyzed from sodium citrate was determined. The sPP was extra efficacious in the early catalytic period, showing approximately threefold itaconate yields increased after 2 h catalysis, when compared to uCA. Furthermore, the itaconate production of sPP was increased from 5 to 8.7 g/L after 30 h of reaction compared to uCA. This self‐assembly strategy showed remarkable potential for the further improvement of itaconate production. Biotechnol. Bioeng. 2017;114: 457–462. © 2016 Wiley Periodicals, Inc.
MiR‐154 directly suppresses DKK2 to activate Wnt signaling pathway and enhance activation of cardiac fibroblasts
Authors: Sun Li‐Ye , Bie Zi‐Dong , Zhang Chuan‐Huan , Li Hua , Li Liu‐Dong , Yang Jun
Published: August 2016

Excessive proliferation of cardiac fibroblasts (CFs) and their transdifferentiation into myofibroblasts leads to expression of α‐smooth muscle actin (α‐SMA), as well as excessive synthesis and secretion of collagens. This process represents an important pathological basis for myocardial fibrosis (MF). MicroRNA (miR)‐154 and the Wnt signaling pathway play key roles in the above process, although their specific interactions are poorly understood. After transfecting CFs with miR‐154 mimics or inhibitors, miR‐154 was found to inhibit the expression of Dickkopf‐related protein 2 (DKK2), while miR‐154 inhibitors upregulated DKK2 expression in a Western blot analysis. In a subsequent dual‐luciferase activity assay, direct binding of miR‐154 to DKK2 was detected. Further experiments demonstrated that transfection of DKK2 siRNA or miR‐154 resulted in increased levels of β‐catenin, α‐SMA, and collagens I and III. Moreover, these changes were observed in association with increases in CF proliferation and migration, and reduced apoptosis. Conversely, transfection of miR‐154 inhibitors or DKK2 overexpression vector resulted in lower expression levels of β‐catenin, α‐SMA, and collagens I and III, suppressed cell proliferation and migration, and enhanced apoptosis. Furthermore, in each assay, when the DKK2 overexpression vector and miR‐154 mimics were co‐transfected, the functions of each component were counteracted by the other. Therefore, in CFs, targeting of DKK2 by miR‐154 leads to upregulation of β‐catenin expression and activation of the classical Wnt signaling pathway and CFs. These results suggest new targets for the clinical treatment of MF and ischemic heart disease.
VEGF expression is regulated by HIF‐1α and ARNT in 3D KYSE‐70, esophageal cancer cell spheroids
Authors: Terashima Jun , Sampei Satoko , Iidzuka Mei , Ohsakama Ayumi , Tachikawa Chie , Satoh Junya , Kudo Kenzo , Habano Wataru , Ozawa Shogo
Published: August 2016

In 3D cultured cell systems, the cells form 3D spheroids that mimic cancer cell spheroids in vivo. Cancer cells form cell spheroids as they grow. The in vivo spheroids do not contain a vascular network; therefore, oxygen and nutrition supplies are insufficient. Specifically, the cells in the core region of the cluster are exposed to higher stress levels than the cells in the outer spheroid layer. As a result, the cells in the spheroid are exposed to low nutrition and hypoxia conditions. To overcome these shortages, angiogenesis is induced in cancer spheroids in vivo. Vascular endothelial growth factor (VEGF) is an important molecule involved in angiogenesis. VEGF is secreted by cancer cells in vivo in response to stress conditions such as hypoxia. VEGF expression in cancer cells is mediated by hypoxia‐inducible factor 1α (HIF1α), which accumulates in cancer cells during hypoxia. In this report, we show that VEGF expression is regulated by HIF1α and that VEGF is secreted to the outside of the spheroid in vitro. Several investigators have reported that HIF1α forms a protein–protein complex with aryl hydrocarbon receptor translocator (ARNT). We report here that not only HIF1α but also ARNT regulates VEGF expression in 3D cancer spheroids. Our results suggest the utility of the in vitro 3D cancer spheroid model for investigating angiogenesis in cancerous tissues.
Identification from step response – The integral equation approach
Authors: Ahmed Salim
Published: August 2016

An overview of identification of continuous‐time models from step responses using the integral equation approach is presented. Both open loop and closed loop identification as well as identification of multiple‐input‐multiple‐output (MIMO) models are considered. Solutions to practical implementation problems are provided and methods for identification with transient initial conditions using raw data as well as estimation algorithms in the presence of disturbances are outlined. The methodologies are presented in a simplified way using the example of a first order model; however, the algorithms are applicable for models with higher orders. Solution techniques for the estimation equations are also discussed. Identification results under different experimental conditions and data quality are presented to demonstrate the performance of the algorithms. A number of experimental and simulation examples are presented to demonstrate the applicability of the approach.
Convergence of the Two‐Dimensional Dynamic Ising‐Kac Model to
Authors: Mourrat Jean-Christophe , Weber Hendrik
Published: August 2016

The Ising‐Kac model is a variant of the ferromagnetic Ising model in which each spin variable interacts with all spins in a neighborhood of radius γ− 1 for around its base point. We study the Glauber dynamics for this model on a discrete two‐dimensional torus for a system size and for an inverse temperature close to the critical value of the mean field model. We show that the suitably rescaled coarse‐grained spin field converges in distribution to the solution of a nonlinear stochastic partial differential equation.

This equation is the dynamic version of the quantum field theory, which is formally given by a reaction‐diffusion equation driven by an additive space‐time white noise. It is well‐known that in two spatial dimensions such equations are distribution valued and a Wick renormalization has to be performed in order to define the nonlinear term. Formally, this renormalization corresponds to adding an infinite mass term to the equation. We show that this need for renormalization for the limiting equation is reflected in the discrete system by a shift of the critical temperature away from its mean field value.© 2016 by the authors. Communications on Pure and Applied Mathematics is published by Wiley Periodicals, Inc., on behalf of the Courant Institute of Mathematics.
Biomedical Innovation: Lessons From the Past and Perspectives for the Future
Authors: Munos BH
Published: August 2016

Back around the turn of the millennium, the future of the pharmaceutical industry was bright. Amazing technologies were converging to enable a top‐to‐bottom reengineering of drug research and development (R&D). The “omics,” combinatorial chemistry, high‐throughput screening, robotic automation, and systems biology, promised to bring order and method to drug research's bewildering complexity. Pharmaceutical executives—many of whom were ill at ease with their scientists' freewheeling ways—were excited. Gushing with an enthusiasm that was typical of the times, a former industry Chief Executive Officer spoke glowingly of the launch of “two to three new blockbusters… each year” driving a quadrupling of revenues.
Authenticity screening of seized whiskey samples using electrophoresis microchips coupled with contactless conductivity detection
Authors: Rezende Kariolanda C. A. , Moreira Roger Cardoso , Logrado Lucio Paulo Lima , Talhavini Márcio , Coltro Wendell K. T.
Published: August 2016

This report describes for the first time the use of microchip electrophoresis (ME) devices integrated with capacitively coupled contactless conductivity detection (C4D) to investigate the authenticity of seized whiskey samples, which were probably adulterated by simple dilution with tap water. The proposed microfluidic platform was explored for the monitoring of anionic species (Cl− and F−) in both original and tampered samples. The best separations were achieved within 70 s using a running buffer composed of lactic acid and histidine (pH = 5.9). ME‐C4D devices were used to analyze samples from three different brands (five samples each). Based on the presence of inorganic anions like Cl−, F−, SO42− and NO2− in different amounts, the authenticity of seized whiskeys was compared to original samples. According to the reported data, the proposed microfluidic platform can be useful to help regulatory authorities in the investigation and monitoring of authenticity of commercialized whiskey beverages.
Meta‐analysis of psychophysiological interactions: Revisiting cluster‐level thresholding and sample sizes
Authors: Smith David V. , Delgado Mauricio R.
Published: August 2016

Within the neuroimaging community, coordinate based meta‐analyses (CBMAs) are essential for aggregating findings across studies and testing whether those studies report similar anatomical locations. This approach has been predominantly applied to studies that focus on whether activation of a brain region is associated with a given psychological process. In a recent paper, we used CBMA to examine a distinct set of studies—that is, those focusing on whether connectivity between brain regions is modulated by a given psychological process (Smith et al. [2016]: Hum Brain Mapp 37:2904–2917). Specifically, we reviewed 284 studies examining brain connectivity with psychophysiological interactions (PPI). Our meta‐analytic results indicated that PPI yields connectivity patterns that are consistent across studies and that can be specific for a given psychological process and seed region. After publication of our findings, we learned that the analysis software we used to conduct our CBMAs (GingerALE v2.3.3) contained an implementation error that led to results that were more liberal than intended. Here, we comment on the impact of this implementation error on the results of our paper, new recommendations for sample sizes in CBMAs, and the importance of communication between software users and developers. We show that our key claims are supported in a reanalysis and that our results are robust to new guidelines on sample sizes. Hum Brain Mapp 38:588–591, 2017. © 2016 Wiley Periodicals, Inc.
Interictal activity is an important contributor to abnormal intrinsic network connectivity in paediatric focal epilepsy
Authors: Shamshiri Elhum A. , Tierney Tim M. , Centeno Maria , St Pier Kelly , Pressler Ronit M. , Sharp David J , Perani Suejen , Cross J Helen , Carmichael David W.
Published: August 2016

Patients with focal epilepsy have been shown to have reduced functional connectivity in intrinsic connectivity networks (ICNs), which has been related to neurocognitive development and outcome. However, the relationship between interictal epileptiform discharges (IEDs) and changes in ICNs remains unclear, with evidence both for and against their influence. EEG‐fMRI data was obtained in 27 children with focal epilepsy (mixed localisation and aetiologies) and 17 controls. A natural stimulus task (cartoon blocks verses blocks where the subject was told “please wait”) was used to enhance the connectivity within networks corresponding to ICNs while reducing potential confounds of vigilance and motion. Our primary hypothesis was that the functional connectivity within visual and attention networks would be reduced in patients with epilepsy. We further hypothesized that controlling for the effects of IEDs would increase the connectivity in the patient group. The key findings were: (1) Patients with mixed epileptic foci showed a common connectivity reduction in lateral visual and attentional networks compared with controls. (2) Having controlled for the effects of IEDs there were no connectivity differences between patients and controls. (3) A comparison within patients revealed reduced connectivity between the attentional network and basal ganglia associated with interictal epileptiform discharges. We also found that the task activations were reduced in epilepsy patients but that this was unrelated to IED occurrence. Unexpectedly, connectivity changes in ICNs were strongly associated with the transient effects of interictal epileptiform discharges. Interictal epileptiform discharges were shown to have a pervasive transient influence on the brain's functional organisation. Hum Brain Mapp 38:221–236, 2017. © 2016 Wiley Periodicals, Inc.
FANCM c.5101C>T mutation associates with breast cancer survival and treatment outcome
Authors: Kiiski Johanna I. , Fagerholm Rainer , Tervasmäki Anna , Pelttari Liisa M. , Khan Sofia , Jamshidi Maral , Mantere Tuomo , Pylkäs Katri , Bartek Jiri , Bartkova Jirina , Mannermaa Arto , Tengström Maria , Kosma Veli‐Matti , Winqvist Robert , Kallioniemi Anne , Aittomäki Kristiina , Blomqvist Carl , Nevanlinna Heli
Published: August 2016

Breast cancer (BC) is a heterogeneous disease, and different tumor characteristics and genetic variation may affect the clinical outcome. The FANCM c.5101C > T nonsense mutation in the Finnish population associates with increased risk of breast cancer, especially for triple‐negative breast cancer patients. To investigate the association of the mutation with disease prognosis, we studied tumor phenotype, treatment outcome, and patient survival in 3,933 invasive breast cancer patients, including 101 FANCM c.5101C > T mutation carriers and 3,832 non‐carriers. We also examined association of the mutation with nuclear immunohistochemical staining of DNA repair markers in 1,240 breast tumors. The FANCM c.5101C > T mutation associated with poor 10‐year breast cancer‐specific survival (hazard ratio (HR)=1.66, 95% confidence interval (CI) 1.09–2.52, p = 0.018), with a more pronounced survival effect among familial cases (HR = 2.93, 95% CI 1.5–5.76, p = 1.80 × 10−3). Poor disease outcome of the carriers was also found among the estrogen receptor (ER) positive subgroup of patients (HR = 1.8, 95% CI 1.09–2.98, p = 0.021). Reduced survival was seen especially among patients who had not received radiotherapy (HR = 3.43, 95% CI 1.6–7.34, p = 1.50 × 10−3) but not among radiotherapy treated patients (HR = 1.35, 95% CI 0.82–2.23, p = 0.237). Significant interaction was found between the mutation and radiotherapy (p = 0.040). Immunohistochemical analyses show that c.5101C > T carriers have reduced PAR‐activity. Our results suggest that FANCM c.5101C > T nonsense mutation carriers have a reduced breast cancer survival but postoperative radiotherapy may diminish this survival disadvantage.
Higher expression of XPF is a critical factor in intrinsic chemotherapy resistance of human renal cell carcinoma
Authors: Zhang Qiao , Shi Jiazhong , Yuan Fang , Wang Huanhuan , Fu Weihua , Pan Jinhong , Huang Yaqin , Yu Jin , Yang Jin , Chen Zhiwen
Published: August 2016

Human renal cancer is extremely resistant to chemotherapy and radiation therapy. This clinical characteristic reduces the efficacy of chemotherapeutic agents in the treatment of recurrence or metastasis following surgical resection. Understanding the mechanism of chemotherapy resistance in renal cell carcinoma remains a significant challenge. In this study, we have shown that varied level of XPF expression was organ‐tissue specific by comparing human renal cancer, bladder cancer, testicular cancer and their normal tissue counterparts, respectively. The expression of XPF was significantly higher in renal cancer than in bladder cancer and testicular cancer and correlated with the clinical characteristic of their chemotherapeutics sensitivity. These novel findings proposed that the intrinsic chemoresistance of human renal cell carcinomas might be derived from the high level of XPF expression. In a panel of five cancer cell lines, decreasing cisplatin sensitivity correlated with increasing levels of XPF expression. Knockdown of XPF expression not only increased sensitivity of renal carcinoma cells to cisplatin treatment by affecting the DNA damage response, including DNA repair, cell cycle regulation and apoptosis, but also increased senescence of renal cancer cell. Furthermore, experiment in vivo confirmed that silenced XPF significantly increased the sensitivity and survival following treatment with cisplatin in xenograft mice bearing renal cell tumor. These findings firstly uncover a partial mechanism of intrinsic chemoresistance in renal cancer and may provide a new approach to break through the obstacle of intrinsic chemoresistance by targeting the XPF protein with a potential new inhibitor.
Heparan sulfate proteoglycans mediate renal carcinoma metastasis
Authors: Qazi Henry , Shi Zhong‐Dong , Song Jonathan W. , Cancel Limary M. , Huang Peigen , Zeng Ye , Roberge Sylvie , Munn Lance L. , Tarbell John M.
Published: August 2016

The surface proteoglycan/glycoprotein layer (glycocalyx) on tumor cells has been associated with cellular functions that can potentially enable invasion and metastasis. In addition, aggressive tumor cells with high metastatic potential have enhanced invasion rates in response to interstitial flow stimuli in vitro. Our previous studies suggest that heparan sulfate (HS) in the glycocalyx plays an important role in this flow mediated mechanostransduction and upregulation of invasive and metastatic potential. In this study, highly metastatic renal cell carcinoma cells were genetically modified to suppress HS production by knocking down its synthetic enzyme NDST1. Using modified Boyden chamber and microfluidic assays, we show that flow‐enhanced invasion is suppressed in HS deficient cells. To assess the ability of these cells to metastasize in vivo, parental or knockdown cells expressing fluorescence reporters were injected into kidney capsules in SCID mice. Histological analysis confirmed that there was a large reduction (95%) in metastasis to distant organs by tumors formed from the NDST1 knockdown cells compared to control cells with intact HS. The ability of these cells to invade surrounding tissue was also impaired. The substantial inhibition of metastasis and invasion upon reduction of HS suggests an active role for the tumor cell glycocalyx in tumor progression.
Effects of nanotopography on the in vitro hemocompatibility of nanocrystalline diamond coatings
Authors: Skoog Shelby A. , Lu Qijin , Malinauskas Richard A. , Sumant Anirudha V. , Zheng Jiwen , Goering Peter L. , Narayan Roger J. , Casey Brendan J.
Published: August 2016

Nanocrystalline diamond (NCD) coatings have been investigated for improved wear resistance and enhanced hemocompatibility of cardiovascular devices. The goal of this study was to evaluate the effects of NCD surface nanotopography on in vitro hemocompatibility. NCD coatings with small (NCD‐S) and large (NCD‐L) grain sizes were deposited using microwave plasma chemical vapor deposition and characterized using scanning electron microscopy, atomic force microscopy, contact angle testing, and Raman spectroscopy. NCD‐S coatings exhibited average grain sizes of 50–80 nm (RMS 5.8 nm), while NCD‐L coatings exhibited average grain sizes of 200–280 nm (RMS 23.1 nm). In vitro hemocompatibility testing using human blood included protein adsorption, hemolysis, nonactivated partial thromboplastin time, platelet adhesion, and platelet activation. Both NCD coatings demonstrated low protein adsorption, a nonhemolytic response, and minimal activation of the plasma coagulation cascade. Furthermore, the NCD coatings exhibited low thrombogenicity with minimal platelet adhesion and aggregation, and similar morphological changes to surface‐bound platelets (i.e., activation) in comparison to the HDPE negative control material. For all assays, there were no significant differences in the blood–material interactions of NCD‐S versus NCD‐L. The two tested NCD coatings, regardless of nanotopography, had similar hemocompatibility profiles compared to the negative control material (HDPE) and should be further evaluated for use in blood‐contacting medical devices. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 253–264, 2017.
Vitamin D Storage in Adipose Tissue of Obese and Normal Weight Women
Authors: Carrelli Angela , Bucovsky Mariana , Horst Ronald , Cremers Serge , Zhang Chengchen , Bessler Marc , Schrope Beth , Evanko John , Blanco Jody , Silverberg Shonni J , Stein Emily M
Published: August 2016

Although vitamin D deficiency is prevalent among obese individuals, its cause is poorly understood. Few studies have measured vitamin D concentrations in adipose of obese (OB) subjects, and none have included normal weight controls (C). The goal of this study was to investigate whether the relationship between body composition, serum 25-hydroxyvitamin D (25OHD), vitamin D in subcutaneous (SQ) and omental (OM) adipose, and total adipose stores of vitamin D differ among OB and C. Obese women undergoing bariatric surgery and normal-weight women undergoing abdominal surgery for benign gynecologic conditions were enrolled. Subjects had measurements of serum 25OHD by high-performance liquid chromatography (HPLC) and body composition by dual-energy X-ray absorptiometry (DXA). Vitamin D concentrations in SQ and OM adipose were measured by mass spectroscopy. Thirty-six women were enrolled. Serum 25OHD was similar between groups (OB 27 ± 2 versus C 26 ± 2 ng/mL; p = 0.71). Adipose vitamin D concentrations were not significantly different in either SQ (OB 34 ± 9 versus C 26 ± 12 ng/g; p = 0.63) or OM compartments (OB 51 ± 13 versus C 30 ± 18 ng/g; p = 0.37). The distribution of vitamin D between SQ and OM compartments was similar between groups. Serum 25OHD was directly related to adipose vitamin D in both groups. Total body vitamin D stores were significantly greater in OB than in C (2.3 ± 0.6 versus 0.4 ± 0.8 mg, respectively; p < 0.01). In summary, although OB had significantly greater total vitamin D stores than C, the relationship between serum 25OHD and fat vitamin D and the overall pattern of distribution of vitamin D between the OM and SQ fat compartments was similar. Our data demonstrate that obese subjects have greater adipose stores of vitamin D. They support the hypotheses that the enlarged adipose mass in obese individuals serves as a reservoir for vitamin D and that the increased amount of vitamin D required to saturate this depot may predispose obese individuals to inadequate serum 25OHD. © 2016 American Society for Bone and Mineral Research.
QTc prolongation during peripheral stem cell apheresis in healthy volunteers
Authors: Korur Aslı , Kozanoglu Ilknur , Buyukkurt Nurhilal , Yeral Mahmut , Kandemir Fatih , Gereklioglu Cigdem , Sariturk Cagla , Asma Suheyl , Solmaz Soner , Boga Can , Ozdogu Hakan
Published: August 2016

Background and aim

Today, voluntary donation of peripheral blood stem cells by healthy donors for allogeneic hemopoietic cell transplantation is common worldwide. Such donations are associated with small but measurable risks of morbidity and mortality. Most complications are associated with citrate infusion during cell collection. We studied the effects of citrate infusion on the QTc and other vital parameters during and after peripheral stem cell apheresis in volunteers.

Method

To ensure that donors were healthy, screening included taking a detailed medical history, physical examination, and laboratory measurements of plasma calcium and magnesium. Corrected QT (QTc) values were assessed using a 12‐lead electrocardiographic platform that derived QTc values automatically.

Results

In all, 141 apheresis procedures were performed. The mean QTc values at baseline, at 2 and 4 h during the procedure, and at 30 min after the procedure, were 347.6 ± 59.5, 349.9 ± 52.8, 391.8 ± 54.0, and 404.8 ± 59.2 ms, respectively. The baseline and 2 h QTcs did not differ significantly, but the baseline QTc did differ significantly from the 4 h and 30 min after the procedure values. The plasma levels of calcium and magnesium did not significantly differ before and after the procedure.

Conclusion

QTc prolongation may develop during leukopheresis, particularly if the procedure takes more than 2 h. Thus, to enhance donor safety, QTc measurement should be standard for all donors. In addition, any family history of sudden death should be noted, to prevent the development of possible fatal arrhythmia in susceptible donors.
Abnormal distribution of GABAA receptors in brain of duchenne muscular dystrophy patients
Authors: Suzuki Yuji , Higuchi Shinya , Aida Izumi , Nakajima Takashi , Nakada Tsutomu
Published: August 2016

Introduction: In this study we sought to: (1) determine the distribution of GABAA receptors (GABAA‐Rs) in the brain of Duchenne muscular dystrophy (DMD) patients; and (2) ascertain if the distribution pattern correlates with cognitive dysfunction. Methods: Fourteen DMD patients [young adult (n = 7, 18–25 years old) and older adult (n = 7, 30–37 years old) groups] and 16 age‐matched normal volunteers participated. GABAA‐R distribution was assessed using 123I‐IMZ‐SPECT. Neuropsychological assessments were performed using 3 different test batteries, the WAIS‐III, WMS‐R, and Wisconsin Card Sorting Test (WCST). Results: All DMD patients showed significant decline in 123I‐IMZ uptake in the prefrontal cortex (P < 0.05). Although no differences were detected in the WAIS‐III and WMS‐R, the WCST scores of DMD patients (2.8 ± 1.9) were significantly lower (P < 0.01) than those of normal volunteers (5.4 ± 0.7). Both abnormalities were more pronounced in older adult patients. Conclusion: The findings demonstrate that DMD is accompanied by a reduction in the prefrontal cortex distribution of GABAA‐Rs. Muscle Nerve 55: 591–595, 2017
Muscle magnetic resonance imaging in spinal muscular atrophy type 3: Selective and progressive involvement
Authors: Durmus Hacer , Yilmaz Ravza , Gulsen‐Parman Yesim , Oflazer‐Serdaroglu Piraye , Cuttini Marina , Dursun Memduh , Deymeer Feza
Published: August 2016

Introduction

In this study we sought to identify magnetic resonance imaging (MRI) signs of selective muscle involvement and disease progression in patients with spinal muscular atrophy type 3b (SMA3b).

Methods

Twenty‐five patients with genetically confirmed SMA3b underwent MRI on a 1.5‐Tesla MR scanner.

Results

MRI showed significantly more severe involvement of the iliopsoas than of the gluteus maximus muscles, and more severe involvement of the triceps brachii than of the biceps brachii muscles. The quadriceps femoris muscles were severely involved. The deltoid, adductor longus, portions of the hamstrings, gracilis, sartorius, and rectus abdominis muscles were well preserved. We found a significant positive correlation between MRI changes and disease duration for gluteus maximus and triceps brachii. Follow‐up MRIs of 4 patients showed disease progression.

Conclusions

This study confirms the pattern of selective muscle involvement suggested by previous studies and further refines muscle MRI changes in SMA3b. Progressive muscle involvement is implicated. Muscle Nerve 55: 651–656, 2017
Assessment of physical fatigability and fatigue perception in myasthenia gravis
Authors: Jordan Berit , Mehl Theresa , Schweden Tabea L.K. , Menge Uwe , Zierz Stephan
Published: August 2016

Introduction

Fatigue includes both performance fatigability and fatigue perception.

Methods

In 32 stable patients with generalized myasthenia gravis (MG) and 17 controls, time‐dependent physical performance was assessed by the arm movement test (AMT) and 6‐minute walk test (6MWT). MG patients presented with low quantitative MG scores (mean 0.5, SD 0.5) and without pathologic decrement. Fatigability was based on calculation of linear trend (LT) reflecting dynamic performance within subsequent constant time intervals. Perception of physical fatigue was analyzed using fatigue questionnaires.

Results

MG patients showed a negative LT in both AMT and 6MWT, significantly differing from stable performance in controls. LT inversely correlated with elevation of acetylcholine receptor antibodies (r = −0.59, P < 0.005) but not with quantitative MG score and fatigue perception.

Conclusions

LT allows quantification of fatigability as an objective measurement of decline in individual performance, even in patients without obvious neuromuscular deficits in routine testing. The missing correlation of experienced fatigue supports the multidimensional fatigue model. Muscle Nerve 55: 657–663, 2017
Relationships between time use and obesity in a representative sample of Americans
Authors: Patel Viral C. , Spaeth Andrea M. , Basner Mathias
Published: August 2016

Objective

To provide a nationally representative analysis of time use in America for insight into behaviors associated with obesity.

Methods

This study utilized 28,503 observations of individuals aged 22 to 70 from the American Time Use Survey, a continuous cross‐sectional survey on time use in America. Linear and logistic regressions were performed to analyze sociodemographic characteristics, determine activity participation levels and time spent in activities, understand nonlinear associations between activity time and BMI, and appreciate differences in activity timing between BMI categories.

Results

Short and long sleep and work were associated with increased BMI. On weekdays, individuals with obesity were more likely to be working at night and sleeping during the day. They were less likely to participate in sports/exercise/recreation, but those that participated did so for amounts of time not different than normal‐BMI individuals. Those with obesity were more likely to watch television almost all hours of the day. Further differences are detailed for health‐related, sedentary, and household activities.

Conclusions

Both short and long sleep, as well as the timing of sleep and work activity, are associated with obesity. Motivation to exercise nonzero amounts may be an appropriate target for intervention. Television is chief among sedentary activities in their association with obesity.
Homeostatic responses to palatable food consumption in satiated rats
Authors: Hume Catherine , Jachs Barbara , Menzies John
Published: August 2016

Objective

Energy intake is regulated by overlapping homeostatic and hedonic systems. Consumption of palatable foods has been implicated in weight gain, but this assumes that homeostatic control systems do not accurately detect this hedonically driven energy intake. This study tested this assumption, hypothesizing that satiated rats would reduce their voluntary food intake and maintain a stable body weight after consuming a palatable food.

Methods

Lean rats or rats previously exposed to an obesogenic diet were schedule‐fed with fixed or varying amounts of palatable sweetened condensed milk (SCM) daily, and their voluntary energy intake and body weight were monitored.

Results

During scheduled feeding of SCM, rats voluntarily reduced bland food consumption and maintained a stable body weight. This behavior was also seen in rats with access to an obesogenic diet and was independent of the predictability of SCM access. However, lean rats offered large amounts of SCM showed an increase in total energy intake. To test whether a nutrient deficiency drove this under‐compensatory behavior, SCM was enriched with protein. However, no effect was seen on voluntary energy intake.

Conclusions

In schedule‐fed rats, compensatory reductions in voluntary energy intake were seen, but under‐compensation was observed if large amounts of SCM were consumed.