bluuebunny/crossref_metadata_2025 huggingface dataset:
Enabling xylose utilization in Yarrowia lipolytica for lipid production
Authors: Li Haibo , Alper Hal S.
Published: July 2016

The conversion of lignocellulosic sugars, in particular xylose, is important for sustainable fuels and chemicals production. While the oleaginous yeast Yarrowia lipolytica is a strong candidate for lipid production, it is currently unable to effectively utilize xylose. By introducing a heterologous oxidoreductase pathway and enabling starvation adaptation, we obtained a Y. lipolytica strain, E26 XUS, that can use xylose as a sole carbon source and produce over 15 g/L of lipid in bioreactor fermentations (29.3% of theoretical yield) with a maximal lipid productivity of 0.19 g/L/h. Genomic sequencing and genetic analysis pointed toward increases in genomic copy number of the pathway and resulting elevated expression levels as the causative mutations underlying this improved phenotype. More broadly, many regions of the genome were duplicated during starvation of Yarrowia. This strain can form the basis for further engineering to enhance xylose catabolic rates and conversion. Finally, this study also reveals the flexibility and dynamic nature of the Y. lipolytica genome, and the means at which starvation can be used to induce genomic duplications.
Risk factors for level V lymph node metastases in solitary papillary thyroid carcinoma with clinically lateral lymph node metastases
Authors: Yang Jing , Gong Yanping , Yan Shuping , Zhu Jingqiang , Li Zhihui , Gong Rixiang
Published: July 2016

The extent of lateral neck dissection (LND) in surgical resection of papillary thyroid carcinoma (PTC) with clinically lateral LNM (LLNM) remains controversial. We aimed to explore the frequency of and risk factors for level V LNM in patients with solitary PTC and clinically LLNM. To analyze the frequency and risk factors for level V LNM, we retrospectively reviewed 220 solitary PTC patients who underwent total thyroidectomy, bilateral central neck dissection, and therapeutic LND. LLNM were present in 82.3% patients, and levels II–V LNM were present in 45.9%, 62.7%, 55.5%, and 12.3% patients, respectively. Ipsilateral level V LNM was significantly associated with tumor size >10 mm, extrathyroidal extension, ipsilateral central LNM ratio ≥50%, and contralateral central LNM (CLNM), bilateral CLNM, and simultaneous levels II–IV LNM. Contralateral CLNM was an independent risk factor for level V LNM. In patients with solitary PTC and clinically LLNM, level V LNM was relatively uncommon. Therefore, routine level V lymphadenectomy may be unnecessary in these patients unless level V LNM is suspected on preoperative examination or associated risk factors, especially contralateral CLNM, are present.
Antitumor activity of combined endostatin and thymidine kinase gene therapy in C6 glioma models
Authors: Chen Yan , Huang Honglan , Yao Chunshan , Su Fengbo , Guan Wenming , Yan Shijun , Ni Zhaohui
Published: July 2016

The combination of Endostatin (ES) and Herpes Simplex Virus thymidine kinase (HSV‐TK) gene therapy is known to have antitumor activity in bladder cancer. The potential effect of ES and TK therapy in glioma has not yet been investigated. In this study, pTK‐internal ribosome entry site (IRES), pIRES‐ES, and pTK‐IRES‐ES plasmids were constructed; pIRES empty vector served as the negative control. The recombinant constructs were transfected into human umbilical vein endothelial cells (HUVECs) ECV304 and C6 rat glioma cell line. Ganciclovir (GCV) was used to induce cell death in transfected C6 cells. We found that ECV304 cells expressing either ES or TK‐ES showed reduced proliferation, decreased migration capacity, and increased apoptosis, as compared to untransfected cells or controls. pTK‐IRES‐ES/GCV or pTK‐IRES/GCV significantly suppressed cell proliferation and induced cell apoptosis in C6 cells, as compared to the control. In addition, the administration of pIRES‐ES, pTK‐IRES/GCV, or pTK‐IRES‐ES/GCV therapy improved animal activity and behavior; was associated with prolonged animal survival, and a lower microvessel density (MVD) value in tumor tissues of C6 glioma rats. In comparison to others, dual gene therapy in form of pTK‐IRES‐ES/GCV had a significant antitumor activity against C6 glioma. These findings indicate combined TK and ES gene therapy was associated with a superior antitumor efficacy as compared to single gene therapy in C6 glioma.
Deep molecular responses for treatment‐free remission in chronic myeloid leukemia
Authors: Dulucq Stéphanie , Mahon Francois‐Xavier
Published: July 2016

Several clinical trials have demonstrated that some patients with chronic myeloid leukemia in chronic phase (CML‐CP) who achieve sustained deep molecular responses on tyrosine kinase inhibitor (TKI) therapy can safely suspend therapy and attempt treatment‐free remission (TFR). Many TFR studies to date have enrolled imatinib‐treated patients; however, the feasibility of TFR following nilotinib or dasatinib has also been demonstrated. In this review, we discuss available data from TFR trials and what these data reveal about the molecular biology of TFR. With an increasing number of ongoing TFR clinical trials, TFR may become an achievable goal for patients with CML‐CP.
A nonlinear principal component analysis to study archeometric data
Authors: Bitetto Alessandro , Mangone Annarosa , Mininni Rosa Maria , Giannossa Lorena C.
Published: July 2016

Statistical techniques, when applied to data obtained by chemical investigations on ancient artworks, are usually expected to recognize groups of objects to classify the archeological finds, to attribute the provenance of items compared with earlier investigated ones, or to determine whether an archaelogical attribution is possible or not. The statistical technique most frequently used in archeometry is the principal component analysis (PCA), because of its simplicity in theory and implementation. However, the application of PCA to archeometric data showed severe limitations because of its linear feature. Indeed, PCA is inadequate to classify data whose behavior describe a curve or a curved subspace of the original data space. As a consequence of it, an amount of information is lost because the multi‐dimensional data space is compressed into a lower‐dimensional subspace including principal components. The aim of this work is then to test a novel statistical technique for archeometry. We propose a nonlinear PCA method to extract maximum chemical information by plotting data on the smallest number of principal components and to answer archeological questions. The higher accuracy and effectiveness of nonlinear PCA approach with respect to standard PCA for the analysis of archeometric data are shown through the study of Apulian red figured pottery (fifth–fourth century BC) coming from some of the most relevant archeological sites of ancient Apulia (Monte Sannace (Gioia del Colle), Egnatia (Fasano), Canosa, Altamura, Conversano, and Arpi(Foggia)). Copyright © 2016 John Wiley & Sons, Ltd.
Design and Synthesis of Aviram–Ratner‐Type Dyads and Rectification Studies in Langmuir–Blodgett (LB) Films
Authors: Jayamurugan Govindasamy , Gowri Vijayendran , Hernández David , Martin Santiago , González‐Orive Alejandro , Dengiz Cagatay , Dumele Oliver , Pérez‐Murano Francesc , Gisselbrecht Jean‐Paul , Boudon Corinne , Schweizer W. Bernd , Breiten Benjamin , Finke Aaron D. , Jeschke Gunnar , Bernet Bruno , Ruhlmann Laurent , Cea Pilar , Diederich François
Published: July 2016

The design and synthesis of Aviram–Ratner‐type molecular rectifiers, featuring an anilino‐substituted extended tetracyanoquinodimethane (exTCNQ) acceptor, covalently linked by the σ‐spacer bicyclo[2.2.2]octane (BCO) to a tetrathiafulvalene (TTF) donor moiety, are described. The rigid BCO spacer keeps the TTF donor and exTCNQ acceptor moieties apart, as demonstrated by X‐ray analysis. The photophysical properties of the TTF‐BCO‐exTCNQ dyads were investigated by UV/Vis and EPR spectroscopy, electrochemical studies, and theoretical calculations. Langmuir–Blodgett films were prepared and used in the fabrication and electrical studies of junction devices. One dyad showed the asymmetric current–voltage (I–V) curve characteristic for rectification, unlike control compounds containing the TTF unit but not the exTCNQ moiety or comprising the exTCNQ acceptor moiety but lacking the donor TTF part, which both gave symmetric I–V curves. The direction of the observed rectification indicated that the preferred electron current flows from the exTCNQ acceptor to the TTF donor.
Chemically Non‐Innocent Cyclic (Alkyl)(Amino)Carbenes: Ligand Rearrangement, C−H and C−F Bond Activation
Authors: Turner Zoë R.
Published: July 2016

A cyclic (alkyl)(amino)carbene (CAAC) was found to undergo unprecedented rearrangements and transformations of its core structure in the presence of Group 1 and 2 metals. Although the carbene was also found to be prone to intramolecular C−H activation, it was competent for intermolecular activation of a variety of sp‐, sp2‐, and sp3‐hybridized C−H bonds. Double C−F activation of hexafluorobenzene was also observed in this work. These processes all hold relevance to the role of these carbenes in catalysis, as well as to their use in the synthesis of new and unusual main group or transition metal complexes.
Plasma Pharmacokinetics of Veledimex, a Small‐Molecule Activator Ligand for a Proprietary Gene Therapy Promoter System, in Healthy Subjects
Authors: Cai Hongliang , Sun Lei , Miao John , Krishman Suma , Lebel Francois , Barrett John A.
Published: July 2016

Major obstacles to developing effective immunotherapy are the ability of tumors to escape the immune system and the toxicity associated with systemic administration. To overcome these challenges, a gene delivery platform technology, RheoSwitch Therapeutic System (RTS), has been developed to enable the regulated expression of a target gene, Ad‐RTS‐IL‐12, administered intratumorally, where IL‐12 expression is controlled via the administration of an oral activator ligand, veledimex. Pharmacokinetics in healthy human subjects indicated that veledimex plasma exposure increased with increasing dose after single‐ and multiple‐dose administration in Labrasol slurry and F‐22 capsule formulations. No apparent formulation or sex‐related difference in veledimex pharmacokinetics (PK) was observed. Minimal or no plasma accumulation of veledimex was observed after once‐daily oral administration for 14 days. Veledimex steady state in plasma was reached after 5 daily doses. Food consumption prior to veledimex administration prolonged and enhanced absorption with no impact on the elimination rate and extent of metabolism of veledimex, resulting in significantly increased systemic exposure to veledimex and its 2 major circulating metabolites. Overall, veledimex was well tolerated and exhibited a PK profile supportive of once‐daily dosing. For enhanced efficacy, veledimex should be taken under fed conditions to ensure optimal absorption and sufficient systemic exposure.
Single‐ and Multiple‐Dose Pharmacokinetics of Immediate‐Release/Extended‐Release Ibuprofen Tablets
Authors: Legg Thomas , Paluch Edward , Jayawardena Shyamalie
Published: July 2016

A single‐dose, randomized, open‐label, crossover study (study 1; n = 35) and a multiple‐dose, randomized, open‐label, crossover study (study 2; n = 28) compared the pharmacokinetics of a new immediate‐release/extended‐release (IR/ER) bilayer tablet formulation of ibuprofen 600 mg every 12 hours with standard ibuprofen 200 mg IR every 4 hours. In both studies, the 2 formulations were bioequivalent to each other for the area under the plasma concentration‐versus‐time curve from time 0 to the last measurable concentration (AUCL), to infinity (AUC∞), and to 12 hours (AUC0–12) and maximum concentration (Cmax). In study 1, food slowed the absorption of ibuprofen from ibuprofen 600 mg IR/ER (lower Cmax) compared with the fasted state but did not affect the overall extent (AUC) of ibuprofen absorption. In study 2, there was no evidence of drug accumulation with multiple doses of ibuprofen IR/ER. In conclusion, ibuprofen 600 mg IR/ER provides a twice‐daily over‐the‐counter analgesic option that is bioequivalent to standard ibuprofen 200 mg IR (every 4 hours) with regard to both the rate (Cmax) and the extent (AUC) of absorption.
Comparison of Capillary and Venous Drug Concentrations After Administration of a Single Dose of Risperidone, Paliperidone, Quetiapine, Olanzapine, or Aripiprazole
Authors: Remmerie Bart , De Meulder Marc , Weiner Sveta , Savitz Adam
Published: July 2016

Risperidone, paliperidone, quetiapine, olanzapine, and aripiprazole are antipsychotic drugs approved for treating various psychiatric disorders, including schizophrenia. The objective of this randomized, parallel‐group, open‐label study was to compare finger‐stick‐based capillary with corresponding venous whole‐blood and plasma concentrations for these drugs after administration of a single dose to healthy volunteers. All whole‐blood and plasma drug concentrations were measured with validated liquid chromatography–tandem mass spectrometry methods. Capillary and venous concentrations (both in plasma and whole blood) were in close agreement, although a time‐dependent difference was observed, most obviously for olanzapine and paliperidone, with slightly higher capillary versus venous drug concentrations during the first hours after administering a single dose. The observed difference between capillary and venous plasma drug concentrations is expected not to be relevant in clinical practice, considering the wide window of therapeutic concentrations and the wide range of drug concentrations in the patient population for a given dose. Based on these results, finger‐stick‐based capillary drug concentrations have been shown to approximate venous drug concentrations.
Quality Control for the Illumina HumanExome BeadChip
Authors: Igo Robert P. , Cooke Bailey Jessica N. , Romm Jane , Haines Jonathan L. , Wiggs Janey L.
Published: July 2016

The Illumina HumanExome BeadChip and other exome‐based genotyping arrays offer inexpensive genotyping of some 240,000 mostly nonsynonymous coding variants across the human genome. The HumanExome chip, with its highly non‐uniform distribution of markers and emphasis on rare coding variants, presents some unique challenges for quality control (QC) and data cleaning. Here, we describe QC procedures for HumanExome data, with examples of challenges specific to exome arrays from our experience cleaning a data set of ∼7,500 samples from the NEIGHBORHOOD Consortium. We focus on standard procedures for QC of genome‐wide array data including genotype calling, sex verification, sample identity verification, relationship checking, and population structure that are complicated by the HumanExome panel's enrichment in rare, exonic variation. © 2016 by John Wiley & Sons, Inc.
Integrative Analysis of Histone ChIP‐seq and RNA‐seq Data
Authors: Klein Hans‐Ulrich , Schäfer Martin
Published: July 2016

The R package epigenomix has been designed to detect differentially transcribed gene isoforms that, in addition, exhibit altered histone modifications at their respective genomic loci. The package provides methods to map histone ChIP‐seq profiles to isoforms and estimate their transcript abundances from RNA‐seq data. Based on the differences observed between case and control samples in the RNA‐seq and ChIP‐seq data, a correlation measure is calculated for each isoform. The distribution of this correlation measure is further investigated by a Bayesian mixture model to (i) reveal the relationship between the studied histone modification and transcriptional activity, and (ii) detect specific isoforms with differences in both transcription values and histone modifications. The method is designed for experiments with a few or no replicates, and is superior to separate analyses of both data types in that setting. This unit illustrates the integrative analysis of ChIP‐seq and RNA‐seq data with epigenomix. © 2016 by John Wiley & Sons, Inc.
A Microbiome DNA Enrichment Method for Next‐Generation Sequencing Sample Preparation
Authors: Yigit Erbay , Feehery George R. , Langhorst Bradley W. , Stewart Fiona J. , Dimalanta Eileen T. , Pradhan Sriharsa , Slatko Barton , Gardner Andrew F. , McFarland James , Sumner Christine , Davis Theodore B.
Published: July 2016

“Microbiome” is used to describe the communities of microorganisms and their genes in a particular environment, including communities in association with a eukaryotic host or part of a host. One challenge in microbiome analysis concerns the presence of host DNA in samples. Removal of host DNA before sequencing results in greater sequence depth of the intended microbiome target population. This unit describes a novel method of microbial DNA enrichment in which methylated host DNA such as human genomic DNA is selectively bound and separated from microbial DNA before next‐generation sequencing (NGS) library construction. This microbiome enrichment technique yields a higher fraction of microbial sequencing reads and improved read quality resulting in a reduced cost of downstream data generation and analysis. © 2016 by John Wiley & Sons, Inc.
The Importance of Titrating Antibodies for Immunocytochemical Methods
Authors: Hoffman Gloria E. , Murphy Kelley J. , Sita Luciane V.
Published: July 2016

When using immunocytochemistry, investigators may not know how to optimize staining or how to troubleshoot the method when staining fails. Lacking are guides for comparing techniques and applying information derived from one staining method to another. Newer methods amplify signal detection, but will not necessarily work at the same primary antibody concentrations used for less sensitive reactions. Recommendations of optimal titers are often not accurate and are not usually accompanied by information on the method used to test those antibodies or the specifics of the assay. When the staining does not work, the investigators do not know how to determine if the antiserum is bad, the tissue is bad, or the method is inappropriate for their staining. This unit describes detailed procedures for determining optimal staining and applying that information to three common immunofluorescence methods. Lastly, a formula is provided for converting among the different methods. © 2016 by John Wiley & Sons, Inc.
Identification of five pyrrolidinyl substituted cathinones and the collision‐induced dissociation of electrospray‐generated pyrrolidinyl substituted cathinones
Authors: Qian Zhenhua , Jia Wei , Li Tao , Hua Zhendong , Liu Cuimei
Published: July 2016

This article reports on the analytical properties of five pyrrolidinyl substituted cathinones: α‐pyrrolidinononaphenone (α‐PNP, 1), 4‐chloro‐α‐pyrrolidinopropiophenone (4‐Cl‐α‐PPP, 2), 4‐chloro‐α‐pyrrolidinovalerophenone (4‐Cl‐α‐PVP, 3), 5‐dihydrobenzofuranpyrovalerone (5‐DBFPV, 4), and 2‐(pyrrolidin‐1‐yl)‐1‐(5,6,7,8‐tetrahydronaphthalen‐2‐yl)hexan‐1‐one (β‐THNPH, 5). These identifications were based on liquid chromatography–quadrupole time‐of‐flight‐mass spectrometry (LC–QTOF–MS), gas chromatography–mass spectrometry (GC–MS) and nuclear magnetic resonance spectroscopy (NMR). To our knowledge, no analytical data about α‐PNP, 4‐Cl‐α‐PPP, 4‐Cl‐α‐PVP, and β‐THNPH have appeared until now, making this the first report on these compounds. Moreover, in order to study the collision‐induced dissociation (CID) characteristic fragmentation routes of pyrrolidinyl substituted cathinones, a total number of 13 pyrrolidinyl substituted cathinones were selected and discussed. The major fragmentation pathways under CID mode are produced, leading to the formation of characteristic ions. Product ions of [M‐C4H9N]+ and CnH2nN+ indicate the presence of pyrrolidinyl substitution. Characteristic fragments are also produced via the cleavages of the CH–N(CH2)4 bond and the CO‐CHN bond. Copyright © 2016 John Wiley & Sons, Ltd.
Incipient sympatric speciation in Midas cichlid fish from the youngest and one of the smallest crater lakes in Nicaragua due to differential use of the benthic and limnetic habitats?
Authors: Kautt Andreas F. , Machado‐Schiaffino Gonzalo , Torres‐Dowdall Julian , Meyer Axel
Published: July 2016

Understanding how speciation can occur without geographic isolation remains a central objective in evolutionary biology. Generally, some form of disruptive selection and assortative mating are necessary for sympatric speciation to occur. Disruptive selection can arise from intraspecific competition for resources. If this competition leads to the differential use of habitats and variation in relevant traits is genetically determined, then assortative mating can be an automatic consequence (i.e., habitat isolation). In this study, we caught Midas cichlid fish from the limnetic (middle of the lake) and benthic (shore) habitats of Crater Lake Asososca Managua to test whether some of the necessary conditions for sympatric speciation due to intraspecific competition and habitat isolation are given. Lake As. Managua is very small (<900 m in diameter), extremely young (maximally 1245 years of age), and completely isolated. It is inhabited by, probably, only a single endemic species of Midas cichlids,Amphilophus tolteca. We found that fish from the limnetic habitat were more elongated than fish collected from the benthic habitat, as would be predicted from ecomorphological considerations. Stable isotope analyses confirmed that the former also exhibit a more limnetic lifestyle than the latter. Furthermore, split‐brood design experiments in the laboratory suggest that phenotypic plasticity is unlikely to explain much of the observed differences in body elongation that we observed in the field. Yet, neutral markers (microsatellites) did not reveal any genetic clustering in the population. Interestingly, demographic inferences based onRAD‐seq data suggest that the apparent lack of genetic differentiation at neutral markers could simply be due to a lack of time, as intraspecific competition may only have begun a few hundred generations ago.
A model coupling the effects of soil moisture and potential evaporation on the tree transpiration of a semi‐arid larch plantation
Authors: Li Zhenhua , Yu Pengtao , Wang Yanhui , Webb Ashley A. , He Cong , Wang Yanbing , Yang Lili
Published: July 2016

Quantifying the tree transpiration (T) response to the coupling effects of changing soil moisture and weather conditions provides insights into water use by forests, especially in dryland regions. This study was conducted in a semi‐arid pure larch (Larix principis‐rupprechtii) plantation in northwest China. The sap flow density of trees, weather conditions in open field, and soil moisture of main root zone (0–60 cm) were measured synchronously and continuously throughout a growing season in 2010. The response of daily T to the relative extractable soil water (REW) and potential evapotranspiration (PET) was analyzed. The T varied in the range of 0.08–2.18 mm/day during the study period. With increasing REW, it initially rose quickly and almost linearly; but after the REW reached a threshold, it leveled off and gradually approached its maximum (Tmax). However, Tmax positively related with PET. Based on the T‐REW and Tmax‐PET relationships, an integrated model (T = (−0.05PET2 + 0.65PET) × (1 −  exp (−5.39REW))) was developed to describe the complex T‐REW‐PET relationship and it fit the measured data well. For the whole study period, due to the limit of PET and REW, the actual T was reduced by 32% (88.6 mm) and 16% (45.0 mm) respectively, compared with potential T. Although this model cannot be widely applied until it is validated with measured data from more sites, it does provide a way to accurately estimate the daily T using REW and PET data and to quantify the coupling effects of changing REW and PET on the T.
Combined neprilysin and renin–angiotensin system inhibition in heart failure with reduced ejection fraction: a meta‐analysis
Authors: Solomon Scott D. , Claggett Brian , McMurray John J.V. , Hernandez Adrian F. , Fonarow Gregg C.
Published: July 2016

Aims

The combined neprilysin/renin–angiotensin system (RAS) inhibitor sacubitril/valsartan reduced cardiovascular death or heart failure hospitalization, cardiovascular death, and all‐cause mortality in a large outcomes trial. While sacubitril/valsartan is the only currently available drug in its class, there are two prior clinical trials in heart failure with omapatrilat, another combined neprilysin/RAS inhibitor. Using all available evidence can inform clinicians and policy‐makers.

Methods and results

We performed a meta‐analysis using data from three trials in heart failure with reduced EF that compared combined neprilysin/RAS inhibition with RAS inhibition alone and reported clinical outcomes: IMPRESS (n = 573), OVERTURE (n = 5770), and PARADIGM‐HF (n = 8399). We assessed the pooled hazard ratio (HR) for all‐cause death or heart failure hospitalization, and for all‐cause mortality in random‐effects models, comparing combined neprilysin/RAS inhibition with ACE inhibition alone. The composite outcome of death or heart failure hospitalization was reduced numerically in patients receiving combined neprilysin/RAS inhibition in all three trials, with a pooled HR of 0.86, 95% confidence interval (CI) 0.76–0.97, P = 0.013. For the endpoint of all‐cause mortality, the pooled HR was 0.88, 95% CI 0.80–0.98, P = 0.021. Combined neprilysin/RAS inhibition compared with ACE inhibition was associated with more hypotension, but less renal dysfunction and hyperkalaemia in all three trials.

Conclusions

Pooled estimates from three trials with two separate drugs of combined neprilysin/RAS inhibition support the use of combined neprilysin/RAS inhibition in heart failure with reduced EF.
Cyclisation of Disulfide‐Rich Conotoxins in Drug Design Applications
Authors: Wu Xiaosa , Huang Yen‐Hua , Kaas Quentin , Craik David J.
Published: July 2016

Conotoxins are disulfide‐rich peptides found in the venoms of marine snails of the genus Conus. They have attracted great attention from the pharmaceutical industry because of their potential uses as drug leads, but like most peptides, conotoxins are susceptible to proteolysis and typically are not orally bioavailable. Here we discuss approaches that have been used to stabilise conotoxins to improve their potential pharmaceutical use. Specifically, we focus on the use of backbone cyclisation to improve their stability in biological fluids. The Microreview provides an introduction to the various classes of conotoxins, including their frameworks (cysteine patterns) and a background on the receptors that they interact with, as well as an analysis of the binding interactions between conotoxins and their receptors.
Considerations on the flow configuration of membrane chromatography devices for the purification of human basic fibroblast growth factor from crude lysates
Authors: Gieseler Gesa , Pepelanova Iliyana , Meyer Annette , Villain Louis , Beutel Sascha , Rinas Ursula , Scheper Thomas
Published: July 2016

Membrane chromatography possesses numerous advantages such as operation at high flow rates, low back pressure, ease of handling and scale up, which make the membrane adsorber process a viable alternative to conventional packed column chromatography. A purification process for the isolation of human recombinant basic fibroblast growth factor (FGF‐2) based on membrane chromatography was investigated using devices with different flow configurations. In the first process, the FGF‐2 capture step was performed with an axial flow device, while the alternative method achieved direct capture of FGF‐2 from unclarified cell lysate with a tangential flow device. In both processes, FGF‐2 purities exceeded 82% and the purified cytokine displayed high biological activity. Binding capacity (BC) from fermentation broth of the axial flow device was 28 mg/mL. This was 50% higher than the BC obtained with the tangential flow device under particle‐free supernatant conditions (18 mg/mL) and 150% higher compared to the BC achieved with unclarified cell lysate (11 mg/mL). While membrane chromatography in tangential flow mode omits clarification and thus reduces the number of stages in the downstream process, it displays lower peak resolution and leads to a lower overall process yield.
γH2AX and p53 responses in TK6 cells discriminate promutagens and nongenotoxicants in the presence of rat liver S9
Authors: Bernacki Derek T. , Bryce Steven M. , Bemis Jeffrey C. , Kirkland David , Dertinger Stephen D.
Published: July 2016

Previous work with a diverse set of reference chemicals suggests that an in vitro multiplexed flow cytometry‐based assay (MultiFlow™ DNA Damage Kit—p53, γH2AX, Phospho‐Histone H3) can distinguish direct‐acting clastogens and aneugens from nongenotoxicants (Bryce SM et al. []: Environ Mol Mutagen 57:171‐189). This work extends this line of investigation to include compounds that require metabolic activation to form reactive electrophiles. For these experiments, TK6 cells were exposed to 11 promutagens and 37 presumed nongenotoxicants in 96 well plates. Unless precipitation or foreknowledge about cytotoxicity suggested otherwise, the highest concentration was 1 mM. Exposure occurred for 4 hr after which time cells were washed to remove S9 and test article. Immediately following the wash and again at 24 hr, cell aliquots were added to wells of a microtiter plate containing the working detergent/stain/antibody cocktail. After a brief incubation, robotic sampling was employed for walk‐away flow cytometric data acquisition. Univariate logistic regression analyses indicated that γH2AX induction and p53 activation provide the greatest degree of discrimination between clastogens and nongenotoxicants. Multivariate prediction algorithms that incorporated both of these endpoints, in each combination of time points, were evaluated. The best performing models correctly predicted 9 clastogens out of 11 and 36 nongenotoxicants out of 37. These results are encouraging as they suggest that an efficient and highly scalable multiplexed assay can effectively identify clastogenic chemicals that require bioactivation. More work is planned with a broader range of chemicals, additional cell lines, and other laboratories to further evaluate the merits and limitations of this approach. Environ. Mol. Mutagen. 57:546–558, 2016. © 2016 Wiley Periodicals, Inc.
Collapse assessment of moment frame buildings, considering vertical ground shaking
Authors: Harrington Cody C. , Liel Abbie B.
Published: July 2016

While many cases of structural damage in past earthquakes have been attributed to strong vertical ground shaking, our understanding of vertical seismic load effects and their influence on collapse mechanisms of buildings is limited. This study quantifies ground motion parameters that are capable of predicting trends in building collapse because of vertical shaking, identifies the types of buildings that are most likely affected by strong vertical ground motions, and investigates the relationship between element level responses and structural collapse under multi‐directional shaking. To do so, two sets of incremental dynamic analyses (IDA) are run on five nonlinear building models of varying height, geometry, and design era. The first IDA is run using the horizontal component alone; the second IDA applies the vertical and horizontal motions simultaneously. When ground motion parameters are considered independently, acceleration‐based measures of the vertical shaking best predict trends in building collapse associated with vertical shaking. When multiple parameters are considered, Housner intensity (SI), computed as a ratio between vertical and horizontal components of a record (SIV/SIH), predicts the significance of vertical shaking for collapse. The building with extensive structural cantilevered members is the most influenced by vertical ground shaking, but all frame structures (with either flexural and shear critical columns) are impacted. In addition, the load effect from vertical ground motions is found to be significantly larger than the nominal value used in US building design. Copyright © 2016 John Wiley & Sons, Ltd.
Thiol oxidation of hemolymph proteins in oysters Crassostrea brasiliana as markers of oxidative damage induced by urban sewage exposure
Authors: Trevisan Rafael , Flores-Nunes Fabrício , Dolores Euler S. , Mattos Jacó J. , Piazza Clei E. , Sasaki Sílvio T. , Taniguchi Satie , Montone Rosalinda C. , Bícego Márcia C. , dos Reis Isis M. M. , Zacchi Flávia L. , Othero Bárbara N.M. , Bastolla Camila L.V. , Mello Danielle F. , Fraga Ana Paula M. , Wendt Nestor , Toledo-Silva Guilherme , Razzera Guilherme , Dafre Alcir L. , de Melo Cláudio M. R. , Bianchini Adalto , Marques Maria R. F. , Bainy Afonso C.D.
Published: July 2016

Urban sewage is a concerning issue worldwide, threatening both wildlife and human health. The present study investigated protein oxidation in mangrove oysters (Crassostrea brasiliana) exposed to seawater from Balneário Camboriú, an important tourist destination in Brazil that is affected by urban sewage. Oysters were exposed for 24 h to seawater collected close to the Camboriú River (CAM1) or 1 km away (CAM2). Seawater from an aquaculture laboratory was used as a reference. Local sewage input was marked by higher levels of coliforms, nitrogen, and phosphorus in seawater, as well as polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), linear alkylbenzenes (LABs), and fecal steroid in sediments at CAM1. Exposure of oysters to CAM1 caused marked bioaccumulation of LABs and decreased PAH and PCB concentrations after exposure to both CAM1 and CAM2. Protein thiol oxidation in gills, digestive gland, and hemolymph was evaluated. Lower levels of reduced protein thiols were detected in hemolymph from CAM1, and actin, segon, and dominin were identified as targets of protein thiol oxidation. Dominin susceptibility to oxidation was confirmed in vitro by exposure to peroxides and hypochlorous acid, and 2 cysteine residues were identified as potential sites of oxidation. Overall, these data indicate that urban sewage contamination in local waters has a toxic potential and that protein thiol oxidation in hemolymph could be a useful biomarker of oxidative stress in bivalves exposed to contaminants. Environ Toxicol Chem 2017;36:1833–1845. © 2016 SETAC
Novel class of collector in electrospinning device for the fabrication of 3D nanofibrous structure for large defect load‐bearing tissue engineering application
Authors: Hejazi Fatemeh , Mirzadeh Hamid , Contessi Nicola , Tanzi Maria Cristina , Faré Silvia
Published: July 2016

Adequate porosity, appropriate pore size, and 3D‐thick shape are crucial parameters in the design of scaffolds, as they should provide the right space for cell adhesion, spreading, migration, and growth. In this work, a novel design for fabricating a 3D nanostructured scaffold by electrospinning was taken into account. Helical spring‐shaped collector was purposely designed and used for electrospinning PCL fibers. Improved morphological properties and more uniform diameter distribution of collected nanofibers on the turns of helical spring‐shaped collector are confirmed by SEM analysis. SEM images elaboration showed 3D pores with average diameter of 4 and 5.5 micrometer inx‐yplane andz‐direction, respectively. Prepared 3D scaffold possessed 99.98% porosity which led to the increased water uptake behavior in PBS at 37°C up to 10 days, and higher degradation rate compared to 2D flat structure. Uniaxial compression test on 3D scaffolds revealed an elastic modulus of 7 MPa and a stiffness of 102MPa, together with very low hysteresis area and residual strain. In vitro cytocompatibility test with MG‐63 osteoblast‐like cells using AlamarBlue™colorimetric assay, indicated a continuous increase in cell viability for the 3D structure over the test duration. SEM observation showed enhanced cells spreading and diffusion into the underneath layers for 3D scaffold. Accelerated calcium deposition in 3D substrate was confirmed by EDX analysis. Obtained morphological, physical, and mechanical properties together within vitrocytocompatibility results, suggest this novel technique as a proper method for the fabrication of 3D nanofibrous scaffolds for the regeneration of critical‐size load bearing defects. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1535–1548, 2017.
Outcomes after resection of occupational cholangiocarcinoma
Authors: Kubo Shoji , Takemura Shigekazu , Tanaka Shogo , Shinkawa Hiroji , Kinoshita Masahiko , Hamano Genya , Ito Tokuji , Koda Masaki , Aota Takanori , Yamamoto Takatsugu , Terajima Hiroaki , Tachiyama Gorou , Yamada Terumasa , Nakamori Shoji , Arimoto Akira , Fujikawa Masahiro , Tomimaru Yoshito , Sugawara Yasuhiko , Nakagawa Kei , Unno Michiaki , Mizuguchi Toru , Takenaka Kenji , Kimura Koichi , Shirabe Ken , Saiura Akio , Uesaka Katsuhiko , Taniguchi Hiroki , Fukuda Akira , Chong Ja‐Mun , Kuwae Yuko , Ohsawa Masahiko , Sato Yasunori , Nakanuma Yasuni
Published: July 2016

Background

Cholangiocarcinoma caused by exposure to 1,2‐dichloropropane and/or dichloromethane is recognized as occupational cholangiocarcinoma. The aim of this study was to investigate the outcomes after resection of occupational cholangiocarcinoma to establish a treatment strategy for this disease.

Methods

Clinicopathological findings and outcomes after surgical intervention in 20 patients with occupational cholangiocarcinoma were investigated.

Results

Of 20 the patients, curative resection was performed in 16 patients. Three patients underwent radiation at the stump of the bile ducts. Adjuvant chemotherapy was performed in 12 patients. Biliary intraepithelial neoplasia, intraductal papillary neoplasm of the bile duct, and/or chronic bile duct injury was detected in most subjects. Intraabdominal infection developed after surgery in nine patients. Cholangiocarcinoma recurred in 12 of the 20 patients. The recurrent tumors in five patients developed at a different part of the bile duct from the primary tumor and a second resection was performed in four of these five patients.

Conclusions

The incidence of postoperative complications including intraabdominal infection was high in patients with occupational cholangiocarcinoma. Multicentric recurrence occurred not infrequently after surgery because the bile ducts had a high potential for the development of carcinoma. The aggressive treatment including second resection for the multicentric recurrence appeared to be effective.
Fieldwork Using the Professional Development Schools Model: Developing a Social Justice Orientation and Multicultural Competency
Authors: Cook Amy L. , Krell Megan M. , Hayden Laura A. , Gracia Robert , Denitzio Kari
Published: July 2016

Practicum fieldwork was conducted in an urban high school setting using a Professional Development Schools (PDS) model, with a focus on multicultural and social justice counseling competencies (MSJCC). Interpretative phenomenological analysis was used to analyze the journal responses of 16 counseling students to ascertain MSJCC development during fieldwork. Themes emerged related to multicultural counseling skills, self‐awareness, understanding educational inequities, and serving as agents of change. Implications of using a PDS model in counselor training are explored.

Se llevó a cabo un trabajo de campo en práctica clínica en una escuela secundaria usando un modelo de Escuelas de Desarrollo Profesional (PDS, por sus siglas en inglés), con un enfoque en las competencias en consejería multicultural y de justicia social (MSJCC, por sus siglas en inglés). Se empleó un análisis fenomenológico interpretativo para analizar las respuestas registradas de 16 estudiantes de consejería para determinar el desarrollo de las MSJCC durante el trabajo de campo. Surgieron temas relacionados con las habilidades en consejería multicultural, la autoconciencia, la comprensión de desigualdades educativas, y la actuación como agentes de cambio. Se exploran las implicaciones de usar un modelo PDS en la formación de consejeros.
A Qualitative Investigation of College Students' Facebook Usage and Romantic Relationships: Implications for College Counselors
Authors: Sherrell Renee S. , Lambie Glenn W.
Published: July 2016

The use of social media is a societal trend influencing the way that individuals communicate with and relate to one another. Moreover, Facebook use may facilitate or hinder individuals' relationship growth and development. The purpose of this article is to (a) review research examining Facebook usage and interpersonal relationships, (b) present qualitative insight into the Facebook experiences of college students (N = 16) from a large southeastern university, and (c) offer implications for college counselors.
Stages of Change in Relationship Status Questionnaire: Development and Validation
Authors: Ritter Kathrin , Handsel Vanessa , Moore Todd
Published: July 2016

This study involved the development of the Stages of Change in Relationship Status (SOCRS) measure in 2 samples of college students. This scale is designed to measure how individuals progress through stages of change when terminating violent and nonviolent intimate relationships. Results indicated that the SOCRS is a reliable and valid tool to assess stages of change consistent with the guiding theory. Implications for practice are discussed.
Metamodernism: A New Philosophical Approach to Counseling
Authors: GARDNER LAUREN
Published: July 2016

Originating in the field of aesthetics, metamodernism is presented as a philosophical framework for understanding how contemporary counselors navigate networks of conflicting obligations and interests. Metamodernism provides a reconciling perspective on dilemmas counselors encounter in diverse social institutions and presents alternative ideas about integrating modernist structural compliance with postmodernist self‐invention.
Overwhelmed With the Burden of Being Myself: A Phenomenological Exploration of the Existential Experiences of Counselors‐in‐Training
Authors: PIERCE L. MARINN
Published: July 2016

Little research exists about the lived experiences of counselors‐in‐training during their practicum and internship experiences. The results of a phenomenological study exploring the existential experiences of counselors‐in‐training are presented. Implications for counselor development and supervision, as well as needs for future research and exploration, are discussed.
The Anguish of Freedom: Using an Existential Approach With Arab Immigrants
Authors: BASMA DAREEN , GIBBONS MELINDA M.
Published: July 2016

Influxes of Arab immigrants and refugees have contributed to the growth of the Arab American population. Migration can trigger feelings of alienation and isolation, identity confusion, and loss of meaning. This article uses an existential framework to explore this population's culture and pre‐ and postmigration stressors and to better conceptualize their needs.
Quantification of the degree of mixing of cellulose nanocrystals in thermoplastics using Raman spectroscopy
Authors: Lewandowska A. E. , Eichhorn S. J.
Published: July 2016

A combination of Raman imaging with image analysis has been used to quantify the degree of mixing of cellulose nanocrystals (CNCs) in melt compounded high‐density polyethylene (HDPE). Raman spectroscopy is shown to provide an accurate ‘fingerprint’ of the composition of the cross‐sectional area of the end section of a formed composite. This information is then converted to a chemical image allowing spatial quantification of the mixing of CNCs in the HDPE. A degree of mixing between CNCs and HDPE is reported, with a strong tendency for the former to agglomerate with little dispersion. Freeze‐dried CNCs show better mixing with HDPE and a lower tendency to agglomerate than spray‐dried CNCs. This approach shows the potential to use Raman spectroscopy to quantify the degree of mixing of CNCs in a thermoplastic matrix. Copyright © 2016 John Wiley & Sons, Ltd.
Composite generalized Laguerre spectral method for nonlinear Fokker–Planck equations on the whole line
Authors: Wang Tian‐jun
Published: July 2016

In this paper, we propose a composite Laguerre spectral method for the nonlinear Fokker–Planck equations modelling the relaxation of fermion and boson gases. A composite Laguerre spectral scheme is constructed. Its convergence is proved. Numerical results show the efficiency of this approach and coincide well with theoretical analysis. Some results on the Laguerre approximation and techniques used in this paper are also applicable to other nonlinear problems on the whole line. Copyright © 2016 John Wiley & Sons, Ltd.
Global stability of a multi‐group model with distributed delay and vaccination
Authors: Xu Jinhu , Geng Yan , Zhou Yicang
Published: July 2016

A delayed multi‐group SVEIR epidemic model with vaccination and a general incidence function has been formulated and studied in this paper. Mathematical analysis shows that the basic reproduction number
plays a key role in the dynamics of the model: the disease‐free equilibrium is globally asymptotically stable when
, while the endemic equilibrium exists uniquely and is globally asymptotically stable when
. For the proofs, we exploit a graph‐theoretical approach to the method of Lyapunov functionals. Our results show that distributed delay has no impact on the global stability of equilibria, and the results improve and generalize some known results. Copyright © 2016 John Wiley & Sons, Ltd.
Needle electromyography of the frontalis muscle in patients with amyotrophic lateral sclerosis
Authors: Pan Hua , Jian Fan , Lin Jinxi , Chen Na , Zhang Zaiqiang , Wang Yongjun , Cui Liying , Kimura Jun
Published: July 2016

Introduction: We sought to determine which muscles to choose for better assessment of the craniobulbar region in establishing the diagnosis of amyotrophic lateral sclerosis (ALS). Methods: We studied the frontalis muscle in 83 controls and compared it with the tongue, sternocleidomastoid (SCM), and trapezius muscles in 105 definite or probable ALS patients (54 bulbar, 51 nonbulbar). Results: More patients achieved complete relaxation of the frontalis muscle than the tongue or SCM. Motor unit potentials were of longer duration and higher amplitude in ALS patients than in controls (P < 0.05). The frontalis had the same frequency of spontaneous potentials as the tongue, SCM, and trapezius muscles in bulbar ALS patients, but fewer than in the trapezius in nonbulbar patients. Conclusions: Examining the frontalis provides useful information in establishing the diagnosis of ALS by identifying clinically evident or subclinical abnormalities in the craniobulbar region. Muscle Nerve 54: 1093–1096, 2016