bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimization of TRPV6 Calcium Channel Inhibitors Using a 3D Ligand‐Based Virtual Screening Method
Authors: Simonin Céline , Awale Mahendra , Brand Michael , van Deursen Ruud , Schwartz Julian , Fine Michael , Kovacs Gergely , Häfliger Pascal , Gyimesi Gergely , Sithampari Abilashan , Charles Roch‐Philippe , Hediger Matthias A. , Reymond Jean‐Louis 
Published: October 2015

AbstractHerein, we report the discovery of the first potent and selective inhibitor of TRPV6, a calcium channel overexpressed in breast and prostate cancer, and its use to test the effect of blocking TRPV6‐mediated Ca2+‐influx on cell growth. The inhibitor was discovered through a computational method, xLOS, a 3D‐shape and pharmacophore similarity algorithm, a type of ligand‐based virtual screening (LBVS) method described briefly here. Starting with a single weakly active seed molecule, two successive rounds of LBVS followed by optimization by chemical synthesis led to a selective molecule with 0.3 μM inhibition of TRPV6. The ability of xLOS to identify different scaffolds early in LBVS was essential to success. The xLOS method may be generally useful to develop tool compounds for poorly characterized targets.
Dirigent Proteins from Cotton (Gossypium sp.) for the Atropselective Synthesis of Gossypol
Authors: Effenberger Isabelle , Zhang Bin , Li Ling , Wang Qiang , Liu Yuxiu , Klaiber Iris , Pfannstiel Jens , Wang Qingmin , Schaller Andreas 
Published: October 2015

AbstractGossypol is a defense compound in cotton plants for protection against pests and pathogens. Gossypol biosynthesis involves the oxidative coupling of hemigossypol and results in two atropisomers owing to hindered rotation around the central binaphthyl bond. (+)‐Gossypol predominates in vivo, thus suggesting stereochemically controlled biosynthesis. The aim was to identify the factors mediating (+)‐gossypol formation in cotton and to investigate their potential for asymmetric biaryl synthesis. A dirigent protein from Gossypium hirsutum (GhDIR4) was found to confer atropselectivity to the coupling of hemigossypol in presence of laccase and O2 as an oxidizing agent. (+)‐Gossypol was obtained in greater than 80 % enantiomeric excess compared to racemic gossypol in the absence of GhDIR4. The identification of GhDIR4 highlights a broader role for DIRs in plant secondary metabolism and may eventually lead to the development of DIRs as tools for the synthesis of axially chiral binaphthyls.
Mechanical performance and flame retardancy of polypropylene composites containing zeolite and multiwalled carbon nanotubes
Authors: Zhao Qing , Hu Yanhong , Wang Xingyi 
Published: October 2015

ABSTRACTIntumescent‐flame‐retarded polypropylene (PP‐IFR) composites were prepared by the incorporation of methyl hydrogen siloxane treated ammonium polyphosphate and dipentaerythritol in a twin‐screw extruder. The effects of zeolite (Z), multiwalled carbon nanotubes (CNTs), and maleic anhydride grafted polypropylene on the flame retardancy, mechanical properties, and thermal stability of PP‐IFR were investigated. The addition of Z and CNT promoted the flame retardancy of PP‐IFR, and the highest limited oxygen index was 35.6%, obtained on PP‐M‐IFR‐2–Z, for which the heat‐release rate, total heat release, and smoke production rate based on cone calorimetry analyses decreased by 45.0, 51.0, and 66.3%, respectively, in comparison with those values of the PP‐IFR composites. Additionally, scanning electron microscopy analyses showed that there was a good interface interaction between the polypropylene matrix and additives. The flexural, tensile, and impact strengths of the PP‐IFR composites were improved significantly with the incorporation of CNT. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 42875.
Hyperbranched polyglycerol/poly(acrylic acid) hydrogel for the efficient removal of methyl violet from aqueous solutions
Authors: Ying Hao , He Guijin , Zhang Lifeng , Lei Qunfang , Guo Yongsheng , Fang Wenjun 
Published: October 2015

ABSTRACTHydrogels were synthesized from hyperbranched polyglycerol (HPG) and acrylic acid through free‐radical polymerization with HPG as the crosslinker. The HPG/poly(acrylic acid) (PAA) hydrogel could absorb cationic dyes in aqueous solutions because of the existence of a porous structure and the large numbers of hydroxyl and carboxylic groups. With methyl violet chosen as a model compound, the HPG/PAA hydrogel reached a maximum adsorption of 394.12 mg/g at a feed concentration of 1 g/L. The highest removal ratio of 98.33% was observed at a feed concentration of 50 mg/L. The effects of the pH, contact time, and feed concentration on the dye adsorption were investigated. The dye adsorption data fit well with the pseudo‐second‐order and Langmuir models. We believe that the HPG/PAA hydrogels could perform well in appropriate applications in the removal of cationic dyes from aqueous solutions because of their high adsorption capacity and environmental friendliness. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 42951.
Current and future prospects for CRISPR‐based tools in bacteria
Authors: Luo Michelle L. , Leenay Ryan T. , Beisel Chase L. 
Published: October 2015

ABSTRACTCRISPR‐Cas systems have rapidly transitioned from intriguing prokaryotic defense systems to powerful and versatile biomolecular tools. This article reviews how these systems have been translated into technologies to manipulate bacterial genetics, physiology, and communities. Recent applications in bacteria have centered on multiplexed genome editing, programmable gene regulation, and sequence‐specific antimicrobials, while future applications can build on advances in eukaryotes, the rich natural diversity of CRISPR‐Cas systems, and the untapped potential of CRISPR‐based DNA acquisition. Overall, these systems have formed the basis of an ever‐expanding genetic toolbox and hold tremendous potential for our future understanding and engineering of the bacterial world. Biotechnol. Bioeng. 2016;113: 930–943. © 2015 Wiley Periodicals, Inc.
Temperature‐sensitive miR‐483 is a conserved regulator of recombinant protein and viral vector production in mammalian cells
Authors: Emmerling Verena V. , Fischer Simon , Stiefel Fabian , Holzmann Karlheinz , Handrick René , Hesse Friedemann , Hörer Markus , Kochanek Stefan , Otte Kerstin 
Published: October 2015

ABSTRACTCell engineering and bioprocess optimizations such as low temperature cultivation represent powerful tools to improve cellular performance and product yields of mammalian production cells. Besides monoclonal antibodies (mABs), novel biotherapeutic formats such as viral vectors will gain increasing importance. Here, we demonstrate that similar to Chinese hamster ovary (CHO) cells, product yields of recombinant adeno‐associated virus (rAAV) producing HeLa cells can be markedly increased by low temperature cultivation. MicroRNAs (miRNAs) are small non‐coding RNAs that critically regulate cell phenotypes. We thus investigated differential miRNA expression in response to mild hypothermia in CHO and HeLa production cells. We discovered miR‐483 to be substantially up‐regulated upon temperature down‐shift in both cell types. Functional validation experiments revealed that introduction of miR‐483 mimics led to a significant increase in both rAAV and mAB production in HeLa and CHO cells, respectively. Furthermore, inhibition of miR‐483 up‐regulation during mild hypothermia significantly decreased product yields, suggesting that miR‐483 is a key regulator of cellular productivity in mammalian cells. In addition, miRNA target gene identification indicated that miR‐483 might regulate genes directly involved in cellular survival and protein expression. Our results highlight that miR‐483 is a valuable tool for product‐independent engineering of mammalian production cells. Biotechnol. Bioeng. 2016;113: 830–841. © 2015 Wiley Periodicals, Inc.
Wer denkt, der Mensch oder sein Gehirn?
Authors: Kirschfeld Kuno 
Published: October 2015

AbstractDie Kritik von Philosophen daran, wie Hirnforscher ihre experimentellen Ergebnisse interpretieren, beruht zum großen Teil auf der klassischen Methode der Philosophie: der Klärung von Begriffen. Danach wird zum Beispiel gefolgert: Die Behauptung, das Gehirn denke, ist Unsinn, denn denken kann nur der Mensch. Im Gegensatz hierzu zeigt die Hirnforschung, dass die im Gehirn ablaufenden Prozesse notwendig und hinreichend sind, um unser Denken zu erklären. Der Autor vertritt den Standpunkt, dass die Klärung von Begriffen deshalb nichts zur Frage der Funktion des Gehirn beitragen kann, weil bei der Entwicklung einer Sprache das damals aktuelle Weltbild in die Begriffe eingeht. Werden früher gebildete Begriffe auch heute noch verwendet, so können sie deswegen veraltet sein und müssen bei ihrer Klärung notwendigerweise in die Irre führen
Alfred Russel Wallace
Authors: Kutschera Ulrich 
Published: October 2015

AbstractAlfred R. Wallace (1823–1913) galt zeitlebens als Außenseiter der Biologie und steht noch heute im Schatten von Charles Darwin. Nach jahrelangen Forschungsreisen war der Freiberufler Wallace, der 22 Bücher und über 700 Publikationen verfasst hat, jedoch auf manchen Gebieten origineller als Darwin. In seinem 100. Todesjahr wird er unter anderem als (Mit)‐Begründer des Selektionsprinzips, der Neo‐Darwin'schen Theorie, Biogeografie, Astrobiologie, evolutionären Anthropologie, Biodiversitätsforschung und Vordenker der Naturschutz‐, Freidenker‐ und Humanistenbewegung gewürdigt, obwohl er als atheistischer Spiritist irrationale Thesen vertrat, die seinem Ansehen bis heute geschadet haben.
Freunde der Finsternis: Asseln und Tausendfüßer
Authors: Petrischak Hannes 
Published: October 2015

AbstractUnter Steinen, Brettern und Blumentöpfen erschließt sich im Garten ein eigener Kosmos: Schaut man darunter, laufen viele Tiere hektisch in Richtung der nächsten Schlupfwinkel. Sowohl Substratzersetzer als auch Räuber sind hier zu Hause und werden in der Nacht aktiv. Neben einigen Käfern, Würmern, Spinnen und Schnecken dominieren Asseln (Isopoda) und Tausendfüßer (Myriapoda) in diesen Boden‐Lebensräumen. Sie zeigen höchst spannende Anpassungen an ihre spezialisierte Lebensweise.
Knöllchenbakterien: Helfer der Landwirtschaft
Authors: Zehner Susanne , Göttfert Michael 
Published: October 2015

AbstractIn diesem Jahr wurde das Knöllchenbakterium durch die VAAM zur “Mikrobe des Jahres” gekürt. Knöllchenbakterium ist ein Sammelbegriff für eine Vielzahl unterschiedlicher Arten, die in der Lage sind, mit Leguminosen eine Wurzelknöllchensymbiose einzugehen. Während der Symbiose sind die zu Bacteroiden differenzierten Bakterien mit einer weiteren Membran umhüllt und sie leben in großer Zahl in Zellen des Knöllchens. Sie fixieren Luftstickstoff, der von den Pflanzen genutzt wird. Im Gegenzug müssen sie komplett von der Pflanze versorgt werden. Die Symbiose wird durch einen Signalaustausch zwischen den Symbiosepartnern initiiert. Die ersten spezifischen Signale werden von der Pflanze im Wurzelraum abgegeben. Es sind Flavonoide, die die Bakterien zur Bildung von Nod‐Faktoren anregen, die wiederum Signale für die Pflanze sind. Neben dieser bei fast allen Rhizobien vorhandenen Grundausstattung sind bei allen Rhizobien extrazelluläre Moleküle in wechselnder Zusammensetzung an der Etablierung der Symbiose beteiligt.
Botschaft aus der Tiefsee: Wie sich Prokaryoten zu Eukaryoten wandelten
Authors: Tetsch Larissa 
Published: October 2015

AbstractDie Entstehung von Eukaryoten aus Prokaryoten, vor allem die damit einhergehende Zunahme der Zellkomplexität, gibt noch immer Rätsel auf. Neue phylogenetische Studien deuten an, dass die Eukarya (die alle Eukaryoten enthaltende Domäne nach C. Woese) aus den Archaea hervorgegangen sind und ihr gemeinsamer Vorfahre deutlich komplexer war, als alle heute bekannten Archaeen. Schwedische Forscher stellten eine Archaeenlinie aus der Tiefsee vor, die den nächsten Verwandten der Eukarya darstellt und wohl ein dynamisches Cytoskelett sowie die Fähigkeit zur Phagozytose besitzt.
Wägeschiffchen im Eigenbau
Authors: Hauk Andrea 
Published: October 2015

AbstractWägen ist eine der häufigsten Labortätigkeiten. Jeder Labormitarbeiter wurde schon bestimmt mehr als einmal in seinem Berufsleben damit konfrontiert, eine bestimmte Menge pulvrige Substanz abzuwiegen, in einen Messkolben zu überführen und daraus eine definierte Lösung herzustellen. Mit ein paar einfachen Handgriffen können Sie sich Ihr Wägeschiffchen selbst falten.
Factors affecting morbidity after conversion of laparoscopic colorectal resections
Authors: Aytac E , Stocchi L , Ozdemir Y , Kiran R P 
Published: October 2015

Abstract

Background
The impact of conversion on postoperative outcomes of laparoscopic colorectal surgery remains controversial. The purpose of this study was to assess whether a conversion results in increased postoperative morbidity and mortality, and to evaluate whether any specific factors affect the outcomes of converted procedures.

Methods
Outcomes of procedures requiring conversion among patients undergoing elective laparoscopic colorectal resection between 1992 and 2011 were compared with those for operations completed laparoscopically. Subset analyses were also performed to evaluate the selective impact of patient-, disease- and treatment-related factors and the timing of conversion during surgery on outcomes. Primary endpoints were postoperative mortality and morbidity.

Results
Of 2483 patients undergoing laparoscopic colorectal resection, 270 (10·9 per cent) required conversion to open surgery. The 30-day postoperative mortality rate was comparable after laparoscopically completed and converted procedures (0·4 versus 0 per cent respectively; P = 0·610). Factors significantly associated with morbidity after conversion were smoking, cardiovascular co-morbidity, previous abdominal operations (particularly colectomy or hysterectomy) and adhesions. Overall morbidity was not affected by conversion (27·0 per cent at 30 days in both groups; P &gt; 0·999). However, patients experiencing morbidity tended to have had earlier conversions: median (range) 40 (15–90) min into surgery versus 50 (15–240) min for those who did not develop morbidity (P = 0·006). The risk of reoperation for postoperative morbidity was higher following conversion because of complications (13 versus 2·9 per cent; P = 0·024).

Conclusion
Conversions of laparoscopic colorectal resection are not associated with increased overall morbidity, regardless of the timing of conversion.
Assessment of abdominoperineal resection rate as a surrogate marker of hospital quality in rectal cancer surgery
Authors: Jorgensen M L , Young J M , Dobbins T A , Solomon M J 
Published: October 2015

Abstract

Background
Rates of abdominoperineal resection (APR) have been suggested as a solitary surrogate marker for comparing overall hospital quality in rectal cancer surgery. This study investigated the value of this marker by examining the associations between hospital APR rates and other quality indicators.

Methods
Hospital-level correlations between risk-adjusted APR rates for low rectal cancer and six risk-adjusted outcomes and six care processes were performed (such as 30-day mortality, complications, timely treatment). The ability of APR rates to discriminate between hospitals' performance was examined by means of hospital variance results in multilevel regression models and funnel plots.

Results
A linked population-based data set identified 1703 patients diagnosed in 2007 and 2008 who underwent surgery for rectal cancer. Some 15·9 (95 per cent confidence interval (c.i.) 14·2 to 17·6) per cent of these patients had an APR. Among 707 people with low rectal cancer, 38·2 (34·6 to 41·8) per cent underwent APR. Although risk-adjusted hospital rates of APR for low rectal cancer varied by up to 100 per cent, only one hospital (1 per cent) fell outside funnel plot limits and hospital variance in multilevel models was not very large. Lower hospital rates of APR for low rectal cancer did not correlate significantly with better hospital-level outcomes or process measures, except for recording of pathological stage (r = −0·55, P = 0·019). Patients were significantly more likely to undergo APR for low rectal cancer if they attended a non-tertiary metropolitan hospital (adjusted odds ratio 2·14, 95 per cent c.i. 1·11 to 4·15).

Conclusion
APR rates do not appear to be a useful surrogate marker of overall hospital performance in rectal cancer surgery.
Simultaneous quantification of morphine and cocaine in hair samples from drug addicts by GC‐EI/MS
Authors: Gouveia Carla Alexandra , Oliveira Ana , Pinho Sandra , Vasconcelos Carlos , Carvalho Félix , Moreira Roxana Falcão , Dinis‐Oliveira Ricardo Jorge 
Published: October 2015

ABSTRACTThe development of analytical techniques that enable the use of hair as an alternative matrix for the analysis of drugs of abuse is useful for confirming the exposure in a larger time window (weeks to months, depending on the length of the hair shaft). In the present study a methodology aimed at the simultaneous quantification of cocaine and morphine in human hair was developed and validated. After decontamination, hair samples (20 mg) were incubated with a mixture of methanol/hydrochloric acid (2:1) at 65 °C overnight (~16 h) in order to extract the drugs of the matrix. Purification was performed by solid‐phase extraction using mixed‐mode extraction cartridges. After derivatization with N‐methyl‐N‐(trimethylsilyl) trifluoroacetamide, blank, standards and samples were analyzed by gas chromatography/electron impact–mass spectrometry (GC‐EI/MS). The method proved to be selective, as there were no interferences of endogenous compounds with the same retention time as cocaine, morphine and ethylmorphine (internal standard). The regression analysis for both analytes showed linearity in the range 0.25–10.00 ng/mg with correlation coefficients ranging from 0.9989 to 0.9991. The coefficients of variation oscillated between 0.83 and 14.60%. The limits of detection were 0.01 and 0.02 ng/mg, and the limits of quantification were 0.03 and 0.06 ng/mg for cocaine and morphine, respectively. The proposed GC‐EI/MS method provided an accurate and simple assay with adequate precision and recovery for the quantification of cocaine and morphine in hair samples. The proof of applicability was performed in hair samples obtained from drug addicts enrolled in a Regional Detoxification Treatment Center. The importance of hair samples is highlighted, since positives results were obtained when urine immunoassay analyses were negative. Copyright © 2012 John Wiley & Sons, Ltd.
Taking the measure of metrics: Interviews with four ASIS&T members
Authors: Sugimoto Cassidy R. 
Published: October 2015

AbstractEditor's SummaryA series of interviews with four ASIS&T members, all outstanding scholars in metric‐related research, provides insights into their interests, motivations and views on research in the area. Christine L. Borgman recalls being intrigued as a student when hearing about the history of bibliometrics, and she sees expanding metrics research methods as one of the most significant recent advances in the field. Blaise Cronin speaks of reading, meeting and corresponding with leaders in the field from early in his own career. He is impressed by the rise of journals other than JASIST covering informetrics, reflecting expanding interest in the field. Katherine W. McCain was drawn to the field when she was recognized for a citation analysis and collection assessment carried out while she served as a biology librarian. Among the challenges McCain identifies are more meaningful analysis of huge datasets, research funding and gaining understanding through the different perspectives of boundary spanners. Howard White recalls how a friendly conversation led to special access to a proprietary data gathering tool, resulting in the first author co‐citation map and his co‐authoring a highly acclaimed article. He notes significant advances in the mathematical foundations of bibliometrics and a rise in importance of bibliometrics for assessing national research programs. All four researchers are pleased to see the rise of altmetrics and data visualization capabilities, though they share concerns about the validity and reliability of metrics‐based research and trustworthiness of platforms and data sets.
Gene expression profiling upon 212Pb‐TCMC‐trastuzumab treatment in the LS‐174T i.p. xenograft model
Authors: Yong Kwon J. , Milenic Diane E. , Baidoo Kwamena E. , Kim Young‐Seung , Brechbiel Martin W. 
Published: October 2015

AbstractRecent studies have demonstrated that therapy with 212Pb‐TCMC‐trastuzumab resulted in (1) induction of apoptosis, (2) G2/M arrest, and (3) blockage of double‐strand DNA damage repair in LS‐174T i.p. (intraperitoneal) xenografts. To further understand the molecular basis of the cell killing efficacy of 212Pb‐TCMC‐trastuzumab, gene expression profiling was performed with LS‐174T xenografts 24 h after exposure to 212Pb‐TCMC‐trastuzumab. DNA damage response genes (84) were screened using a quantitative real‐time polymerase chain reaction array (qRT‐PCR array). Differentially regulated genes were identified following exposure to 212Pb‐TCMC‐trastuzumab. These included genes involved in apoptosis (ABL, GADD45α, GADD45γ, PCBP4, and p73), cell cycle (ATM, DDIT3, GADD45α, GTSE1, MKK6, PCBP4, and SESN1), and damaged DNA binding (DDB) and repair (ATM and BTG2). The stressful growth arrest conditions provoked by 212Pb‐TCMC‐trastuzumab were found to induce genes involved in apoptosis and cell cycle arrest in the G2/M phase. The expression of genes involved in DDB and single‐strand DNA breaks was also enhanced by 212Pb‐TCMC‐trastuzumab while no modulation of genes involved in double‐strand break repair was apparent. Furthermore, the p73/GADD45 signaling pathway mediated by p38 kinase signaling may be involved in the cellular response, as evidenced by the enhanced expression of genes and proteins of this pathway. These results further support the previously described cell killing mechanism by 212Pb‐TCMC‐trastuzumab in the same LS‐174T i.p. xenograft. Insight into these mechanisms could lead to improved strategies for rational application of radioimmunotherapy using α‐particle emitters.
A critique of the ontology of consumer enchantment
Authors: Ostergaard Per , Fitchett James , Jantzen Christian 
Published: October 2015

ABSTRACTThe concept of enchantment offers a plausible explanation of the lures and thrills of consumer culture. We examine the theoretical foundation of the concept through a critique of Ritzer's enchantment thesis. We begin by assessing the enchantment/disenchantment discourse through a review of the main theoretical contributions to the area, first summarizing Max Weber's initial outline of the notion of disenchantment in the Protestant Ethic and Spirit of Capitalism. We then consider Colin Campbell's critique of Weber and George Ritzer's development in Enchanting a Disenchanted World. Finally, we apply Jean Baudrillard's Order of Simulacra to further resolve some of the open questions concerning the possibility of enchantment in contemporary consumer culture. Copyright © 2013 John Wiley & Sons, Ltd.