bluuebunny/crossref_metadata_2025 huggingface dataset:
Stimulation through very late antigen‐4 and ‐5 improves the multifunctionality and memory formation of CD8+ T cells
Authors: Hosoi Hayato , Ikeda Hiroaki , Imai Naoko , Amaike Chisaki , Wang Linan , Orito Yuki , Yamane Makiko , Ueno Hiroaki , Ideno Mitsuko , Nukaya Ikuei , Enoki Tatsuji , Mineno Junichi , Takesako Kazutoh , Hirano Satoshi , Shiku Hiroshi
Published: April 2014

T cells express multiple integrin molecules. The significance of signaling through these molecules on acquisition of T‐cell effector functions and memory formation capacity remains largely unknown. Moreover, the impact of stimulation through these signals on the generation of T cells for adoptive immunotherapy has not been elucidated. In this study, using a recombinant fragment of fibronectin, CH‐296, we demonstrated that stimulation via very late Ag (VLA)‐4 and VLA‐5 in human and BALB/c mouse CD8+ T cells, in combination with TCR stimulation, enhances effector multifunctionality and in vivo memory formation. Using TCR‐transgenic mouse‐derived CD8+ T cells expressing TCR specific for the syngeneic CMS5 fibrosarcoma‐derived tumor Ag, we showed that stimulation by CH‐296 improved the ability of tumor‐specific CD8+ T cells to inhibit CMS5 tumor growth when adoptively transferred into hosts with progressing tumors. Improved antitumor effects were associated with decreased infiltration of Foxp3+CD4+ Treg cells in tumors. These results suggest that stimulation via VLA‐4 and VLA‐5 modulates the qualities of effector T cells and could potentially increase the efficacy of adoptive therapy against cancer.
The human long noncoding RNA lnc‐IL7R regulates the inflammatory response
Authors: Cui Huachun , Xie Na , Tan Zheng , Banerjee Sami , Thannickal Victor John , Abraham Edward , Liu Gang
Published: April 2014

Long noncoding RNAs (lncRNAs), once thought to be transcriptional noise, have been recently shown to regulate a variety of biological processes. However, there is not much knowledge regarding their roles in the inflammatory response. In this study, we performed human lncRNA microarray assays and identified a number of lncRNAs that demonstrated altered expression in response to LPS stimulation. Of these lncRNAs, lnc‐IL7R, which overlaps with the 3′untranslated region (3′UTR) of the human interleukin‐7 receptor α‐subunit gene (IL7R) gene, was significantly upregulated in LPS‐treated cells. Functionally, lnc‐IL7R was capable of diminishing the LPS‐induced inflammatory response, demonstrated by elevated expression of LPS‐induced E‐selectin, VCAM‐1, IL‐6, and IL‐8 in lnc‐IL7R knockdown cells. Mechanistically, we found that lnc‐IL7R knockdown diminished trimethylation of histone H3 at lysine 27 (H3K27me3), a hallmark of silent transcription, at the proximal promoters of the inflammatory mediators. Our data suggest that lnc‐IL7R contributes another layer of complexity in regulation of the inflammatory response.
Relative Kinetic Reactivities of Boronic Acids and Boronate Ions toward 1,2‐Diols
Authors: Okamoto Takuya , Tanaka Asumi , Watanabe Eisuke , Miyazaki Takehiro , Sugaya Tomoaki , Iwatsuki Satoshi , Inamo Masahiko , Takagi Hideo D. , Odani Akira , Ishihara Koji
Published: April 2014

The following reaction systems, with and without proton ambiguity, were set up for direct measurements of the rate constants of borate and boronate ions: boric acid [B(OH)3] and 4,5‐dihydroxy‐1,3‐benzenedisulfonic acid disodium salt (Tiron); 3‐nitrophenylboronic acid [3‐NO2PhB(OH)2] and Tiron; phenylboronic acid [PhB(OH)2] and 4‐nitrocatechol; boric acid and 4‐nitrocatechol. Each rate constant for boric or boronic acid is larger than that for the conjugate borate or boronate ion for the reaction systems without proton ambiguity. These results explicitly indicate that the widespread belief that the rate constants of boronate ions are several orders of magnitude larger than those of the conjugate boronic acids is erroneous. The relative kinetic reactivities of RB(OH)2 and RB(OH)3– were investigated in relation to the linear free energy relationships between the rate constants and acidities of the boronic acids and diols.
Domino Recombinant γ‐Isomerization and Reverse Wacker Oxidation of γ‐Vinyl‐γ‐butyrolactone: Synthesis of (+)‐trans‐, (–)‐ and (+)‐Disparlures
Authors: Bethi Venkati , Kattanguru Pullaiah , Fernandes Rodney A.
Published: April 2014

A domino palladium‐catalyzed recombinant γ‐isomerization and reverse Wacker oxidation of γ‐vinyl‐γ‐butyrolactone has been explored. The strategy has been used in the stereoselective synthesis of (+)‐trans‐, (–)‐ and (+)‐disparlures. The synthesis was achieved in seven to eight steps from D‐glucono‐δ‐lactone with overall yields of 19.3, 20.7 and 22.6 %, respectively.
Fluorinated Sulfoximines: Preparation, Reactions and Applications
Authors: Shen Xiao , Hu Jinbo
Published: April 2014

The selective incorporation of fluorine atoms or fluorinated moieties into organic molecules has become a “hot” research topic in modern organic chemistry. However, selective and efficient synthesis of organofluorine compounds greatly depends on the development of powerful fluorination or fluoroalkylation reagents and reactions. In this context, the past decade has witnessed rapid research progress in the development of α‐fluoro sulfoximines as versatile fluoroalkylation reagents. Many efficient nucleophilic, electrophilic and radical fluoroalkylation reactions based on α‐fluoro sulfoximine reagents have been developed; among these, several chiral sulfoximine reagents were successfully used in the synthesis of enantiomerically enriched organofluorine compounds. It was found that α‐fluoro sulfoximines show unique chemical behaviour characteristics (such as difluorocarbene and fluoroalkyl radical reactivities) significantly different from those of their non‐fluorinated counterparts. In addition to the rapid development of fluorinated sulfoximines in organic synthesis, research into their application in materials science has also attracted increasing attention. Sulfoximines are important bioactive substances, and more recently the synthesis and application of fluorinated sulfoximines has attracted much attention in life sciences and the pharmaceutical industry. In this microreview we summarize the preparation, reactions and applications of fluorinated sulfoximines (mainly α‐fluoro sulfoximines).
Diversity study of 12 X‐chromosomal STR loci in Hui ethnic from China
Authors: Meng Hao‐Tian , Han Jun‐Tao , Zhang Yu‐Dang , Liu Wen‐Juan , Wang Tian‐Ju , Yan Jiang‐Wei , Huang Jing‐Feng , Du Wei‐An , Guo Jian‐Xin , Wang Hong‐Dan , Zhang Yu‐Hong , Zhou Ru‐Hua , Zhu Bo‐Feng , Wei Xing
Published: April 2014

X‐chromosomal STRs (X‐STRs) have been used as complements of autosomal STR application in recent years. In this work, we present population genetic data of 12 X‐STRs including DXS101, DXS10159, DXS10162, DXS10164, DXS6789, DXS7133, DXS7423, DXS7424, DXS8378, DXS981, GATA165B12, and GATA31E08 loci in a sample of 231 unrelated healthy individuals from the Hui ethnic group in Ningxia Hui Autonomous Region, China. Allelic frequencies of the 12 X‐STR loci and haplotypic frequencies of the reported linkage groups (DXS7424‐DXS101 and DXS10159‐DXS10164‐DXS10162) were investigated in the group, respectively. No STR loci showed significant deviations from the Hardy–Weinberg equilibriums and no linkage disequilibriums of pairwise loci were found after Bonferroni correction, respectively. A combined power of discrimination in female individuals was 0.999999999985 and that in male individuals was 0.99999967, respectively. The combined mean exclusion chance in deficiency cases, normal trios and duo cases were 0.999934, 0.995754, and 0.999796, respectively. Significant differences were observed from 0 to 8 loci, when making comparisons between the data of Hui ethnic group and previously reported data from other 16 populations. The results indicated the new panel of 12 X‐STR loci might be useful for forensic science application.
Carbon dioxide biofixation by Chlorella vulgaris at different CO2 concentrations and light intensities
Authors: Clément‐Larosière Barbara , Lopes Filipa , Gonçalves Ana , Taidi Behnam , Benedetti Marc , Minier Michel , Pareau Dominique
Published: April 2014

In order to develop an effective CO2 mitigation process using microalgae for potential industrial application, the growth and physiological activity of Chlorella vulgaris in photobioreactor cultures were studied. C. vulgaris was grown at two CO2 concentrations (2 and 13% of CO2 v/v) and at three incident light intensities (50, 120 and 180 μmol m−2 s−1) for 9 days. The measured specific growth rate was similar under all conditions tested but an increase in light intensity and CO2 concentration affected the biomass and cell concentrations. Although carbon limitation was observed at 2% CO2, similar cellular composition was measured in both conditions. Light limitation induced a net change in the growth behavior of C. vulgaris. Nitrogen limitation seemed to decrease the nitrogen quota of the cells and rise the intracellular carbon:nitrogen ratio. Exopolysaccharide production per cell appeared to be affected by light intensity. In order to avoid underestimation of the CO2 biofixation rate of the microalgae, exopolysaccharide production was taken into account. The maximum CO2 removal rate (0.98 g CO2 L−1 d−1) and the highest biomass concentration (4.14 g DW L−1) were determined at 13% (v/v) CO2 and 180 μmol m−2 s−1. Our results show that C. vulgaris has a real potential for industrial CO2 remediation.
From h to p efficiently: optimal implementation strategies for explicit time‐dependent problems using the spectral/hp element method
Authors: Bolis A. , Cantwell C. D. , Kirby R. M. , Sherwin S. J.
Published: April 2014

We investigate the relative performance of a second‐order Adams–Bashforth scheme and second‐order and fourth‐order Runge–Kutta schemes when time stepping a 2D linear advection problem discretised using a spectral/hp element technique for a range of different mesh sizes and polynomial orders. Numerical experiments explore the effects of short (two wavelengths) and long (32 wavelengths) time integration for sets of uniform and non‐uniform meshes. The choice of time‐integration scheme and discretisation together fixes a CFL limit that imposes a restriction on the maximum time step, which can be taken to ensure numerical stability. The number of steps, together with the order of the scheme, affects not only the runtime but also the accuracy of the solution. Through numerical experiments, we systematically highlight the relative effects of spatial resolution and choice of time integration on performance and provide general guidelines on how best to achieve the minimal execution time in order to obtain a prescribed solution accuracy. The significant role played by higher polynomial orders in reducing CPU time while preserving accuracy becomes more evident, especially for uniform meshes, compared with what has been typically considered when studying this type of problem.© 2014. The Authors. International Journal for Numerical Methods in Fluids published by John Wiley & Sons, Ltd.
The ENCODE Project and Perspectives on Pathways
Authors: Tragante Vinicius , Moore Jason H. , Asselbergs Folkert W.
Published: April 2014

The recently completed ENCODE project is a new source of information on metabolic activity, unveiling knowledge about evolution and similarities among species, refuting the myth that most DNA is “junk” and has no actual function. With this expansive resource comes a challenge: integrating these new layers of information into our current knowledge of single‐nucleotide polymorphisms and previously described metabolic pathways with the aim of discovering new genes and pathways related to human diseases and traits. Further, we must determine which computational methods will be most useful in this pursuit. In this paper, we speculate over the possible methods that will emerge in this new, challenging field.
A comparison of nutrient export at two agricultural catchments: insight into the effect of increasing urban land cover in southern Ontario
Authors: Raney Shanel M. , Eimers M. Catherine
Published: April 2014

This study compared concentrations and export of total phosphorus (TP; including dissolved and particulate forms) and nitrogen (N) between quickflow and delayed flow at two adjacent agricultural catchments (Jennings and McLarens Creeks), one of which is undergoing increased urbanization. Annual runoff, frequency of quickflow events in the growing season (GS), and chloride (Cl−) concentrations and export were greater at the more urbanized Jennings Creek. There were only modest differences in TP and total dissolved P between the two catchments, with the largest difference occurring in the GS, when the urbanized Jennings Creek had higher TP concentrations and export. In contrast, the majority of N export was as dissolved inorganic nitrate‐N (NO3−–N), and NO3−–N concentrations and export were consistently greater at the more agricultural McLarens Creek. Particulate P was sensitive to increases in quickflow, with particulate P accounting for approximately 75% of TP export during GS events. In contrast, NO3−–N export was less influenced by hydrologic conditions than P and appears to be delivered to these streams primarily by subsurface flow, which resulted in greater NO3−–N export during delayed flow compared with events at both catchments. Overall, these results suggest that urban cover at Jennings Creek has impacted streamflow with more frequent quickflow events during the GS and substantially higher stream Cl−, although the influence of urban increases at the expense of agricultural land on P and N export was less clear. Copyright © 2014 John Wiley & Sons, Ltd.
The interplay between alcohol consumption, oral hygiene, ALDH2 and ADH1B in the risk of head and neck cancer
Authors: Tsai Sen‐Tien , Wong Tung‐Yiu , Ou Chun‐Yen , Fang Sheen‐Yie , Chen Ken‐Chung , Hsiao Jenn‐Ren , Huang Cheng‐Chih , Lee Wei‐Ting , Lo Hung‐I , Huang Jehn‐Shyun , Wu Jiunn‐Liang , Yen Chia‐Jui , Hsueh Wei‐Ting , Wu Yuan‐Hua , Yang Ming‐Wei , Lin Forn‐Chia , Chang Jang‐Yang , Chang Kwang‐Yu , Wu Shang‐Yin , Liao Hsiao‐Chen , Lin Chen‐Lin , Wang Yi‐Hui , Weng Ya‐Ling , Yang Han‐Chien , Chang Jeffrey S.
Published: April 2014

Alcohol consumption is an established risk factor for head and neck cancer (HNC). The major carcinogen from alcohol is acetaldehyde, which may be produced by humans or by oral microorganisms through the metabolism of ethanol. To account for the different sources of acetaldehyde production, the current study examined the interplay between alcohol consumption, oral hygiene (as a proxy measure for the growth of oral microorganisms), and alcohol‐metabolizing genes (ADH1B and ALDH2) in the risk of HNC. We found that both the fast (*2/*2) and the slow (*1/*1 + *1/*2) ADH1B genotypes increased the risk of HNC due to alcohol consumption, and this association differed according to the slow/non‐functional ALDH2 genotypes (*1/*2 + *2/*2) or poor oral hygiene. In persons with the fast ADH1B genotype, the HNC risk associated with alcohol drinking was increased for those with the slow/non‐functional ALDH2 genotypes. For those with the slow ADH1B genotypes, oral hygiene appeared to play an important role; the highest magnitude of an increased HNC risk in alcohol drinkers occurred among those with the worst oral hygiene. This is the first study to show that the association between alcohol drinking and HNC risk may be modified by the interplay between genetic polymorphisms of ADH1B and ALDH2 and oral hygiene. Although it is important to promote abstinence from or reduction of alcohol drinking to decrease the occurrence of HNC, improving oral hygiene practices may provide additional benefit.
Human papillomavirus infection is rare in nonmalignant tonsil tissue in the UK: Implications for tonsil cancer precursor lesions
Authors: Palmer Elizabeth , Newcombe Robert G. , Green Adele C. , Kelly Carole , Noel Gill O. , Hall Gillian , Fiander Alison N. , Pirotte Evelyne , Hibbitts Sam J. , Homer Jarrod , Powell Ned G.
Published: April 2014

The incidence of human papillomavirus (HPV)‐associated tonsil cancer is increasing but the prevalence of HPV, and of premalignant precursors, in tonsil tissue is unknown. We aimed to assess prevalence of HPV infection in nonmalignant tonsillar crypt epithelia and to histopathologically characterise positive samples. Formalin‐fixed paraffin‐embedded (FFPE) tonsil tissue specimens were obtained from an age‐ and sex‐stratified random sample of patients aged 0–69 years whose paired tonsils were archived following elective tonsillectomy at hospitals throughout England and Southern Scotland from 2004 to 2008. Homogenised fresh‐frozen tonsil tissue was also obtained from archive for two random subsets of males aged 25–34 and over 44. HPV status was assessed in all samples for 20 mucosal HPV types by GP5+/6+ polymerase chain reaction (PCR) enzyme immunoassay and by HPV16 type‐specific PCR targeting the E6 gene. In the homogenised material, HPV status was also assessed for 44 HPV types by SPF10‐PCR enzyme immunoassay. Of 4,095 randomly sampled FFPE specimens, amplifiable DNA was extracted from 3,377 (82.5%) and from 511 of 524 (97.5%) homogenised tonsils. HPV DNA was identified in 0 of 3,377 (0%, 95% CI 0–0.089%) fixed samples and 0 of 511 (0%, 95% CI 0–0.58%) homogenised samples. This suggests HPV infection may be rare in tonsil reticulated crypt epithelia. Furthermore, we found no evidence of HPV‐associated premalignant neoplasia. These data suggest that if HPV‐associated premalignant lesions do occur, they are likely to be rare and may have a high risk of progression to carcinoma.
Multiscale Quantum‐Classical Simulations of Enzymes
Authors: Doron Dvir , Weitman Michal , Vardi‐Kilshtain Alexandra , Azuri Asaf , Engel Hamutal , Major Dan T.
Published: April 2014

Enzymes are remarkably efficient catalysts evolved to perform well‐defined and highly specific chemical transformations. Studying the nature of enzymatic rate enhancements is highly important from several aspects, including the rational design of synthetic catalysts and transition‐state inhibitors. Herein, we describe recent progress in our group in the development of multiscale simulation methods and their application to several enzyme systems. In particular, we describe the use of combined quantum mechanics/molecular mechanics (QM/MM) methods in classical and quantum simulations. The development of various novel path‐integral methods is reviewed. These methods are tailor‐made for enzyme systems, where only a few degrees of freedom involved in the chemistry need to be quantized. The application of the hybrid QM/MM quantum‐classical simulation approach to three case studies is presented. The first case involves proton transfer in nitroalkane oxidase, where the enzyme employs tunneling as a catalytic fine‐tuning tool. The second case presented involves orotidine 5′‐monophosphate decarboxylase, where multidimensional free energy simulations together with kinetic isotope effects are combined in the study of the reaction mechanism. Finally, we discuss the monoterpene cyclase bornyl diphosphate synthase, where non‐statistical dynamics is a key component in enzyme function.
Low‐frequency sonication may alter surface topography of endoprosthetic components and damage articular cartilage without eradicating biofilms completely
Authors: Singh Gurpal , Hameister Rita , Feuerstein Bernd , Awiszus Friedemann , Meyer Heiko , Lohmann Christoph H.
Published: April 2014

Two‐stage exchange arthroplasty is the current standard of care for arthroplasty‐related infections. Reinfection rates up to 30% are reported, and there is significant morbidity for the patient. In cases of failure, arthrodesis or amputation may result. Ultrasonic treatment has the potential to eradicate biofilms and avoid two‐stage exchange arthroplasty. Data in the specific context of arthroplasty infections is scant, and there is debate regarding optimal frequency and intensity of treatment. Surface topography alterations of the endoprosthetic components and damage to adjacent bone and cartilage have not been investigated. We found incomplete biofilm eradication and significant increase in surface roughness (maximum peak‐to‐valley height) of cobalt‐chrome unicondylar knee components as well as reduction in articular cartilage thickness area from 10 retrieved femoral heads after low‐frequency sonication treatment according to manufacturer‐specified recommendations. Our data collectively suggest that sonication treatment for biofilm eradication in arthroplasty infections may not be effective and surface topography alterations may potentially reduce implant longevity. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 1835–1846, 2014.
Aberrant neuronal differentiation and inhibition of dendrite outgrowth resulting from endoplasmic reticulum stress
Authors: Kawada Koichi , Iekumo Takaaki , Saito Ryo , Kaneko Masayuki , Mimori Seisuke , Nomura Yasuyuki , Okuma Yasunobu
Published: April 2014

Neural stem cells (NSCs) play an essential role in development of the central nervous system. Endoplasmic reticulum (ER) stress induces neuronal death. After neuronal death, neurogenesis is generally enhanced to repair the damaged regions. However, it is unclear whether ER stress directly affects neurogenesis‐related processes such as neuronal differentiation and dendrite outgrowth. We evaluated whether neuronal differentiation and dendrite outgrowth were regulated by HRD1, a ubiquitin ligase that was induced under mild conditions of tunicamycin‐induced ER stress. Neurons were differentiated from mouse embryonic carcinoma P19 cells by using retinoic acid. The differentiated cells were cultured for 8 days with or without tunicamycin and HRD1 knockdown. The ER stressor led to markedly increased levels of ER stress. ER stress increased the expression levels of neuronal marker βIII‐tubulin in 8‐day‐differentiated cells. However, the neurites of dendrite marker microtubule‐associated protein‐2 (MAP‐2)‐positive cells appeared to retract in response to ER stress. Moreover, ER stress markedly reduced the dendrite length and MAP‐2 expression levels, whereas it did not affect the number of surviving mature neurons. In contrast, HRD1 knockdown abolished the changes in expression of proteins such as βIII‐tubulin and MAP‐2. These results suggested that ER stress caused aberrant neuronal differentiation from NSCs followed by the inhibition of neurite outgrowth. These events may be mediated by increased HRD1 expression. © 2014 The Authors Journal of Neuroscience Research Published by Wiley Periodicals, Inc.
Subseasonal variations of Indian summer monsoon with special emphasis on drought and excess rainfall years
Authors: Singh P. , Vasudevan V. , Chowdary J. S. , Gnanaseelan C.
Published: April 2014

Indian Summer Monsoon Rainfall (ISMR) experiences quasi‐periodic drought and excess rainfall. In this study we examined the contribution of individual month's (June–September) rainfall in the seasonal excess (deficit). Analysis of 110 years (1901–2010) of observed precipitation and 20th century reanalysis data highlights the importance of subseasonal variations of rainfall in modulating Indian summer monsoon. A month which contributes to seasonal excess (deficit) is primarily controlled by large‐scale La Niña (El Niño) forcing but with favourable local conditions from the tropical Indian Ocean. On the other hand excess (deficit) rainfall of an individual month which is not contributing to seasonal excess (deficit) is controlled mainly by the local forcing. Such local forcing however is short lived and does not persist more than a month. Our analysis reveals that June is not contributing considerably to the seasonal excess rainfall in the recent years. On the other hand contribution of September rainfall to the seasonal extremes is more frequent in the recent years. During September enhanced El Niño (La Niña) conditions and the local forcing contribute to the seasonal ISMR deficit (excess). It is important to note that none of the above 110 years experienced excess (deficit) rainfall during all the four monsoon months except 1972. This study advocates the need of subseasonal (or monthly) rainfall prediction for better socio‐economic benefits.
Evolution of the Raman backscattered intensity used to analyze the micromechanisms of deformation of various polypropylene blends in situ during a uniaxial tensile test
Authors: Chaudemanche S. , Ponçot M. , André S. , Dahoun A. , Bourson P.
Published: April 2014

This paper presents a study of the evolution of the Raman backscattered intensity used to follow the modifications of polymer microstructure in real time during a tensile test. The context of this study is the coupling of the VideoTraction™ system with a Raman spectrometer, which has already led to in‐situ measurements of molecular chains orientation and crystallinity. The polypropylene blends will be characterized optically at the same probing wavelength by incoherent light scattering to understand phenomena enlightened by Raman spectroscopy. Then, a discussion on the Raman intensity evolution is conducted, with the possible contribution of Raman spectroscopy to describe stages of the volume damage micromechanism. Copyright © 2014 John Wiley & Sons, Ltd.
Complex Coacervation of Polyelectrolytes Studied by Spin‐Label EPR Spectroscopy
Authors: Lappan Uwe , Wiesner Brigitte , Scheler Ulrich
Published: April 2014

Spin‐labeled poly(ethylene‐alt‐maleic acid) (SL‐P(E‐alt‐MA)) with 2.5 mol% spin‐labeled repeat units is prepared to study the interaction of this polyanion with an oppositely charged polyelectrolyte by electron paramagnetic resonance (EPR) spectroscopy. The internal rotation of the spin label and the segmental rotational mobility of the polyanion in aqueous solution are determined by simulating the line shapes of the experimental EPR spectra as a function of temperature. The complex formation of SL‐P(E‐alt‐MA), a weak polyanion, with the strong polycation poly(diallyldimethylammonium chloride) (PDADMAC) is studied, in dependence of the mixing ratio. If the spin‐labeled polyanion is the excess component, the spectrum of a slow‐moving component is superimposed by the spectrum of a fast‐moving component. In the opposite case, the spectra are dominated by a slow‐moving component.

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BCRP Inhibition: from Data Collection to Ligand‐Based Modeling
Authors: Montanari Floriane , Ecker Gerhard F.
Published: April 2014

Breast Cancer Resistance Protein (BCRP, gene ABCG2) is an efflux transporter from the ABC transporters family. It is known to be responsible for the multidrug resistance phenomenon observed in some cancers and is also involved in drug‐drug interactions in the liver. Prediction and assessment of inhibition of BCRP is of great interest in the drug development process. This paper presents the largest open dataset currently available for BCRP inhibition, along with the methodology used to compile it. It contains 978 unique compounds with corresponding bioactivities, extracted from 47 studies. The presence of duplicates allowed us to set up thresholds on reported activities to obtain a labelled dataset suitable for learning classification models. Exploratory data analysis and predictive modelling lead to the identification of substructures important for inhibition. We find that the substructures that characterize inhibitors are in line with known SAR relationships of BCRP inhibitors, while the substructures characterizing the non‐inhibitors are novel.
The future development potential of chain haulage technology in longwall mining and an appraisal of its application limitations / Das zukünftige Entwicklungspotenzial der Kettenfördertechnik im Strebbau und eine Abschätzung ihrer Einsatzgrenzen
Authors: Philipp Günther , Çalık Fatih
Published: April 2014

The use of link chains became the decisive success factor in the mechanisation of coal mining in longwall face working. The development of chain technology in recent decades has been characterised by the rapid development of larger chains with more and more compactness and complex geometries. This article discusses potential further steps in development and the limitations of conventional chain technology. The objective of development is to increase conveyor capacity while at the same time improving operational safety. The conveyor capacity is limited by the actual loading cross section achievable and the chain's speed; both these parameters cannot be increased at will. Research relating to the fatigue strength of chains and the management of the required pre‐tension force/slack of return chain indicates that, from the perspective of chain technology, longer longwall mining faces are possible than are mined today.

Der Einsatz von Gliederketten wurde bei der Mechanisierung der Gewinnung von Kohle im Strebbau zum entscheidenden Erfolgsfaktor. Die Entwicklung der Kettentechnik in den letzten Jahrzehnten ist gekennzeichnet durch eine rasante Entwicklung größerer Ketten mit immer kompakteren und komplexeren Geometrien. Der vorliegende Beitrag diskutiert mögliche weitere Entwicklungsschritte und die Grenzen der konventionellen Kettentechnik. Ein Ziel der Entwicklungsbemühungen ist die Erhöhung der Förderkapazitäten bei gleichzeitiger Steigerung der Betriebssicherheit. Die Förderkapazität ist durch den tatsächlich realisierbaren Beladungsquerschnitt und die Kettengeschwindigkeit begrenzt; beide sind nicht beliebig zu erhöhen. Untersuchungen zu der Auslegung über die Zeitfestigkeit von Ketten und über die Beherrschung der erforderlichen Vorspannkräfte bzw. Hängkette zeigen, dass aus der Perspektive der Kettentechnik größere Streblängen als bisher möglich sind.
German mining industry overview
Authors: Wedig Martin
Published: April 2014

This report provides a brief overview of the German mining industry with some specific examples of planning and equipment used in underground and open‐cast coal mining, in potash mining as well as in sand and gravel quarries.
Incat disability score: A critical analysis of its measurement properties
Authors: Breiner Ari , Barnett Carolina , Bril Vera
Published: April 2014

Background: The INCAT (Inflammatory Neuropathy Cause and Treatment) disability score is a measure of activity limitation. It is used frequently as a primary endpoint in inflammatory polyneuropathy clinical trials. A comprehensive critical analysis of its measurement properties has not been performed. Methods: Critical analysis of measurement properties. Results: The INCAT disability score was derived based on items from Guy's Neurological Disability Scale (GNDS), a disability measure intended for application in multiple sclerosis. Strengths of the INCAT score include evaluation of upper and lower limb dysfunction, ease of administration (feasibility), high face validity, and high reliability. Weaknesses of the scale include concerns about methodological quality of validation studies; failure to properly capture activity limitations due to proximal arm weakness, or fatigue; heavy individual item weighting; and poor sensitivity for detection of clinically important change. Conclusions: Although the INCAT scale has been an effective tool in inflammatory polyneuropathy studies, its limitations may warrant development of new scales. Muscle Nerve 50:164–169, 2014
Urological evaluation of patients that had undergone in utero myelomeningocele closure: A prospective assessment at first presentation and early follow‐up. Do their bladder benefit from it?
Authors: Macedo Antonio , Leal Marcela , Rondon Atila , Ortiz Valdemar , Moron Antonio Fernandes , Cavalheiro Sérgio
Published: April 2014

Aims

To report our data on initial urological presentation after in utero myelomeningocele (MMC) closure.

Methods

A prospective urological assessment at first presentation was designed for patients that had undergone in utero MMC closure and referred to our urological facility. The protocol consisted of detailed medical history, renal sonography, voiding cystourethrogram, and urodynamic evaluation.

Results

In utero MMC closure was performed in 19 patients at gestational age of 25.6 weeks 25–27. Birth occurred at a mean gestational age of 31.8 weeks 26–36. Hyperactive bladder was observed in 89.5% 17/19. Bladder compliance was normal in two cases (10.5%), was markedly reduced in 10 patients (52.6%) and not possible to be determined due to urinary leakage in 7 patients (36.8%). We observed normal bladder capacity in 8 patients (42.1%), reduced in 11 (57.9%), and detrusor‐sphincter dyssynergia in 9 patients (47.4%). Underactive bladder was diagnosed in one case. Clean Intermittent Catheterization was initiated by 11 patients (57.9%) mostly in association with anticholinergics 10/11. Vesicoureteral reflux was found in 5 patients (26.3%) and 9 had pyelonephritis at a mean follow‐up of 5.4 months 2–17.

Conclusions

Our data suggested that despite in utero MMC surgery, patients are at risk for bladder abnormal function and renal deterioration and should be aggressively treated, not differently from those operated in the post‐natal term. This study has the merit of being a prospectively set evaluation performed by one investigator, including the urodynamic study. We acknowledge the need of long‐term follow up. Neurourol. Urodynam. 34:461–464, 2015. © 2014 Wiley Periodicals, Inc.
Impact of nocturia on sleep and quality of life: A brief, selected review for the International Consultation on Incontinence Research Society (ICI‐RS) nocturia think tank
Authors: Bliwise Donald L. , Rosen Raymond C. , Baum Neil
Published: April 2014

Nocturia, the need to awaken at night to void, is a highly prevalent disorder that negatively affects nocturnal sleep, increases daytime tiredness, and adversely impacts quality of life. In this selective review, we provide the reader an overview of current work in this area. From the perspective of disturbed sleep, two divergent perspectives have emerged from the literature when discussing nocturia. The first is that a patient awakens because of an urge to urinate. The second is that a patient awakens during the night for some reason unrelated to urinary urge (e.g., an awakening from an environmental source or from intrinsic lightening of sleep) and then decides to void while awake. In the few studies that have inquired about nocturia as a cause of awakenings, nocturia often ranks above the traditional psychological or physical factors. Not only is nocturia likely to disrupt sleep, but it may impact waking quality of life as well. A number of generic and nocturia‐related questionnaires have been used to quantify the effect of nocturia on quality of life. In this short paper, we introduce the reader to several key studies in these important areas. Neurourol. Urodynam. 33:S15–S18, 2014. © 2014 Wiley Periodicals, Inc.
The economic impact of nocturia
Authors: Holm‐Larsen Tove
Published: April 2014

Sleep disturbances associated with nocturia cause direct, indirect, and intangible costs. Direct costs are primarily associated with injuries from falling. Indirect costs are associated with loss of work productivity. Intangible costs include emotional distress, behavioral modifications, feelings of loss of control, poor mood, and cancellation of planned activities. A study that compared the number of falls for patients with varying numbers of voids per night demonstrated that the incremental risk (population attributable risk [PAR]) of falling as a result of nocturia (≥2 voids compared with ≤1 void) was 16.2%. Using the 16.2% PAR, the annual direct cost of nocturia in the USA was estimated at $1.5 billion. An analysis in the EU‐15 countries estimated the total annual cost of hospitalizations for hip fracture due to severe nocturia to be approximately €1 billion. Studies have shown that periods of sick leave are significantly greater in both men and women who have more nocturnal voids, with an estimated annual indirect cost of nocturia of $61 billion in the USA. A similar European analysis showed an estimated annual cost of lost work productivity due to nocturia of €29 billion in the EU‐15. The intangible personal costs of nocturia are related to diminished quality of life and overall health status. High‐quality articles on the cost of illness associated with nocturia, as well as cost‐benefit analyses of nocturia treatment, are generally lacking. Neurourol. Urodynam. 33:S10–S14, 2014. © 2014 Wiley Periodicals, Inc.
Room Temperature, Metal‐Free Arylation of Aliphatic Alcohols
Authors: Ghosh Raju , Lindstedt Erik , Jalalian Nazli , Olofsson Berit
Published: April 2014

Diaryliodonium salts are demonstrated as efficient arylating agents of aliphatic alcohols under metal‐free conditions. The reaction proceeds at room temperature within 90 min to give alkyl aryl ethers in good to excellent yields. Aryl groups with electron‐withdrawing substituents are transferred most efficiently, and unsymmetric iodonium salts give chemoselective arylations. The methodology has been applied to the formal synthesis of butoxycaine.
A novel method for a high‐strength electrospun meta‐aramid nanofiber by microwave treatment
Authors: Oh Hyun Ju , Han Song Hee , Kim Seong Su
Published: April 2014

Electrospun nanofibers have attracted great attention as potential reinforcements in composite application due to their high specific surface area, high porosity, and versatility. Because the electrospun nanofibers exhibit relatively low mechanical strength due to low crystallinity and random alignment, many researchers have tried to enhance the mechanical strength through various approaches, such as heat treatment and fiber orientation control. These methods, however, are difficult to control and require the use of high temperatures and sophisticated apparatuses, and high costs. In this study, we investigate a novel microwave technique to fabricate high‐strength electrospun meta‐aramid nanofiber mats. To optimize the microwave irradiation conditions, the electrospun nanofiber was treated at varying levels of moisture and for different irradiation times. Field emission scanning electron microscopy was used to observe the surface morphology of the electrospun nanofiber mats at the different irradiation times. The changes in the crystallinity and thermal properties were investigated using X‐ray diffraction and thermogravimetric analysis measurements. Tensile tests were performed to measure the mechanical strength of the meta‐aramid nanofiber mats with respect to each parameter. As a result, any residual solvents and salts were removed, and the degree of crystallization was dramatically increased by microwave irradiation under wet conditions. These effects led to a 2.8‐fold increase in the tensile strength of the nanofiber mats compared with an untreated mat. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2014, 52, 807–814
A systematic review of spousal couple‐based intervention studies for couples coping with cancer: direction for the development of interventions
Authors: Li Qiuping , Loke Alice Yuen
Published: April 2014

Objective

With the research focus on family caregiving shifting from the individual to the dyadic level, it is suggested that the caregiver‐patient dyad as a unit be the focus and direction of caregiving interventions for families coping with cancer. The objectives in conducting this review were to explore the existing interventions for spousal couples coping with cancer in terms of type of intervention, contents, approach, and outcome measurements; and to identify directions for the development of interventions.

Methods

A systematic search of four databases was conducted to identify articles published in English or Chinese from the launch of the databases to March 2013. Studies were located using an electronic search, a manual search, and an author search.

Results

A total of 17 articles were identified and included in this review. These interventions focused mainly on patient caregiving and caregiver self care, and usually lasted for 6 weeks using a face‐to‐face group mode, with follow‐up at around 3 months. The outcome measures can be grouped into three main dimensions: dyadic appraisal, dyadic coping, and dyadic adjustments. Positive outcomes were reported for these interventions, including improvements in communication, dyadic coping, the quality of life of both the patients and their partners, psychosocial distress, sexual functioning, and marital satisfaction.

Conclusions

These findings highlighted the positive outcomes of couple‐based interventions that focus on couples coping with cancer. Future studies on couple‐based interventions should be conducted in different cultures, such as in Asian countries. Collaboration between researchers and clinicians is crucial to ensure the development of effective and accessible supportive interventions targeting couples coping with cancer. Copyright © 2014 John Wiley & Sons, Ltd.
Use of inhaled iloprost in children with pulmonary hypertension
Authors: Moreno‐Galdó Antonio , Torrent‐Vernetta Alba , de Mir Messa Inés , Amigo Sandra Rovira , Piña Ferran Gran , Gartner Silvia , Brotons Dimpna Albert
Published: April 2014

Pulmonary hypertension (PH) in children is a serious disorder, for which the major goal of treatment is to prevent progressive vascular remodeling, and improve clinical status and survival. Iloprost is approved for the treatment of PH in adults; however, few studies have evaluated its effects in children. The objective of this study is to analyze the long‐term effects of inhaled iloprost treatment in children with PH. A retrospective study was conducted in patients treated with iloprost between 2000 and 2012. Patients with left–right cardiac shunt and persistent PH of the newborn were excluded. The cohort comprised 22 patients (15 females) with a median age of 2.6 years. Twelve patients had pulmonary arterial hypertension including idiopathic (n = 6), hereditary (n = 2) and associated (congenital heart disease [n = 3], and schistosomiasis [n = 1]). One patient had pulmonary veno‐occlusive disease, six patients had PH secondary to lung disease and three had multifactorial PH. Median mean pulmonary arterial pressure was 55 mmHg and median pulmonary vascular resistance was 15.5 Wood units. Good tolerability was observed, with the exception of one case of recurring abdominal pain. PH resolved in two patients, with functional capacity improvement in 10 patients and stabilization in three patients. The clinical condition of six patients deteriorated; two died, and two received lung transplants. In conclusion, the results of this uncontrolled study showed that iloprost was effective and well tolerated in children. However, further research is needed to support this study, as PH is a serious condition that can require organ transplantation or result in death. Pediatr Pulmonol. 2015; 50:370–379. © 2014 Wiley Periodicals, Inc.
The left‐hand behaviour of polymer composites with Fe‐based microwires
Authors: Qin F. X. , Luo Y. , Peng H. X. , Tang J. , Ipatov M. , Zhukova V. , Zhukov A. , Gonzalez J.
Published: April 2014

In the present paper, we deal with the electromagnetic properties of Fe‐rich microwire polymer meta‐composites prepared by embedding glass‐coated Fe‐based microwires into the E‐glass prepreg matrices in a parallel fashion. The free‐space measurement shows that a transmission window was created by adjusting the wire spacing below 7mm, which indicates that double negative index had been obtained. The correlation between the left‐handed feature with the local dielectric response has been established. The ‘natural' double negative behaviour is attributed to the intrinsic domain structure of Fe‐based ferromagnetic wires. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Output‐based H2 optimal controllers for a class of discrete‐time stochastic linear systems with periodic coefficients
Authors: Dragan Vasile , Morozan Toader , Stoica Adrian‐Mihail
Published: April 2014

The aim of the paper is to present a design procedure of the optimal controller minimizing the H2‐type norm of discrete‐time stochastic linear systems with periodic coefficients simultaneously affected by a nonhomogeneous but periodic Markov chain and state and control multiplicative white noise perturbations. Firstly, two H2‐type norms for the linear stochastic systems under consideration were introduced. These H2‐type norms may be viewed as measures of the effect of the additive white noise perturbations on the regulated output of the considered system. Before deriving of the state space representation of the optimal controller, some useful formulae of the two H2‐type norms were obtained. These formulae are expressed in terms of periodic solutions of some suitable linear equations and are derived in the absence of some additional assumptions regarding the Markov chain other than the periodicity of the sequence of the transition probability matrices. Further, it is shown that the optimal H2 controller depends on the stabilizing solutions of some specific systems of coupled Riccati equations, which generalize the well‐known control and filtering equations from linear time invariant case. For the readers convenience, the paper presents iterative numerical algorithms for the computations of the stabilizing solutions of these Riccati type systems. The theoretical developments are illustrated by numerical examples. Copyright © 2014 John Wiley & Sons, Ltd.
TET2 Deficiency Inhibits Mesoderm and Hematopoietic Differentiation in Human Embryonic Stem Cells
Authors: Langlois Thierry , da Costa Reis Monte-Mor Barbara , Lenglet Gaëlle , Droin Nathalie , Marty Caroline , Le Couédic Jean-Pierre , Almire Carole , Auger Nathalie , Mercher Thomas , Delhommeau François , Christensen Jesper , Helin Kristian , Debili Najet , Fuks François , Bernard Olivier A. , Solary Eric , Vainchenker William , Plo Isabelle
Published: April 2014

Ten-eleven-translocation 2 (TET2) belongs to the TET protein family that catalyzes the conversion of 5-methylcytosine into 5-hydroxymethylcytosine and plays a central role in normal and malignant adult hematopoiesis. Yet the role of TET2 in human hematopoietic development remains largely unknown. Here, we show that TET2 expression is low in human embryonic stem cell (ESC) lines and increases during hematopoietic differentiation. shRNA-mediated TET2 knockdown had no effect on the pluripotency of various ESCs. However, it skewed their differentiation into neuroectoderm at the expense of endoderm and mesoderm both in vitro and in vivo. These effects were rescued by reintroducing the targeted TET2 protein. Moreover, TET2-driven differentiation was dependent on NANOG transcriptional factor. Indeed, TET2 bound to NANOG promoter and in TET2-deficient cells the methylation of the NANOG promoter correlated with a decreased in NANOG expression. The altered differentiation resulting from TET2 knockdown in ESCs led to a decrease in both the number and the cloning capacities of hematopoietic progenitors. These defects were due to an increased apoptosis and an altered gene expression profile, including abnormal expression of neuronal genes. Intriguingly, when TET2 was knockdown in hematopoietic cells, it increased hematopoietic development. In conclusion, our work suggests that TET2 is involved in different stages of human embryonic development, including induction of the mesoderm and hematopoietic differentiation. Stem Cells  2014;32:2084–2097
Indeterminate Comprehension
Authors: Simon Jonathan A. ,   Philosophy Documentation Center
Published: April 2014

Can we solve the Problem of the Many, and give a general account of the indeterminacy in definite descriptions that give rise to it, by appealing to metaphysically indeterminate entities? I argue that we cannot. I identify a feature common to the relevant class of definite descriptions, and derive a contradiction from the claim that each such description is satisfied by a metaphysically indeterminate entity.