bluuebunny/crossref_metadata_2025 huggingface dataset:
Petrus van Musschenbroek and Newton’s ‘vera stabilisque Philosophandi methodus’
Authors: Ducheyne Steffen
Published: December 2015

Zusammenfassung: Petrus van Musschenbroek und Newtons ‚vera stabilisque Philosophandi methodus‘. In der Forschungsliteratur dominiert die Auffassung, Petrus van Musschenbroek sei Anhänger der Newton’schen Methodologie gewesen, d.h. ein Naturphilosoph, der sich trotz gelegentlicher Abweichung von Newtons Doktrinen an Newtons methodologischen Grundsätzen orientiert habe. Nur wenige Gelehrte haben bis heute im Detail untersucht, was der Satz, Musschenbroek sei Newtons Methode gefolgt, bedeutet. Der vorliegende Aufsatz versucht diese Lücke zu schließen.

Summary: Petrus van Musschenbroek and Newton’s ‘vera stabilisque Philosophandi methodus’. According to a dominant view in the scholarly literature, Musschenbroek is to be considered a follower of Newton’s methodology, i.e. as a natural philosopher who, although he occasionally departed from Newton’s doctrines, aligned himself to Newton’s methodological views. Few scholars have, however, explained in full detail what it means to claim that Musschenbroek followed Newton’s method. The purpose of this essay is to get more grip on this matter.
Diether Sperlich, Dorothee Früh, Wilhelm Weinberg (1862–1937) – Der zweite Vater des Hardy‐Weinberg‐Gesetzes, (Acta Biohistorica 15) Rangsdorf: Basilisken‐Presse 2015.
Authors: Wessel Andreas
Published: December 2015

290 S., € 39,00. ISBN 978‐3‐941365‐47‐6.
Andrea Adams, Psychopathologie und „Rasse“. Verhandlungen „rassischer“ Differenz in der Erforschung psychischer Leiden (1890–1933), (Science Studies) Bielefeld: transcript 2013. / Alexa Geisthövel,­ Intelligenz und Rasse. Franz Boas’ psychologischer Antirassismus zwischen Amerika und Deutschland, 1920–1942, (Histoire 51) Bielefeld: transcript 2013.
Authors: Schmuhl Hans‐Walter
Published: December 2015

333 S., br., € 34,99. ISBN 978‐3‐8376‐2468‐7. / 325 S., br., € 35,99. ISBN 978‐3‐8376‐2560‐8.
Development of Bifunctional Inhibitors of Polo‐Like Kinase 1 with Low‐Nanomolar Activities Against the Polo‐Box Domain
Authors: Scharow Andrej , Knappe Daniel , Reindl Wolfgang , Hoffmann Ralf , Berg Thorsten
Published: December 2015

Polo‐like kinase 1 (Plk1), a validated cancer target, harbors a protein–protein interaction domain referred to as the polo‐box domain (PBD), in addition to its enzymatic domain. Although functional inhibition either of the enzymatic domain or of the PBD has been shown to inhibit Plk1, so far there have been no reports of bifunctional agents with the potential to target both protein domains. Here we report the development of Plk1 inhibitors that incorporate both an ATP‐competitive ligand of the enzymatic domain, derived from BI 2536, and a functional inhibitor of the PBD, based either on the small molecule poloxin‐2 or on a PBD‐binding peptide. Although these bifunctional agents do not seem to bind both protein domains simultaneously, the most potent compound displays low‐nanomolar activity against the Plk1 PBD, with excellent selectivity over the PBDs of Plk2 and Plk3. Our data provide insights into challenges and opportunities relating to the optimization of Plk1 PBD ligands as potent Plk1 inhibitors.
Induction of pancreatic β cell gene expression in mesenchymal stem cells
Authors: Mehrfarjam Zahra , Esmaeili Fariba , Shabani Leila , Ebrahimie Esmaeil
Published: December 2015

Transdifferentiattion potential of mesenchymal stem cells (MSCs) into insulin‐producing cells (IPCs) has been suggested recently. In our recent works, we demonstrated the high performance of mouse neonate pancreas extract (MPE) in the production of functional IPCs from carcinoma stem cells. In this study, MPE was used to generate IPCs from MSCs without any genetic manipulation. To this end, bone marrow MSCs were isolated and characterized. In order to differentiate, MSCs were induced by selection of nestin‐expressing cells and treatment with 100 μg/mL MPE. Morphological features of the differenti­ated cells were confirmed by dithizone staining. Immunoreactivity to insulin receptor beta, proinsulin, insulin, and C‐peptide was observed by immunoflourescence. We also quantified glucose‐dependent insulin production and secretion by ELISA. Real‐time PCR indicated the expressions of β cell‐related genes, PDX‐1, INS1, INS2, EP300, and CREB1, in IPC cells. Possible pathways governed by CREB1, EP300, and PDX‐1 transcription factors in differentiation of MSCs to IPCs were determined based on Gene Set Enrichment (GSE) approach at P = 0.05. Pathway discovery highlighted the negative regulatory effects of MIR124‐2, HDAC5 protein, REST, and NR0B2 transcription factors on expression of CREB1, EP300, and PDX‐1 and inhabitation of IPC differentiations. In contrast, a crosstalk between FOXA2 and TCF7L2 transcription factors, DNA‐PK complex, KAT2B protein positively interacting with PDX‐1, CREB1, EP300 resulted in the induction of IPC and following insulin production. In conclusion, we report an efficient, simple, and easy method for production of functional IPCs from MSCs by MPE treatment.
Magnesium regulates neural stem cell proliferation in the mouse hippocampus by altering mitochondrial function
Authors: Jia Shanshan , Mou Chengzhi , Ma Yihe , Han Ruijie , Li Xue
Published: December 2015

In the adult brain, neural stem cells from the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ) of the cortex progress through the following five developmental stages: radial glia‐like cells, neural progenitor cells, neuroblasts, immature neurons, and mature neurons. These developmental stages are linked to both neuronal microenvironments and energy metabolism. Neurogenesis is restricted and has been demonstrated to arise from tissue microenvironments. We determined that magnesium, a key nutrient in cellular energy metabolism, affects neural stem cell (NSC) proliferation in cells derived from the embryonic hippocampus by influencing mitochondrial function. Densities of proliferating cells and NSCs both showed their highest values at 0.8 mM [Mg2+]o, whereas lower proliferation rates were observed at 0.4 and 1.4 mM [Mg2+]o. The numbers and sizes of the neurospheres reached the maximum at 0.8 mM [Mg2+]o and were weaker under both low (0.4 mM) and high (1.4 mM) concentrations of magnesium. In vitro experimental evidence demonstrates that extracellular magnesium regulates the number of cultured hippocampal NSCs, affecting both magnesium homeostasis and mitochondrial function. Our findings indicate that the effect of [Mg2+]o on NSC proliferation may lie downstream of alterations in mitochondrial function because mitochondrial membrane potential was highest in the NSCs in the moderate [Mg2+]o (0.8 mM) group and lower in both the low (0.4 mM) and high (1.4 mM) [Mg2+]o groups. Overall, these findings demonstrate a new function for magnesium in the brain in the regulation of hippocampal neural stem cells: affecting their cellular energy metabolism.
Defect‐Rich Metal Nanocrystals in Catalysis
Authors: Xie Shuifen , Xu Qingchi , Huang Xiaoqing
Published: December 2015

Metal nanocrystals with high concentrations of surface defects are well known to material scientists, but have been given less attention by the catalysis community. In this concept, we advocate that engineered metal nanocrystals with rich defects could be a new platform for exploration as highly active heterocatalysts. Metal nanocrystals with rich defects are analyzed in detail to illustrate the structural features, including twin boundaries (TBs) and grain boundaries (GBs). We also discuss the recent advances in synthetic methods for making metal nanocrystals with rich TBs/GBs to provide inspiration for a further rational synthesis. Typical catalytic measurements are highlighted to stress the positive correlation between the concentration of surface defects and the catalytic performances of metal nanocrystals.
An Electrocatalyst Based on Carbon Nanotubes Coated with Poly(vinylpyrrolidone) Shows a High Tolerance to Carbon Monoxide in a Direct Methanol Fuel Cell
Authors: Yang Zehui , Nakashima Naotoshi
Published: December 2015

We describe a facile method to enhance the CO tolerance of a fuel‐cell electrocatalyst dramatically based on carbon nanotubes. The electrocatalyst is composed of Pt deposited on carbon nanotubes wrapped in poly[2,2′‐(2,6‐pyridine)‐5,5′‐bibenzimidazole] (PyPBI) further covered by poly(vinylpyrrolidone) (PVP) through multipoint hydrogen bonding interactions between the PyPBI and PVP. The PVP‐coated electrocatalyst showed a ∼10 times higher CO tolerance compared to the non‐PVP‐coated electrocatalyst under a high (4 m) methanol concentration. Additionally, the PVP‐coated electrocatalyst showed an enhancement in the Pt stability because of the stabilization of the Pt‐NP by the PyPBI and PVP. After the durability test, the PVP‐coated electrocatalyst still showed ∼8 times higher CO tolerance because of the presence of the PVP bound stably with PyPBI. This study provides useful information for the design and fabrication of a state‐of‐the‐art anodic electrocatalyst for direct methanol fuel cells.
Bifunctionality and Mechanism of Electrodeposited Nickel–Phosphorous Films for Efficient Overall Water Splitting
Authors: Jiang Nan , You Bo , Sheng Meili , Sun Yujie
Published: December 2015

Efficient, stable, and low‐cost electrocatalysts are crucial for realizing large‐scale water splitting. Herein, we report that electrodeposited nickel–phosphorous (Ni–P) films can act as efficient bifunctional electrocatalysts for overall water splitting. The as‐prepared Ni–P films exhibit remarkable catalytic performance for both H2 and O2 evolution reactions (HER and OER) in alkaline media, achieving a current density of 10 mA cm−2 at overpotentials of −93 mV for HER and 344 mV for OER with Tafel slopes of 43 and 49 mV dec−1, respectively, rivaling the performance of Pt and IrO2. Various techniques were employed to probe the composition and morphology of the Ni–P films prior to and post catalysis, revealing the major composition of the as‐prepared and post‐HER films as metallic nickel and nickel phosphide, which partially transform to nickel oxides during OER. It was also found that the catalytic rate of OER catalyzed by Ni–P was first order in the activity of the hydroxide anion.
Cyano‐Functionalized Triarylamines on Coinage Metal Surfaces: Interplay of Intermolecular and Molecule–Substrate Interactions
Authors: Müller Kathrin , Moreno‐López Juan Carlos , Gottardi Stefano , Meinhardt Ute , Yildirim Handan , Kara Abdelkader , Kivala Milan , Stöhr Meike
Published: December 2015

The self‐assembly of cyano‐functionalized triarylamine derivatives on Cu(111), Ag(111) and Au(111) was studied by means of scanning tunnelling microscopy, low‐energy electron diffraction, X‐ray photoelectron spectroscopy and density functional theory calculations. Different bonding motifs, such as antiparallel dipolar coupling, hydrogen bonding and metal coordination, were observed. Whereas on Ag(111) only one hexagonally close‐packed pattern stabilized by hydrogen bonding is observed, on Au(111) two different partially porous phases are present at submonolayer coverage, stabilized by dipolar coupling, hydrogen bonding and metal coordination. In contrast to the self‐assembly on Ag(111) and Au(111), for which large islands are formed, on Cu(111), only small patches of hexagonally close‐packed networks stabilized by metal coordination and areas of disordered molecules are found. The significant variety in the molecular self‐assembly of the cyano‐functionalized triarylamine derivatives on these coinage metal surfaces is explained by differences in molecular mobility and the subtle interplay between intermolecular and molecule–substrate interactions.
Shape‐Memory Platinum(II) Complexes: Intelligent Vapor‐History Sensor with ON–OFF Switching Function
Authors: Shigeta Yasuhiro , Kobayashi Atsushi , Ohba Tadashi , Yoshida Masaki , Matsumoto Takeshi , Chang Ho‐Chol , Kato Masako
Published: December 2015

A novel platinum(II)–diimine complex, [Pt(CN)2(H2dcphen)] (1; H2dcphen=4,7‐dicarboxy‐1,10‐ phenanthroline), was synthesized and its vapochromic shape‐memory behavior was evaluated. The as‐synthesized amorphous purple solid, [Pt(CN)2(H2dcphen)]⋅2 H2O (1 P), exhibited vapochromic behavior in the presence of alcoholic vapors through transformation to a red, crystalline, porous, vapor‐adsorbed form, 1 R⊃vapor. The obtained 1 R⊃vapor complex released the adsorbed vapors upon heating without collapse of the porous structure. The vaporfree, porous 1 R⊃open could detect water or n‐hexane vapor, although these vapors could not induce 1 P‐to‐1 R⊃vapor transformation, and 1 R⊃open could easily be converted to the initial 1 P by manual grinding. These results indicate that 1 is a new shape‐memory material that functions through formation and collapse of the porous framework with an emission change upon vapor‐adsorption and grinding; this enables it to exhibit vapor history and ON–OFF switching sensing functions.
Expanding the Chemistry of Molecular U2+ Complexes: Synthesis, Characterization, and Reactivity of the {[C5H3(SiMe3)2]3U}− Anion
Authors: Windorff Cory J. , MacDonald Matthew R. , Meihaus Katie R. , Ziller Joseph W. , Long Jeffrey R. , Evans William J.
Published: December 2015

The synthesis of new molecular complexes of U2+ has been pursued to make comparisons in structure, physical properties, and reactivity with the first U2+ complex, [K(2.2.2‐cryptand)][Cp′3U], 1 (Cp′=C5H4SiMe3). Reduction of Cp′′3U [Cp′′=C5H3(SiMe3)2] with KC8 in the presence of 2.2.2‐cryptand or 18‐crown‐6 generates [K(2.2.2‐cryptand)][Cp′′3U], 2‐K(crypt), or [K(18‐crown‐6)(THF)2][Cp′′3U], 2‐K(18c6), respectively. The UV/Vis spectra of 2‐K and 1 are similar, and they are much more intense than those of U3+ analogues. Variable temperature magnetic susceptibility data for 1 and 2‐K(crypt) reveal lower room temperature χMT values relative to the experimental values for the 5f3 U3+ precursors. Stability studies monitored by UV/Vis spectroscopy show that 2‐K(crypt) and 2‐K(18c6) have t1/2 values of 20 and 15 h at room temperature, respectively, vs. 1.5 h for 1. Complex 2‐K(18c6) reacts with H2 or PhSiH3 to form the uranium hydride, [K(18‐crown‐6)(THF)2][Cp′′3UH], 3. Complexes 1 and 2‐K(18c6) both reduce cyclooctatetraene to form uranocene, (C8H8)2U, as well as the U3+ byproducts [K(2.2.2‐cryptand)][Cp′4U], 4, and Cp′′3U, respectively.
Photoswitchable “Turn‐on” Fluorescence Diarylethenes: Substituent Effects on Photochemical Properties and Electrochromism
Authors: Ai Qi , Pang Shichong , Ahn Kwang‐Hyun
Published: December 2015

A series of “turn‐on” fluorescence diarylethenes derived from 2,3‐bis(2‐methylbenzo[b]thiophen‐3‐yl)‐5,6‐dihydro‐4H‐thieno[2,3‐b]thiopyran‐4‐one (1) with alkyl and acetyl substituents were synthesized. The photochemical and photophysical properties of these derivatives, including the photoreaction of crystalline 1, were thoroughly investigated to reveal substituent effects on their properties. The results indicated that alkyl substituents did not significantly affect the absorption and emission spectra of the diarylethenes. However, large absorption and emission wavelength shifts were observed for the diarylethene with an acetyl substituent due to extension of π–π conjugation. Significantly, all of the fluorescent ring‐closed forms of the compounds isomerized to their ring‐open forms in the presence of Cu2+ in the dark. EPR results provide clear evidence for the formation of the compound 1 radical cation intermediate that might be generated in the reaction between c‐1 and Cu2+. DFT calculations found that the ground‐state activation energy for ring‐opening of 1.+ was approximately 9.2 kcal mol−1 lower than that of 1 without Cu2+, such that a Cu2+‐catalyzed oxidative cycloreversion reaction at room temperature might be possible.
Triphenylphosphine‐Mediated Deoxygenative Reduction of CF3SO2Na and Its Application for Trifluoromethylthiolation of Aryl Iodides
Authors: Yang Yi , Xu Long , Yu Siqi , Liu Xiaoqiang , Zhang Yu , Vicic David A.
Published: December 2015

We report herein a practical method for taming Langlois’ reagent CF3SO2Na to generate CuSCF3 by a triphenylphospine‐mediated deoxygenative reduction process. This chemistry highlights a novel utilization of the inherent CF3S skeleton of Langlois’ reagent as a CF3S feedstock under mild conditions. The CuSCF3 intermediate generated by this protocol can react with a wide array of supporting ligands to furnish several air‐stable [LCu(SCF3)] complexes as valuable trifluoromethylthiolating agents. In addition, the CuSCF3 intermediate can be directly employed for the trifluoromethylthiolation of (hetero)aryl iodides with operational simplicity and atomic efficiency.
Pyrimidine Triazole Thioether Derivatives as Toll‐Like Receptor 5 (TLR5)/Flagellin Complex Inhibitors
Authors: Yan Lei , Liang Jiaqi , Yao Chengbo , Wu Peiyao , Zeng Xianfeng , Cheng Kui , Yin Hang
Published: December 2015

Protein–protein interactions have been regarded as “undruggable” despite their importance in many biological processes. The complex formed between host toll‐like receptor 5 (TLR5) and flagellin, a globular protein that is the main component of a bacterial flagellum, plays a vital role in a number of pathogen defenses, immunological diseases and cancers. Through high‐throughput screening, we identified two hits with a common pharmacophore, which were used to successfully develop a series of small‐molecule probes as novel inhibitors of flagellin binding to TLR5. In a multitude of assays, 4‐((4‐benzyl‐5‐(pyridin4yl)‐4H‐1,2,4‐triazol‐3‐yl)thio)pyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidine (TH1020) was identified as a potent antagonist of TLR5 signaling with promising activity (IC50=0.85±0.12 μm) and specificity. Furthermore, TH1020 was shown to repress the expression of downstream TNF‐α signaling pathways mediated by the TLR5/flagellin complex formation. Based on molecular docking simulation, TH1020 is suggested to compete with flagellin and disrupt its association with TLR5. TH1020 provides a much‐needed molecular probe for studying this important protein–protein interaction and a lead compound for identifying novel therapeutics targeting TLR5.
Spectrum of epidemiological and clinical findings in patients with heart failure with preserved ejection fraction stratified by study design: a systematic review
Authors: Vaduganathan Muthiah , Michel Alexander , Hall Kathryn , Mulligan Claire , Nodari Savina , Shah Sanjiv J. , Senni Michele , Triggiani Marco , Butler Javed , Gheorghiade Mihai
Published: December 2015

Background

Heart failure with preserved ejection fraction (HFpEF) represents a major global and economic burden, but its epidemiological, clinical, and outcome data have varied according to study design.

Methods and results

We conducted a systematic review of published HFpEF clinical trials and observational studies (community‐based studies and registries) from August 1998 to July 2013 using PubMed and EMBASE databases. Two independent investigators manually screened and extracted relevant data. We included 62 articles (19 describing clinical trials, 12 describing community‐based observational studies, and 31 describing registries). The ejection fraction (EF) cut‐off values ranged widely for HFpEF from >40% to >55%. However, differences in EF cut‐offs were not clearly associated with incidence and prevalence data across studies. Of all patients with heart failure in community studies, 33–84% had HFpEF, which tended to be higher than reported in registries. The HFpEF patients in included studies were primarily older, white (>70%) patients with hypertension (∼50–90%) and coronary artery disease (up to 60%). All‐cause mortality and all‐cause hospitalizations ranged from 13% to 23% (26–50 months follow‐up) and 55% to 67% (37–50 months follow‐up), respectively, in clinical trials; cardiovascular causes accounted for 70% of both outcomes. All‐cause mortality tended to be higher in registries than in clinical trials and community‐based observational studies up to 5 years into follow‐up.

Conclusions

Important differences in EF thresholds, epidemiological indices, clinical profiles, treatment patterns, and outcomes exist across contemporary HFpEF clinical trials, observational studies, and registries. Precision in definition and inclusion of more uniform populations may facilitate improved profiling of HFpEF patients.
Nonredundant roles of keratinocyte‐derived IL‐34 and neutrophil‐derived CSF1 in Langerhans cell renewal in the steady state and during inflammation
Authors: Wang Yaming , Bugatti Mattia , Ulland Tyler K. , Vermi William , Gilfillan Susan , Colonna Marco
Published: December 2015

IL‐34 and colony‐stimulating factor 1 (CSF1) are two alternative ligands for the CSF1 receptor that play nonredundant roles in the development, survival, and function of tissue macrophages and Langerhans cells (LCs). In this study, we investigated the spatio‐temporal production of IL‐34 and its impact on skin LCs in the developing embryo and adult mice in the steady state and during inflammation using Il34LacZ reporter mice and newly generated inducible Il34‐knockout mice. We found that IL‐34 is produced in the developing skin epidermis of the embryo, where it promotes the final differentiation of LC precursors. In adult life, LCs required IL‐34 to continually self‐renew in the steady state. However, during UV‐induced skin damage, LC regeneration depended on neutrophils infiltrating the skin, which produced large amounts of CSF1. We conclude that LCs require IL‐34 when residing in fully differentiated and anatomically intact skin epidermis, but rely on neutrophil‐derived CSF1 during inflammation. Our demonstration that neutrophils are an important source of CSF1 during skin inflammation may exemplify a mechanism through which neutrophils promote their subsequent replacement with mononuclear phagocytes.
Role of the MHC restriction during maturation of antigen‐specific human T cells in the thymus
Authors: Hesnard Leslie , Legoux François , Gautreau Laetitia , Moyon Melinda , Baron Olivier , Devilder Marie‐Claire , Bonneville Marc , Saulquin Xavier
Published: December 2015

In the thymus, a T‐cell repertoire able to confer protection against infectious and noninfectious agents in a peptide‐dependent, self‐MHC‐restricted manner is selected. Direct detection of Ag‐specific thymocytes, and analysis of the impact of the expression of the MHC‐restricting allele on their frequency or function has never been studied in humans because of the extremely low precursor frequency. Here, we used a tetramer‐based enrichment protocol to analyze the ex vivo frequency and activation‐phenotype of human thymocytes specific for self, viral and tumor‐antigens presented by HLA‐A*0201 (A2) in individuals expressing or not this allele. Ag‐specific thymocytes were quantified within both CD4CD8 double or single‐positive compartments in every donor. Our data indicate that the maturation efficiency of Ag‐specific thymocytes is poorly affected by HLA‐A2 expression, in terms of frequencies. Nevertheless, A2‐restricted T‐cell lines from A2+ donors reacted to A2+ cell lines in a highly peptide‐specific fashion, whereas their alloreactive counterparts showed off‐target activity. This first ex vivo analysis of human antigen‐specific thymocytes at different stages of human T‐cell development should open new perspectives in the understanding of the human thymic selection process.
Study of intact virus‐like particles of human papillomavirus by capillary electrophoresis
Authors: Bettonville Virginie , Nicol Jérôme T. J. , Thelen Nicolas , Thiry Marc , Fillet Marianne , Jacobs Nathalie , Servais Anne‐Catherine
Published: December 2015

Virus‐like particles of human papillomavirus (HPV‐VLP), resulting from the self‐assembly of the capsid proteins (L1 or L1 and L2), have been widely used to study HPV as they are similar to the native virion. Moreover, two prophylactic vaccines, Gardasil® and Cervarix®, are based on HPV‐VLP L1. Analytical techniques currently used to characterize HPV‐VLP, such as SDS‐PAGE, Western blot, ELISA, are time‐consuming and semiquantitative. In this study, CE was evaluated for the analysis of intact HPV16‐VLP. The usefulness of capillary inner wall coating as well as various BGEs, pH, and detergent additives were investigated. Reproducible HPV‐VLP analysis in CE was achieved using poly(ethylene oxide)‐coated capillary and a BGE containing high salt concentration and low SDS concentration. The developed method enables HPV‐VLP detection in less than 10 min (migration times RSD: 1.6%). The identity of HPV‐VLP peak was confirmed by comparison with a sample obtained from a wild‐type baculovirus and with VLP‐based vaccine, Gardasil®, after adjuvant dissolution. Finally, we applied the developed methodology to VLP‐based vaccines, demonstrating that CE could be successfully used for vaccine quality control.
Examining the Relationships Between Bone Tissue Composition, Compositional Heterogeneity, and Fragility Fracture: A Matched Case-Controlled FTIRI Study
Authors: Boskey Adele L , Donnelly Eve , Boskey Elizabeth , Spevak Lyudmila , Ma Yan , Zhang Wei , Lappe Joan , Recker Robert R
Published: December 2015

Fourier transform infrared imaging (FTIRI) provides information on spatial distribution of the chemical composition of thin tissue specimens at ∼7 µm spatial resolution. This study of 120 age- and bone mineral density (BMD)-matched patients was designed to investigate the association of FTIRI variables, measured in iliac crest biopsies, with fragility fractures at any site. An earlier study of 54 women found hip BMD to be a significant explanatory variable of fracture risk for cortical bone but not for cancellous bone. In the current study, where age and BMD were controlled through matching, no such association was observed, validating the pairing scheme. Our first study of unmatched iliac crest biopsies found increases in collagen maturity (cancellous and cortical bone) and mineral crystal size (cortical bone only) to be a significant explanatory variable of fracture when combined with other covariates. The ratio for collagen maturity has been correlated to the amount of enzymatic collagen cross-links. To assess the impact of other FTIRI variables (acid phosphate substitution, carbonate-to-phosphate ratio, and the pixel distribution [heterogeneity] of all relevant FTIRI variables), we examined biopsies from a matched case-controlled study, in which 60 women with fractures were each paired with an age- and BMD-matched female control. With the matched data set of 120 women, conditional logistic regression analyses revealed that significant explanatory variables of fracture were decreased carbonate-to-phosphate ratio in both cancellous (odds ratio [OR] = 0.580, 95% confidence interval [CI] 0.37–0.909, p = 0.0176) and cortical bone (OR = 0.519, 95% CI 0.325–0.829, p = 0.0061), and increased heterogeneity (broadened pixel distribution) of collagen maturity for cancellous bone (OR = 1.549, 95% CI 1.002–2.396, p = 0.0491). The observation that collagen maturity was no longer linked to fracture in age- and BMD-matched samples suggests that age-dependent variation in collagen maturity may be a more important contributory factor to fragility fractures than previously thought. © 2015 American Society for Bone and Mineral Research.
Metacognitive Reflection and Insight Therapy (MERIT) With a Patient With Severe Symptoms of Disorganization
Authors: de Jong Steven , van Donkersgoed Rozanne , Pijnenborg G.H.M. , Lysaker Paul H.
Published: December 2015

One recent development within the realm of psychotherapeutic interventions for schizophrenia has been a shift in focus from symptom management to consideration of metacognition, or the processes by which people synthesize information about themselves and others in an integrated manner. One such approach, metacognitive reflection and insight therapy (MERIT); in particular, offers a description of 8 therapeutic activities that should occur in each session, resulting in the stimulation and growth of metacognitive capacity. In this report, we present a description of 12 sessions with a patient suffering from schizophrenia manifesting significantly disorganized symptoms. Each MERIT element is described along with observed clinical and metacognitive gains. As illustrated in this report, these procedures helped the patient move from a state of having no complex ideas about himself or others, to one in which he could begin to develop integrated and realistic ideas about himself and others and use that capacity to think about life challenges.
Mitigating the Effects of Nonadherence in Clinical Trials
Authors: Shiovitz Thomas M. , Bain Earle E. , McCann David J. , Skolnick Phil , Laughren Thomas , Hanina Adam , Burch Daniel
Published: December 2015

Accounting for subject nonadherence and eliminating inappropriate subjects in clinical trials are critical elements of a successful study. Nonadherence can increase variance, lower study power, and reduce the magnitude of treatment effects. Inappropriate subjects (including those who do not have the illness under study, fail to report exclusionary conditions, falsely report medication adherence, or participate in concurrent trials) confound safety and efficacy signals. This paper, a product of the International Society for CNS Clinical Trial Methodology (ISCTM) Working Group on Nonadherence in Clinical Trials, explores and models nonadherence in clinical trials and puts forth specific recommendations to identify and mitigate its negative effects. These include statistical analyses of nonadherence data, novel protocol design, and the use of biomarkers, subject registries, and/or medication adherence technologies.
MALDI imaging reveals lipid changes in the skin of leprosy patients before and after multidrug therapy (MDT)
Authors: de Macedo Cristiana S. , Anderson David M. , Pascarelli Bernardo M. , Spraggins Jeffrey M. , Sarno Euzenir N. , Schey Kevin L. , Pessolani Maria Cristina V.
Published: December 2015

Leprosy still represents a health problem in several countries. Affecting skin and peripheral nerves, it may lead to permanent disabilities. Disturbances on skin lipid metabolism in leprosy were already observed; however, the localization and distribution of lipids could not be accessed. The role of lipids on infectious disease has been fully addressed only recently, as they directly influence immune response. Matrix‐assisted laser desorption/ionization imaging mass spectrometry provides a powerful tool to localize and identify lipids in tissues. The aim of this work was to study and compare the changes in lipid distribution of skin biopsies taken from leprosy patients before and after multidrug therapy (MDT). Different species of phosphatidic acid, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, sphingomyelin and phosphatidylcholine were detected. Differences in skin lipid signal intensities, as well as in their localization, were observed before and after MDT in every patient. In general, lipid distribution in the skin after MDT had a pattern similar to control skin samples, where most of the lipids were located in the upper part of the dermis and epidermis. This study opens paths to a better understanding of lipid functions in leprosy pathogenesis and immune response. Copyright © 2015 John Wiley & Sons, Ltd.
Foscarnet, zidovudine and dolutegravir combination efficacy and tolerability for late stage HIV salvage therapy: A case‐series experience
Authors: Delory Tristan , Papot Emmanuelle , Rioux Christophe , Charpentier Charlotte , Auge‐Courtoi Claire , Michard Florence , Peytavin Gilles , Descamps Diane , Matheron Sophie , Yazdanpanah Yazdan
Published: December 2015

Salvage therapy including foscarnet (PFA), zidovudine (ZDV) and an optimized background ART (OBT) has been shown to be effective in patients with advanced HIV infection, and no therapeutic options. Dolutegravir (DTG) may offer a more active combination. Objective was to describe efficacy and tolerability of PFA–ZDV–DTG containing regimen. In our cohort, we identified patients who: (i) had plasma HIV‐1 RNA load (pVL) >50 c/ml (>100 for HIV‐2) on combination ART (cART); (ii) had at least 1 PI/r, 1 NRTI, 1 NNRTI (for HIV‐1), and at least 1 raltegravir resistance mutations; (iii) were naive to DTG; and (iv) initiated on a PFA–ZDV–DTG containing‐regimen with 48 weeks (W48) of follow‐up. Out of 5 patients, 2 were infected with HIV‐2. At PFA–ZDV–DTG initiation, CD4 cell count was (/mm3) of 64, 40, 10, in HIV‐1, and 37, 199, in HIV‐2 infected patients; and pVL (log10 c/ml) of 4.8, 5.1, 4.4, in HIV‐1, and 3.6, 4.2, in HIV‐2 infected patients, respectively. Median OBT genotypic sensitivity score was 1.5 [1–2]. PFA was discontinued in one patient, due to an acute renal failure. At W48, one HIV‐1 infected patient had a pVL <50 c/ml and two <200 c/ml; the two HIV‐2 infected patients had pVL >100 c/ml. No lack of treatment adherence was observed. In treatment experienced HIV‐infected patients, failing cART and without other therapeutic options, a PFA–ZDV–DTG combination therapy could be effective. Renal adverse events should be monitored. J. Med. Virol. 88:1204–1210, 2016. © 2015 Wiley Periodicals, Inc.
Identification and evaluation of the chemical similarity of Yindan xinnaotong samples by ultra high performance liquid chromatography with quadrupole time‐of‐flight mass spectrometry fingerprinting
Authors: Gong Leilei , Haiyu Xu , Wang Lan , Xiaojie Yin , Huijun Yuan , Songsong Wang , Cheng Long , Ma Xiaojing , Gao Shuangrong , Liang Rixin , Yang Hongjun
Published: December 2015

Yindan xinnaotong, a compound preparation used in traditional Chinese medicine, is composed of eight herbs: Ginkgo biloba leaf (yinxingye), Salvia miltiorrhizae (danshen), Herba gynostemmatis (jiaogulan), Erigerontis herba (dengzhanxixin), Allii sativi bulbus (dasuan), Notoginseng radixe rhizoma (sanqi), Crataegi fructus (shanzha), and Borneolum (tianranbingpian). Yindan xinnaotong is primarily used to treat cardiovascular and cerebrovascular diseases. However, to date, no scientific methods have been established to assess the quality of Yindan xinnaotong. Therefore, a combinatorial method was developed based on chemical constituent identification and fingerprint analysis to assess the consistency of Yindan xinnaotong quality. In this study, ultra high performance liquid chromatography coupled with time‐of‐flight mass spectrometry was used to identify the chemical components of Yindan xinnaotong soft capsules. Approximately 74 components were detected, of which 70, including flavonoids, ginkgolide, phenolic acid, diterpenoid tanshinones, and ginsenoside, were tentatively identified. A fingerprint analysis was also conducted to evaluate the uniformity of the quality of Yindan xinnaotong soft capsules. Ten batches of Yindan xinnaotong soft capsules were analyzed. All of the resulting chromatograms were imported into the “Similarity Evaluation System for Chromatographic Fingerprints of TCM” (Chinese Pharmacopoeia Commission, version 2004A). The similarity scores of common peaks from these samples ranged from 0.903–1.000, indicating that samples from different batches were highly correlated.
Studies of the separation performance of silanized silica gel for simulated distillation
Authors: Boczkaj Grzegorz , Momotko Malwina , Przyjazny Andrzej , Kamiński Marian
Published: December 2015

We present the results of investigations of the chromatographic (sorptive) properties of silanized silica gel as a stationary phase for gas chromatography used for simulated distillation. Commercially available silanized sorbent (particle diameter range 63–200 μm, average pore size 60 Å) was sieved to obtain the 80–100 mesh fraction (180–150 μm). The obtained results revealed that silanized silica gel allows the complete separation of a mixture of n‐ and iso‐alkanes in the C1–C7 range. Such a separation is achieved with a temperature program starting with an initial temperature of 50˚C, which is advantageous because the gas chromatograph oven does not have to be cooled below room temperature. The use of temperature programming with a final temperature of 300˚C ensures separation and elution of all mixture components from C1 to n‐C28 in one run. This study confirms the applicability of silanized silica gel as a stationary phase for the investigation of distillation temperature distribution of gasoline and diesel fuel based on the simulated distillation procedure according to ASTM D2887. The deviations of individual points of distillation curve obtained using ASTM D2887 and columns packed with silanized silica gel were within the reproducibility range of the standard procedure.
Light‐Controlled Radical Polymerization of Functional Methacrylates Prepared by Enzymatic Transacylation
Authors: Mommer Stefan , Köhler Jens , Keul Helmut , Möller Martin
Published: December 2015

Well‐defined homo and block copolymers are prepared with methyl methacrylate, pentyl methacrylate, 3‐phenylpropyl methacrylate, and 6‐thiobenzoylhexyl methacrylate using Ir(ppy)3 as a catalyst. It is shown that the advantages of the light‐controlled radical polymerization can be exploited also for these special monomers as prepared by enzymatic transacylation without time‐consuming labor‐intensive removal of side products. Furthermore, it is shown that the polymerization is significantly affected even by small variations in the irradiation and therefore also by choice of the light source. In contrast to our recent report we therefore recommend removal of the heterogeneous supported enzyme by filtration before polymerization. Because of the sensitivity of the polymerization process to the irradiation, turbidity caused by the bead‐supported enzyme can affect the reproducibility of the polymer preparation. Results obtained with methyl methacrylate as monomer could only be transferred to the above‐mentioned functional monomers by proper choice of the light source. On the basis of kinetic investigations, the effect of the irradiation source, the catalyst concentration, and the alcohol residue on the methacrylate used are discussed. Finally, the optimized experimental conditions are applied for the preparation of different block copolymers.

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Microstructure and property of Ni60A/WC composite coating fabricated by fiber laser cladding
Authors: Wang K.‐M. , Fu H.‐G. , Lei Y.‐P. , Yang Y.‐W. , Li Q.‐T. , Su Z.‐Q.
Published: December 2015

Laser clad Ni60A/WC composite coating was fabricated on the surface of Q235 steel by using 6 kW fiber laser. The morphology, composition, and microhardness of composite coating were studied by using scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), X‐ray diffraction (XRD), and micro‐hardness tester. The results show that in the process of fiber laser cladding Ni60A/WC composite coating, residual WC particles partially dissolve and react with other elements to form eutectics, which exists in the shape of lumpy, strip and spherical. The main structures of laser cladding are γ‐Ni, WC, W2C, M7C3, M23C6 etc. From the hardness analysis, the average hardness of the composite coating is four times of the substrate.
A superconvergence result of the natural convection equations
Authors: Huang Pengzhan , Ma Xiaoling , Askar Rena
Published: December 2015

This paper presents a superconvergence result of the stationary natural convection equations. The superconvergence result is obtained by applying a coarse mesh projection for finite element approximation. This projection method is actually a postprocessing procedure that constructs a new approximation based on a high order polynomial on coarse mesh, under some regularity assumption. Finally, numerical experiment is presented for testing, which confirms the theoretic analysis. Copyright © 2015 John Wiley & Sons, Ltd.
Structure, morphology, and properties of LDPE/sepiolite nanofiber nanocomposite
Authors: Zhang Quan‐tong , Li Shao‐xian , Hu Xiao‐ping , Wang Peng‐ji , Zeng Jian‐bing , Wang Xiu‐li , Wang Yu‐zhong
Published: December 2015

Sepiolite (SEP) nanofibers have been modified by grafting with poly(pentaerythritol diphosphonate dichloride‐hexamethylendiamine) (PSPHD) and compounded with low density polyethylene (LDPE) to form a nanocomposite. The various modified SEPs were characterized by X‐ray photoelectron spectroscopy, Fourier transform infrared, transmission electron microscopy (TEM), and thermogravimetric analysis. The Fourier transform infrared and X‐ray photoelectron spectroscopy tests show that covalent bonding exists between SEP fiber and modifiers. The nanoscale size and morphologies of SEP fiber and modified SEP nanofibers can be observed clearly by TEM. The thermogravimetric analysis results reveal that the multi‐step thermal degradation process of SEP fiber is changed by grafting modification. The various LDPE/SEP nanocomposites were characterized by scanning electron micrograph, TEM, dynamic mechanical analysis, and tensile test. The results suggest that a good interfacial modification effect has been obtained between PSPHD‐SEP and LDPE matrix. A particular improvement in tensile strength is reflected in tensile tests. Dynamic mechanical analysis shows that the storage moduli (E') of PSPHD‐SEP/LDPE nanocomposites are much higher than that of neat LDPE and a‐SEP/LDPE systems. Copyright © 2015 John Wiley & Sons, Ltd.
Nonlinear optical responses in hydrogenated graphene structures
Authors: Zapata‐Peña Reinaldo , Anderson Sean M. , Mendoza Bernardo S. , Shkrebtii Anatoli I.
Published: December 2015

Abstractauthoren We present a theoretical study of the optical spin injection, optical current injection, and second harmonic generation of two 50% hydrogenated graphene structures: CH‐alt and CH‐up. Optical spin injection, under the incidence of circularly polarized light onto nonmagnetic semiconductors, creates spin‐polarized electrons in the conduction bands. Optical current injection and second‐harmonic generation are nonlinear second‐order effects that are allowed in materials without inversion symmetry. The results are calculated in a full electronic band structure scheme within DFT in the LDA approximation. Our results show an anisotropic behavior in the optical responses of the spin, the current injection, and second harmonic generation. We obtained maximum absolute magnitudes of the degree of spin polarization of 61 and 64% for thealtandupstructures, respectively, and it is also possible to optically generate an injection current coming mainly from the carbon layer on bothaltandupsystems. Besides, we found that both structures are excellent candidates for second harmonic generation.
Gastrodin Ameliorates Oxidative Stress and Proinflammatory Response in Nonalcoholic Fatty Liver Disease through the AMPK/Nrf2 Pathway
Authors: Qu Li‐Li , Yu Bin , Li Zheng , Jiang Wen‐Xiao , Jiang Jian‐Dong , Kong Wei‐Jia
Published: December 2015

This study was designed to investigate the antioxidative, antiinflammatory and metabolism‐regulating effects of gastrodin (GSTD) in the treatment of nonalcoholic fatty liver disease (NAFLD). Oleic acid (OA) was used to induce steatosis in HL‐7702 cells; a high‐fat or high‐fat and high‐cholesterol diet was used to induce NAFLD in mice and rats. Our results showed that GSTD significantly increased hepatic superoxide dismutase (SOD) but decreased reactive oxygen species (ROS)/malondialdehyde (MDA) and reduced the mRNA levels of proinflammatory cytokines both in vitro and in vivo. GSTD promoted the phosphorylation of nuclear factor erythroid‐2‐related factor‐2 (Nrf2) at serine (Ser) 40, stimulated its nuclear translocation and increased hepatic expression of heme oxygenase‐1 (HO‐1). GSTD activated AMP‐activated protein kinase (AMPK), suppressed hepatic steatosis, lowered serum triglyceride (TG)/glucose and decreased body weight gain in animals with NAFLD. The stimulating effects of GSTD on the Nrf2 pathway as well as its antioxidative/antiinflammatory activities were abolished by compound C in OA‐treated HL‐7702 cells. In summary, our results demonstrate that GSTD activates the AMPK/Nrf2 pathway, ameliorates oxidative stress/proinflammatory response and improves lipid metabolism in NAFLD. Our findings may support the future clinical application of GSTD for the treatment of NAFLD to reduce hepatic steatosis, oxidative stress and proinflammatory response. Copyright © 2015 John Wiley & Sons, Ltd.
Design and implementation of a block‐backstepping based tracking control for nonholonomic wheeled mobile robot
Authors: Rudra Shubhobrata , Barai Ranjit Kumar , Maitra Madhubanti
Published: December 2015

This paper presents formulation of a novel block‐backstepping based control algorithm to overcome the challenges posed by the tracking and the stabilization problem for a differential drive wheeled mobile robot (WMR). At first, a two‐dimensional output vector for the WMR has been defined in such a manner that it would decouple the two control inputs and, thereby, allow the designer to formulate the control laws for the two inputs one at a time. Actually, the decoupling has been carried out in a way to convert the system into block‐strict feedback form. Thereafter, block‐backstepping control algorithm has been utilized to derive the expressions of the control inputs for the WMR system. The proposed block‐backstepping technique has further been enriched by incorporating an integral action for enhancing the steady state performance of the overall system. Global asymptotic stability of the overall system has been analyzed using Lyapunov stability criteria. Finally, the proposed control algorithm has been implemented on a laboratory scale differential drive WMR to verify the effectiveness of the proposed control law in real‐time environment. Indeed, the proposed design approach is novel in the sense that it has judiciously exploited the nonholonomic constraint of the WMR to result in a reduced order block‐backstepping controller for the WMR, and thereby, it has eventually yielded a compact expression of the control law that is amenable to real‐time implementation. Copyright © 2015 John Wiley & Sons, Ltd.
Stochastic consensus control with finite frequency specification for Markov jump networks
Authors: Luan Xiaoli , Zhou Chaojie , Ding Zhengtao , Liu Fei
Published: December 2015

A stochastic finite frequency consensus protocol for directed networks with Markov jump topologies and external disturbances is proposed in this paper. By introducing the frequency band information into consensus control design, the disagreement dynamics of interconnected networks asymptotically converge to zero with an improved level of disturbance attenuation in the specific frequency band. In addition, the new model transformation approach is presented by exploring certain features of Laplacian matrix in real Jordan form, which leads to more generality of the designed protocol. A numerical example validates the potential of the developed results. Copyright © 2015 John Wiley & Sons, Ltd.