bluuebunny/crossref_metadata_2025 huggingface dataset:
Eomesodermin Expression in CD4+ T Cells Restricts Peripheral Foxp3 Induction
Authors: Lupar Ekaterina , Brack Maria , Garnier Laure , Laffont Sophie , Rauch Katharina S. , Schachtrup Kristina , Arnold Sebastian J. , Guéry Jean-Charles , Izcue Ana
Published: October 2015

CD4+ T cells polarize into effector Th subsets characterized by signature transcription factors and cytokines. Although T-bet drives Th1 responses and represses the alternative Th2, Th17, and Foxp3+ regulatory T cell fates, the role of the T-bet–related transcription factor eomesodermin (Eomes) in CD4+ T cells is less well understood. In this study, we analyze the expression and effects of Eomes in mouse CD4+ T lymphocytes. We find that Eomes is readily expressed in activated CD4+ Th1 T cells in vivo. Eomes+ CD4+ T cells accumulated in old mice, under lymphopenic conditions in a T cell transfer model of colitis, and upon oral Ag administration. However, despite its expression, genetic deletion of Eomes in CD4+ T cells did not impact on IFN-γ production nor increase Th2 or Th17 responses. In contrast, Eomes deficiency favored the accumulation of Foxp3+ cells in old mice, after in vivo differentiation of Eomes-deficient naive CD4+ T cells, and in response to oral Ag in a cell-intrinsic way. Enforced Eomes expression during in vitro regulatory T cell induction also reduced Foxp3 transcription. Likewise, bystander Eomes-deficient CD4+ T cells were more efficient at protecting from experimental autoimmune encephalitis compared with wild-type CD4+ T cells. This enhanced capacity of Eomes-deficient CD4+ T cells to inhibit EAE in trans was associated with an enhanced frequency of Foxp3+ cells. Our data identify a novel role for Eomes in CD4+ T cells and indicate that Eomes expression may act by limiting Foxp3 induction, which may contribute to the association of EOMES to susceptibility to multiple sclerosis.
Phenotypic and Morphological Properties of Germinal Center Dark Zone Cxcl12-Expressing Reticular Cells
Authors: Rodda Lauren B. , Bannard Oliver , Ludewig Burkhard , Nagasawa Takashi , Cyster Jason G.
Published: October 2015

The germinal center (GC) is divided into a dark zone (DZ) and a light zone (LZ). GC B cells must cycle between these zones to achieve efficient Ab affinity maturation. Follicular dendritic cells (FDCs) are well characterized for their role in supporting B cell Ag encounter in primary follicles and in the GC LZ. However, the properties of stromal cells supporting B cells in the DZ are relatively unexplored. Recent work identified a novel stromal population of Cxcl12-expressing reticular cells (CRCs) in murine GC DZs. In this article, we report that CRCs have diverse morphologies, appearing in open and closed networks, with variable distribution in lymphoid tissue GCs. CRCs are also present in splenic and peripheral lymph node primary follicles. Real-time two-photon microscopy of Peyer’s patch GCs demonstrates B cells moving in close association with CRC processes. CRCs are gp38+ with low to undetectable expression of FDC markers, but CRC-like cells in the DZ are lineage marked, along with FDCs and fibroblastic reticular cells, by CD21-Cre– and Ccl19-Cre–directed fluorescent reporters. In contrast to FDCs, CRCs do not demonstrate dependence on lymphotoxin or TNF for chemokine expression or network morphology. CRC distribution in the DZ does require CXCR4 signaling, which is necessary for GC B cells to access the DZ and likely to interact with CRC processes. Our findings establish CRCs as a major stromal cell type in the GC DZ and suggest that CRCs support critical activities of GC B cells in the DZ niche through Cxcl12 expression and direct cell–cell interactions.
Mechanistic Target of Rapamycin Complex 1/S6 Kinase 1 Signals Influence T Cell Activation Independently of Ribosomal Protein S6 Phosphorylation
Authors: Salmond Robert J. , Brownlie Rebecca J. , Meyuhas Oded , Zamoyska Rose
Published: October 2015

Ag-dependent activation of naive T cells induces dramatic changes in cellular metabolism that are essential for cell growth, division, and differentiation. In recent years, the serine/threonine kinase mechanistic target of rapamycin (mTOR) has emerged as a key integrator of signaling pathways that regulate these metabolic processes. However, the role of specific downstream effectors of mTOR function in T cells is poorly understood. Ribosomal protein S6 (rpS6) is an essential component of the ribosome and is inducibly phosphorylated following mTOR activation in eukaryotic cells. In the current work, we addressed the role of phosphorylation of rpS6 as an effector of mTOR function in T cell development, growth, proliferation, and differentiation using knockin and TCR transgenic mice. Surprisingly, we demonstrate that rpS6 phosphorylation is not required for any of these processes either in vitro or in vivo. Indeed, rpS6 knockin mice are completely sensitive to the inhibitory effects of rapamycin and an S6 kinase 1 (S6K1)–specific inhibitor on T cell activation and proliferation. These results place the mTOR complex 1-S6K1 axis as a crucial determinant of T cell activation independently of its ability to regulate rpS6 phosphorylation.
Stopping Financial Fraud in Churches
Authors: Gray Dahli , Villamarin Rodrigo
Published: October 2015

This article reports the results of a survey administered in March 2015 about financial fraud in churches, which has been and continues to be a concern academics and professionals must address. The survey results focus on concepts and techniques for preventing, detecting, and resolving church financial fraud. Two hundred (200) adults were invited to complete the survey. Sixty five percent (65%) responded providing strong support for changes such as requiring churches to apply for tax-exempt status, provide financial statements based on strong internal control systems, and use consultants (e.g., Certified Public Accountants, Certified Fraud Examiners) to help develop and implement changes.
Enhancing high performance of emergency unit by improving the management emergency team system of the Plateau State Specialist Hospital Nigeria
Authors: Coker-Farrell Elizabeth Y.S , Yildam Fabong Jemchang , Luka Moses Farrell , Secim Hikmet
Published: October 2015

There are challenges with the management of the emergency units of healthcare organizations in Nigeria; these have been observed from the high mortality rate, high level of left before examination (LBE) of the patients, low response time to acute care patients and poor turnaround time by the healthcare givers to address emergency situations. Therefore there is an urgent need to address the situation and solve the problems best ways possible by improving the management emergency team (MET) system of the healthcare organization. These was achieved by quantitative methodology application through the distribution of questionnaires, interviews and personal observation of the situation, hence improving the quality and quantity of the man power which is the human resources with qualified and well trained medical personnel, adding also to the management emergency team are police protocol officers who can give police report immediately for unconscious accident victims on arrival for emergency treatment, eliminating need for unavailable consent form before treatment, adding intensive training programs for MET system, emergency hotlines and ambulance assistance for patients, adequate supplies of oxygen and facilities that are up-to-date for the emergency unit. These solutions have increased the stability of the emergency unit, lower mortality rate, increased the efficiency of the team, improved response time, higher survival rate, improving the staff efficiency and effectiveness, after which it is observed that the emergency unit is on high-performance level, with good survey feedback by patients and their relatives.
Publiek en privaat: een spannende relatie in de bouw- en infraketen
Authors: Verhees Frits , van Marrewijk Alfons , Leendertse Wim , Arts Jos
Published: October 2015

De Nederlandse rijksoverheid maakt steeds meer gebruik van DBFM(O)-contracten om grootschalige bouw- en infraprojecten te ontwikkelen en te realiseren (DBFM(O) staat voor Design, Build, Finance, Maintain en eventueel Operate). De organisatie en inrichting van deze contracten en projecten zijn ‘als vanzelfsprekend’ gegroeid en gestandaardiseerd, veelal gebaseerd op de internationale praktijk en buitenlandse voorbeelden. Dit artikel zet uiteen hoe DBFM(O)-projecten georganiseerd en gestructureerd worden door publieke en private partijen. Uit internationaal onderzoek blijkt dat de resultaten wisselend zijn, maar de potentiële voordelen van DBFM(O) zijn groot. Deze potentie blijkt uit de eerste praktijkervaringen in Nederland, maar we kennen inmiddels ook de eerste negatieve gevolgen voor betrokken risicodragende partijen. We onderscheiden bij DBFM(O) zes ‘conventies’ met onderliggende spanningen waar praktijk en wetenschap, in de Nederlandse verhoudingen, kritisch op zullen moeten reflecteren.
Quasi‐10‐day wave in the atmosphere
Authors: Forbes Jeffrey M. , Zhang Xiaoli
Published: October 2015

In the classical theory of oscillations on a spherical‐rotating Earth, the quasi‐10‐day wave (Q10DW) exists as a westward propagating “free” or “unforced” normal mode oscillation with zonal wave number s = 1. In the present study, we employ Thermosphere Ionosphere Mesosphere Energetics and Dynamics/Sounding of the Atmosphere using Broadband Emission Radiometry temperature measurements between 20 and 100 km and ±50° latitude, and extending from 2002 to 2013, to provide a comprehensive perspective on the Q10DW as it actually exists in the atmosphere. Climatological seasonal‐latitudinal structures are presented which demonstrate that the Q10DW is weakest during summer months and equatorward of ±50° latitude but otherwise has amplitudes ranging from 1.0 K at ∼45 km to ∼5 K at 100 km. Seasonal asymmetries and significant interannual variability also exist. The mean period of the Q10DW is 9.8 days with a standard deviation of about 0.4 day. On average the Q10DW conforms reasonably well with theoretical expectations for a normal mode subject to the effects of dissipation and mean winds, at least below 80 km. Above 80 km this conformity often breaks down. Several factors potentially contributing to this nonconformity are discussed.
Evaluation of high‐level clouds in cloud resolving model simulations with ARM and KWAJEX observations
Authors: Liu Zheng , Muhlbauer Andreas , Ackerman Thomas
Published: October 2015

In this study, we evaluate high‐level clouds in a cloud resolving model during two convective cases, ARM9707 and KWAJEX. The simulated joint histograms of cloud occurrence and radar reflectivity compare well with cloud radar and satellite observations when using a two‐moment microphysics scheme. However, simulations performed with a single moment microphysical scheme exhibit low biases of approximately 20 dB. During convective events, two‐moment microphysical overestimate the amount of high‐level cloud and one‐moment microphysics precipitate too readily and underestimate the amount and height of high‐level cloud. For ARM9707, persistent large positive biases in high‐level cloud are found, which are not sensitive to changes in ice particle fall velocity and ice nuclei number concentration in the two‐moment microphysics. These biases are caused by biases in large‐scale forcing and maintained by the periodic lateral boundary conditions. The combined effects include significant biases in high‐level cloud amount, radiation, and high sensitivity of cloud amount to nudging time scale in both convective cases. The high sensitivity of high‐level cloud amount to the thermodynamic nudging time scale suggests that thermodynamic nudging can be a powerful “tuning” parameter for the simulated cloud and radiation but should be applied with caution. The role of the periodic lateral boundary conditions in reinforcing the biases in cloud and radiation suggests that reducing the uncertainty in the large‐scale forcing in high levels is important for similar convective cases and has far reaching implications for simulating high‐level clouds in super‐parameterized global climate models such as the multiscale modeling framework.
Modifications to WRF's dynamical core to improve the treatment of moisture for large‐eddy simulations
Authors: Xiao Heng , Endo Satoshi , Wong May , Skamarock William C. , Klemp Joseph B. , Fast Jerome D. , Gustafson William I. , Vogelmann Andrew M. , Wang Hailong , Liu Yangang , Lin Wuyin
Published: October 2015

Yamaguchi and Feingold (2012) note that the cloud fields in their large‐eddy simulations (LESs) of marine stratocumulus using the Weather Research and Forecasting (WRF) model exhibit a strong sensitivity to time stepping choices. In this study, we reproduce and analyze this sensitivity issue using two stratocumulus cases, one marine and one continental. Results show that (1) the sensitivity is associated with spurious motions near the moisture jump between the boundary layer and the free atmosphere, and (2) these spurious motions appear to arise from neglecting small variations in water vapor mixing ratio (qv) in the pressure gradient calculation in the acoustic substepping portion of the integration procedure. We show that this issue is remedied in the WRF dynamical core by replacing the prognostic equation for the potential temperature θ with one for the moist potential temperature θm=θ(1 + 1.61qv), which allows consistent treatment of moisture in the calculation of pressure during the acoustic substeps. With this modification, the spurious motions and the sensitivity to the time stepping settings (i.e., the dynamic time step length and number of acoustic sub‐steps) are eliminated in both of the example stratocumulus cases. This modification improves the applicability of WRF for LES applications, and possibly other models using similar dynamical core formulations, and also permits the use of longer time steps than in the original code.
Estimation of human‐induced changes in terrestrial water storage through integration of GRACE satellite detection and hydrological modeling: A case study of the Yangtze River basin
Authors: Huang Ying , Salama Mhd. Suhyb , Krol Maarten S. , Su Zhongbo , Hoekstra Arjen Y. , Zeng Yijian , Zhou Yunxuan
Published: October 2015

Quantifying the human effects on water resources plays an important role in river basin management. In this study, we proposed a framework, which integrates the Gravity Recovery and Climate Experiment (GRACE) satellite estimation with macroscale hydrological model simulation, for detection and attribution of spatial terrestrial water storage (TWS) changes. In particular, it provides valuable insights for regions where ground‐based measurements are inaccessible. Moreover, this framework takes into account the feedback between land and atmosphere and innovatively put forward several suggestions (e.g., study period selection, hydrological model selection based on soil moisture‐climate interactions) to minimize the uncertainties brought by the interaction of human water use with terrestrial water fluxes. We demonstrate the use of the proposed framework in the Yangtze River basin of China. Our results show that, during the period 2003–2010, the TWS was continually increasing in the middle and south eastern reaches of the basin, at a mean rate of about 3 cm yr−1. This increment in TWS was attributed to anthropogenic modification of the hydrological cycle, rather than natural climate variability. The dominant contributor to the TWS excess was found to be intensive surface water irrigation, which recharged the water table in the middle and south eastern parts of the basin. Water impoundment in the Three Gorges Reservoir (TGR) is found to account for nearly 20% of the human‐induced TWS increment in the region where the TGR is located. The proposed framework gives water managers/researchers a useful tool to investigate the spatial human effects on TWS changes.
Evidence Evaluation and Evidence Integration in Legal Decision‐Making: Order of Evidence Presentation as a Moderator of Context Effects
Authors: Charman Steve D. , Carbone Jon , Kekessie Seyram , Villalba Daniella K.
Published: October 2015

Legal decision‐making studies often demonstrate context effects: People's initial beliefs about a suspect's guilt influence their evaluation of subsequent evidence. We examine three potential moderators of these context effects: Order of evidence presentation, ability to ruminate, and valence of the initial belief (innocence or guilt). College students (n = 382) were presented with DNA evidence (incriminating or exonerating) and an ambiguous alibi in one of two orders (or just the alibi), and then evaluated how strongly the alibi incriminated the suspect and the suspect's likelihood of guilt. Results indicated that alibi evaluation exhibited context effects when (i) initial beliefs were of guilt (but not of innocence) and when (ii) evaluating subsequent evidence (but not when retroactively evaluating prior evidence). Rumination failed to moderate any effects. The integration of evidence exhibited recency effects: DNA had a greater impact on participants' beliefs in the suspect's guilt when presented last rather than first. Copyright © 2015 John Wiley & Sons, Ltd.
Maximizing Transfection Efficiency of Vertically Aligned Silicon Nanowire Arrays
Authors: Elnathan Roey , Delalat Bahman , Brodoceanu Daniel , Alhmoud Hashim , Harding Frances J. , Buehler Katrin , Nelson Adrienne , Isa Lucio , Kraus Tobias , Voelcker Nicolas H.
Published: October 2015

Vertically aligned silicon nanowire (VA‐SiNW) arrays are emerging as a powerful new tool for gene delivery by means of mechanical transfection. In order to utilize this tool efficiently, uncertainties around the required design parameters need to be removed. Here, a combination of nanosphere lithography and templated metal‐assisted wet chemical etching is used to fabricate VA‐SiNW arrays with a range of diameters, heights, and densities. This fabrication strategy allows identification of critical parameters of surface topography and consequently the design of SiNW arrays that deliver plasmid with high transfection efficiency into a diverse range of human cells whilst maintaining high cell viability. These results illuminate the cell‐materials interactions that mediate VA‐SiNW transfection and have the potential to transform gene therapy and underpin future treatment modalities.
Two‐Dimensional Nanomaterials for Biomedical Applications: Emerging Trends and Future Prospects
Authors: Chimene David , Alge Daniel L. , Gaharwar Akhilesh K.
Published: October 2015

Two‐dimensional (2D) nanomaterials are ultrathin nanomaterials with a high degree of anisotropy and chemical functionality. Research on 2D nanomaterials is still in its infancy, with the majority of research focusing on elucidating unique material characteristics and few reports focusing on biomedical applications of 2D nanomaterials. Nevertheless, recent rapid advances in 2D nanomaterials have raised important and exciting questions about their interactions with biological moieties. 2D nanoparticles such as carbon‐based 2D materials, silicate clays, transition metal dichalcogenides (TMDs), and transition metal oxides (TMOs) provide enhanced physical, chemical, and biological functionality owing to their uniform shapes, high surface‐to‐volume ratios, and surface charge. Here, we focus on state‐of‐the‐art biomedical applications of 2D nanomaterials as well as recent developments that are shaping this emerging field. Specifically, we describe the unique characteristics that make 2D nanoparticles so valuable, as well as the biocompatibility framework that has been investigated so far. Finally, to both capture the growing trend of 2D nanomaterials for biomedical applications and to identify promising new research directions, we provide a critical evaluation of potential applications of recently developed 2D nanomaterials.
Mechanoresponsive Luminescent Molecular Assemblies: An Emerging Class of Materials
Authors: Sagara Yoshimitsu , Yamane Shogo , Mitani Masato , Weder Christoph , Kato Takashi
Published: October 2015

The possibility to change the molecular assembled structures of organic and organometallic materials through mechanical stimulation is emerging as a general and powerful concept for the design of functional materials. In particular, the photophysical properties such as photoluminescence color, quantum yield, and emission lifetime of organic and organometallic fluorophores can significantly depend on the molecular packing, enabling the development of molecular materials with mechanoresponsive luminescence characteristics. Indeed, an increasing number of studies have shown in recent years that mechanical force can be utilized to change the molecular arrangement, and thereby the optical response, of luminescent molecular assemblies of π‐conjugated organic or organometallic molecules. Here, the development of such mechanoresponsive luminescent (MRL) molecular assemblies consisting of organic or organometallic molecules is reviewed and emerging trends in this research field are summarized. After a brief introduction of mechanoresponsive luminescence observed in molecular assemblies, the concept of “luminescent molecular domino” is introduced, before molecular materials that show turn‐on/off of photoluminescence in response to mechanical stimulation are reviewed. Mechanically stimulated multicolor changes and water‐soluble MRL materials are also highlighted and approaches that combine the concept of MRL molecular assemblies with other materials types are presented in the last part of this progress report.
Impact of postoperative endoscopy upon clinical outcomes after endoscopic sinus surgery
Authors: Schlosser Rodney J. , Storck Kristina , Smith Timothy L. , Mace Jess C. , Rudmik Luke , Shahangian Arash , Soler Zachary M.
Published: October 2015

Background

After endoscopic sinus surgery (ESS), endoscopy is used to gauge surgical success and clinical outcomes. Prior studies have not examined this topic prospectively using validated outcome metrics across multiple institutions.

Methods

A multi‐institutional, prospective study of patients with chronic rhinosinusitis (CRS) who underwent ESS completed the 22‐item Sino‐Nasal Outcome Test (SNOT‐22), missed productivity, and medication usage questionnaires 6 months postoperatively. Lund‐Kennedy endoscopy scoring (LKES) was performed with reviewers blinded to patient‐reported data. A control cohort of non‐CRS patients was recruited for comparison.

Results

Complete data was available on 183 CRS patients and 48 non‐CRS control patients. Approximately 50% of patients achieve perfect or near perfect endoscopy (LKES 0 to 2) after ESS. Postoperative endoscopy correlated with total SNOT‐22 scores (r = 0.278, p < 0.001), with the strongest correlations to rhinologic and extranasal subdomains in the nasal polyp cohort. Improved postoperative endoscopy was associated with decreased antibiotic and oral steroid usage, but had little association with missed productivity. Among patients who achieved near perfect postoperative endoscopy, those with nasal polyps had SNOT‐22 scores that were similar to non‐CRS control patients (mean SNOT‐22 scores 17.7 and 16.3, respectively). However, CRS patients without nasal polyps remained more symptomatic than non‐CRS controls and CRS with nasal polyps patients despite nearly perfect endoscopy (mean SNOT‐22 score 21.6).

Conclusion

Postoperative endoscopy correlates with SNOT‐22 and medication usage in CRS patients. Polyp patients who achieve near perfect endoscopy have similar symptoms to healthy controls; however, nonpolyp patients with near perfect endoscopy still have rhinologic and extranasal symptoms that are worse than healthy controls.
Heterometallische Ringe: physikalische Eigenschaften und Verwendung als supramolekulare Bausteine
Authors: McInnes Eric J. L. , Timco Grigore A. , Whitehead George F. S. , Winpenny Richard E. P.
Published: October 2015

Heterometallische Ringe wurden in großer Zahl hergestellt, angefangen von den ersten Cr7M‐Ringen mit M=NiII, ZnII und MnII bis hin zu Ringen mit vierzehn Metallen in der cyclischen Struktur. Bekannte Beispiele entweder außen durch Carboxylate oder innen durch Fluoride oder ein fünffach deprotoniertes Polyol verbrückt. Die Ringgröße wird durch Template gesteuert, z. B. durch Ammonium‐ oder Imidazoliumionen, Alkalimetalle oder Koordinationsverbindungen. Die Ringe können funktionalisiert werden und wirken dadurch als Liganden, sie lassen sich außerdem zum Aufbau von organisch‐anorganischen Rotaxanen oder von Makromolekülen mit bis zu 200 Metallzentren verwenden. Eine Reihe von physikalischen Studien wurde an heterometallischen Ringen durchgeführt, darunter magnetische Messungen, inelastische Neutronenstreuung (einschließlich Einkristallmessungen), paramagnetische Elektronenresonanzspektroskopie (einschließlich Messungen der Phasengedächtniszeiten), NMR‐Spektroskopie (Lösung und Festkörper) und polarisierte Neutronenstreuung. Die Ringe sind somit ideale Modellsystem, um Einblicke in den Magnetismus bei austauschgekoppelten Systemen zu gewinnen.
Katalyse von Radikalreaktionen: Konzepte aus Sicht der Radikalchemie
Authors: Studer Armido , Curran Dennis P.
Published: October 2015

Das Gebiet der Katalyse von Radikalreaktionen erfuhr in jüngster Zeit höchste Aufmerksamkeit. Viele interessante Radikalreaktionen wurden entdeckt und dann über Katalysezyklen erklärt. Diese Zyklen stellen allerdings selten den einzigen Weg vom Substrat zum Produkt dar. Die meisten Radikalreaktionen weisen intrinsische Ketten auf, die das Potential haben, das Produkt auch ohne Katalysator zu bilden. Wie wissen wir nun, ob eine in “katalytischen Mengen” zugegebene Verbindung einen Katalysator, einen Initiator oder gar etwas anderes darstellt? Im vorliegenden Aufsatz besprechen wir kritisch sowohl Katalysator‐freie als auch katalytische Radikalreaktionen aus Sicht der Radikalchemie. Grundlagen der Kinetik und Thermodynamik von Radikalreaktionen werden genutzt, um die Probleme der Initiierung, Propagation und Inhibierung von Radikalreaktionen zu adressieren. Katalyse von Radikalreaktionen unterscheidet sich von anderen Gebieten der Katalyse in mehreren Aspekten. Wohingegen intrinsische Kettenreaktionen schwierig zu katalysieren sind, da die zugrundeliegenden individuellen Schritte so schnell ablaufen, bieten ineffiziente Kettenprozesse und nicht‐Kettenprozesse verschiedene Möglichkeiten der Katalyse. Wir illustrieren Konzepte der Katalyse von Radikalreaktionen mit ausgewählten Beispielen aus der klassischen, aber auch der jüngsten Literatur.
Binding‐Induced DNA Nanomachines Triggered by Proteins and Nucleic Acids
Authors: Zhang Hongquan , Lai Maode , Zuehlke Albert , Peng Hanyong , Li Xing‐Fang , Le X. Chris
Published: October 2015

We introduce the concept and operation of a binding‐induced DNA nanomachine that can be activated by proteins and nucleic acids. This new type of nanomachine harnesses specific target binding to trigger assembly of separate DNA components that are otherwise unable to spontaneously assemble. Three‐dimensional DNA tracks of high density are constructed on gold nanoparticles functionalized with hundreds of single‐stranded oligonucleotides and tens of an affinity ligand. A DNA swing arm, free in solution, is linked to a second affinity ligand. Binding of a target molecule to the two ligands brings the swing arm to AuNP and initiates autonomous, stepwise movement of the swing arm around the AuNP surface. The movement of the swing arm, powered by enzymatic cleavage of conjugated oligonucleotides, cleaves hundreds of oligonucleotides in response to a single binding event. We demonstrate three nanomachines that are specifically activated by streptavidin, platelet‐derived growth factor, and the Smallpox gene. Substituting the ligands enables the nanomachine to respond to other molecules. The new nanomachines have several unique and advantageous features over DNA nanomachines that rely on DNA self‐assembly.
Synthesis of a “Masked” Terminal Nickel(II) Sulfide by Reductive Deprotection and its Reaction with Nitrous Oxide
Authors: Hartmann Nathaniel J. , Wu Guang , Hayton Trevor W.
Published: October 2015

The addition of 1 equiv of KSCPh3 to [LRNiCl] (LR={(2,6‐iPr2C6H3)NC(R)}2CH; R=Me, tBu) in C6H6 results in the formation of [LRNi(SCPh3)] (1: R=Me; 2: R=tBu) in good yields. Subsequent reduction of 1 and 2 with 2 equiv of KC8 in cold (−25 °C) Et2O in the presence of 2 equiv of 18‐crown‐6 results in the formation of “masked” terminal NiII sulfides, [K(18‐crown‐6)][LRNi(S)] (3: R=Me; 4: R=tBu), also in good yields. An X‐ray crystallographic analysis of these complexes suggests that they feature partial multiple‐bond character in their NiS linkages. Addition of N2O to a toluene solution of 4 provides [K(18‐crown‐6)][LtBuNi(SNNO)], which features the first example of a thiohyponitrite (κ2‐[SNNO]2−) ligand.
Hydrogenated rosin ester latexes/waterborne polyacrylate blends for pressure‐sensitive adhesives
Authors: Zhang KaiTao , Shang Shibin , Sun PeiPei , Shen MingGui , Wang Dan
Published: October 2015

Diethylene glycol ester of hydrogenated rosin (DGE‐HR) emulsion was prepared via phase inversion method and then blended with waterborne (wb) polyacrylate for pressure‐sensitive adhesives (PSAs). The preparation conditions of DGE‐HR emulsion were studied. DGE‐HR emulsion with an average particle size of about 220 nm was obtained. Furthermore, the thermal, adhesive, and viscoelastic properties and the morphology of DGE‐HR/polyacrylate composite were investigated. Thermal analysis indicated that glass transition temperatures (Tg) of the DGE‐HR/polyacrylate blends became higher as the DGE‐HR content increased and DGE‐HR did not have a significant influence on thermal stability of the blend films. Atomic Force Microscopy (AFM) observation revealed that the DGE‐HR particles added had a good miscibility with acrylic particles. Additionally, for these tackified acrylic PSAs, positive correlations between mechanical performance and viscoelastic response at bonding and debonding frequencies were also found. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 42965.
Absence of Early Neuronal Death in the Olivocochlear System Following Acoustic Overstimulation
Authors: Reuss Stefan , Closhen Christina , Riemann Randolf , Jaumann Mirko , Knipper Marlies , Rüttiger Lukas , Wolpert Stephan
Published: October 2015

This study was conducted to examine possible effects of noise trauma on olivocochlear (OC) neurons. Anesthetized rats were exposed to a continuous 10 kHz pure tone at 120 dB sound pressure level for 2 hrs. The effects of treatment were verified by recordings of auditory brainstem response and distortion product otoacoustic emission. Three or 8 days after acoustic trauma, rats received unilateral injections of an aqueous solution of the retrograde neuronal tracer Fluorogold (FG) into the scala tympani to identify OC neurons (OCN). Five days after FG injection, brains were perfusion‐fixed, and brainstem sections were cut and analyzed with respect to FG‐labeled neurons. We found that, in both groups, numbers of OCN were similar to that of controls. The incubation of a second set of sections with antibodies against choline‐acetyltransferase (the enzyme responsible for acetylcholine synthesis) showed the cholinergic neurons of the brainstem, however, without suggesting differences between groups. Our study, the first to investigate noise trauma effects on identified OCN, revealed that no visible alterations occurred in 2 weeks following trauma, neither in identified OCN nor in choline‐acetyltransferase‐immunofluorescence. At this time, auditory brainstem response and distortion product otoacoustic emission measurements showed severe signs of hearing loss. The mechanisms leading to hearing loss upon noise trauma apparently do not involve degeneration of OCN. Anat Rec, 299:103–110, 2016. © 2015 Wiley Periodicals, Inc.
CHARACTERIZATION OF A NEW KUNITZ‐TYPE SERINE PROTEASE INHIBITOR FROM THE HARD TICK Rhipicephalus hemaphysaloides
Authors: Cao Jie , Shi Lei , Zhou Yongzhi , Gao Xiao , Zhang Houshuang , Gong Haiyan , Zhou Jinlin
Published: October 2015

A new Kunitz‐type serine protease inhibitor, Rhipilin‐2, was identified in the tick Rhipicephalus hemaphysaloides. The cDNA sequence of Rhipilin‐2 is 693 bp, and it encodes a deduced 195 amino acid protein with a size of 22 kDa. Bioinformatic analysis shows that Rhipilin‐2 belongs to the Kunitz‐type family of inhibitors, containing one Kunitz domain with homology to the tissue factor pathway inhibitor. Using Real time polymerase chain reaction (Real time‐PCR), Rhipilin‐2 mRNA transcripts were detected in tick salivary glands and midgut. Blood feeding induced transcript expression. The recombinant protein was expressed in insect Sf9 cells and confirmed by immunofluorescence test and Western blot analysis with an anti‐His antibody. The purified recombinant Rhipilin‐2 inhibited serine protease trypsin and elastase, but not thrombin. The anticoagulant activity of Rhipilin‐2 was shown by delaying normal clotting of rabbit plasma in the activated partial thromboplastin time tests. These results indicate that Rhipilin‐2 is a novel Kunitz‐type serine protease inhibitor involved in tick blood feeding.
Sleep Apnea and the Risk of Incident Gout: A Population‐Based, Body Mass Index–Matched Cohort Study
Authors: Zhang Yuqing , Peloquin Christine E. , Dubreuil Maureen , Roddy Edward , Lu Na , Neogi Tuhina , Choi Hyon K.
Published: October 2015

Objective

Sleep apnea is associated with hyperuricemia owing to hypoxia‐induced nucleotide turnover. We undertook this study to assess the relationship between incident sleep apnea and the risk of incident gout.

Methods

Using data from The Health Improvement Network in the UK, we identified individuals with a first‐ever physician diagnosis of sleep apnea. For each patient with sleep apnea, up to 5 individuals without sleep apnea were matched by sex, age, birth year, and body mass index (within ±0.5 kg/m2). We estimated the incidence rates of gout and examined the relationship between sleep apnea and the risk of incident gout using a Cox proportional hazards model, adjusting for potential confounders. In addition, we assessed the rate difference in gout due to sleep apnea using an additive hazard model.

Results

Among 9,865 patients with newly diagnosed sleep apnea and 43,598 matched individuals without sleep apnea, we identified 270 incident cases of gout over 1 year of followup, resulting in incidence rates of 8.4 per 1,000 person‐years and 4.8 per 1,000 person‐years, respectively. The crude and multivariable rate ratios of incident gout in patients with sleep apnea were 1.7 (95% confidence interval [95% CI] 1.3, 2.2) and 1.5 (95% CI 1.1, 2.1), respectively. The corresponding rate differences between patients with sleep apnea and the comparison cohort were 3.6 (95% CI 1.6, 5.6) and 2.8 (95% CI 0.7, 4.9) per 1,000 person‐years. The effect of sleep apnea persisted across subgroups.

Conclusion

This general population–based study indicates that sleep apnea is independently associated with an increased risk of incident gout. Future research should examine the potential benefits of correcting sleep apnea–induced hypoxia on the risk of hyperuricemia and gout flares.
Characterization, Modeling and H∞ control of n‐DOF Piezoelectric Actuators: application to A 3‐DOF Precise Positioner
Authors: Habineza Didace , Rakotondrabe Micky , Gorrec Yann Le
Published: October 2015

This paper deals with the characterization, the modeling and the closed‐loop control of multivariable piezoelectric actuators, with an application to a 3‐DOF piezoelectric tube scanner, widely used in precise positioning. These actuators are typified by hysteresis and creep nonlinearities, badly damped oscillation and strong couplings between their axis. First, during the modeling, we propose to decouple the system and to use a linear model where the couplings and the two nonlinearities are integrated through an external fictive disturbance. From the obtained monovariable systems, monovariable H∞ controllers are calculated by using specifications based on model approximation. The experimental tests demonstrate the efficiency of the method to reject simultaneously the couplings, hysteresis, creep and badly damped oscillations. Furthermore, the bandwidth of the closed‐loop and the open‐loop systems are compared and the results show that the proposed control technique allows to achieve a convenient closed‐loop bandwidth and precision for all the axis of the precise positioner.
The environmental dependence of the fractions of red star‐forming and blue passive galaxies
Authors: Deng X.‐F. , Chen Y.Q. , Jiang P. , Ding Y.P. , Song J.
Published: October 2015

Using two volume‐limited Main galaxy samples of the Sloan Digital Sky Survey Data Release 6 (SDSS DR6) with the luminosity –20.0 ≤ Mr ≤ –18.5 and –22.40 ≤ Mr ≤–20.16, we have explored the environmental dependence of the fractions of red star‐forming and blue passive galaxies. It is found that the fractions of red star‐forming and blue passive galax‐ies decline mildly with increasing local density in the luminous volume‐limited sample, but in the faint volume‐limited sample these fractions rise slightly with increasing local density except that the fraction of red star‐forming decreases with density in the densest regime. Only according to statistical results of this study, it is difficult to reach the conclusion: there is an environmental dependence for color beyond that for star formation activities or for star formation activities beyond that for color. In this condition, we preferentially believe that star formation activities and color possiblely have equally strong environmental dependence. In the faint volume‐limited sample, we observe that the fraction of star‐forming galaxies‐the density relation has a “critical density” at the projected local density PLD ≈ 1 h–2 Mpc–2: below this density the fraction of star‐forming galaxies is high and nearly constant, while above this density this fraction drops rapidly. Thus, it is possible that in the densest regime of the faint volume‐limited sample, there is an environmental dependence for star formation activities beyond that for color, which leads to the fraction of red star‐forming decreasing with density in the densest regime of the faint volume‐limited sample (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Absolute and geometric parameters of the W UMa‐type contact binary V404 Pegasi
Authors: Gürol B. , Terzioğlu Z. , Gürsoytrak S.H. , Gökay G. , Derman E.
Published: October 2015

We present the results of our investigation of the geometrical and physical parameters of the W UMa‐type binary V404 Peg from analysis of CCD (BVRI) light curves and radial velocity data. The photometric data were obtained during 2010 at Ankara University Observatory (AUO). Light and radial velocity observations were analyzed simultaneously by using the well‐known Wilson‐Devinney (2007 revision) code to obtain absolute and geometrical parameters. Our solution indicates that V404 Peg is an A‐type overcontact binary with a mass ratio of q = 0.243 and an overcontact degree of f = 32.1 %. Combining our light curves with the radial velocity curves from Maciejewski & Ligeza (2004), we determined the absolute parameters of this system as follows: a = 2.672 R⊙, M1 = 1.175 M⊙, M2 = 0.286 M⊙, R1 = 1.346 R⊙, and R2 = 0.710 R⊙. Finally, we discuss the evolutionary condition of the system (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Cloning and characterization of a thermostable detergent‐compatible recombinant keratinase from Bacillus pumilus KS12
Authors: Rajput Rinky , Sharma Richa , Gupta Rani
Published: October 2015

Functional expression of a keratinase from a potential feather‐degrading bacterium, Bacillus pumilus KS12, was achieved in Escherichia coli using pEZZ18 vector. The enzyme was constitutively secreted at 37°C and 300 rpm after 18 H of incubation and was purified to homogeneity using diethylaminoethyl‐Sepharose column. It was completely stable within the pH range of 7.0–10.0 with optima at pH 9.0, and temperature 30°C–90°C with optima at 70°C. It had high thermostability with a t1/2 of more than 4 H at 70°C, more than 2 H at 80°C, and 30 Min at 90°C. The enzyme was identified as a serine hydrolase as it was completely inhibited by 10 mM phenylmethylsulfonyl fluoride. It retained more than 90% relative activity in the presence of chelating agents such as ethylenediaminetetraacetic acid and 1,10‐o‐phenanthroline. It was also a thiol‐activated enzyme with 3.32‐ and fourfold activation in the presence of 10 mM dithiothreitol and β‐mercaptoethanol. The keratinase exhibited high detergent compatibility and oxidation stability with an eight‐ and fivefold enhancement in the presence of triton X‐100 and saponin, respectively. It hydrolyzed a large array of protein substrates with a keratinolytic–caseinolytic ratio of more than 0.5. Amidolytic activity revealed its cleavage on phenylalanine → leucine → alanine–p‐nitroanilides. In addition, electrospray ionization–mass spectrometry analysis of hydrolyzed insulin B‐chain revealed cleavage between Leu6–Cys7, Cys7–Gly8, Tyr16–Leu17, Cys19–Gly20, Gly23–Phe24, Phe24–Phe25, and Phe25–Tyr26 residues.
Genetic engineering of the pancreatic β‐cell line MIN6 to express bacterial globin proteins protects cells from nitrosative stress
Authors: Frey Alexander D. , Schmid Vinzenz H. , Kallio Pauli T.
Published: October 2015

Susceptibility of pancreatic β‐cells to nitric oxide (NO) is a prime issue in type 1 diabetes mellitus. NO is produced by intraislet‐resident macrophages or by the β‐cells themselves after cytokine stimulation, leading to reduction of viability and apoptosis. We have previously demonstrated a potent NO detoxification activity of bacterial globin proteins. Unlike the mammalian counterparts, these proteins can possess an intramolecular reductase domain, which increases the catalytic NO turnover. Constitutive expression of either Ralstonia eutropha flavohemoglobin or Vitreoscilla hemoglobin increased the cellular viability of MIN6 β‐cell cultures exposed to the NO donor sodium nitroprusside (SNP) maximally by 42.8% and 33.8%, respectively, relative to the wild‐type MIN6 control. Addition of SNP to a final concentration of 100 μM induced caspase activity. Under these conditions, no significant induction of caspase activity was observed in the globin‐protected cells, whereas in the parental MIN6 cells, caspase activity was increased by 57 ± 2%. Treatment of β‐cells with a combination of interleukin‐1β, interferon‐γ, and tumor necrosis factor‐α stimulated the generation of NO in vivo, and the heterologous expression of globin proteins could protect β‐cells to a small extent from the cytokine challenge.
Techno‐economics of microalgae production and conversion to refinery‐ready oil with co‐product credits
Authors: Manganaro James L. , Lawal Adeniyi , Goodall Brian
Published: October 2015

The economics of the production of hydrotreated algal oil (HTAO) along with co‐production of animal feed and nutraceuticals (omega‐3 oils) was explored. Base case calculations were for commercial scale production of 10 000 barrels per day of HTAO with nutraceuticals claiming only 0.05% of the raw algae oil (AO). The sensitivity of economics to critical parameters was studied. The greatest sensitivity of sales price was to the algae doubling time. Doubling time might be reduced by increasing pond velocity or other mixing‐inducing means. Other important parameters were oil content, CAPEX, and moisture content of post‐extracted algal residue. Algal area weight productivity (g/m2/day) was calculated from four parameters: initial algal concentration, pond depth, residence time in pond, and algae doubling time. Using presently accepted operating parameter values and with co‐product credits, the estimated plant gate price was ~ $10/gal. However, it was shown that there is significant potential for enhanced economics through moderate improvements in many areas. Credits for co‐production of animal feed and nutraceuticals were $3.24/gal and $0.14/gal, respectively. At constant oil area productivity (gal/acre/yr), the trade‐off between oil content and area weight productivity favors oil content. In the limit of 100% oil content (no solid co‐product) a sale price of $7.90/gal was estimated. Hydrotreatment of AO was discussed. Municipal waste‐water tertiary treatment was briefly discussed but not deemed viable on a large scale. An easy‐to‐use Excel spreadsheet for material and energy balances and economics was developed as a flexible scouting tool. The symbol ‘$’ denotes US dollars. © 2015 Society of Chemical Industry and John Wiley & Sons, Ltd
Physiologically based pharmacokinetic models of small molecules and therapeutic antibodies: a mini‐review on fundamental concepts and applications
Authors: Ferl Gregory Z. , Theil Frank‐Peter , Wong Harvey
Published: October 2015

The mechanisms of absorption, distribution, metabolism and elimination of small and large molecule therapeutics differ significantly from one another and can be explored within the framework of a physiologically based pharmacokinetic (PBPK) model. This paper briefly reviews fundamental approaches to PBPK modeling, in which drug kinetics within tissues and organs are explicitly represented using physiologically meaningful parameters. The differences in PBPK models applied to small/large molecule drugs are highlighted, thus elucidating differences in absorption, distribution and elimination properties between these two classes of drugs in a systematic manner. The absorption of small and large molecules differs with respect to their common extravascular routes of delivery (oral versus subcutaneous). The role of the lymphatic system in drug distribution, and the involvement of tissues as sites of elimination (through catabolism and target mediated drug disposition) are unique features of antibody distribution and elimination that differ from small molecules, which are commonly distributed into the tissues but are eliminated primarily by liver metabolism. Fundamental differences exist in the ability to predict human pharmacokinetics based upon preclinical data due to differing mechanisms governing small and large molecule disposition. These differences have influence on the evolving utilization of PBPK modeling in the discovery and development of small and large molecule therapeutics. Copyright © 2015 John Wiley & Sons, Ltd.