bluuebunny/crossref_metadata_2025_split huggingface dataset:
The extracellular region of Lrp4 is sufficient to mediate neuromuscular synapse formation
Authors: Gomez Andrea M. , Burden Steven J. 
Published: October 2011

AbstractNeuromuscular synapse formation requires an exchange of signals between motor neurons and muscle. Agrin, supplied by motor neurons, binds to Lrp4 in muscle, stimulating phosphorylation of MuSK and recruitment of a signaling complex essential for synapse‐specific transcription and anchoring of key proteins in the postsynaptic membrane. Lrp4, like the LDLR and other Lrp‐family members, contains an intracellular region with motifs that can regulate receptor trafficking, as well as assembly of an intracellular signaling complex. Here, we show that the intracellular region of Lrp4 is dispensable for Agrin to stimulate MuSK phosphorylation and clustering of acetylcholine receptors in cultured myotubes. Moreover, muscle‐selective expression of a Lrp4‐CD4 chimera, composed of the extracellular and transmembrane regions of Lrp4 and the intracellular region of CD4, rescues neuromuscular synapse formation and the neonatal lethality of lrp4 mutant mice, demonstrating that Lrp4, lacking the Lrp4 intracellular region, is sufficient for presynaptic and postsynaptic differentiation. Developmental Dynamics 240:2626–2633, 2011. © 2011 Wiley Periodicals, Inc.
A clonal model for human CD8+ regulatory T cells: Unrestricted contact‐dependent killing of activated CD4+ T cells
Authors: Hu Dan , Liu Xia , Zeng Wanyong , Weiner Howard L. , Ritz Jerome 
Published: October 2011

AbstractPrevious studies in murine systems have demonstrated that CD8+ Treg cells down‐regulate immune responses in vivo through suppressing activated CD4+ T cells. Here we describe novel regulatory CD8+ T‐cell clones isolated from healthy human peripheral blood following in vitro stimulation with autologous Epstein–Barr virus (EBV)‐specific CD4+ T cells. TCR activation of CD4+ target T cells was required for CD8+ Treg cells to exert suppressive activity, which was mediated through lysis of CD4+ targets in a cell contact‐dependent manner. Suppression was independent of Foxp3 expression in CD8+ Treg cells, HLA compatibility between CD8+ Treg cells and CD4+ target cells and antigen‐specificity of CD4+ target T cells. CD8+ Treg clones expressed CD3 and a variety of TCR Vβ chains as well as CD56, CD69, CD62L and CD95 but did not express CD16, CD161, CXCR4 and CCR7. When used together, antibodies specific for CD11a/CD18 and CD8 inhibited suppressive activity of CD8+ Treg clones. The ability to establish clonal CD8+ T cells that maintain regulatory function in vitro will facilitate further studies to define this population in vivo and to identify the mechanisms used for recognition and suppression of activated target cells.
Intestinal macrophages – specialised adaptation to a unique environment
Authors: Bain Calum C. , Mowat Allan McI. 
Published: October 2011

AbstractInterest in intestinal mononuclear phagocytes (MPs), both DCs and macrophages (Mφs), has exploded in the recent years. In this Viewpoint we will detail how resident intestinal lamina propria (LP) Mφs possess distinctive properties that reflect adaptation to a unique microenvironment. They play quite different roles in the normal and inflamed mucosa and, as we will show, the existing paradigms of differentiated Mφ subsets and of ‘resident’ versus ‘inflammatory’ monocytes based on other tissues may not apply to the gut. Strategies for targeting Mφs as a means of dampening intestinal inflammation will need to take account of these unique characteristics.
Inflammatory signaling in macrophages: Transitions from acute to tolerant and alternative activation states
Authors: Ivashkiv Lionel B. 
Published: October 2011

AbstractAcute inflammatory activation of macrophages by Toll‐like and related receptors is characterized by transient activation of MAPK‐, NF‐κB‐ and IRF‐mediated signaling pathways and expression of pro‐inflammatory genes. This activation state is inherently unstable and often transitions into a state of ‘tolerance’ characterized by diminished signaling, repressive chromatin modifications, and an alternative gene expression program. This Viewpoint describes signaling and epigenetic mechanisms associated with transition to tolerant states, which are proposed to correspond to alternative activation states programmed by the original inflammatory stimuli.
Macrophage activation governs schistosomiasis‐induced inflammation and fibrosis
Authors: Barron Luke , Wynn Thomas A. 
Published: October 2011

AbstractMacrophages regulate the initiation, maintenance, and resolution of chronic inflammatory responses and their function depends on their activation status. Studies in mice infected with the helminth parasite Schistosoma mansoni have been particularly helpful in defining the in vivo function of classically and alternatively activated macrophages (AAMϕs). These studies have shown that AAMϕs protect mice from acute and chronic S. mansoni infection through distinct mechanisms, which are discussed in this Viewpoint.
Memory lapses in graft‐versus‐host disease
Authors: Flutter Barry , Veliça Pedro , Chakraverty Ronjon 
Published: October 2011

Abstract“Faster, better, more” is the conventional benchmark used to define responses of memory T cells when compared with their naïve counterparts. In this issue of the European Journal of Immunology, Mark and Warren Shlomchik and colleagues [Eur. J. Immunol. 2011. 41: 2782–2792] make the intriguing observation that murine memory CD4+ T‐cell populations enriched for alloreactive precursors are fully capable of rejecting allogeneic skin grafts but yet are incapable of inducing significant graft‐versus‐host disease. These observations add to the emerging concept that memory CD4+ T‐cell development is more nuanced and complex than predicted by conventional models. In particular, the data suggest that it may be just as important to consider what naïve or effector cells have “lost” in their transition to memory.
Revisiting the protective and pathogenic roles of neutrophils: Ly‐6G is key!
Authors: Bao Yan , Cao Xuetao 
Published: October 2011

AbstractThe physiological and pathophysiological roles of neutrophils in immune homeostasis and disease have been investigated extensively by way of anti‐Gr‐1 mAb‐mediated depletion experiments; however, the ability of the anti‐Gr‐1 mAb to specifically deplete neutrophils has long been questioned and it is now known that this mAb, which binds Ly6C and Ly6G, is also able to deplete monocytes and subsets of CD8+ T cells. This, therefore, casts doubt on the previous conclusions regarding the role of neutrophils drawn from studies using this mAb. Another mAb, which targets Ly6G only, has recently been shown to deplete neutrophils specifically and a study by Carr et al. (Eur. J. Immunol. 2011. 41: 2666–2676) in this issue of the European Journal of Immunology utilizes this Ly‐6G mAb to reveal the precise role of neutrophils during Listeria monocytogenes (LM) infection. Carr et al. find that monocytes/macrophages, rather than neutrophils, dominate the initial control of LM growth in the spleen, whereas neutrophils in the liver are key for host resistance to LM infection. These data suggest that the previously reported protective or pathogenic roles of neutrophils in disease models need to be reconsidered through anti‐Ly6G mAb‐mediated depletion experiments.
Group 10 Metal Complexes of a Ferrocene‐Based N‐Heterocyclic Carbene: Syntheses, Structures and Catalytic Applications
Authors: Siemeling Ulrich , Färber Christian , Bruhn Clemens , Fürmeier Sven , Schulz Tim , Kurlemann Michael , Tripp Sandra 
Published: October 2011

AbstractThis paper focuses on complexes of the N‐heterocyclic carbene (NHC) 1‐Np, which contains a 1,1′‐ferrocenediyl backbone and neopentyl substituents at the N atoms flanking the divalent C atom. 1‐Np is a ring‐expanded NHC with a ring size of six atoms. The square‐planar group 10 metal complexes [{PdCl(μ‐Cl)(1‐Np)}2], cis‐[PdCl2(1‐Np)(PPh3)], trans‐[PdCl2(1‐Np)2] and trans‐[NiCl2(1‐Np)(PPh3)] have been prepared by the reaction of 1‐Np with trans‐[PdCl2(PhCN)2], [PdCl2(PPh3)2], cis‐[PdCl2(COD)] (COD = cycloocta‐1,5‐diene) and [NiCl2(PPh3)2], respectively. In addition, the carbene–borane adduct 1‐Np–BF3 has been obtained by serendipity. All new compounds have been structurally characterised by single‐crystal X‐ray diffraction, which demonstrates the pronounced trans influence of 1‐Np. 1‐Np has been compared with the ring‐expanded NHC 1,3‐diisopropyltetrahydropyrimid‐2‐ylidene (THP‐iPr) in the context of homogeneous catalysis, which utilises analogous palladium NHC complexes known to be particularly effective in the case of NHC = THP‐iPr. The catalytic performance of cis‐[PdCl2(1‐Np)(PPh3)] in Suzuki–Miyaura cross‐coupling reactions of PhB(OH)2 with aryl bromides Br–p‐C6H4–R is similar to that reported for cis‐[PdCl2(THP‐iPr)(PPh3)]. With aryl chlorides, however, the latter complex is superior to its 1‐Np analogue. The catalytic performance reported for trans‐[PdCl2(THP‐iPr)2] in Mizoroki–Heck reactions of n‐butyl acrylate with aryl bromides Br–p‐C6H4–R is equal to (R = H) or moderately better than that of trans‐[PdCl2(1‐Np)2] [R = C(O)Me, OMe].
Synthesis of Enantiomerically Pure 3‐Amino‐2‐methylenealkanoates (Aza‐Morita–Baylis–Hillman Adducts) Mediated by Cinchona Alkaloids
Authors: Martelli Gianluca , Orena Mario , Rinaldi Samuele 
Published: October 2011

Abstract3‐Substituted (Z)‐2‐(bromomethyl)propenoates reacted with (S)‐1‐(4‐methoxyphenyl)ethylamine in the presence of astoichiometric amount of quinidine to yield (R)‐3‐[(tert‐butoxycarbonyl)amino]‐2‐methylenealkanoates (aza‐Morita–Baylis–Hillman adducts) in enantiomerically pure form.
Trace determination of perchlorate using electromembrane extraction and capillary electrophoresis with capacitively coupled contactless conductivity detection
Authors: Kiplagat Isaac K. , Doan Thi Kieu Oanh , Kubáň Pavel , Boček Petr 
Published: October 2011

AbstractElectromembrane extraction (EME) and CE with capacitively coupled contactless conductivity detection (CE‐C4D) was applied to rapid and sensitive determination of perchlorate in drinking water and environmental samples. Porous polypropylene hollow fiber impregnated with 1‐heptanol acted as a supported liquid membrane (SLM) and perchlorate was transported and preconcentrated in the fiber lumen on application of electric field. High selectivity of perchlorate determination and its baseline separation from major inorganic anions was achieved in CE‐C4D using background electrolyte solution consisting of 7.5 mM L‐histidine and 40 mM acetic acid at pH 4.1. The analytical method showed excellent parameters in terms of reproducibility; RSD values for migration times and peak areas at a spiked concentration of 15 μg/L of perchlorate (US EPA recommended limit for drinking water) were below 0.2 and 8.7%, respectively, in all examined water samples. Linear calibration curves were obtained for perchlorate in the concentration range 1–100 μg/L (r2≥0.999) with limits of detection at 1 μg/L for tap water and at 0.25–0.35 μg/L for environmental and bottled potable water samples. Recoveries at 15 μg/L of perchlorate were between 95.9 and 106.7% with minimum and maximum recovery values for snow and bottled potable water samples, respectively.
A new approach to solving Poisson system for free surface nonhydrostatic flow simulations
Authors: Chegini Fatemeh , Namin Masoud Montazeri 
Published: October 2011

SUMMARYA nonhydrostatic finite volume model is presented to simulate free surface flow in a two‐dimensional vertical plane. The algorithm is based on a projection method including the solution of the pressure Poisson equation (PPE). The model is developed in a Cartesian grid in which the size of all the cells in the computational domain, excluding those of the top layer, is constant in time. To simulate the variable water surface, the heights of the top layer cells are variable and proportional to the local water elevation. Taking the layout of the grid system into consideration, a new method is proposed to solve the PPE derived in Cartesian coordinates. In this method, the system of pressure equations is divided into two subsystems, namely a subsystem for the upper layer cells and another for the remaining cells. The coefficient matrix of the former is variable with respect to time, whereas that of the latter remains constant. Therefore, the coefficient matrix of the latter subsystem can be inversed once and saved throughout the simulation. The application of this procedure reduces the computational cost compared with other PPE solvers in certain conditions. The model is applied to simulate a series of numerical tests including strong vertical accelerations and is verified against analytical and experimental results, demonstrating satisfactory performance. Copyright © 2011 John Wiley & Sons, Ltd.
Wiedergeburt aus dem Geist Europas
Authors: Kreft Wolfgang 
Published: October 2011

AbstractBewegte Geschichte im Kartenbild: Der historisch‐topografische Atlas schlesischer Städte blickt in seinem ersten Band auf die Grenzstadt Görlitz / Zgorzelec. Das Projekt will zum Grundlagenwerk für die vergleichende Städteforschung werden.
„Aktiv mitgestalten!”︁
Authors: Wagner Dorothea , Cancik‐Kirschbaum Eva , Al‐Shamery Katharina 
Published: October 2011

AbstractStimmen für die Wissenschaft: Bei der vom 7. November bis 5. Dezember 2011 stattfindenden Fachkollegienwahl wird das „Parlament der Wissenschaft”︁ gewählt — eine unverzichtbare Grundlage für die wissenschaftliche Selbstverwaltung / Mehr als 100 000 Forscherinnen und Forscher sind zum Online‐Urnengang eingeladen.
Selbstbewusster Blick in die Zeit „danach”︁
Authors: Kleiner Matthias 
Published: October 2011

AbstractDas Finale der Exzellenzinitiative hat gerade erst begonnen — doch bereits jetzt muss die Wissenschaft über die künftige Förderung der Spitzenforschung nachdenken. Notwendig ist ein produktiver und konstruktiver Dialog mit der Politik. Wichtige Eckpunkte dafür liegen nahe.
Evaluation of an approximation method for assessment of overall significance of multiple‐dependent tests in a genomewide association study
Authors: Moskvina Valentina , O'Dushlaine Colm , Purcell Shaun , Craddock Nick , Holmans Peter , O'Donovan Michael C. 
Published: October 2011

AbstractWe describe implementation of a set‐based method to assess the significance of findings from genomewide association study data. Our method, implemented in PLINK, is based on theoretical approximation of Fisher's statistics such that the combination of P‐vales at a gene or across a pathway is carried out in a manner that accounts for the correlation structure, or linkage disequilibrium, between single nucleotide polymorphisms. We compare our method to a permutation‐based product of P‐values approach and show a typical correlation in excess of 0.98 for a number of comparisons. The method gives Type I error rates that are less than or equal to the corresponding nominal significance levels, making it robust to the effects of false positives. We show that in broadly similar populations, reference data sets of markers are an appropriate substrate for deriving marker‐marker linkage disequilibrium (LD), negating the need to access individual level genotypes, greatly facilitating its generic applicability. We show that the method is thus robust to LD‐associated bias and has equivalent performance to permutation‐based methods, with a significantly shorter runtime. This is particularly relevant at a time of increasing public availability of significantly larger genetic data sets and should go a long way to assist in the rapid analysis of these data sets. Genet. Epidemiol. 2011. © 2011 Wiley Periodicals, Inc.35:861‐866, 2011
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of GS-9450 in Subjects With Nonalcoholic Steatohepatitis
Authors: Ratziu Vlad , Sheikh Muhammad Y. , Sanyal Arun J. , Lim Joseph K. , Conjeevaram Hari , Chalasani Naga , Abdelmalek Manal , Bakken Anezi , Renou Christophe , Palmer Melissa , Levine Robert A. , Bhandari Raj B. , Cornpropst Melanie , Liang Wei , King Benjamin , Mondou Elsa , Rousseau Franck S. , McHutchison John , Chojkier Mario 
Published: October 2011

Abstract

In nonalcoholic steatohepatitis (NASH), the extent of hepatocyte apoptosis correlates with disease severity. Reducing hepatocyte apoptosis with the selective caspase inhibitor GS-9450 has a potential for altering the course of the liver disease. In this phase 2, double-blind study, 124 subjects with biopsy-proven NASH were randomized to once-daily placebo or 1, 5, 10, or 40 mg GS-9450 for 4 weeks. Absolute and percent changes from baseline in ALT levels, AST levels, and caspase-3–cleaved cytokeratin (CK)-18 fragments at week 4 were assessed by an analysis of covariance model with adjustment for baseline values. In the 40-mg group, mean (SD) ALT decreased by 47 (43) U/L from baseline to week 4 (

P

< 0.0001 versus placebo), and the proportion of subjects with normal ALT increased from 0% to 35% at week 4. In the 40-mg group, mean AST decreased by 13 U/L from baseline (not significant), and the proportion with normal AST increased from 20% at baseline to 48% at week 4. By week 4, mean CK-18 fragment levels had decreased to 393 (723) U/L in the GS-9450 10-mg group and 125 (212) U/L in the 40-mg group, but these reductions were not statistically significant. No serious adverse events were reported during treatment, and the percentage of subjects with at least one treatment-emergent grade 3 or 4 laboratory abnormality ranged from 11.5% to 17% across the GS-9450 treatment groups versus 35% in the placebo group.

Conclusion :

GS-9450 treatment induced significant reductions in ALT levels in NASH patients. Reductions in CK-18 fragment levels also occurred, although they were not statistically significant. At appropriate therapeutic indices, selective caspase inhibitors may be a promising treatment option in patients with NASH. (Hepatology 2012)
Triterpenoids from the Stems of Schisandra glaucescens
Authors: Meng Fan‐Yu , Sun Jia‐Xiang , Li Xue , Pi Hui‐Fang , Zhang Peng , Ruan Han‐Li 
Published: October 2011

AbstractTwo new lanostane triterpenoids, schiglauzic acid (1) and schiglaucyclozic acid (2), together with two known ones, anwuweizic acid (3) and manwuweizic acid (4), were isolated from the stems of Schisandra glaucescens. Their structures were determined on the basis of extensive spectroscopic methods, including two‐dimensional NMR techniques, and were further confirmed by X‐ray crystallographic analysis.
Boric Acid‐Catalyzed Direct Condensation of Carboxylic Acids with Benzene‐1,2‐diamine into Benzimidazoles
Authors: Maraš Nenad , Kočevar Marijan 
Published: October 2011

AbstractThe applicability of boric acid catalysis for the direct condensation of carboxylic acids with benzene‐1,2‐diamine to give 2‐substituted benzimidazoles was investigated. It was found that catalytic amounts (5–10 mol‐%) of boric acid efficiently promote the cyclocondensation of aliphatic carboxylic acids in refluxing toluene. In addition, the relatively neutral conditions allow the use of acid‐sensitive substrates and give rise to specific transformations and selectivities that are not observed with some classical methods. Benzoic acids were found to be less reactive than aliphatic acids and thus require refluxing xylene for better efficiency. Phenylboronic acid was found to be inactive as a catalyst due to its rapid consumption by condensation with benzene‐1,2‐diamine to give a 2‐phenylbenzodiazaborole.
Influence of aquifer properties and the spatial and temporal distribution of recharge and abstraction on sustainable yields in semi‐arid regions
Authors: Hugman Rui , Stigter Tibor Y. , Monteiro José Paulo , Nunes Luís 
Published: October 2011

AbstractThis paper aims to contribute to understanding the importance of four factors on the determination of sustainable yields: (i) aquifer properties; (ii) temporal distribution of recharge; (iii) temporal distribution of groundwater pumping; and (iv) spatial distribution of pumping wells. It is important to comprehend how the present‐day and future vulnerability of groundwater systems to pumping activities depend on these critical factors and what the risks are of considering sustainable yield as a fixed percentage of mean annual recharge (MAR). A numerical model of the Querença–Silves aquifer in Portugal is used to develop hypothetical scenarios with which these factors are studied. Results demonstrate the aquifer properties, particularly the storage coefficient, have an important role in determining the resilience of an aquifer and therefore to which degree it is dependent on the spatial and temporal distribution of abstraction and recharge, as well as the occurrence of extreme events. Sustainable yields are determined for the developed scenarios based on specific criteria rather than a fraction of MAR. Under simplified current recharge and abstraction conditions, the sustainable yield was determined at approximately 73% of MAR or 76 million m3. When considering a concentration of rainfall in time, as predicted by climate scenarios for the region, sustainable yield could drop to ca 70% of MAR. However, a more even distribution of pumping volumes throughout the year could increase this value. The location of the pumping wells is seen to affect the distribution of hydraulic heads in the aquifer, albeit without significant changes in sustainable yield. Copyright © 2011 John Wiley & Sons, Ltd.
Forecasting with Medium and Large Bayesian VARS
Authors: Koop Gary M. 
Published: October 2011

SUMMARYThis paper is motivated by the recent interest in the use of Bayesian VARs for forecasting, even in cases where the number of dependent variables is large. In such cases factor methods have been traditionally used, but recent work using a particular prior suggests that Bayesian VAR methods can forecast better. In this paper, we consider a range of alternative priors which have been used with small VARs, discuss the issues which arise when they are used with medium and large VARs and examine their forecast performance using a US macroeconomic dataset containing 168 variables. We find that Bayesian VARs do tend to forecast better than factor methods and provide an extensive comparison of the strengths and weaknesses of various approaches. Typically, we find that the simple Minnesota prior forecasts well in medium and large VARs, which makes this prior attractive relative to computationally more demanding alternatives. Our empirical results show the importance of using forecast metrics based on the entire predictive density, instead of relying solely on those based on point forecasts. Copyright © 2011 John Wiley & Sons, Ltd.
Bioactive composite bone cement based on α‐tricalcium phosphate/tricalcium silicate
Authors: Morejón‐Alonso Loreley , Ferreira Oscar Jacinto Bareiro , Carrodeguas Raúl Garcia , dos Santos Luis Alberto 
Published: October 2011

AbstractSilicon compounds are known as bioactive materials that are able to bond to the living bone tissue by inducing an osteogenic response through the stimulation and activation of osteoblasts. To improve the bioactive and mechanical properties of an α‐Ca3PO4‐based cement, the effects of the addition of Ca3SiO5 (C3S) on physical, chemical, mechanical, and biological properties after soaking in simulated body fluid (SBF) were studied. The morphological and structural changes of the material during immersion were analyzed by X‐ray diffraction and scanning electron microscopy. The results showed that it is possible to increase the compressive strength of the cement by adding 5% of C3S. Higher C3S contents enhance bioactivity and biocompatibility by the formation of a dense and homogeneous hydroxyapatite layer within 7 days; however, compressive strength decreases drastically as a consequence of delayed hydrolysis of α‐Ca3(PO4)2. An increment in setting times and degradation rate of composites containing C3S was also observed. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.