bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the arc and curve complex of a surface
Authors: KORKMAZ MUSTAFA , PAPADOPOULOS ATHANASE 
Published: December 2009

AbstractWe study the arc and curve complex AC(S) of an oriented connected surface S of finite type with punctures. We show that if the surface is not a sphere with one, two or three punctures nor a torus with one puncture, then the simplicial automorphism group of AC(S) coincides with the natural image of the extended mapping class group of S in that group. We also show that for any vertex of AC(S), the combinatorial structure of the link of that vertex characterizes the type of a curve or of an arc in S that represents that vertex. We also give a proof of the fact if S is not a sphere with at most three punctures, then the natural embedding of the curve complex of S in AC(S) is a quasi-isometry. The last result, at least under some slightly more restrictive conditions on S, was already known. As a corollary, AC(S) is Gromov-hyperbolic.
Looking back and looking ahead: local empowerment and governance in the Annapurna Conservation Area, Nepal
Authors: BARAL NABIN , STERN MARC J. 
Published: December 2009

SUMMARYDiversifying governance models for protected areas serves as one strategy to address some of the challenges they are facing. This paper explores the potential of local communities to be the primary actor in the governance of the Annapurna Conservation Area (ACA) following its planned handover to them in 2012. In doing so, the paper serves as an important baseline from which to monitor a new experiment in protected area governance. During the summer of 2007, the executive members and implementing staff of the Conservation Area Management Committees (CAMCs) were interviewed and local villagers surveyed. Both quantitative and qualitative data were collected to assess the CAMCs’ capacities to manage ACA without outside support. All CAMCs had more than a decade of managerial experience and considerable local support. Villagers largely considered the CAMCs as legitimate institutions, and their executive members as trustworthy. CAMC members were confident about assuming management responsibility of the area. The devolution of power to an overarching local council to govern ACA will present some challenges, especially with regard to lower-performing CAMCs. However, key factors identified in the literature as critical to good governance portend positive prospects for the transition.
3 Ounces Is All You Need
Authors: Suiter Debra M. , Leder Steven B. 
Published: December 2009

AbstractAccurate screening of individuals who are at risk for oropharyngeal dysphagia is critically important because of the negative outcomes associated with the disorder. This article provides a review of a recently published study in which results of the 3-ounce water swallow test were compared with results of instrumental dysphagia testing. Clinical implications are discussed.
The Modified Barium Swallow Impairment Profile (MBSImP): A New Standard Physiologic Approach to Swallowing Assessment and Targeted Treatment
Authors: Sandidge John 
Published: December 2009

Abstract
One of the most critical roles of a speech-language pathologist (SLP) is making decisions from a swallowing assessment about life sustaining and life quality issues such as the ability to continue to eat and drink. The optimal swallowing assessment requires recognizing subtle variations in the physiologic components and events that comprise an intact, healthy swallowing mechanism. No voluntary standard currently exists for swallowing evaluation terminology, measurement, or reporting. Bonnie Martin-Harris, a practicing clinician and researcher, sought to evaluate if a protocol that standardized language, administration/measurement of contrast viscosities, and reporting method could be validly and reliably executed for the modified barium swallow study (MBSS). A five-year study supported by the National Institute on Deafness and Other Communication Disorders (NIDCD) rigorously tested the content and external validity and reliability of a method that resulted in developing a standardized tool, the Modified Barium Swallow Impairment Profile (MBSImP) (Martin-Harris et al., 2008). A web-based learning environment is under construction and will be available for any clinician who desires training and competence in using the MBSImP. This article provides background on development of the MBSImP, the importance and benefit of standardized, objective assessment, and detail on features and status of the MBSImP web site.
Creating a Swallow Screening Program at Mass General Hospital: A Model for Development and Implementation
Authors: Cohen Audrey K. 
Published: December 2009

AbstractThe Massachusetts General Hospital-Swallow Screening Tool (MGH-SST) is a two-part dysphagia screening tool for use by trained staff working with acute neuroscience patients. It was developed in 2004 for use on our neuroscience inpatient units using factors sensitive to aspiration risk. The MGH-SST provides early detection of those at risk for aspiration, guides the decision whether a patient can safely eat or drink, and acts as a trigger for appropriate speech--language pathology (SLP) consult for a comprehensive swallow evaluation. A staff education module was developed including a training video with clinical examples to simulate disordered clinical features, as well as a competency assessment. The MGH-SST was validated using trained nurses with patients with a broad range of neurological and neurosurgical injuries, comparing the MGH-SST results to an instrumental dysphagia assessment, fiberoptic endoscopic evaluation of swallowing (FEES). It was found to be a valid and effective screening to identify patients at risk for dysphagia. Elements critical to the success of a dysphagia screening program include multi-disciplinary collaboration, administrative support, comprehensive training to ensure reliable and consistent administration, and continuous performance measurements.
Reflux symptoms in wind instrument players
Authors: CAMMAROTA G. , MASALA G. , CIANCI R. , PALLI D. , BENDINELLI B. , GALLI J. , PANDOLFI F. , GASBARRINI A. , LANDOLFI R. 
Published: December 2009

Aliment Pharmacol Ther 31, 593–600SummaryBackground  An occupation‐related susceptibility of orchestral wind instrument players to gastro‐oesophageal reflux was hypothesized.Aim  To compare reflux symptoms reported by wind instrument players with those reported by players of other instruments.Methods  A questionnaire was distributed to 1083 musicians (414 wind instrument players and 669 players of other instruments) from 21 Italian orchestras to obtain information on reflux symptoms in the year preceding the survey together with selected individual characteristics and lifestyle habits. Crude and adjusted prevalence rate ratios (PRR) were computed by a model including gender, age, body mass index, smoking status, alcohol consumption and other confounding factors.Results  Wind instrument players reported a higher prevalence of heartburn in the previous year than the other instrument players (adjusted PRR 1.23, CI 95% 1.04–1.46). Wind instrument players also reported higher, although not fully significant, prevalence of regurgitation (adjusted PRR 1.22, CI 95% 0.97–1.54). Flute and double‐reed instrument players seem to carry a higher risk of reflux symptoms.Conclusions  Wind instrument players reported a prevalence of typical reflux symptoms higher than other instrument players.
Pleiotropic effects of intravascular haemolysis on vascular homeostasis
Authors: Kato Gregory J. , Taylor James G. 
Published: December 2009

SummaryThe breakdown of senescent or defective red blood cells releases red cell contents, especially haemoglobin, which scavenges nitric oxide (NO) and decomposes to haem and free iron. These are potent oxidants, all of which have promoted the evolution of inducible and vasculoprotective compensatory pathways to rapidly clear and detoxify haemoglobin, haem and iron. Chronic haemolytic red cell disorders as diverse as sickle cell disease, thalassaemia, unstable haemoglobinopathy, cytoskeletal defects and enzymopathies have been linked to a clinical constellation of pulmonary hypertension, priapism, leg ulceration and possibly cerebrovascular disease and thrombosis. Besides free haemoglobin, haemolysis has been associated with extracellular arginase that limits substrate availability to NO synthase, endogenous inhibitors of NO synthase activity, and inappropriate activation of haemostatic pathways. This article reviews the haemolytic disorders that have been reported to manifest vascular complications, and explores the speculative possibility that haemolysis mediates some of the vascular complications of inflammation and diabetes.
The proteasome inhibitor CEP‐18770 enhances the anti‐myeloma activity of bortezomib and melphalan
Authors: Sanchez Eric , Li Mingjie , Steinberg Jeffrey A. , Wang Cathy , Shen Jing , Bonavida Benjamin , Li Zhi‐Wei , Chen Haiming , Berenson James R. 
Published: December 2009

SummaryThe anti‐multiple myeloma (MM) efficacy of bortezomib has led to the development of other proteasome inhibitors (PI), including CEP‐18770 which has shown anti‐MM effects in preclinical studies. However, the efficacy of orally (PO) or intravenously (IV) administered CEP‐18770 in multiple MM models and in combination with conventional anti‐MM therapies has not been evaluated. Herein, we show that CEP‐18770 combined with melphalan or bortezomib induces synergistic inhibition of MM cell viability in vitro. In MM xenograft models, the addition of CEP‐18770 IV to melphalan completely prevented the growth of both melphalan‐sensitive and melphalan‐resistant tumours. The combination of CEP‐18770 IV and bortezomib induced complete regression of bortezomib‐sensitive tumours and markedly delayed progression of bortezomib‐resistant tumours compared to treatment with either agent alone. Single agent CEP‐18770 PO also showed marked anti‐MM effects in these xenograft models. These studies provide strong preclinical rationale for further development of this novel PI in the treatment of MM as a monotherapy as well as combined with either melphalan or bortezomib.
ITD‐ and FL‐induced FLT3 signal transduction leads to increased C/EBPβ‐LIP expression and LIP/LAP ratio by different signalling modules
Authors: Haas Sandra C. , Huber René , Gutsch Romina , Kandemir Judith D. , Cappello Christian , Krauter Jürgen , Duyster Justus , Ganser Arnold , Brand Korbinian 
Published: December 2009

SummaryFLT3 receptor‐associated signalling plays a role in proliferation and leukaemia. The transcription factor C/EBPβ may be involved in malignancy with its alternative translation product C/EBPβ‐LIP. We investigated a potential connection between FLT3 signalling and the C/EBPβ system in FLT3‐internal tandem duplication (ITD)‐positive leukaemia cells and FLT3‐ITD‐ or FLT3‐wild type (WT)‐transfected 32D cells. In FLT3‐ITD‐positive cells or when ITD sequences were inserted into the FLT3‐WT receptor, significant LIP levels, increased LIP/LAP ratios, and enhanced proliferation rates were detected, which were reduced by FLT3 inhibition. In FLT3‐WT cells, incubation with FLT3 receptor ligand (FL) also elevated LIP, LIP/LAP, and proliferation, albeit to a lesser extent. CEBPB‐directed siRNA decreased both LIP and proliferation rates in FLT3‐ITD‐positive and FL‐stimulated FLT3‐WT‐positive cells. PI3K inhibition affected ITD‐associated and FL‐induced LIP levels. Rapamycin, an inhibitor of mTOR involved in CEBPB translation, completely blocked the increase in LIP in FL‐stimulated FLT3‐WT‐ but not FLT3‐ITD‐positive cells. In contrast, the ITD‐associated LIP elevation was mediated by p90‐ribosomal‐S6‐kinase. This is the first report showing a LIP increase in the presence of ITD or following FL exposure. Our data suggest fundamental differences in the signalling cascades activated via ITD mutations or following FL stimulation, indicating the need for adapted molecular therapy.
Mimotope vaccination for therapy of allergic asthma: anti‐inflammatory effects in a mouse model
Authors: Wallmann J. , Epstein M. M. , Singh P. , Brunner R. , Szalai K. , El‐Housseiny L. , Pali‐Schöll I. , Jensen‐Jarolim E. 
Published: December 2009

SummaryBackground
One of the concerns of allergen‐specific immunotherapy is the possible boost of inflammatory allergen‐specific T lymphocytes. To address this problem, treatment with B cell epitopes devoid of allergen‐specific T cell epitopes would be a promising alternative.Objective
In this study, we examined the therapeutic potency of a single mimotope, mimicking a structural IgE epitope of grass pollen allergen Phl p 5 in an established memory mouse model of acute allergic asthma.Methods
In the experimental set‐up, BALB/c mice were primed with intraperitoneal injections of recombinant Phl p 5a (rPhl p 5a) and subsequently aerosol challenged with the nebulized allergen. Mice developed signs of bronchial asthma including hypereosinophilia around bronchi, goblet cell hyperplasia and enhanced mucus production.Results
When the mice were subsequently treated with the grass pollen mimotope coupled to keyhole limpet haemocyanin, bronchial eosinophilic inflammation and mucus hypersecretion decreased. Further, a decrease of Th2 cytokines IL‐4 and IL‐5 could be observed in the bronchoalveolar lavage (BAL). In contrast to rPhl p 5a, the mimotope was in vitro not able to stimulate splenocytes to proliferation or IL‐5 production. Despite not affecting the levels of pre‐existing IgE, vaccination with the single mimotope thus rendered anti‐inflammatory effects in a mouse model of acute asthma.Conclusion
From our data, we conclude that vaccination with a mimotope peptide representing a single IgE epitope of the allergen Phl p 5a and being devoid of allergen‐specific T cell epitopes is able to down‐regulate inflammation in acute asthma. Cite this as: J. Wallmann, M. M. Epstein, P. Singh, R. Brunner, K. Szalai, L. El‐Housseiny, I. Pali‐Schöll and E. Jensen‐Jarolim, Clinical & Experimental Allergy, 2010 (40) 650–658.
Antigenic dietary protein guides maturation of the host immune system promoting resistance to Leishmania major infection in C57BL/6 mice
Authors: Amaral Joana F. , Gomes‐Santos Ana C. , Paula‐Silva Josiely , Nicoli Jacques R. , Vieira Leda Q. , Faria Ana M. C. , Menezes Juscilene S. 
Published: December 2009

SummaryThe immature immune system requires constant stimulation by foreign antigens during the early stages of life to develop properly and to create efficient immune responses against later infections. We have previously shown that intake of antigenic dietary protein is critical for inducing maturation of the immune system as well as for the development of T helper type 1 (Th1) immunity. In this study, we show that administration of an amino acid (aa)‐based diet during the development of the immune system subsequently resulted in inefficient control of Leishmania major infection in adult C57BL/6 mice. Compared with mice fed a control protein‐containing diet, adult aa‐fed mice showed a decreased interferon (IFN)‐γ response to parasite antigens and insufficient production of nitric oxide (NO), which is crucial to parasite death. However, no deviation towards Th2‐specific immunity to L. major was observed. Phenotypic analysis of antigen‐presenting cells (APCs) from aa‐fed mice revealed deficient levels of the costimulatory molecules CD40 and CD80, and low levels of interleukin (IL)‐12 produced by peritoneal macrophages, revealing an early stage of maturation of these cells. APCs isolated from aa‐fed mice were unable to stimulate a Th1 response in vitro. Both phenotypic features of T cells from aa‐fed mice and their ability to produce a Th1 response in the presence of mature APCs were unaffected when compared with T cells from control mice. The results presented here support the notion that regulation of Th1 immunity to infection includes environmental factors such as dietary proteins, which provide a natural source of stimulation that contributes to the process of maturation of APCs.
Hypoxic stress up‐regulates the expression of Toll‐like receptor 4 in macrophages via hypoxia‐inducible factor
Authors: Kim So Young , Choi Yong Jun , Joung Sun Myung , Lee Byung Ho , Jung Yi‐Sook , Lee Joo Young 
Published: December 2009

SummaryToll‐like receptors (TLRs) are germline‐encoded innate immune receptors that recognize invading micro‐organisms and induce immune and inflammatory responses. Deregulation of TLRs is known to be closely linked to various immune disorders and inflammatory diseases. Cells at sites of inflammation are exposed to hypoxic stress, which further aggravates inflammatory processes. We have examined if hypoxic stress modulates the TLR activity of macrophages. Hypoxia and CoCl2(a hypoxia mimetic) enhanced the expression of TLR4 messenger RNA and protein in macrophages (RAW264.7 cells), whereas the messenger RNA of other TLRs was not increased. To determine the underlying mechanism, we investigated the role of hypoxia‐inducible factor 1 (HIF‐1) in the regulation of TLR4 expression. Knockdown of HIF‐1α expression by small interfering RNA inhibited hypoxia‐induced and CoCl2‐induced TLR4 expression in macrophages, while over‐expression of HIF‐1α potentiated TLR4 expression. Chromatin immunoprecipitation assays revealed that HIF‐1α binds to the TLR4 promoter region under hypoxic conditions. In addition, deletion or mutation of a putative HIF‐1‐binding motif in the TLR4 promoter greatly attenuated HIF‐1α‐induced TLR4 promoter reporter expression. Up‐regulation of TLR4 expression by hypoxic stress enhanced the response of macrophages to lipopolysaccharide, resulting in increased expression of cyclooxygenase‐2, interleukin‐6, regulated on activation normal T cell expressed and secreted, and interferon‐inducible protein‐10. These results demonstrate that TLR4 expression in macrophages is up‐regulated via HIF‐1 in response to hypoxic stress, suggesting that hypoxic stress at sites of inflammation enhances susceptibility to subsequent infection and inflammatory signals by up‐regulating TLR4.
Suboptimal engagement of the T‐cell receptor by a variety of peptide–MHC ligands triggers T‐cell anergy
Authors: Sadegh‐Nasseri Scheherazade , Dalai Sarat K. , Korb Ferris Laura C. , Mirshahidi Saied 
Published: December 2009

SummaryT cells recognize antigen via the T‐cell receptor (TCR) and produce a spectrum of responses that range from activation to anergy or cell death. The variety of outcomes may be dictated by the strength of the signals transmitted upon cognate recognition of the TCR. The physiological outcome of TCR engagement is determined by several factors, including the avidity of the ligand for TCR, the duration of engagement, and the presence and nature of accessory molecules present on antigen‐presenting cells (APCs). In this review, we discuss a model of anergy induced by presentation of low densities of peptide–major histocompatibility complex (MHC) ligand in CD4+ T cells and compare it to anergy induced by altered peptide ligands in an effort to identify a unifying mechanism. We suggest that altered peptide ligand (APL) and low densities of agonist ligands induce anergy by engaging less than optimal numbers of TCRs. The physiological impacts of anergy in memory CD4+ T cells are discussed.
Anti‐Aspergillus human host defence relies on type 1 T helper (Th1), rather than type 17 T helper (Th17), cellular immunity
Authors: Chai Louis Y. A. , Van De Veerdonk Frank , Marijnissen Renoud J. , Cheng Shih‐Chin , Khoo Ai Leng , Hectors Magda , Lagrou Katrien , Vonk Alieke G. , Maertens Johan , Joosten Leo A. B. , Kullberg Bart‐Jan , Netea Mihai G. 
Published: December 2009

SummaryBoth interferon‐γ‐producing type 1 T helper (Th1)‐ and interleukin‐17 (IL‐17)‐producing Th17 cells have been proposed to be involved in anti‐fungal host defence. Although invasive aspergillosis is one of the most severe human fungal infections, little is known regarding the relative importance of the Th1 versus Th17 cellular immune pathways for the human anti‐Aspergillus host defence. Using human peripheral blood mononuclear cells and a system consisting of monocyte‐derived macrophages with lymphocytes, we found that Aspergillus fumigatus is a weak inducer of human IL‐17 but induces a strong Th1 response. These data were validated by the very low IL‐17 levels in bronchoalveolar lavage fluid and serum of patients with invasive aspergillosis. Surprisingly, live A. fumigatus reduced IL‐17 production induced by mitogenic stimuli. This effect was mediated through the propensity of A. fumigatus to metabolize tryptophan and release kynurenine, which modulates the inflammatory response through inhibition of IL‐17 production. In conclusion, A. fumigatus does not stimulate production of IL‐17 and human host defence against aspergillosis may not rely on potent Th17 responses.
The expression and function of Nod‐like receptors in neutrophils
Authors: Ekman Anna‐Karin , Cardell Lars Olaf 
Published: December 2009

SummaryNeutrophils make up an essential part of the innate immune system, and are involved both in the initial responses to pathogens, and in orchestrating later immune responses. Neutrophils recognize pathogens through pattern‐recognition receptors (PRRs), which are activated by microbial motifs. The Nod‐like receptors (nucleotide‐binding domain leucine‐rich repeat containing family; NLRs) constitute a recently discovered group of PRRs whose role in the neutrophil immune responses is not yet characterized. The present study aimed to investigate the expression and function of NLRs in neutrophils. Neutrophils were isolated from human peripheral blood, and the presence of nucleotide‐binding oligomerization domain 1 (NOD1), NOD2 and NACHT‐LRR‐PYD‐containing protein 3 (NLRP3) was evaluated with flow cytometry and immunohistochemistry. The expression of NOD1, NOD2 and NLRP3 messenger RNA was determined using real‐time reverse transcription–polymerase chain reaction. Changes in neutrophil cytokine secretion, phenotype and migration following agonist‐induced activation were studied using enzyme‐linked immunosorbent assay, flow cytometry and a chemotaxis assay, respectively. No expression of NOD1 was found in isolated neutrophils and stimulation with the NOD1 ligand γ‐d‐glutamyl‐meso‐diaminopimelic acid induced no signs of activity. In contrast, a marked expression of NOD2 and NLRP3 was found. NOD2 activation with MurNAc‐l‐Ala‐d‐isoGln (MDP) resulted in interleukin‐8 secretion, CD62 ligand down‐regulation, CD11b up‐regulation and increased migration towards an inflammatory stimulus. NLRP3 activation with alum caused interleukin‐1β secretion and facilitated migration. Altogether, this suggests that NLRs may be a previously unknown pathway for neutrophil activation.