bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence for Distinct Mechanisms in the Shapingof the CD4 T Cell Repertoire in Histologically DistinctMyasthenia Gravis – Associated Thymomas
Authors: Ströbel P. , Helmreich M. , Kalbacher H. , Müller-Hermelink H. K. , Marx A. 
Published: June 2008

The major histocompatibility complex (MHC) class II is involved both in thymocyte maturation
and peptide presentation and might thus play a key role in the pathogenesis of paraneoplastic
myasthenia gravis (MG) in thymomas. To further investigate this issue, we analyzed
and scored the expression of epithelial class II expression in 35 thymomas (medullary, MDT;
mixed, MXT; cortical and well differentiated thymic carcinoma, CT / WDTC) and correlated
it with the histological tumor subtype, prevalence of MG and thymocyte maturation, which
was analyzed by flow cytometry and RT‐PCR. Our results show that both MHC class II
expression and thymocyte maturation are highly dependent on the histological tumor subtype.
CT / WDTC retain features of the normal outer thymic cortex, namely substantial MHC class
II expression together with normal early thymocyte maturation until late phases of positive
selection, but disturbed terminal thymopoiesis. By contrast, MDT and MXT retain features of
the normal inner cortex and the medulla with low to absent class II expression and highly
abnormal early thymocyte maturation including impaired positive selection, while terminal T
cell maturation in MXT appeared undisturbed. There was no correlation between MHC class
II expression and MG status for a given tumor subtype. In conclusion, our results provide evidence
for a different histogenesis of cortical thymomas and well differentiated carcinomas on
the one hand and mixed and medullary thymomas on the other.Decreased expression levels of MHC class II, although of crucial importance for abnormal
intratumorous maturation, are not sufficient to explain the emergence of paraneoplastic MG.
Characterization of Series Resistances and Mobility Attenuation Phenomena in Short Channel MOS Transistors
Authors: El Abbassi A. , Amhouche Y. , Bendada E. , Rmaily R. , Raïs K. 
Published: June 2008

As the scaling proceeds, the transverse electric field increase, and a mobility attenuation
phenomenon becomes of primordial interest. Indeed, the high transverse electric field is
generally ascribed [1] to surface roughness scattering in the channel and consequently
reduce effective mobility of carriers. In short channel MOSFET, the Source‐Drain
resistance Rsd influence strongly the effective mobility.The aim of this work is therefore to propose an original method especially conceived
for the extraction of the series resistance Rsd. Using the approach of the Surface
Roughness Scattering which enables a consistent modelling of the mobility to be
obtained from low to high electric field [2], this allow to determine all model parameters
in particular a Series Resistance from the plot of the transfer characteristic drain current
Idversus gate voltage Vg Curves.
Stability of the Cauchy-Jensen Functional Equation in "Equation missing" -Algebras: A Fixed Point Approach
Authors: Park Choonkil , An Jong Su 
Published: June 2008

Abstractwe prove the Hyers-Ulam-Rassias stability of "Equation missing"-algebra homomorphisms and of generalized derivations on "Equation missing"-algebras for the following Cauchy-Jensen functional equation "Equation missing", which was introduced and investigated by Baak (2006). The concept of Hyers-Ulam-Rassias stability originated from the stability theorem of Th. M. Rassias that appeared in (1978).
Polymorphisms in DNA Repair Genes, Smoking, and Pancreatic Adenocarcinoma Risk
Authors: McWilliams Robert R. , Bamlet William R. , Cunningham Julie M. , Goode Ellen L. , de Andrade Mariza , Boardman Lisa A. , Petersen Gloria M. 
Published: June 2008

Abstract
Base excision repair and nucleotide excision repair are vital responses to multiple types of DNA damage, including damage from tobacco exposure. Single-nucleotide polymorphisms (SNP) in these pathways may affect DNA repair capacity and therefore influence risk for cancer development. We performed a clinic-based, case-control study comprising 481 consecutive patients with confirmed pancreatic adenocarcinoma and 625 healthy controls. Allele and genotype frequencies for 16 SNPs in DNA repair genes ERCC1, XPD/ERCC2, XPC, XPF/ERCC4, OGG1, and XRCC1 were compared after adjusting for age, sex, and smoking history. Subgroup analysis by sex and smoking history was performed. Carriers of one or two XPF/ERCC4 minor alleles at R415Q had decreased risk of pancreatic adenocarcinoma compared with those who had two major alleles [odds ratio (OR), 0.59; 95% confidence interval (95% CI), 0.40–0.85]. Heavy smokers (&gt;40 pack-years) had increased risk for cancer if they were carriers of at least one minor allele for XPD/ERCC2 at D312N (OR, 2.78; 95% CI, 1.28–6.04) or D711D (OR, 2.19; 95% CI, 1.01–4.73). No other significant differences in risk were identified. Minor alleles in DNA repair genes XPF/ERCC4 and XPD/ERCC2 were associated with altered risk for pancreatic cancer. [Cancer Res 2008;68(12):4928–35]
Effects of von Willebrand factor concentration and platelet collision on shear-induced platelet activation
Authors: Gao Zhenyue , Liu Fang , Yu Ziqiang , Bai Xia , Zhuang Fengyuan , Yang Chun , Ruan Changgeng 
Published: June 2008

SummaryThe binding of plasma von Willebrand factor (vWF) to platelet glycoprotein (GP) Ibα in a high shear stress field, and subsequent integrin-GPIIb/IIIa-vWF conjunction induces platelet aggregation (SIPA). However, the specific biomechanical mechanism of the vWF-GPIb interaction still remains to be elucidated. A parallel-plate rectangular flow chamber was built to simulate a stenopeic artery flow pattern. Using the flow chamber, we examined shear- induced platelet activation (SIPAct) at different vWF concentrations (5–25 µg/ml) and several simulated stenotic high shear rates. P-selectin expression on the platelets and annexin V binding to the platelets were used as two markers of platelet activation. At different localized shear rates (3,000 s-1–9,500 s-1), the percentage of annexin V and P-selectin positive cells increased from 8.3 ± 0.4% to 22.3 ± 1.8% ( p 0.05) and from 17.4 ± 0.5% to 33.5 ± 2.5% (p 0.05),respectively. As the vWF concentration increased from 5 µg/ml to 25 µg/ml, the annexinV binding rate increased from 7.2 ± 0.6% to 53.4 ± 3.8% (p 0.05), and P-selectin expression increased from 16.5 ± 1.2% to 65.9 ± 5.2% (p 0.05). A test in a uniform shear field using cone-plate viscometer rheometry showed that the platelet activation rate was proportional to the platelet concentration. This result suggests that platelet collision is one of the impact factors of SIPAct.
Salsolinol, an endogenous neurotoxin, enhances platelet aggregation and thrombus formation
Authors: Lim Kyung-Min , Noh Ji-Yoon , Chung Seung-Min , Kim Keunyoung , Hong Suyoung , Shin Sue , on Jong-HyunYo , Bae Ok-Nam , Kim Young-Dae , Chung Jin-Ho 
Published: June 2008

SummarySalsolinol, an endogenous neurotoxin, is known to be involved in the neuropathy of Parkinson’s disease and chronic alcoholism. In these diseases, increased thrombotic events are also commonly reported, yet the mechanism underlying remains poorly understood. Here we report that salsolinol can enhance agonist-induced platelet aggregation and granular secretion, which is essential in the thrombus formation. In rat and human platelets, agonist-induced platelet aggregation was significantly increased by salsolinol in a concentration-dependent manner. Agonist-induced granular secretions of serotonin and concomitant P-selectin expression were also augmented by salsolinol. α2-adrenergic blockers attenuated the salsolinol-enhanced aggregation and the inhibition of cyclic AMP generation was found, suggesting the involvement of α2-adrenergic receptor-mediated pathways in these events. In accord with the in-vitro results, in an arterial and venous thrombosis model in vivo in the rat, salsolinol shortened vessel occlusion time and increased thrombus formation, respectively. In conclusion, we demonstrated that sal-solinol can enhance agonist-induced aggregation and granular secretion in platelets through α2-adrenergic receptor activation, which resulted in the increased thrombus formation in vivo.These results suggest that salsolinol-enhanced platelet aggregation could be a possible contributing factor to the thrombotic events observed in Parkinson’s disease and alcoholism.
The biphasic transmittance waveform: An early marker of sepsis in patients with neutropenia
Authors: Hussain Nazia , Hodson Dan , Marcus Robert , Baglin Trevor , Luddington Roger 
Published: June 2008

SummaryTransmittance waveform (TW) analysis has been proposed as a method of both prediction and monitoring of non-overt and overt disseminated intravascular coagulation. This study assessed the use of the rapid TW of the activated partial thromboplastin time in the detection of sepsis in 49 consecutive neutropenic haemato-oncology patients. A slope 1 cut-off value of –0.050 was found to be optimum giving 85% sensitivity with 92% specificity and positive and negative predictive values of 62% and 98%, respectively. Furthermore a worsening slope 1 value at 24 hours was indicative of a 60% increase in mortality risk. Haemato-oncology patients have a significantly increased risk of developing sepsis during intensive chemotherapy, exacerbated by the resultant neutopenia. This sepsis may progress extremely rapidly and is associated with a high mortality. Early diagnosis is therefore critical and is currently made on a predominantly clinical basis with supporting microbiological evidence 2–3 days later. This study showed that TW offers an early marker, predictive of sepsis in neutropenic patients. It correlates with subsequent microbiological results and may identify patients at greater risk of clinical deterioration who may require more intensive early therapy or observation. It may also provide a useful marker to monitor the effects of treatment.
Potential protective role of apoprotein J (clusterin) in atherogenesis: Binding to enzymatically modified low-density lipoprotein reduces fatty acid-mediated cytotoxicity
Authors: Lux Cornelia A. , Paprotka Kerstin , Torzewski Michael , Dersch Katrin , Koch-Brandt Claudia , Husmann Matthias , Schwarz Margarethe , Spath Lena , Bhakdi Sucharit 
Published: June 2008

SummaryFollowing entrapment in the arterial intima, low-density lipoprotein (LDL) can be modified by hydrolytic enzymes to yield a lipoprotein derivative that binds C-reactive protein, activates complement, and is rapidly taken up by monocytes/macrophages. Free fatty acids contained in enzymatically modified LDL (E-LDL) render the lipoprotein cytotoxic due to their capacity to trigger programmed cell death. Apoprotein J (ApoJ) alias clusterin is a multifunctional glycoprotein with cytoprotective and anti-inflammatory properties. It interacts with diverse substrates, is present in the intima and the media of arteries with atherosclerotic lesions and is also synthesized by smooth muscle cells during development of atherosclerosis. We report that ApoJ binds to E-LDL but not to native LDL. Binding resulted in marked reduction of cytotoxicity of E-LDL on smooth muscle cells, as revealed by determination of caspase activity, annexin binding, and cellular ATP. ApoJ was detected immunohistochemically in early atherosclerotic lesions, where it was found to colocalize with E-LDL. In atherosclerotic lesions, ApoJ may thus subserve protective functions through its capacity to inactivate C5b-9 complement complexes and by reducing the cytotoxic effects of modified LDL on cells that gain contact with the lipoprotein.
Possible mechanisms contributing to oxidative inactivation of activated protein C: Molecular dynamics study
Authors: Nalian Armen , Iakhiaev Alexei V. 
Published: June 2008

SummaryActivated protein C (APC) is a serine protease, an effector enzyme of the natural anticoagulant pathway. APC is approved for treatment of severe sepsis characterized by the increased concentrations of H2O2 and hypochlorite. We found that treatment of APC with these oxidants markedly inhibits the cleavage of the APC-specific chromogenic substrate, suggesting that oxidants can induce changes in the structure of the active site of APC. Resistance of oxidant-treated APC to chemical digestion with cyanogen bromide (CNBr) implies that methionine oxidation can at least in part be responsible for inhibition of APC. Since methionine residues, the main targets of oxidants in APC, are not included in the active site, we hypothesize that oxidation induces allosteric changes in the architecture of the catalytic triad of APC. Using molecular dynamics (MD) simulations we found that methionine oxidation alters the distance between cSer 195Oγ and cHis57 Nε2 atoms placing them in positions unfavorable for the catalysis. At the same time, neither distances between Cα atoms of the catalytic triad cAsp102-cHis57-cSer195, nor the overall structure of APC changed significantly after oxidation of the methionine residues. Disruption of the H-bond between Nδ1 of cHis57 and carboxyl group of cAsp 102, which can take place during the hypochlorite-induced modification of cHis57,dramatically changed the architecture of the catalytic triad in oxidized APC. This mechanism could contribute to APC inactivation by hypochlorite concurrently with methionine oxidation. These are novel findings, which describe potentially pathophysiologically relevant changes in the functional stability of APC exposed to the oxidative stress.
Phenotypic heterogeneity in the gray platelet syndrome extends to the expression of TREM family member, TLT-1
Authors: Bermejo Emilsé , Combrié Robert , McVicar Daniel W. , Washington A.Valance , Nurden Alan T. , Nurden Paquita 
Published: June 2008

SummaryThe Gray platelet syndrome (GPS) is a rare inherited disorder linked to undefined molecular abnormalities that prevent the formation and maturation of α-granules. Here, we report studies on two patients from unrelated families that confirm phenotypic heterogeneity in the disease. First we used immunoelectron microscopy (I-EM) to confirm that TREM-like transcript-1 (TLT-1) is mostly localized to α-granule membranes of normal platelets. Then we performed Western blotting (WB) and flow cytometry with permeabilized platelets to show that TLT - 1 is selectively reduced in the platelets of patient 1, previously noted to be deficient in glycoprotein (GP)VI (Nurden et al., Blood 2004; 104: 107–114).Yet both TLT - 1 and GPVI were normally expressed in platelets of patient 2. Usual levels of JAM-C and claudin-5, also members of the immunoglobulin receptor family, were detected in platelets of both patients. In contrast, P-selectin was markedly decreased for patient 1 but not patient 2.Two metalloproteases, MMP-2 and MMP-9 were normally present. As predicted, platelets of patient 1 showed little labelling for TLT - 1 in I-EM, whereas residual Fg was seen in small vesicular structures and P-selectin lining vacuoles or channels of what may be elements of the surface-connected canalicular system. Our results identify TLT - 1 as a glycoprotein potentially targeted in platelets of GPS patients, while decreases in at least three membrane glycoproteins suggest that an unidentified proteolytic activity may contribute to the phenotype in some patients with this rare disease.
Protease activated receptor 1 (PAR-1) activation by thrombin is protective in human pulmonary artery endothelial cells if endothelial protein C receptor is occupied by its natural ligand
Authors: Bae Jong-Sup , Rezaie Alireza R. 
Published: June 2008

SummaryWe recently demonstrated that the occupancy of endothelial protein C receptor (EPCR) by its natural ligand activated protein C (APC)/protein C switches the protease activated receptor 1 (PAR-1)-dependent signaling specificity of thrombin from a disruptive to a protective effect in cultured human umbilical vein endothelial cells. Given the phenotypic differences between endothelial cells in venular and arterial beds, in this study we evaluated the signaling function of thrombin in human pulmonary artery endothelial cells (HPAECs) before and after treating them with PC-S195A which lacks catalytic activity but exhibits a normal affinity for EPCR. As expected, both thrombin and thrombin receptor agonist peptide (TRAP) enhanced the permeability barrier of HPA ECs; however, both PAR-1 agonists exhibited a potent barrier protective effect when the cells were treated with PC-S195A prior to stimulation by the agonists. Interestingly, similar toAPC, thrombin exhibited a potent cytoprotective activity in the LPS-induced permeability and TNF-α-induced apoptosis and adhesion assays in the PC-S195A treated HPAECs. Treatment of HPAECs with the cholesterol depleting molecule methyl-β-cyclodextrin eliminated the protective effect of both APC and thrombin. These results suggest that the occupancy of EPCR by its natural ligand recruits PA R-1 to a protective signaling pathway within lipid rafts of HPAECs. Based on these results we conclude that the activation of PAR-1 by thrombin would initiate a protective response in intact arterial vascular cells expressing EPCR. These findings may have important ramifications for understanding the mechanism of the participation of the vascular PAR-1 in pathophysiology of the inflammatory disorders.
The C50T polymorphism of the cyclooxygenase-1 gene and the risk of thrombotic events during low-dose therapy with acetyl salicylic acid
Authors: van Oijen Martijn G. H. , Sundaresan Santosh , Brouwer Marc A. , te Morsche Rene H. M. , Keuper Wessel , Peters Wilbert H. M. , Drenth Joost P . H. , Verheugt Freek W. A. , Clappers Nick 
Published: June 2008

SummaryAspirin prevents thrombotic events by inhibiting platelet cyclooxygenase-1 (COX-1), thus reducing thromboxane A2 formation and platelet aggregation. The C50T polymorphism of COX-1 is associated with an impaired inhibition of both thromboxane production and in-vitro platelet aggregation by aspirin. We studied whether this polymorphism is also associated with the risk of clinical thrombotic events in patients using aspirin. We included 496 patients admitted to our Coronary Care Unit for various indications treated with aspirin 80 mg daily. Genotyping for the C50T polymorphism demonstrated that 86.7% of the patients had the common genotype, and 13.3% had the variant (12.5% heterozygous, 0.8% homozygous). Baseline variables were well balanced, except that patients with the common genotype more frequently used aspirin prior to admission compared to those patients with the variant genotype. The composite primary endpoint of myocardial infarction, stroke, and/or cardiovascular death occurred in 98 patients (19.8%). Myocardial infarction occurred in 9.6% of patients, stroke in 1.6%, and cardiovascular death in 12.1%.The unadjusted hazard ratio (95% CI) for the primary endpoint for patients with the variant versus the common genotype was 1.07 (0.62–1.85), p=0.8.The adjusted hazard ratio was 0.86 (0.49–1.50), p=0.6. In prior laboratory studies the COX-1 C50T polymorphism was associated with an impaired inhibitory effect of aspirin on thromboxane production and platelet function. However, in this cohort of patients using low-dose aspirin for secondary prevention the polymorphism was not associated with a higher risk of atherothrombotic events.
Forging Buddhist Credentials as a Tool of Legitimacy and Ethnic Identity: A Study of Arakan's Subjection in Nineteenth-Century Burma
Authors: Leider Jacques 
Published: June 2008

AbstractThe kingdom of Arakan was conquered by the Burmese in 1785 and annexed by the British after the first Anglo-Burmese War (1824-6). Resistance to the occupation was followed by campaigns of pacification that entailed social disruption. Starting with an analysis of the religious motives for King Bodawphaya's quest to conquer Arakan, this article focuses on the use of local religious traditions to bolster ethnic self-identification and resist the process of integration. Based on little explored indigenous and Western primary sources, this essay attempts to make a contribution to the social history of Buddhism in Arakan. Le royaume d'Arakan fut conquis en 1785 par les Birmans. Après la première guerre anglobirmane (1824-6), il fut annexé par les Anglais. La résistance arakanaise aux occupants provoqua des campagnes d'oppression qui eurent un impact considérable sur la société. L'article que voici propose une analyse des motifs religieux qui sous-tendent la conquête par le roi Bodawphaya (1781-1819). L'attention se porte ensuite sur le recours aux traditions locales qui étayaient l'identité communautaire et permettaient de résister au processus d'intégration. Cette enquête fondée sur des sources primaires indigènes et occidentales offre ainsi une contribution à l'histoire sociale du bouddhisme en Arakan.
Individuation, particularisation et détermination selon Plotin
Authors: Aubry Gwenaëlle 
Published: June 2008

AbstractPlotinus' formulation of the problem of the individual should not be reduced to the question of whether or not one can accept Forms of Individuals. First, if Plotinus does indeed posit an intelligible foundation of individuality, there are no grounds to identify this foundation with a Form: it must rather be considered a logos. Second, we must, in addition to this intelligible “principle of distinction”, allow for a sensible “principle of individuation”: the living body. Finally, we have to distinguish a third level: that of the hêmeis, the individual as a person, capable of freedom and consciousness. This latter's compatibility with the other two seems problematic, so that the real difficulty may lie in this tension, in Plotinus' thought, between an ontological and an ethical concept of the individual.
Creating Comparability Differently: Disassembling Ethnographic Comparison in Law-in-Action
Authors: Scheffer Thomas 
Published: June 2008

AbstractEthnographic comparison identifies and analyses core mechanisms which integrate and drive various ethnographic fields. This is exemplified here by what we term, following Luhmann, "the binding mechanism" – which we identify in criminal cases from England, the United States and Germany. By choosing criminal cases as the dynamic frames of "their" (participants') activity and "our" (observers') analysis, thick comparison questions the sources of stability found in structural comparisons of legal doctrines, namely fixed items, definite meaning, and detached contexts. This paper discusses how these features of structural comparison are replaced by more dynamic components, such as becomings, involvements, and formations.
Multi-Sited Comparison of "Doing Regulation"
Authors: Sørensen Estrid 
Published: June 2008

AbstractGeorge Marcus (1995) emphasizes that multi-sited ethnography embodies within itself a comparative dimension. For our general understanding of comparison, however, multi-sited ethnography lacks a crucial component: a grounding or tertium comparationis. This article proposes a multi-sited comparison which does not take as its point of departure any tertium comparationis but instead identifies this as an outcome. The method of comparison was developed amidst a multisited ethnography of "doing regulation," here with reference to computer games and the regulatory purpose of protecting minors from harmful media content.
Gaining Insight from Incomparability: Exploratory Comparison in Studies of Social Practices
Authors: Schmidt Robert 
Published: June 2008

AbstractThis paper suggests an experimental approach to comparison. It is argued that comparing should be detached from the question of adequacy in order to regain it as an analytical and explorative tool. This approach is put to work by comparing boxing to computer programming. Drawing on comparisons of sports practices to other social practices by Mead and Bourdieu, the paper deploys sports comparison quite similarly. In a comparative perspective the practice of writing code for software is depicted by using means and modes of description developed from an ethnography of boxing. This serves for illuminating and understanding programming's gestural and embodied logic.