bluuebunny/crossref_metadata_2025 huggingface dataset:
Kinetic characteristics of ductal carcinoma in situ (DCIS) in dynamic breast MRI using computer-assisted analysis
Authors: Vag Tibor , Baltzer Pascal A. T. , Dietzel Matthias , Benndorf Matthias , Gajda Mieczyslaw , Camara Oumar , Kaiser Werner A.
Published: October 2010

Background: Enhancement characteristics of breast lesions are regarded as a major criterion for their differential diagnosis in dynamic breast MRI (bMRI). However, ductal carcinoma in situ (DCIS) exhibits a highly heterogeneous enhancement pattern when kinetic analysis is performed conventionally by manual placement of region of interest (ROI) and therefore its diagnosis remains challenging.

Purpose: To compare enhancement characteristics of DCIS lesions on dynamic bMRI using manual ROI placement with computer-aided analysis and to evaluate whether the latter might increase the detection rate of kinetic features suspicious for malignancy.

Material and Methods: The enhancement patterns of 47 histopathologically verified pure DCIS lesions were evaluated on bMRI images using manual ROI placement as well as a commercially available computer analysis software. The latter is able to automatically assess enhancement characteristics of a whole lesion pixelwise. Kinetic features evaluated included classification of lesion enhancement pattern into washout, plateau or persistent curve type. A washout and plateau enhancement pattern are regarded as suggestive for malignancy.

Results: Morphological classification revealed focus-like enhancement in 2 lesions, mass enhancement in 11, and non-mass enhancement in 34. Manual placement of ROI demonstrated a suspicious enhancement pattern in 51.1% of the DCIS lesions, which could not be significantly increased using computer-aided analysis. Of the mass and non-mass-enhancing DCIS lesions, 90.9% and 38.3%, respectively, demonstrated suspicious kinetic curves. After application of the automated analysis software, the detection rate of suspicious enhancement patterns was unchanged in mass DCIS lesions and increased to 52.9% in non-mass DCIS lesions ( P=0.33). However, the increase in the detection of washout curves alone was significant ( P=0.02). In all, 40% of G1, 41.1% of G2, and 60% of G3 lesions demonstrated a suspicious curve type with manual evaluation. Computer analysis increased the detection of suspicious enhancement patterns in a non-significant manner to 50%, 58.8%, and 70%, respectively.

Conclusion: The detection of suspicious enhancement curves could not be significantly increased in DCIS lesions when using computer-aided analysis despite a significantly higher detection rate of washout curves alone.
A practical approach to interpretation of MRI of the temporomandibular joint
Authors: Moen Ketil , Hellem Sølve , Geitung Jonn Terje , Skartveit Liv
Published: October 2010

Background: Temporomandibular disorders (TMDs) such as pain, joint sounds, and impaired movement are common, and magnetic resonance imaging (MRI) is now the method of choice for diagnostic assessment.

Purpose: To describe MR criteria chosen and the amount of temporomandibular joint (TMJ) pathology registered when examining MR images from patients referred to a university hospital for imaging of their TMJs.

Material and Methods: The TMJs of 152 consecutive patients, 102 women and 40 men, referred for MRI during an 18 month period were imaged with a 1.5 T imaging system. Twelve asymptomatic students, seven women and five men, gave informed consent and acted as a control group.

Results: Moderate to extensive disk displacement was registered in 53% of the patients’ TMJs, and 38% of the disks were deformed. Degenerative changes registered were flattening of the condyle heads in 50% of the TMJs and erosion of their cortical surfaces in 30%. Osteophytes were present in 31% of the condyles and bone marrow edema in 30%. Marked to extensive effusion in synovial compartments was registered in 39% of the studied TMJs. In the control group, none of the TMJs showed anterior disk displacement, deformed disks or degenerative changes, but 8 of the 24 joints showed marked effusion. A tendency for a higher amount of disk displacement and deformation was seen among young age groups and more degenerative changes in older age groups, but differences among groups were not significant when tested with chi-square analysis.

Conclusion: Defined MR criteria that allow for comparative assessment are presented. According to these criteria, a large proportion of the patients referred for MR examination showed morphologic changes indicating TMJ pathology.
Knee cartilage quality assessed with dGEMRIC in rheumatoid arthritis patients before and after treatment with a TNF inhibitor
Authors: Tiderius Carl Johan , Sandin Joakim , Svensson Jonas , Dahlberg Leif E. , Jacobsson Lennart
Published: October 2010

Background: TNF-α inhibitors are potent anti-inflammatory drugs that have revolutionized the treatment of rheumatoid arthritis (RA). Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) is a non-invasive method to study cartilage quality, in particular the glycosaminoglycan (GAG) content.

Purpose: To evaluate knee cartilage quality before and after treatment with a TNF-α inhibitor (infliximab) in patients with RA using dGEMRIC and to study clinical parameters and serum cartilage oligomeric protein (COMP) after the same treatment.

Material and Methods: Seven patients with chronic RA received infusions of 3 mg/kg infliximab at weeks 0, 2, 6, 14, and 22. Clinical examination, serum COMP level, and dGEMRIC scans (1.5 T) were performed at baseline and after 7 months. The dGEMRIC index (ms), reflecting cartilage GAG content, was calculated using an inversion recovery sequence in the femoral weight-bearing cartilage. Seven years after treatment, charts were reviewed regarding joint replacement surgery (TKA).

Results: Clinical parameters showed an improvement for all patients after the 7-month treatment period. Serum COMP decreased from 13±4.5 to 11±3.4 (µg, mean ± SD) µg/ml ( P<0.05). The dGEMRIC index was lower at follow-up than at baseline, 332±85 and 382±69 (ms, mean ± SD), respectively ( P<0.05), indicating loss of GAG. The two patients with the lowest dGEMRIC index had received a TKA 7 years after treatment.

Conclusion: This longitudinal study indicates a substantial GAG loss from the knee cartilage matrix in patients with chronic RA. Treatment with infliximab does not seem to protect the cartilage from further deterioration despite improvements in clinical parameters and decreased serum COMP.
Constats d'infraction, accidents de la route et certitude relative de la peine : une évaluation quasi-expérimentale des effets contextuels et structurels de la dissuasion policière
Authors: Beaudoin Isabelle , Blais Étienne
Published: October 2010

Results of studies using cross-section and time series data call into question the utility of deterrence theory to explain the relationship between arrests and crime. In this study, we propose that the absence of a relationship between arrests and the crime rate is explained, in part, by the omission of notions of contextual and structural deterrence in the analysis. Contextual deterrence would be produced when the risk of arrest is increased to an unacceptable level for the population and this risk is maintained over a lengthy period of time. Structural deterrence underscores the importance of considering police jurisdictions as a unit of analysis, since the sentence would affect the exposed population. In order to demonstrate the utility of such notions, we have evaluated the effect of the Road and Traffic Safety Team of the Montreal Police Service on collisions involving injuries. Our results show that the introduction of the Road and Traffic Safety Team was followed by an immediate and sustained increase in police activity, which, in turn, led to a gradual decrease in collisions with injury. These results show the importance of including the concepts of contextual and structural effects in the study of the general deterrent effect of sentencing.
Inter-professional Education in the Acute-Care Setting: The Clinical Instructor's Point of View
Authors: Chau Jennifer , Denomme Jocelyn , Murray Judy , Cott Cheryl A.
Published: October 2010

Purpose: The purpose of this study was to gain an understanding of the opportunities and challenges involved in providing clinical inter-professional education (IPE) to physical therapy (PT) students in the acute-care setting from the perspective of PT clinical instructors (CIs).

Methods: Focus groups were conducted in four acute-care hospitals in Toronto. Participants were recruited using a purposive and convenience sampling approach in order to enhance our understanding of the perceptions of acute-care PT CIs. Eighteen full-time PT CIs with an average of 11 years in practice participated. A constant comparative process was employed to identify recurrent issues and themes within and between groups.

Results: Three main themes emerged from the focus groups: (1) Clinical IPE happens when inter-professional collaboration (IPC) occurs; however, IPC differs according to setting, access to other professions, time, support, and structure. (2) IPE is a lifelong learning process that applies to both CIs and students. (3) Student preparedness is a prerequisite for clinical IPE.

Conclusions: IPC is an integral part of clinical IPE that requires ongoing commitment and reflection by CIs to ensure that they are ready to instruct students who have some preparation in formal IPE. More knowledge about providing clinical IPE in a structured manner, through academic and health institutions, will allow CIs to become role models for future generations of PT students.
Incorporating Spatial Structures in Ecological Inference: An Information Theory Approach
Authors: Bernardini Papalia Rosa
Published: October 2010

This paper introduces an Information Theory-based method for modeling economic aggregates and estimating their sub-group (sub-area) decomposition when no individual or sub-group data are available. This method offers a flexible framework for modeling the underlying variation in sub-group indicators, by addressing the spatial dependency problem. A basic ecological inference problem, which allows for spatial heterogeneity and dependence, is presented with the aim of first estimating the model at the aggregate level, and then of employing the estimated coefficients to obtain the sub-group level indicators.
2-((Pyren-1-ylmethylamino)methyl)quinolin-8-ol
Authors: Fernández-Lodeiro Javier , Nuñez Cristina , Capelo José Luis , Lodeiro Carlos
Published: October 2010

A new fluorescent compound L1 derived from 1-pyrenemethylamine hydrochloride (A) has been synthesized by classical Schiff-base reaction between (A) and 8-hydroxyquinoline-2-carbaldehyde (B) followed by a chemical reduction with NaBH4. The chemical structure was confirmed by elemental analysis, FAB-MS spectrometry and by IR, UV-vis and 1H-NMR spectroscopy. The photophysical characterization was achieved by UV-vis and emission spectroscopy and lifetime measurements. Compound L1 was explored as pH fluorescent chemosensor in water-acetonitrile (95.5/0.5 v:v) solutions.
Allosteric Inhibitors of NMDA Receptor Functions
Authors: Popescu Gabriela K. , Murthy Swetha , Borschel William F.
Published: October 2010

NMDA receptors are glutamate-activated ion-channels involved in many essential brain functions including learning, memory, cognition, and behavior. Given this broad range of function it is not surprising that the initial attempts to correct NMDA receptor-mediated pathologies with en-mass receptor blockade were derailed by unacceptable side effects. Recent successes with milder or more targeted pharmaceuticals and increasing knowledge of how these receptors operate offer new incentives for rational development of effective NMDA receptor-targeted therapies. In this article we review evidence that L-alanine, a glycine-site partial agonist and pregnanolone sulfate, a use-dependent allosteric inhibitor, while attenuating NMDA receptor activity to similar levels elicit remarkably dissimilar functional outcomes. We suggest that detailed understanding of NMDA receptor activation mechanisms and of structural correlates of function will help better match modulator with function and neurological condition and may unleash the yet untapped potential of NMDA receptor pharmaceutics.
Oleic and Undecylenic Acids as Renewable Feedstocks in the Synthesis of Polyols and Polyurethanes
Authors: Lligadas Gerard , Ronda Juan C. , Galià Marina , Cádiz Virginia
Published: October 2010

Nowadays, the utilization of raw materials derived from renewable feedstock is in the spotlight of the chemical industry, as vegetable oils are one of the most important platform chemicals due to their universal availability, inherent biodegradability and low price. Taking into account that polyurethanes are one of the most important industrial products exhibiting versatile properties suitable for use in many fields, our research is focused on exploiting fatty acids in the preparation of biobased polyols and polyurethanes. This review is organized as a function of the nature of the final polyurethane systems; hence we describe the preparation of linear thermoplastic and crosslinked polyurethanes derived from oleic and undecylenic acids-based diols and polyols, respectively.
De la médiation médicale. Les conventions d'usage des médicaments psychotropes
Authors: Le Moigne Philippe
Published: October 2010

Résumé. La prescription de médicaments psychotropes peut offrir une réponse face à la détresse. Néanmoins, cette perspective reste suspendue au crédit accordé par la population au soutien médical et à l'influence que l'interaction entre patients et médecins exerce en propre sur la décision de prescrire. Ces mécanismes, qu'on résume par la notion de médiation médicale, conditionnent un usage thérapeutique qui ne paraît pas structuré par la réglementation sanitaire, par les préconisations de la clinique ou bien encore par une inspection rigoureuse des risques de dépendance. L'article souligne en effet, à travers la présentation commentée du public consommateur et des logiques d'échanges qui organisent la consultation, l'incidence de repères concurrents, hérités pour l'essentiel des normes d' identité et de statut. Cette organisation appuie une légitimité thérapeutique centrée sur la prise en charge des publics inactifs, soit la constitution d'un espace de soin d'abord voué à la gestion de l'incapacité et donc à certaines formes seulement de régularisation du malheur.
Définition de la performance hospitalière : une enquête auprès des divers acteurs stratégiques au sein des hôpitaux
Authors: Guisset Ann-Lise , Sicotte Claude , Leclercq Pol , D'Hoore William
Published: October 2010

Résumé. Cet article présente les résultats d'une enquête menée auprès des cadres et des représentants syndicaux des hôpitaux belges francophones sur leur conception de la performance. Le questionnaire a été construit à partir d'un modèle théorique de la performance développé par Sicotte et al. (1998), lui-même reposant sur la théorie de l'action sociale de Parsons (1951, 1977). L'analyse factorielle des réponses confirme le fait que la performance est perçue comme un construit multidimensionnel. De plus, la structure factorielle se rapproche assez bien du modèle théorique de départ, avec cependant quelques réorganisations intéressantes des items à l'intérieur et entre les dimensions. Enfin, la comparaison des scores factoriels fait ressortir des divergences d'opinion importantes entre les différentes catégories professionnelles sur les caractéristiques des hôpitaux considérés comme performants.
Le travail invisible des équipes de soutien et conseil en soins palliatifs au domicile
Authors: Mino Jean-Christophe , Lert France
Published: October 2010

The invisible work of home palliative care support teams

Medical care of the dying patient is shaped by a specific model, the palliative care model. Born 30 years ago in Great Britain, this model has spread in the health care System across western countries. In France, its spread is mainly supported by small specialised teams gatthering physicians, nurses, psychologists, social workers who afford consultance, training, support to health care workers and lay carers. This paper presents a research based on monographs of three home palliative care support teams. This text emphasises the invisible work relying on a typology of activities, their context and objectives.
La double expérience des personnes atteintes d'une maladie neuromusculaire rétraction et extension
Authors: Winance Myriam
Published: October 2010

The two-faced experience of people suffering from neuromuscular diseases: retraction and extension

Focusing on the experience of people suffering from neuromuscular diseases, the author shows that the disease and the use of technical aids to survive and to live are not only disrupting the self (biographical disruption), but also transforming the links which define the person, its body and its world. The disease produces a movement of retraction: the person' s body and world are simultaneously reduced. The adjustment, material and emotional, to the wheelchair produces a movement of extension. This analyses leads to the suspension of body's and person's boundaries. The adjustment is both opening and closing of the person.
Médecine gratuite ou santé pour tous ? Réflexions sur l'expérience algérienne
Authors: Guillermou Yves
Published: October 2010

Free medical care or health for ail? Reflections about the Algerian experience

The problem of general access to medical care is a major problem till nowadays, especially in the Third World countries where financial obstacles tend to exclude large categories of population from the health care System. The Algerian experience of setting up a free of cost health care System deserves a heedful investigation, on condition of taking its context into account. This radical measure has been attended by a considerable endeavour in increasing the care supply and unifying the public health sector, contributing to a substantial improvement of the general health condition of the population. Nevertheless, this ambitious policy, excluding any real consult with the users, will face contradictions that will be sharpened by the economic and political crisis, calling in question the whole System.
Le normal et le pathologique : dépressivité et usages de drogue à l'adolescence
Authors: Peretti-Watel Patrick
Published: October 2010

Résumé. Cet article vise à préciser la relation entre humeur dépressive et usages d'alcool, de tabac et de cannabis à l'adolescence, en questionnant le caractère normal ou pathologique de cette humeur. Parmi les adolescents ayant participé à l'enquête auto-administrée ESPAD 1999, 23 % présentent de nombreux signes dépressifs mais, pour la plupart, ces signes ne sont pas accompagnés de manifestations plus graves (tentatives de suicide, fugue...), ni d'usages de drogue plus fréquents que dans le reste de l'échantillon. En discussion, cet article s'interroge sur l'opportunité d'interpréter les usages de drogue à l'adolescence comme l'expression de problèmes psychologiques.
Renouveau managérial dans le contexte des réformes des services de santé : mirage ou réalité ?
Authors: Dubois Carl-Ardy
Published: October 2010

Managerialism and reforms of health services: mirage or reality?

In using data drawn from two case studies targeting two Canadian provinces, this paper examines both discursive strategies and practices associated with the renewal of the management of public services. It looks to determine how both managerialist discourses and techniques have been integrated into reforms and to what extent they have altered or perpetuated the existing dynamics in terms of accountability and management. Our analysis suggests that, into the context of Canadian public services, antibureaucratic claims driven by the managerial ideology have translated into a bureaucratic persistence and a new technology of control associated with a strong focus on performance measurement and analytic tool.
Isolation and characterization of 50 nuclear microsatellite markers for Cathaya argyrophylla, a Chinese endemic conifer
Authors: Wang Zhao‐Shan , Sun Hai‐Qin , Wang Hong‐Wei , Ge Song
Published: October 2010

• Premise of the study: Microsatellite primers were developed for the endangered Cathaya argyrophylla (Pinaceae) to investigate its genetic diversity and population genetic structure, as well as its evolutionary history.

• Methods and Results: Fifty dinucleotide microsatellite loci were identified in two populations. The number of alleles per locus ranged from 1 to 6, with a mean of 2.84. The observed and expected heterozygosities ranged from 0 to 0.889 and from 0 to 0.779, respectively.

• Conclusions: These markers will facilitate further studies on the population genetics and evolutionary history of Cathaya argyrophylla.
Use of waste from the marble industry as filler for the production of self-compacting concretes
Authors: Valdez P. , Barragán B. , Girbes I. , Shuttleworth N. , Cockburn A.
Published: October 2010

This study evaluates the possibilities of using residual slurry from the cutting and superficial treatment of marble for the production of self-compacting concrete (SCC). The study considers the replacement of 30% of cement by the waste material, and assessed the effects on SCC properties in fresh and hardened states. Rheological characteristics were evaluated at the paste and concrete levels. Physical-mechanical characterization considers the rate of shrinkage and compressive strength gain. Pastes and concrete properties using waste marble as filler are compared with mixtures that include limestone filler, either added to the concrete or the cement. For the same dosage, an improvement in the flowability was observed in SCC with waste marble filler. The mechanical properties of the SCC adopting marble waste are equivalent to the SCC with limestone filler. The study shows that residual slurry from the processing of marble can represents an appropriate filler to be used in SCC.
Inhibition of Matrix Metalloproteinase-3 and -13 Synthesis Induced by IL-1β in Chondrocytes from Mice Lacking Microsomal Prostaglandin E Synthase-1
Authors: Gosset Marjolaine , Pigenet Audrey , Salvat Colette , Berenbaum Francis , Jacques Claire
Published: October 2010

Joint destruction in arthritis is in part due to the induction of matrix metalloproteinase (MMP) expression and their inhibitors, especially MMP-13 and -3, which directly degrade the cartilage matrix. Although IL-1β is considered as the main catabolic factor involved in MMP-13 and -3 expression, the role of PGE2 remains controversial. The goal of this study was to determine the role of PGE2 on MMP synthesis in articular chondrocytes using mice lacking microsomal PGE synthase-1 (mPGES-1), which catalyses the rate-limiting step of PGE2 synthesis. MMP-3 and MMP-13 mRNA and protein expressions were assessed by real-time RT-PCR, immunoblotting, and ELISA in primary cultures of articular chondrocytes from mice with genetic deletion of mPGES-1. IL-1β–induced PGE2 synthesis was dramatically reduced in mPGES-1−/− and mPGES-1+/− compared with mPGES-1+/+ chondrocytes. A total of 10 ng/ml IL-1β increased MMP-3 and MMP-13 mRNA, protein expression, and release in mPGES-1+/+ chondrocytes in a time-dependent manner. IL-1β–induced MMP-3 and MMP-13 mRNA expression, protein expression, and release decreased in mPGES-1−/− and mPGES-1+/− chondrocytes compared with mPGES-1+/+ chondrocytes from 8 up to 24 h. Otherwise, MMP inhibition was partially reversed by addition of 10 ng/ml PGE2 in mPGES-1−/− chondrocytes. Finally, in mPGES-1−/− chondrocytes treated by forskolin, MMP-3 protein expression was significantly decreased compared with wild-type, suggesting that PGE2 regulates MMP-3 expression via a signaling pathway dependent on cAMP. These results demonstrate that PGE2 plays a key role in the induction of MMP-3 and MMP-13 in an inflammatory context. Therefore, mPGES-1 could be considered as a critical target to counteract cartilage degradation in arthritis.
Temporal Differences in the Dependency on Phosphoinositide-Dependent Kinase 1 Distinguish the Development of Invariant Vα14 NKT Cells and Conventional T Cells
Authors: Finlay David K. , Kelly April P. , Clarke Rosemary , Sinclair Linda V. , Deak Maria , Alessi Dario R. , Cantrell Doreen A.
Published: October 2010

This study uses two independent genetic strategies to explore the requirement for phosphoinositide-dependent kinase-1 (PDK1) in the development of mature T cell populations from CD4/CD8 double-positive thymocytes. The data show that CD4/CD8 double-positive thymocytes that do not express PDK1 or express a catalytically inactive PDK1 mutant fail to produce mature invariant Vα14 NKT cells but can differentiate to conventional CD4, CD8, or regulatory T cell subsets in the thymus. The PDK1 requirement for Vα14 NKT cell development reflects that these cells require the PDK1 substrate protein kinase B to meet the metabolic demands for proliferative expansion in response to IL-15 or AgR stimulation. There is also constitutive PDK1 signaling in conventional α/β T cells that is not required for lineage commitment of these cells but fine-tunes the expression of coreceptors and adhesion molecules. Also, although PDK1 is dispensable for thymic development of conventional α/β T cells, peripheral cells are reduced substantially. This reflects a PDK1 requirement for lymphopenia-induced proliferation, a process necessary for initial population of the peripheral T cell niche in neonatal mice. PDK1 is thus indispensable for T cell developmental programs, but the timing of the PDK1 requirement is unique to different T cell subpopulations.
A Butyrophilin Family Member Critically Inhibits T Cell Activation
Authors: Yamazaki Tomohide , Goya Iñigo , Graf Daniel , Craig Suzanne , Martin-Orozco Natalia , Dong Chen
Published: October 2010

The costimulatory molecules in the B7-CD28 families are important in the regulation of T cell activation and tolerance. The butyrophilin family of proteins shares sequence and structure homology with B7 family molecules; however, the function of the butyrophilin family in the immune system has not been defined. In this study, we performed an analysis on multiple butyrophilin molecules and found that butyrophilin-like (BTNL)1 molecule functions to dampen T cell activation. BTNL1 mRNA was broadly expressed, but its protein was only found in APCs and not T cells. The putative receptor for BTNL1 was found on activated T cells and APCs. Also, recombinant BTNL1 molecule inhibited T cell proliferation by arresting cell cycle progression. The administration of neutralizing Abs against BTNL1 provoked enhanced T cell activation and exacerbated disease in autoimmune and asthma mouse models. Therefore, BTNL1 is a critical inhibitory molecule for T cell activation and immune diseases.
Generation of Mucosal Dendritic Cells from Bone Marrow Reveals a Critical Role of Retinoic Acid
Authors: Feng Ting , Cong Yingzi , Qin Hongwei , Benveniste Etty N. , Elson Charles O.
Published: October 2010

It is unknown how dendritic cells (DCs) become specialized as mucosal DCs and maintain intestinal homeostasis. We report that a subset of bone marrow cells freshly isolated from C57BL/6 mice express the retinoic acid (RA)-synthesizing enzyme aldehyde dehydrogenase family 1, subfamily A2 (ALDH1a2) and are capable of providing RA to DC precursors in the bone marrow microenvironment. RA induced bone marrow-derived DCs to express CCR9 and ALDH1a2 and conferred upon them mucosal DC functions, including induction of Foxp3+ regulatory T cells, IgA-secreting B cells, and gut-homing molecules. This response of DCs to RA was dependent on a narrow time window and stringent dose effect. RA promoted bone marrow-derived DC production of bioactive TGF-β by inhibiting suppressor of cytokine signaling 3 expression and thereby enhancing STAT3 activation. These RA effects were evident in vivo, in that mucosal DCs from vitamin A-deficient mice had reduced mucosal DC function, namely failure to induce Foxp3+ regulatory T cells. Furthermore, MyD88 signaling enhanced RA-educated DC ALDH1a2 expression and was required for optimal TGF-β production. These data indicate that RA plays a critical role in the generation of mucosal DCs from bone marrow and in their functional activity.
IDO Upregulates Regulatory T Cells via Tryptophan Catabolite and Suppresses Encephalitogenic T Cell Responses in Experimental Autoimmune Encephalomyelitis
Authors: Yan Yaping , Zhang Guang-Xian , Gran Bruno , Fallarino Francesca , Yu Shuo , Li Hongmei , Cullimore Melissa L. , Rostami Abdolmohamad , Xu Hui
Published: October 2010

Experimental autoimmune encephalomyelitis (EAE) is a Th1 and Th17 cell-mediated autoimmune disease of the CNS. IDO and tryptophan metabolites have inhibitory effects on Th1 cells in EAE. For Th17 cells, IDO-mediated tryptophan deprivation and small molecule halofuginone-induced amino acid starvation response were shown to activate general control nonrepressed 2 (GCN2) kinase that directly or indirectly inhibits Th17 cell differentiation. However, it remains unclear whether IDO and tryptophan metabolites impact the Th17 cell response by mechanisms other than the GCN2 kinase pathway. In this article, we show that IDO-deficient mice develop exacerbated EAE with enhanced encephalitogenic Th1 and Th17 cell responses and reduced regulatory T cell (Treg) responses. Administration of the downstream tryptophan metabolite 3-hydroxyanthranillic acid (3-HAA) enhanced the percentage of Tregs, inhibited Th1 and Th17 cells, and ameliorated EAE. We further demonstrate that Th17 cells are less sensitive to direct suppression by 3-HAA than are Th1 cells. 3-HAA treatment in vitro reduced IL-6 production by activated spleen cells and increased expression of TGF-β in dendritic cells (DCs), which correlated with enhanced levels of Tregs, suggesting that 3-HAA–induced Tregs contribute to inhibition of Th17 cells. By using a DC–T cell coculture, we found that 3-HAA–treated DCs expressed higher levels of TGF-β and had properties to induce generation of Tregs from anti-CD3/anti-CD28–stimulated naive CD4+ T cells. Thus, our data support the hypothesis that IDO induces the generation of Tregs via tryptophan metabolites, such as 3-HAA, which enhances TGF-β expression from DCs and promotes Treg differentiation.
BCL6 Is Required for Differentiation of Ig-Like Transcript 3-Fc–Induced CD8+ T Suppressor Cells
Authors: Chang Chih-Chao , Vlad George , D’Agati Vivette D. , Liu Zhuoru , Zhang Qing-yin , Witkowski Piotr , Torkamani Ali A. , Stokes Michael B. , Ho Eric K. , Cortesini Raffaello , Suciu-Foca Nicole
Published: October 2010

Ig-like transcript 3 (ILT3) is an inhibitory receptor expressed by tolerogenic dendritic cells. When human CD8+ T cells are allostimulated in the presence of recombinant ILT3-Fc protein, they differentiate into antigenic specific T suppressor (Ts) cells that inhibit CD4 and CD8 T cell effector function both in vitro and in vivo. ILT3-Fc–induced CD8+ Ts cells express high amounts of BCL6 that are crucial to their function. Knockdown of BCL6 from unprimed human T cells prevents their differentiation into Ts cells, whereas ex vivo overexpression of BCL6 converts CD8+ T cells into Ts cells. NOD/SCID mice transplanted with human pancreatic islets and humanized by injection of human PBMCs tolerate the graft and develop BCL6high CD8+ Ts cells when treated with ILT3-Fc before or after the onset of rejection. This indicates that ILT3-Fc acts through BCL6 and is a potent immunosuppressive agent for reversing the onset of allo- or possibly autoimmune attacks against pancreatic islets.
Active Immunization with Amyloid-β 1–42 Impairs Memory Performance through TLR2/4-Dependent Activation of the Innate Immune System
Authors: Vollmar Patrick , Kullmann Jennifer S. , Thilo Barbara , Claussen Malte C. , Rothhammer Veit , Jacobi Hortenzia , Sellner Johann , Nessler Stefan , Korn Thomas , Hemmer Bernhard
Published: October 2010

Active immunization with amyloid-β (Aβ) peptide 1–42 reverses amyloid plaque deposition in the CNS of patients with Alzheimer’s disease and in amyloid precursor protein transgenic mice. However, this treatment may also cause severe, life-threatening meningoencephalitis. Physiological responses to immunization with Aβ1–42 are poorly understood. In this study, we characterized cognitive and immunological consequences of Aβ1–42/CFA immunization in C57BL/6 mice. In contrast to mice immunized with myelin oligodendrocyte glycoprotein (MOG)35–55/CFA or CFA alone, Aβ1–42/CFA immunization resulted in impaired exploratory activity, habituation learning, and spatial-learning abilities in the open field. As morphological substrate of this neurocognitive phenotype, we identified a disseminated, nonfocal immune cell infiltrate in the CNS of Aβ1–42/CFA-immunized animals. In contrast to MOG35–55/CFA and PBS/CFA controls, the majority of infiltrating cells in Aβ1–42/CFA-immunized mice were CD11b+CD14+ and CD45high, indicating their blood-borne monocyte/macrophage origin. Immunization with Aβ1–42/CFA was significantly more potent than immunization with MOG35–55/CFA or CFA alone in activating macrophages in the secondary lymphoid compartment and peripheral tissues. Studies with TLR2/4-deficient mice revealed that the TLR2/4 pathway mediated the Aβ1–42-dependent proinflammatory cytokine release from cells of the innate immune system. In line with this, TLR2/4 knockout mice were protected from cognitive impairment upon immunization with Aβ1–42/CFA. Thus, this study identifies adjuvant effects of Aβ1–42, which result in a clinically relevant neurocognitive phenotype highlighting potential risks of Aβ immunotherapy.
Rapid T Cell Receptor Delineation Reveals Clonal Expansion Limitation of the Magnitude of the HIV-1–Specific CD8+ T Cell Response
Authors: Balamurugan Arumugam , Ng Hwee L. , Yang Otto O.
Published: October 2010

TCRs mediate CTL specificity, but TCRs recognizing the same epitope often differ between persons due to their stochastic derivation. The role of this variability in the pathogenesis of virus infections and malignancies has been technically difficult to study. We apply an adaptation of TCR spectratyping to study HIV-specific CTLs, defining the clonal breadth and sequences of epitope-specific TCRs from PBMCs without cellular sorting or molecular cloning. Examining 48 CTL responses in 12 persons reveals a mean of 4.5 ± 2.7 clones per response, of both public and private clonotypes. The number of identified epitope-specific TCRs correlates with CTL frequency across epitopes, suggesting that clonal breadth limits the magnitude of the CTL response against HIV-1 in vivo. HLA A- and B-restricted CTLs are similar in their TCR breadth in this small cohort, preliminarily suggesting that qualitative differences may account for their disparate impacts on pathogenesis. Overall, these findings demonstrate that the magnitude of the CTL response in chronic HIV-1 infection is constrained by TCR clonal breadth, suggesting maximal expansion of CTLs in response to chronic antigenic stimulation.
Lung Cancer Risk and Genetic Polymorphisms in DNA Repair Pathways: A Meta‐Analysis
Authors: Kiyohara Chikako , Takayama Koichi , Nakanishi Yoichi
Published: October 2010

Genetic variations in DNA repair genes are thought to modulate DNA repair capacity and are suggested to be related to lung cancer risk. We conducted a meta‐analysis of epidemiologic studies on the association between genetic polymorphisms in both base excision repair and nucleotide excision repair pathways, and lung cancer. We found xeroderma pigmentosum complementation group A (XPA) G23A (odds ratio (OR) = 0.76, 95% confidence interval (CI) = 0.61–0.94), 8‐oxoguanine DNA glycosylase 1 (OGG1) Ser326Cys (OR = 1.22, 95% CI = 1.02–1.45), and excision repair cross‐complementing group 2 (ERCC2) Lys751Gln (OR = 1.27, 95% CI = 1.10–1.46) polymorphisms were associated with lung cancer risk. Considering the data available, it can be conjectured that if there is any risk association between a single SNP and lung cancer, the risk fluctuation will probably be minimal. Advances in the identification of new polymorphisms and in high‐throughput genotyping techniques will facilitate the analysis of multiple genes in multiple DNA repair pathways. Therefore, it is likely that the defining feature of future epidemiologic studies will be the simultaneous analysis of large samples of cases and controls.
Psychological career resources in relation to organisational commitment: An exploratory study
Authors: Ferreira Nadia , Basson Johan , Coetzee Melinde
Published: October 2010

Orientation: The impact of the current skills shortage and demands for retaining talented and skilled staff in a rapidly changing careers context and the consequences for employee loyalty, morale and commitment have led to a renewed interest in the motives, values and career meta-competencies that determine individuals’ psychological attachment to their organisations and occupations.Research purpose: The aim of the study was to determine the relationship between the psychological career resources (as measured by the Psychological Career Resources Inventory) and organisational commitment (as measured by the Organisational Commitment Scale).Motivation for study: There appears to be a need for research on the psychological career resources that enhance individuals’ career agency in proactively managing their career and the way in which these attributes influence their psychological attachment to the organisation in order to guide human resource and career-development support practices in retaining valuable staff.Research design, approach and method: A quantitative survey was conducted on a convenience sample of 358 employed adults at managerial and staff levels in the field of economic and management services.Main findings/results: Correlational and stepwise regression analyses revealed a number of significant relationships between the two variables.Practical implications: Managers and human resource practitioners need to recognise how people’s career preferences and career meta-competencies influence their sense of psychological attachment to the organisation.Contribution: The findings add to existing career literature on the psychological factors that affect the retention of staff and provide valuable information that can be used to inform career-development support practices in the contemporary world of work.
Langerhan′s cell histiocytosis: A single institutional experience
Authors: Singh Tejinder , Satheesh C T , Appaji L , Aruna Kumari B S , Mamatha H S , Giri G V , Rao Clementina Rama
Published: October 2010

Background: Langerhans cell histiocytosis (LCH) is a disease that primarily affects bone but can be associated with a clinical spectrum that ranges from a solitary bone lesion with a favorable natural history to a multisystem, life-threatening disease process. Aim: We analyzed our single institutional experience of managing children with LCH. Settings and Design: A total of 40 children of LCH, managed in tertiary cancer center in South India in the period from 2001 to 2005, were evaluated retrospectively. Materials and Methods: Clinicopathological features, laboratory findings, treatment modalities and long-term outcome were analyzed. Results: Children were aged between 2 months and 12 years, with a mean of 3 years. Majority of the children were below 5 years of age. Group B constituted a bulk of children. Disseminated cases were less (five patients). Liver function dysfunction was seen in four (10%) children. Pulmonary interstitial infiltrates were seen in two (5%) cases. Diabetes insipidus manifested in three patients. There was one death. Conclusion: A better understanding of the etiology and pathogenesis of LCH will result in more directed and efficacious treatment regimens.
Ovarian tumors in pediatric age group - A clinicopathologic study of 10 years′ cases in West Bengal, India
Authors: Bhattacharyya Nirmal Kumar , De Anuradha , Bera Pranati , Mongal Sristidhar , Chakraborty Subrata , Bandopadhyay Rajat
Published: October 2010

Background and objectives: Objective in this retrospective study is to find out the incidence of different ovarian tumors of girls up to 20 years of age observed in last ten years in North Bengal Medical College and to correlate clinical and gross findings with histopathologic findings and to compare the incidence with other studies and follow-up of patients with malignant ovarian tumors. Materials and Methods: Findings were retrieved from records of different pathological reports and clinical reports. Results: Total 151 cases of ovarian tumors were received in pathology department in which 34 cases were malignant (22.6%). Amongst malignant cases, 66% are of germ-cell origin-dysgerminoma being the commonest. Strikingly we got 9 cases of malignant surface epithelial tumor. As per follow-up records most of the dysgerminoma came in stage IA and recovered fully following chemotherapy and radiotherapy. Amongst other malignant tumors, few lost the follow-up management and others expired due to metastasis. Conclusions: Patients from hilly areas of North Bengal and low socio-economic status led to lower detection rate of ovarian tumors in early stage which are absolutely necessary for proper guidelines of management to reduce mortality.
Computational Study of Scission Neutrons in Low-Energy Fission: Stationary and Time-Dependent Approaches
Authors: Rizea M. , Carjan N.
Published: October 2010

The emission of scission neutrons from fissioning nuclei is of high practical interest. To study this process we have used the sudden approximation and also a more realistic approach that takes into account the scission dynamics. Numerically, this implies the solution of the bi-dimensional Schrödinger equation, both stationary and time-dependent. To describe axially symmetric extremely deformed nuclear shapes, we have used the Cassini parametrization. The Hamiltonian is discretized by using finite difference approximations of the derivatives. The main computational challenges are the solution of algebraic eigenvalue problems and of linear systems with large sparse matrices. We have employed appropriate procedures (Arnoldi and bi-conjugate gradients). The numerical solutions have been used to evaluate physical quantities, like the number of emitted neutrons per scission event, the primary fragments’ excitation energy and the distribution of the emission points.
Exponential Compact Higher Order Scheme for Nonlinear Steady Convection-Diffusion Equations
Authors: Sanyasiraju Y. V. S. S. , Mishra Nachiketa
Published: October 2010

This paper presents an exponential compact higher order scheme for Convection-Diffusion Equations (CDE) with variable and nonlinear convection coefficients. The scheme is for one-dimensional problems and produces a tri-diagonal system of equations which can be solved efficiently using Thomas algorithm. For two-dimensional problems, the scheme produces an accuracy over a compact nine point stencil which can be solved using any line iterative approach with alternate direction implicit procedure. The convergence of the iterative procedure is guaranteed as the coefficient matrix of the developed scheme satisfies the conditions required to be positive. Wave number analysis has been carried out to establish that the scheme is comparable in accuracy with spectral methods. The higher order accuracy and better rate of convergence of the developed scheme have been demonstrated by solving numerous model problems for one and two-dimensional CDE, where the solutions have the sharp gradient at the solution boundary.
Computational Study of Interstitial Hydrogen Atoms in Nano-Diamond Grains Embedded in an Amorphous Carbon Shell
Authors: Silverman Amihai , Hoffman Alon , Adler Joan
Published: October 2010

The properties of hydrogen atoms in a nano-diamond grain surrounded by an amorphous carbon shell are studied with Tight Binding computer simulations. Our samples model nano-diamond grains, of a few nanometers in size, that nucleate within an amorphous carbon matrix, as observed in deposition from a hydrocarbon rich plasma. The calculations show that the average hydrogen interstitial formation energy in the amorphous region is lower than in the nano-diamond core, therefore hydrogen interstitial sites in the in the amorphous region are more stable than in the nano-diamond core. This formation energy difference is the driving force for the diffusion of hydrogen atoms from nano-diamond grains into amorphous carbon regions. An energy well was observed on the amorphous side of the nano-diamond amorphous carbon interface: hydrogen atoms are expected to be trapped here. This scenario agrees with experimental results which show that hydrogen retention of diamond films increases with decreasing grain size, and suggest that hydrogen is bonded and trapped in nano-diamond grain boundaries and on internal grain surfaces.
An integrated modeling study on the effects of mineral dust and sea salt particles on clouds and precipitation
Authors: Solomos S. , Kallos G. , Kushta J. , Astitha M. , Tremback C. , Nenes A. , Levin Z.
Published: October 2010

Abstract. The amount of airborne particles that will nucleate and form cloud droplets under specific atmospheric conditions, depends on their number concentration, size distribution and chemical composition. Aerosol is affected by primary particle emissions, gas-phase precursors, their transformation and interaction with atmospheric constituents, clouds and dynamics. A comprehensive assessment of these interactions requires an integrated approach; most studies however decouple aerosol processes from cloud and atmospheric dynamics and cannot account for all the feedbacks involved in aerosol-cloud-climate interactions. This study addresses aerosol-cloud-climate interactions with the Integrated Community Limited Area Modeling System (ICLAMS) that includes online parameterization of the physical and chemical processes between air quality and meteorology. ICLAMS is an extended version of the Regional Atmospheric Modeling System (RAMS) and it has been designed for coupled air quality – meteorology studies. Model sensitivity tests for a single-cloud study as well as for a case study over the Eastern Mediterranean illustrate the importance of aerosol properties in cloud formation and precipitation. Mineral dust particles are often coated with soluble material such as sea-salt, thus exhibiting increased CCN efficiency. Increasing the percentage of salt-coated dust particles by 15% in the model resulted in more vigorous convection and more intense updrafts. The clouds that were formed extended about 3 km higher and the initiation of precipitation was delayed by one hour. Including on-line parameterization of the aerosol effects improved the model bias for the twenty-four hour accumulated precipitation by 7%. However, the spatial distribution and the amounts of precipitation varied greatly between the different aerosol scenarios. These results indicate the large portion of uncertainty that remains unresolved and the need for more accurate description of aerosol feedbacks in atmospheric models and climate change predictions.