bluuebunny/crossref_metadata_2025 huggingface dataset:
Determination of nickel content in the semimembranosus muscle of pigs produced in Vojvodina
Authors: Tomovic Vladimir , Petrovic Ljiljana , Kevresan Zarko , Dzinic Natalija , Jokanovic Marija
Published: December 2010

The content of nickel was investigated in the M. semimembranosus of
sixty-nine pigs from ten different genetic lines produced in Vojvodina.
Nickel was determined by flame atomic absorption spectrometry after
mineralization by dry ashing. The difference in the nickel content in the
analyzed muscle tissues among different genetic lines of pigs was not
significant (P > 0.05). Nickel levels ranged from 12.93 to 80.18 ?g/100 g,
with a general average of 32.41 ?g/100 g. The average level of nickel was
found to be higher than the levels observed in pork in some developed
countries.
The test of eight tree species resistance to the attack of Armillaria mellea and A. ostoyae by artificial infection
Authors: Keca Nenad
Published: December 2010

In the forest ecosystems in Serbia five Armillaria species are present.
Understanding differences in the pathogenicity of Armillaria species to the
tree species is of a great importance for the foresters. The aim of study was
to test susceptibility of eight forest tree species to attack of Armillaria
mellea and A. ostoyae. The sticks of Hazel previously infected with mycelium
of two Armillaria were placed next to the root collar of two years old
seediling. In the period of eighteen months health status of tested seedlings
was observed. Differences in susceptibility among tested tree species was
observed, while there was no difference in the pathogenicity between
Armillaria mellea and A. ostoyae. The most susceptible species were Serbian
Spruce, Common Fir, Scots and Austrian Pine, following by Spruce and Douglas
Fir, while more resistant were Pedunculate and Sessile oak.
Production potential of the soil and the basic elements of productivity of the most widely spred sessil types in the u. N.P. „Djerdap”
Authors: Knezevic Milan , Milosevic Rajko , Kosanin Olivera
Published: December 2010

This paper is on the results of the soil and its production potential in the
types of forests of sessile oaks (Quercus petraea) in the area of the
National Park ?Djerdap? in the community units of Zlatica, Djerdap, Strbacko
korito, Desna reka and Kozica. There are the most widely spread types of the
sprout forests of the sessile oaks in the research area, deep deluvium,
luvisoil, eutric cambsoils, and a great number of subtypes of acid brown
soil. Considering the fact that the production potential of the defined types
of soil depends on the depth, skeleton and other physical characteristics
which determine acception, keeping and moving of water and this means that
the production value of the studied soils is in the direct correlation with
physical-geographical conditions of the environment. Taking into account that
solum is well developed and the low contents of skeleton, all the studied
soil in the most widely spread types of sessile oaks in the area of N.P.
?Djerdap?, are very productive natural habitats. The exception is acid brown
soil, which characteristics vary as well as their production potential. Apart
from a good production potential of the studied soils within this paper,
sessile forests in the researched areas irrationally use production potential
of the habitat. In the research area in the last 20 years, the processes of
devitalizing and the appearance of decaying of sessile oaks are expressed. In
the sessile forests of Serbia, there are forests of the production and
protection character, and the structure of the sessile forests at global
level is characterized by not normal state with domination of middle aged and
in great extent mature withering ingredients, what is the main cause of
insufficiently used good potential of the soil.
Typological affiliation clima-regional belt of mountain beech on Veliki Jastrebac
Authors: Milosevic Rajko
Published: December 2010

This paper presents the results of typology study and typology classification
of ceno-ecological groups types of the mountain beech forest on the Veliki
Jastrebac. These forests in relation to the typological background are
classified into five units (types). Each of these types are characterized by
a certain specificity which is expressed through ecology, cenology and
production characteristics what makes the basis for a different and
appropriate approach to defining objectives of silvicultural management and
upbringing objectives and planning action.
Regularly varying solutions of perturbed Euler differential equations and related functional differential equations
Authors: Takaŝi Kusano , Maric Vojislav
Published: December 2010

An asymptotic analysis in the framework of Karamata regularly varying
functions is performed for the solutions of second order linear differential
and functional differential equations in the critical case i.e., when
condition (1.5) as given below, holds.
How to improve the quality of the tissue sample obtained by percutaneous liver biopsy
Authors: Sporea Ioan , Popescu Alina , Şirli Roxana
Published: December 2010

The evaluation of liver lesions in patients with chronic hepatopathy is mandatory for assessing prognosis and sometimes for making treatment decisions. The liver biopsy (LB) is still considered the gold standard for the evaluation of chronic hepatopathy, despite the fact that noninvasive methods (serologic markers and transient elastography or real-time elastography) are being used more often. The quality of the hepatic tissue sample obtained at biopsy is important for the correct diagnosis. Usually, a liver specimen is considered to be adequate for pathological examination if it is no less than 20 mm and preferably more than 25 mm and if it includes 8 to 11 portal tracts. To improve the quality of the tissue sample obtained by percutaneous LB, we believe it is optimal for the operator to use the Menghini needle technique with two intrahepatic passages (specimens up to 4 cm in length can be obtained), to use echo guidance or ultrasonographic assistance, to have extensive personal experience (defined as having performed between 50 and 100 biopsies), and to assess the length of the tissue sample immediately after the LB, and, in the event the specimen is inadequate in length, to rapidly perform another passage.
How Effective Are Family Literacy Programs?
Authors: van Steensel Roel , McElvany Nele , Kurvers Jeanne , Herppich Stephanie
Published: December 2010

This meta-analysis examines the effects of family literacy programs on children’s literacy development. It analyzes the results of 30 recent effect studies (1990–2010), covering 47 samples, and distinguishes between effects in two domains: comprehension-related skills and code-related skills. A small but significant mean effect emerged ( d = 0.18). There was only a minor difference between comprehension- and code-related effect measures ( d = 0.22 vs. d = 0.17). Moderator analyses revealed no statistically significant effects of the program, sample, and study characteristics inferred from the reviewed publications. The results highlight the need for further research into how programs are carried out by parents and children, how program activities are incorporated into existing family literacy practices, and how program contents are transferred to parents.
Evaluation of Cognitive Loads Imposed by Traditional Paper-Based and Innovative Computer-Based Instructional Strategies
Authors: Khalil Mohammed K. , Mansour Mahmoud M. , Wilhite Dewey R.
Published: December 2010

Strategies of presenting instructional information affect the type of cognitive load imposed on the learner's working memory. Effective instruction reduces extraneous (ineffective) cognitive load and promotes germane (effective) cognitive load. Eighty first-year students from two veterinary schools completed a two-section questionnaire that evaluated their perspectives on the educational value of a computer-based instructional program. They compared the difference between cognitive loads imposed by paper-based and computer-based instructional strategies used to teach the anatomy of the canine skeleton. Section I included 17 closed-ended items, rated on a five-point Likert scale, that assessed the use of graphics, content, and the learning process. Section II included a nine-point mental effort rating scale to measure the level of difficulty of instruction; students were asked to indicate the amount of mental effort invested in the learning task using both paper-based and computer-based presentation formats. The closed-ended data were expressed as means and standard deviations. A paired t test with an alpha level of 0.05 was used to determine the overall mean difference between the two presentation formats. Students positively evaluated their experience with the computer-based instructional program with a mean score of 4.69 (SD=0.53) for use of graphics, 4.70 (SD=0.56) for instructional content, and 4.45 (SD=0.67) for the learning process. The mean difference of mental effort (1.50) between the two presentation formats was significant, t=8.26, p≤.0001, df=76, for two-tailed distribution. Consistent with cognitive load theory, innovative computer-based instructional strategies decrease extraneous cognitive load compared with traditional paper-based instructional strategies.
The Complex Role of Veterinary Clinical Teachers: How Is Their Role Perceived and What Is Expected of Them?
Authors: Bolt David M. , Witte Thomas H. , Lygo-Baker Simon
Published: December 2010

The purpose of this study was to identify personal attributes in veterinary clinical teachers that are valued most by members of their work environment (fellow faculty, clinical training scholars [CTS; residents], undergraduate students, and referring veterinary surgeons) and to determine whether the opinions of these subgroups differed. Faculty (n=50), CTS (n=35), students (n=200), and referring veterinary surgeons (n=25) were presented with a list of 15 potentially desirable attributes. Respondents were asked to rank the three most important and the three least important attributes of effective clinical teachers. Respondents were also asked to select in which of the three main activities (clinical service, teaching, or research) in which clinical teachers currently invest the most and the least effort and in which they should invest the most and the least effort. All respondent groups agreed that “competence–knowledge” was among the most desirable attributes. Faculty, undergraduate students, and referring veterinary surgeons additionally included “enthusiasm” in the top three, whereas CTS regarded “respects independence” as more important. All respondent groups consistently chose “scholarly activity” as one of the three least important characteristics. A similar number of faculty members (38%) expressed that the greatest effort should be invested in clinical service or teaching, and the greatest proportions of CTS (44%) and students (56%) felt that most emphasis should be put on teaching alone. The differences in opinion between respondent groups regarding importance of attributes and emphasis of activity indicate that what is perceived as effective performance of clinical teachers differs depending on the role of those who engage with them.
Six-Minute Walk Test for Persons with Mild or Moderate Disability from Multiple Sclerosis: Performance and Explanatory Factors
Authors: Wetzel Jane L. , Fry Donna K. , Pfalzer Lucinda A.
Published: December 2010

Purpose: The primary purpose of this study was to determine the extent to which health factors, functional measures, and pulmonary impairment explain performance on 6-Minute Walk Test (6MWT) distance in ambulatory persons with multiple sclerosis (MS). Another purpose was to determine the effect of disability and age on 6MWT performance and explanatory factors.

Methods: A cross-sectional study design was used to evaluate factors that explain performance on the 6MWT in 64 community-dwelling persons with MS-related disability (Expanded Disability Status Scale [EDSS] 3.8±1.6). Of the 64 participants, 43 (67.2%) exhibited mild disability (EDSS <4.0) and 21 (32.8%) had moderate disability (EDSS 4.0–6.5). A regression analysis compared 6MWT performance to measures of health factors (EDSS, number of medications, number of comorbidities, resting HR, systolic and diastolic blood pressure [BP]); physical performance (functional stair test [FST], sit-to-stand test [SST], static standing balance [BAL], Fatigue Severity Scale [FSS], Activities-specific Balance Confidence [ABC] Scale); and pulmonary function (forced expiratory volume in 1 second [FEV1], forced vital capacity [FVC], maximal voluntary ventilation [MVV], maximal inspiratory pressure [MIP], maximal expiratory pressure [MEP]).

Results: EDSS, ABC, FST, SST, BAL, MVV, MIP, and MEP were significantly associated with 6MWT distance after adjusting for age. Multiple step-wise linear regression analysis revealed that ABC, FST, and BAL were significant and independent explanatory factors of 6MWT distance. ABC and FST explained 75% of the variance in 6MWT performance (R2=0.75). Curvilinear regression analysis revealed that the FST is the most significant explanatory factor for 6MWT distance, explaining 79% of the variance (R2=0.79).

Conclusions: 6MWT performance in persons with MS was explained by balance confidence (ABC) and stair-climbing ability (FST). The ABC and FST may be practical clinical measures for explaining walking ability and determining risk for disablement in persons with MS.
Bioactive Dehydrotyrosyl and Dehydrodopyl Compounds of Marine Origin
Authors: Sugumaran Manickam , Robinson William E.
Published: December 2010

The amino acid, tyrosine, and its hydroxylated product, 3,4-dihydroxyphenylalanine (dopa), plays an important role in the biogenesis of a number of potentially important bioactive molecules in marine organisms. Interestingly, several of these tyrosyl and dopa‑containing compounds possess dehydro groups in their side chains. Examples span the range from simple dehydrotyrosine and dehydrodopamines to complex metabolic products, including peptides and polycyclic alkaloids. Based on structural information, these compounds can be subdivided into five categories: (a) Simple dehydrotyrosine and dehydrotyramine containing molecules; (b) simple dehydrodopa derivatives; (c) peptidyl dehydrotyrosine and dehydrodopa derivatives; (d) multiple dehydrodopa containing compounds; and (e) polycyclic condensed dehydrodopa derivatives. These molecules possess a wide range of biological activities that include (but are not limited to) antitumor activity, antibiotic activity, cytotoxicity, antioxidant activity, multidrug resistance reversal, cell division inhibition, immunomodulatory activity, HIV-integrase inhibition, anti-viral, and anti-feeding (or feeding deterrent) activity. This review summarizes the structure, distribution, possible biosynthetic origin, and biological activity, of the five categories of dehydrotyrosine and dehydrodopa containing compounds.
Peut-on filmer le devenir, comment et jusqu’où ?
Authors: Friedmann Daniel
Published: December 2010

L’auteur analyse la série documentaire Que deviendront-ils?, la plus longue tentative de filmer le changement au long cours produite par la télévision française, où le réalisateur s’efforce de restituer, à raison d’un film par an, sur plus de douze ans, le devenir scolaire, social et affectif d’élèves du lycée Paul-Valéry, depuis leur entrée en sixième jusqu’à l’âge de 25 ans.
Le jeu avec le « je »
Authors: Mehl Dominique
Published: December 2010

L’article propose tout d’abord une typologie de la télévision de l’intimité: d’un côté, la mise en scène de l’exposition de soi à travers des témoignages sur la vie privée; de l’autre, le spectacle de l’épreuve de soi par le truchement d’expérimentations vécues. Il invite ensuite à identifier le socle commun qui sous-tend ces émissions: la promotion de personnes ordinaires et la construction des intrigues autour de la monstration du relationnel. Il étudie les modifications de l’espace public modelé par ces expériences et expérimentations. Il interroge enfin les modèles culturels véhiculés par ces programmes: du «libéralisme culturel», qui invite à la tolérance vis-à-vis de modes de vie différents, au «relativisme culturel», qui plaide pour l’équivalence des références normatives.
L’activité du point de vue de l’acteur et la question de l'intersubjectivité
Authors: Lahlou Saadi
Published: December 2010

La «subcam», caméra miniature fixée à hauteur des yeux, enregistre l’activité en vue subjective. Portée par des volontaires, elle permet d’analyser en détail sur le terrain des phénomènes comme la captation de l’attention, le lien entre déterminants internes et externes du comportement, l’intersubjectivité. On présente ici avec des illustrations empiriques les aspects techniques, méthodologiques, éthiques et théoriques, notamment les stratégies d’analyse, et la question de l’intersubjectivité et du «pacte psychosocial».
Le travail entre corps et technique
Authors: Bidet Alexandra
Published: December 2010

L’association entre travail, corps et technicité est le plus souvent faite au prix d’une conception réductrice du travail comme labor ou comme oeuvre. En nous appuyant sur des traditions qui partagent une perspective anthropologique, nous montrons l’intérêt d’appréhender autrement le lien entre travail, corps et technique. Saisir le travail comme une activité technicienne permet en effet d’explorer ce qui s’y fabrique: l’émergence d’objets, de sujets, d’élaborations normatives, d’attachements sensibles, de savoirs professionnels.
Dix thèses sur les sciences, la recherche scientifique et le monde social, 1945-2010
Authors: Pestre Dominique
Published: December 2010

Résumé La science moderne n’est pas seulement une accumulation de savoirs, elle est un outil pour refaire le monde. L’article analyse les relations de cette science moderne aux techniques, à l’économique et au politique. Il offre une périodisation pour le cas de la France.
Une histoire en chiffres de l'enseignement supérieur en France
Authors: Prost Antoine , Cytermann Jean-Richard
Published: December 2010

Résumé Cet article offre une sélection de données statistiques pertinentes sur l’histoire de l’enseignement supérieur en France. Les domaines couverts sont les suivants : les étudiants, les diplômes, les enseignants et les BIATOSS, les dépenses et quelques comparaisons internationales.
Les transformations de la carte universitaire depuis les années 1960 : constats et enjeux
Authors: Baron Myriam
Published: December 2010

Résumé Évoquer les transformations de la carte universitaire en France au cours des 50 dernières années conduit à s’interroger sur le niveau géographique privilégié mais aussi sur la production et l’utilisation de tels documents. Ces quelques jalons posés, la carte universitaire du début des années 2000 est brossée à grands traits : d’une part, en se référant aux villes et à leur hiérarchie, très présente dans la structuration du « fait universitaire » ; d’autre part, en accordant une place significative à la dimension régionale, qui révèle de remarquables évolutions au cours des 25 dernières années. Ces caractéristiques ne peuvent être uniquement les conséquences du dernier plan « U 2 000 ». Les exemples de la Bretagne et de l’Ile-de-France montrent que les décisions ont été prises dès le début des années 1960. Ce qui conduit à s’interroger sur les relations entre productions cartographiques et aménagements du territoire.
Quand l'université s'ancre au territoire. Collaborations académiques et territoriales à Lyon (1958-2009)
Authors: Aust Jérôme
Published: December 2010

Résumé L’article analyse le développement des relations entre universités et territoires dans l’agglomération lyonnaise. En adoptant une perspective historique (1958-2009), il montre que l’intensification des relations entre universités et territoires prend sens au carrefour de logiques internationales, nationales et locales. Le renouvellement des exécutifs locaux et académiques, l’internationalisation de la concurrence universitaire et urbaine, les recompositions de la gestion publique territoriale et des politiques universitaires incitent universitaires et élus locaux à renforcer leur coopération. L’article montre ensuite que les coopérations académiques et territoriales sont aussi marquées par des évolutions progressives dans leur contenu. En s’institutionnalisant au fil du temps, ces collaborations se redéfinissent partiellement pour donner de nouveaux visages aux liens entre universités et territoires.
Une discipline « utile » dans l'enseignement supérieur : promotion et appropriations de la gestion (1965-1975)
Authors: Pavis Fabienne
Published: December 2010

Résumé Centré sur l’enseignement supérieur de gestion en France, cet article vise à rendre compte des conditions et des effets, notamment pour les étudiants, de l’académisation d’une discipline « utile ». Il restitue tout d’abord l’argumentaire utilisé pour promouvoir et rénover l’enseignement supérieur de gestion à partir du milieu des années 1960 : cet enseignement doit favoriser la modernisation économique du pays. Puis il se focalise sur la mise en œuvre de cette politique en insistant sur ses appropriations différenciées en fonction de la position dans l’espace, très hiérarchisé, des institutions de formation et en fonction des ressources des agents qui s’y investissent comme enseignants jeunes diplômés et comme étudiants. Une offre de nouvelles positions académiques apparaît au sein des écoles de commerce et à l’université. Si les nouveaux spécialistes sont devenus incontournables dans les institutions de formation à la gestion, leur position professionnelle demeure ambiguë : leurs tutelles leur reprochent ou de trop se prendre au jeu académique ou de trop se prendre au jeu entrepreneurial. Les étudiants quant à eux ont pu profiter du renouvellement pédagogique et de la revalorisation des études commerciales, mais un constat d’inertie s’impose : une ségrégation sociale forte des étudiants demeure dans cet enseignement de gestion massifié.
Les revues de sciences humaines et sociales face à l'évaluation
Authors: Galvez-Behar Gabriel
Published: December 2010

Résumé L’article souligne l’importance accrue des revues dans la vie universitaire et culturelle. Étudiant l’application des nouvelles procédures d’évaluation auxquelles elles sont soumises, l’article analyse l’ethos de l’évaluateur, les processus par lesquels évaluer, c’est choisir, et enfin les limites de l’évaluation.
Les amitiés virtuelles dans la vie réelle
Authors: Lethiais Virginie , Roudaut Karine
Published: December 2010

Résumé Les réflexions proposées dans cet article sont issues d’une recherche interdisciplinaire en sciences sociales, s’appuyant sur une enquête de terrain qui mobilise des méthodologies quantitatives et qualitatives. L’objectif est double : d’une part, faire le lien entre les caractéristiques sociales des individus et leur utilisation d’Internet comme « média relationnel », c’est-à-dire dans le but de faire de nouvelles connaissances ; d’autre part, cerner les différentes modalités de construction des sociabilités amicales via Internet du point de vue des acteurs sociaux, en comprendre les motivations, et faire le lien avec les amitiés « réelles ». Cette double approche nous permet de caractériser les profils sociaux des individus qui se tournent vers ce nouveau mode de sociabilité. Internet apparaît comme un moyen additionnel de rencontrer de nouvelles personnes et donc de renforcer une vie sociale le plus souvent déjà riche dans le monde réel.
Bcl6 Is Required for the Development of Mouse CD4+ and CD8α+ Dendritic Cells
Authors: Ohtsuka Hiromi , Sakamoto Akemi , Pan Jing , Inage Sumina , Horigome Satoshi , Ichii Hirohito , Arima Masafumi , Hatano Masahiko , Okada Seiji , Tokuhisa Takeshi
Published: December 2010

Th2-type inflammation spontaneously shown in Bcl6-knockout (KO) mice is mainly caused by bone marrow (BM)-derived nonlymphoid cells. However, the function of dendritic cells (DCs) in Bcl6-KO mice has not been reported. We show in this article that the numbers of CD4+ conventional DCs (cDCs) and CD8α+ cDCs, but not of plasmacytoid DCs, were markedly reduced in the spleen of Bcl6-KO mice. Generation of cDCs from DC progenitors in BM cells was perturbed in the spleen of irradiated wild-type (WT) mice transferred with Bcl6-KO BM cells, indicating an intrinsic effect of Bcl6 in cDC precursors. Although cDC precursors were developed in a Bcl6-KO BM culture with Fms-like tyrosine kinase 3 ligand, the cDC precursors were more apoptotic than WT ones. Also p53, one of the molecular targets of Bcl6, was overexpressed in the precursors. The addition of a p53 inhibitor to Bcl6-KO BM culture protected apoptosis, suggesting that Bcl6 is required by cDC precursors for survival by controlling p53 expression. Furthermore, large numbers of T1/ST2+ Th2 cells were naturally developed in the spleen of Bcl6-KO mice. Th2 skewing was accelerated in the culture of WT CD4 T cells stimulated with Ags and LPS-activated Bcl6-KO BM-derived DCs, which produced more IL-6 and less IL-12 than did WT DCs; the addition of anti–IL-6 Abs to the culture partially abrogated the Th2 skewing. These results suggest that Bcl6 is required in cDC precursors for survival and in activated DCs for modulating the cytokine profile.
EC144, a Synthetic Inhibitor of Heat Shock Protein 90, Blocks Innate and Adaptive Immune Responses in Models of Inflammation and Autoimmunity
Authors: Yun Theodore J. , Harning Erin K. , Giza Keith , Rabah Dania , Li Ping , Arndt Joseph W. , Luchetti David , Biamonte Marco A. , Shi Jiandong , Lundgren Karen , Manning Anthony , Kehry Marilyn R.
Published: December 2010

Heat shock protein 90 (Hsp90) is a molecular chaperone involved in folding and stabilizing multiple intracellular proteins that have roles in cell activation and proliferation. Many Hsp90 client proteins in tumor cells are mutated or overexpressed oncogenic proteins driving cancer cell growth, leading to the acceptance of Hsp90 as a potential therapeutic target for cancer. Because several signal transduction molecules that are dependent on Hsp90 function are also involved in activation of innate and adaptive cells of the immune system, we investigated the mechanism by which inhibiting Hsp90 leads to therapeutic efficacy in rodent models of inflammation and autoimmunity. EC144, a synthetic Hsp90 inhibitor, blocked LPS-induced TLR4 signaling in RAW 264.7 cells by inhibiting activation of ERK1/2, MEK1/2, JNK, and p38 MAPK but not NF-κB. Ex vivo LPS-stimulated CD11b+ peritoneal exudate cells from EC144-treated mice were blocked from phosphorylating tumor progression locus 2, MEK1/2, and ERK1/2. Consequently, EC144-treated mice were resistant to LPS administration and had suppressed systemic TNF-α release. Inhibiting Hsp90 also blocked in vitro CD4+ T cell proliferation in mouse and human MLRs. In vivo, semitherapeutic administration of EC144 blocked disease development in rat collagen-induced arthritis by suppressing the inflammatory response. In a mouse collagen-induced arthritis model, EC144 also suppressed disease development, which correlated with a suppressed Ag-specific Ab response and a block in activation of Ag-specific CD4+ T cells. Our results describe mechanisms by which blocking Hsp90 function may be applicable to treatment of autoimmune diseases involving inflammation and activation of the adaptive immune response.
The Vitamin D Analog, TX527, Promotes a Human CD4+CD25highCD127low Regulatory T Cell Profile and Induces a Migratory Signature Specific for Homing to Sites of Inflammation
Authors: Baeke Femke , Korf Hannelie , Overbergh Lut , Verstuyf Annemieke , Thorrez Lieven , Van Lommel Leentje , Waer Mark , Schuit Frans , Gysemans Conny , Mathieu Chantal
Published: December 2010

The use of hypocalcemic vitamin D analogs is an appealing strategy to exploit the immunomodulatory actions of active vitamin D in vivo while circumventing its calcemic side effects. The functional modulation of dendritic cells by these molecules is regarded as the key mechanism underlying their ability to regulate T cell reactivity. In this article, we demonstrate the capacity of the vitamin D analog, TX527, to target T cells directly. Microarray analysis of purified human CD3+ T cells, cultured in the presence of TX527, revealed differential expression of genes involved in T cell activation, proliferation, differentiation, and migratory capacity. Accordingly, functional analysis showed a TX527-mediated suppression of the T cell proliferative capacity and activation status, accompanied by decreased expression of effector cytokines (IFN-γ, IL-4, and IL-17). Furthermore, TX527 triggered the emergence of CD4+CD25highCD127low regulatory T cells featuring elevated levels of IL-10, CTLA-4, and OX40 and the functional capacity to suppress activation and proliferation of effector T cells. Moreover, the vitamin D analog profoundly altered the homing receptor profile of T cells and their migration toward chemokine ligands. Remarkably, TX527 not only modulated skin-homing receptors as illustrated for the parent compound, but also reduced the expression of lymphoid organ-homing receptors (CD62L, CCR7, and CXCR4) and uniquely promoted surface expression of inflammatory homing receptors (CCR5, CXCR3, and CXCR6) on T cells. We conclude that TX527 directly affects human T cell function, thereby inhibiting effector T cell reactivity while inducing regulatory T cell characteristics, and imprints them with a specific homing signature favoring migration to sites of inflammation.
Targeting the CXCR4–CXCL12 Axis Mobilizes Autologous Hematopoietic Stem Cells and Prolongs Islet Allograft Survival via Programmed Death Ligand 1
Authors: Fiorina Paolo , Jurewicz Mollie , Vergani Andrea , Petrelli Alessandra , Carvello Michele , D’Addio Francesca , Godwin Jonathan G. , Law Kenneth , Wu Erxi , Tian Ze , Thoma Gebhard , Kovarik Jiri , La Rosa Stefano , Capella Carlo , Rodig Scott , Zerwes Hans-Guenter , Sayegh Mohamed H. , Abdi Reza
Published: December 2010

Antagonism of CXCR4 disrupts the interaction between the CXCR4 receptor on hematopoietic stem cells (HSCs) and the CXCL12 expressed by stromal cells in the bone marrow, which subsequently results in the shedding of HSCs to the periphery. Because of their profound immunomodulatory effects, HSCs have emerged as a promising therapeutic strategy for autoimmune disorders. We sought to investigate the immunomodulatory role of mobilized autologous HSCs, via target of the CXCR4-CXL12 axis, to promote engraftment of islet cell transplantation. Islets from BALB/c mice were transplanted beneath the kidney capsule of hyperglycemic C57BL/6 mice, and treatment of recipients with CXCR4 antagonist resulted in mobilization of HSCs and in prolongation of islet graft survival. Addition of rapamycin to anti-CXCR4 therapy further promoted HSC mobilization and islet allograft survival, inducing a robust and transferable host hyporesponsiveness, while administration of an ACK2 (anti-CD117) mAb halted CXCR4 antagonist-mediated HSC release and restored allograft rejection. Mobilized HSCs were shown to express high levels of the negative costimulatory molecule programmed death ligand 1 (PD-L1), and HSCs extracted from wild-type mice, but not from PD-L1 knockout mice, suppressed the in vitro alloimmune response. Moreover, HSC mobilization in PD-L1 knockout mice failed to prolong islet allograft survival. Targeting the CXCR4–CXCL12 axis thus mobilizes autologous HSCs and promotes long-term survival of islet allografts via a PD-L1–mediated mechanism.
Molecular and Functional Characterization of Cynomolgus Monkey IgG Subclasses
Authors: Jacobsen Frederick W. , Padaki Rupa , Morris Arvia E. , Aldrich Teri L. , Armitage Richard J. , Allen Martin J. , Lavallee Jennifer C. , Arora Taruna
Published: December 2010

Studies for vaccine and human therapeutic Ab development in cynomolgus monkeys (cynos) are influenced by immune responses, with Ab responses playing a significant role in efficacy and immunogenicity. Understanding the nature of cyno humoral immune responses and characterizing the predominant cyno IgG types produced and the Fc–FcγR interactions could provide insight into the immunomodulatory effects of vaccines. Anti-drug Ab responses against human IgG therapeutic candidates in cynos may affect efficacy and safety assessments because of the formation of immune complexes. There is, however, limited information on the structure and function of cyno IgG subclasses and how they compare with human IgG subclasses in Fc-dependent effector functions. To analyze the functional nature of cyno IgG subclasses, we cloned four cyno IgG C regions by using their sequence similarity to other primate IgGs. The four clones, cyno (cy)IGG1, cyIGG2, cyIGG3, cyIGG4, were then used to construct chimeric Abs. The sequence features of cyno IgG subclasses were compared with those of rhesus monkey and human IgG. Our data show that rhesus monkey and cyno IgG C regions are generally highly conserved, with differences in the hinge and hinge-proximal CH2 regions. Fc-dependent effector functions of cyno IgG subclasses were assessed in vitro with a variety of binding and functional assays. Our findings demonstrate distinctive functional properties of cyno IgG subclasses. It is notable that human IgG1 was less potent than cyno IgG1 in cyno FcγR binding and effector functions, with the differences emphasizing the need to carefully interpret preclinical data obtained with human IgG1 therapeutics.
Epitope Hierarchy of Spontaneous CD4+ T Cell Responses to LAGE-1
Authors: Kudela Pavol , Sun Zhaojun , Fourcade Julien , Janjic Bratislav , Kirkwood John M. , Maillere Bernard , Zarour Hassane M.
Published: December 2010

NY-ESO-1 and LAGE-1 represent highly homologous cancer-germline Ags frequently coexpressed by many human cancers, but not by normal tissues, except testis. In contrast to NY-ESO-1, little is known about spontaneous immune responses to LAGE-1. In the current study, we report on spontaneous LAGE-1–specific CD4+ T cells isolated from PBLs of patients with advanced LAGE-1+/NY-ESO-1+ melanoma and directed against three promiscuous and immunodominant epitopes. Strikingly, although the three LAGE-1–derived epitopes are highly homologous to NY-ESO-1–derived epitopes, LAGE-1–specific CD4+ T cells did not cross-react with NY-ESO-1. LAGE-1–specific CD4+ T cells produced Th1-type and/or Th2-type cytokines and did not exert inhibitory effects on allogenic T cells. We observed that most patients with spontaneous NY-ESO-1–specific responses exhibited spontaneous CD4+ T cell responses to at least one of the three immunodominant LAGE-1 epitopes. Additionally, nearly half of the patients with spontaneous LAGE-1–specific CD4+ T cell responses had circulating LAGE-1–specific Abs that recognized epitopes located in the C-terminal portion of LAGE-1, which is distinct from NY-ESO-1. Collectively, our findings define the hierarchy of immunodominance of spontaneous LAGE-1–specific CD4+ T cell responses in patients with advanced melanoma. These findings demonstrate the capability of LAGE-1 to stimulate integrated cellular and humoral immune responses that do not cross-react with NY-ESO-1. Therefore, they provide a strong rationale for the inclusion of LAGE-1 peptides or protein in vaccine trials for patients with NY-ESO-1+/LAGE-1+ tumors.
The Role of Germline Promoters and I Exons in Cytokine-Induced Gene-Specific Class Switch Recombination
Authors: Dunnick Wesley A. , Shi Jian , Holden Victoria , Fontaine Clinton , Collins John T.
Published: December 2010

Germline transcription precedes class switch recombination (CSR). The promoter regions and I exons of these germline transcripts include binding sites for activation- and cytokine-induced transcription factors, and the promoter regions/I exons are essential for CSR. Therefore, it is a strong hypothesis that the promoter/I exons regions are responsible for much of cytokine-regulated, gene-specific CSR. We tested this hypothesis by swapping the germline promoter and I exons for the murine γ1 and γ2a H chain genes in a transgene of the entire H chain C-region locus. We found that the promoter/I exon for γ1 germline transcripts can direct robust IL-4–induced recombination to the γ2a gene. In contrast, the promoter/I exon for the γ2a germline transcripts works poorly in the context of the γ1 H chain gene, resulting in expression of γ1 H chains that is <1% the wild-type level. Nevertheless, the small amount of recombination to the chimeric γ1 gene is induced by IFN-γ. These results suggest that cytokine regulation of CSR, but not the magnitude of CSR, is regulated by the promoter/I exons.
MRI findings in Hirayama disease
Authors: Raval Monali , Kumari Rima , Dung Dung Aldrin Anthony , Guglani Bhuvnesh , Gupta Nitij , Gupta Rohit
Published: December 2010

The objective of the study was to study the magnetic resonance imaging (MRI) features of Hirayama disease on a 3 Tesla MRI scanner. Nine patients with clinically suspected Hirayama disease were evaluated with neutral position, flexion, contrast-enhanced MRI and fast imaging employing steady-state acquisition (FIESTA) sequences. The spectrum of MRI features was evaluated and correlated with the clinical and electromyography findings. MRI findings of localized lower cervical cord atrophy (C5-C7), abnormal curvature, asymmetric cord flattening, loss of attachment of the dorsal dural sac and subjacent laminae in the neutral position, anterior displacement of the dorsal dura on flexion and a prominent epidural space were revealed in all patients on conventional MRI as well as with the dynamic 3D-FIESTA sequence. Intramedullary hyperintensity was seen in four patients on conventional MRI and on the 3D-FIESTA sequence. Flow voids were seen in four patients on conventional MRI sequences and in all patients with the 3D-FIESTA sequence. Contrast enhancement of the epidural component was noted in all the five patients with thoracic extensions. The time taken for conventional and contrast-enhanced MRI was about 30-40 min, while that for the 3D-FIESTA sequence was 6 min. Neutral and flexion position MRI and the 3D-FIESTA sequence compliment each other in displaying the spectrum of findings in Hirayama disease. A flexion study should form an essential part of the screening protocol in patients with suspected Hirayama disease. Newer sequences such as the 3D-FIESTA may help in reducing imaging time and obviating the need for contrast.
Transient splenial lesion: Further experience with two cases
Authors: Singh Paramjeet , Gogoi Dhrubajyoti , Vyas Sameer , Khandelwal Niranjan
Published: December 2010

Transient splenial lesions (TSL) of the corpus callosum are uncommon radiologic findings that are seen in a number of clinical conditions with varied etiologies. They were first described a decade earlier in patients with epilepsy and hence were thought to be seizure or seizure therapy related. Subsequently, more cases were described by different observers in diseases with different etiologies, and the list is still increasing. Awareness of these lesions is necessary as they are an uncommon finding and have to be differentiated from other infective/noninfective causes. MRI is the imaging modality of choice as these lesions are not seen on routine noncontrast CT scan. The authors here describe two cases which showed TSL, with complete/partial resolution on follow-up scans. The authors also present a review of the literature.
Ultrasound-guided omental biopsy: Review of 173 patients
Authors: Govindarajan Padmapriya , Keshava Shyamkumar N
Published: December 2010

Background: Omental biopsy has conventionally been performed using a surgical approach. USG-guided omental biopsy is a safe and effective alternative. The purpose of this study was to assess the utility of USG guidance for biopsy of the greater omentum. Study design: Retrospective study. Materials and Methods: We retrospectively reviewed all omental biopsies performed under USG guidance from April 2006 to March 2010 in a tertiary care hospital. Results: One hundred and seventy-three patients were included. Out of these, 82 (47%) patients were diagnosed to have malignancies, 58 (34%) patients had granulomatous inflammation either suggestive of or consistent with tuberculosis, 29 (17%) patients were diagnosed to have inconclusive biopsy results, and 4 (2%) patients had an inadequate sample for histopathological examination. There were no major procedure-related complications. Conclusion: USG-guided biopsy of the omentum is a safe and effective procedure. A thickened omentum can serve as an easily accessible site for biopsy, especially in patients who have ascites of unknown etiology and in those with a history of previous malignancy.
Migrating biliary stent with final destination at the ileocecal junction causing intestinal obstruction and obstructive biliopathy
Authors: Rasalkar Darshana D , Paunipagar Bhawan K , Sonavane Bhawna
Published: December 2010

Endoscopic plastic biliary stent insertion is a minimally invasive, well-established procedure for the management of benign biliary pathology. We report a case of a migrating stent for over two days, which finally got impacted at the ileocecal junction, leading to intestinal obstruction and obstructive biliopathy. Radiological findings depicted the exact site of the dislodged biliary stent and its related complications, both of which were successfully treated in a nonoperative stepwise manner.
Technical note: Dynamic MRI in a complicated giant posterior urethral diverticulum
Authors: Kundum Prasad R , Gupta Arun K , Thottom Prasad V , Jana Manisha
Published: December 2010

Congenital posterior urethral diverticulum is an uncommon anomaly, sometimes complicated by infection or calculi formation. A conventional voiding cystourethrogram (VCUG) is the most commonly used diagnostic modality. Dynamic magnetic resonance imaging (MRI) has not been frequently described in this entity. We describe a case of posterior urethral diverticulum complicated with secondary calculi, where the patient was evaluated using dynamic MRI and conventional VCUG.
Congenital nasal pyriform aperture stenosis: A rare cause of nasal airway obstruction in a neonate
Authors: Thomas Elsa M , Gibikote Sridhar , Panwar Jyoti S , Mathew John
Published: December 2010

Congenital nasal pyriform aperture stenosis (CNPAS) is a rare cause of nasal airway obstruction that clinically mimics choanal atresia, but needs to be differentiated from the latter because of the widely divergent modes of management. We present a case of CNPAS, to highlight the importance of recognizing the classic signs of CNPAS on cross-sectional imaging.
Torsion of the greater omentum: A rare preoperative diagnosis
Authors: Tandon Ankit Anil , Lim Kian Soon
Published: December 2010

Torsion of the greater omentum is a rare acute abdominal condition that is seldom diagnosed preoperatively. We report the characteristic computed tomography (CT) scan findings and the clinical implications of this unusual diagnosis in a 41-year-old man, who also had longstanding right inguinal hernia. Awareness of omental torsion as a differential diagnosis in the acute abdomen setting is necessary for correct patient management.
Pictorial essay: Ultrasonography in ′tennis leg′
Authors: Shah Jeshil R , Shah Bipin R , Shah Ankit S
Published: December 2010

Tennis leg is caused by a rupture of the medial head of the gastrocnemius muscle, usually at its distal musculotendinous junction region. However, tears in this muscle and its tendon are also included under the term ′tennis leg′. It is seen regularly in practice and is an important cause of a painful calf. The common USG findings include: disruption of the pinnate pattern of the distal medial gastrocnemius, usually near the junction of the triceps surae (which is the echogenic line between the gastrocnemius, the soleus, and the plantaris muscles), fluid tracking along the fascia, adjacent hematoma, and intramuscular tears as well as hematomas. USG is useful for confirming the diagnosis, excluding other causes of a painful calf, for assessing the severity of the disease, and in follow-up.
Malignant brachial plexopathy: A pictorial essay of MRI findings
Authors: Iyer Veena R , Sanghvi Darshana A , Merchant Nikhil
Published: December 2010

For imaging, the brachial plexus is a technically and anatomically challenging region of the peripheral nervous system. MRI has a central role in the identification and accurate characterization of malignant lesions arising here, as also in defining their extent and the status of the adjacent structures. The purpose of this pictorial essay is to describe the MRI features of primary and secondary malignant brachial plexopathies and radiation-induced brachial nerve damage.
Thyroiditis mimicking relapse of acute lymphoblastic leukemia: Gallium-67 scan suggested the diagnosis
Authors: Othman Saleh
Published: December 2010

Acute lymphoblastic leukemia (ALL) is the most common form of leukemia in childhood and accounts for 85% of cases. ALL frequently presents as an infectious process with an abrupt onset of high fever. Thyroid disease has been reported to have a strong association with acute leukemia. Gallium (Ga-67) citrate has been used in the investigation of patients labeled as having pyrexia of unknown origin. We report a case of a 13-year-old female patient who presented with fever and suspected disease relapse after a period of disease remission; however, gallium-67 citrate whole body scan suggested the diagnosis of thyroiditis.
Impact of aftertreatment devices on primary emissions and secondary organic aerosol formation potential from in-use diesel vehicles: results from smog chamber experiments
Authors: Chirico R. , DeCarlo P. F. , Heringa M. F. , Tritscher T. , Richter R. , Prévôt A. S. H. , Dommen J. , Weingartner E. , Wehrle G. , Gysel M. , Laborde M. , Baltensperger U.
Published: December 2010

Abstract. Diesel particulate matter (DPM) is a significant source of aerosol in urban areas and has been linked to adverse health effects. Although newer European directives have introduced increasingly stringent standards for primary PM emissions, gaseous organics emitted from diesel cars can still lead to large amounts of secondary organic aerosol (SOA) in the atmosphere. Here we present results from smog chamber investigations characterizing the primary organic aerosol (POA) and the corresponding SOA formation at atmospherically relevant concentrations for three in-use diesel vehicles with different exhaust aftertreatment systems. One vehicle lacked exhaust aftertreatment devices, one vehicle was equipped with a diesel oxidation catalyst (DOC) and the third vehicle used both a DOC and diesel particulate filter (DPF). The experiments presented here were obtained from the vehicles at conditions representative of idle mode, and for one car in addition at a speed of 60 km/h. An Aerodyne high-resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS) was used to measure the organic aerosol (OA) concentration and to obtain information on the chemical composition. For the conditions explored in this paper, primary aerosols from vehicles without a particulate filter consisted mainly of black carbon (BC) with a low fraction of organic matter (OM, OM/BC < 0.5), while the subsequent aging by photooxidation resulted in a consistent production of SOA only for the vehicles without a DOC and with a deactivated DOC. After 5 h of aging ~80% of the total organic aerosol was on average secondary and the estimated "emission factor" for SOA was 0.23–0.56 g/kg fuel burned. In presence of both a DOC and a DPF, only 0.01 g SOA per kg fuel burned was produced within 5 h after lights on. The mass spectra indicate that POA was mostly a non-oxidized OA with an oxygen to carbon atomic ratio (O/C) ranging from 0.10 to 0.19. Five hours of oxidation led to a more oxidized OA with an O/C range of 0.21 to 0.37.