bluuebunny/crossref_metadata_2025 huggingface dataset:
Geographic Concentration and Development Potential of Poultry Microenterprises and Value Chain: A Study Based on Suitable Sites in Gazipur, Bangladesh
Authors: Khaleda Syeda , Murayama Yuji
Published: August 2013

In Bangladesh, many poultry microenterprises (MEs) have flourished through the lending of microcredit to the poor. These MEs are linked to the value chain and play a significant role in poverty reduction. Not all of these MEs are located in favorable places. Almost all are developed utilizing homestead lands, which results in poor input supply and marketing facilities, and causes higher costs and less profit. This paper tries to uncover the constraints in value chain development, mainly those related to its physical and infrastructural environment; verify the potential of MEs through an analysis of their geographic concentration in sites with different suitability levels; and make recommendations as to how to overcome the constraints, with a view to ensuring higher profit levels for vulnerable poor. The suitability of sites was delineated through Geographic Information System (GIS). The analysis—a combination of field survey data with a site suitability map of farms/MEs concentration—is important, because it helps to validate the GIS analysis-based results of sites’ suitability, helps supporters to design interventions in areas where the farms exist, and thus, helps farmers in vulnerable sites to lift themselves out of poverty.
A Label Free Colorimetric Assay for the Detection of Active Botulinum Neurotoxin Type A by SNAP-25 Conjugated Colloidal Gold
Authors: Halliwell Jennifer , Gwenin Christopher
Published: August 2013

Botulinum neurotoxins are one of the most potent toxins known to man. Current methods of detection involve the quantification of the toxin but do not take into account the percentage of the toxin that is active. At present the assay used for monitoring the activity of the toxin is the mouse bioassay, which is lengthy and has ethical issues due to the use of live animals. This report demonstrates a novel assay that utilises the endopeptidase activity of the toxin to detect Botulinum neurotoxin in a pharmaceutical sample. The cleaving of SNAP-25 is monitored via UV-Visible spectroscopy with a limit of detection of 373 fg/mL and has been further developed into a high throughput method using a microplate reader detecting down to 600 fg/mL of active toxin. The results show clear differences between the toxin product and the placebo, which contains the pharmaceutical excipients human serum albumin and lactose, showing that the assay detects the active form of the toxin.
Roots Tourism: Blackbirding and the South Sea Islander Diaspora
Authors: Cheer Joseph , Reeves Keir
Published: August 2013

Roots tourism and diaspora travel are inextricably aligned and embody more than just another avenue for the expansion of tourism. This article, using Vanuatu as the context, argues that roots tourism has far broader implications for diaspora, especially in so far as geopolitical relationships
between colonial powers and their former outposts are concerned. The return sojourns of Australia's South Sea Islander diaspora are used in this article to highlight the phenomenon of roots tourism. The circumstances surrounding the arrival of the first islanders during what became known as
the blackbirding era, beginning in the 1860s through to the early 1900s, is subject to contestation as to whether this constituted free or forced labor. Such narratives are common among diaspora when evaluating the legacy of colonialism, particularly when the specter of exploitation and mistreatment
resonates. Roots tourism and the travel of diaspora are aimed at reconciling the ensuing questions of identity, culture, and place. This article argues that roots tourism offers personal relief and restitution as well as contributes to broader sociopolitical advancement between the descendants
of the colonized and present-day institutions.
The Diaspora Market and Homeland Representations: Implications for Niche Marketing
Authors: Chhabra Deepak
Published: August 2013

This study seeks to unveil important information related to Indian diaspora tourists and examines promotional representations of India by the travel trade in the US. Key motivations of visits to India include the desire to strengthen family and friendly connections, to be in touch with
themselves, and to feel a sense of belonging. For the most part, perceived images of India are congruent with the most frequently observed themes in the promotional representations. Representative dissonance to a moderate extent is also noted. The results of the study offer important implications
for the travel trade and the homeland government on how to appeal to this niche market.
Diaspora Tourism and Homeland Attachment: An Exploratory Analysis
Authors: Huang Wei-Jue , Haller William J. , Ramshaw Gregory P.
Published: August 2013

Diaspora tourism refers to the travel of people in diaspora to their ancestral homelands in search of their roots or to feel connected to their personal heritage. Whereas most tourists become attached to a destination after repeat visits, the tourist-destination relation in diaspora tourism is unique because tourists with immigrant origins often feel connected to the people, culture, and heritage of the destination before actually visiting the place. This study explores the relationship between second-generation immigrants' attachment to their ancestral homeland and their journey back "home," focusing on whether or not the second generation could feel at home in their parents' country of origin versus their current country of residence. This study employs secondary data from two studies on second-generation immigrants in the US: the Children of Immigrants Longitudinal Study and the Immigration and Intergenerational Mobility in Metropolitan Los Angeles study. Findings revealed that there was an association between the number of diaspora tourism trips and feeling at home in their parents' country of origin. Second-generation immigrants who considered both America and their ancestral homeland as home took the highest number of trips, and their transnational attachment to two countries reflected the dual loyalty and identity of people in diaspora. In addition, those who experienced extended stays were more likely to feel at home in their ancestral homeland. Whereas such relationship was not necessarily causal, both length and frequency of diaspora tourism trips were found to be associated with immigrants' connection to the land of their ancestors.
Exploring the Conceptual Boundaries of Diaspora and Battlefield Tourism: Australians' Travel to the Gallipoli Battlefield, Turkey, as a Case Study
Authors: Lockstone-Binney Leonie , Hall John , Atay Lutfi
Published: August 2013

Historical tourism resources associated with diasporic communities and battlefields would at face value appear to have little in common. On closer inspection, however, diaspora and battlefield tourism share several elements in common. These commonalities are explored in greater detail,
with an eye to investigating battlefield tourism sites indelibly linked to the birth of modern nations, where it is argued that there is a particularly blurred boundary between these two forms of tourism that must be recognized. The Gallipoli battlefield, Turkey, provides the contextual anchor
for this discussion in suggesting that a key reason Australians travel to this foreign place to is to find out what it means to be an Australian. The prominence of this battlefield in the psyche of Australians is borne out of the involvement of the Australian and New Zealand Army Corps (Anzac)
in the First World War campaign that commenced at what is now known as Anzac Cove at Gallipoli on April 25, 1915. This campaign was the first united action of the fledging Australian nation bought together through federation in 1901. Qualitative data collected from Australians visiting the
Gallipoli battlefields in Turkey during 2010 is used to explore whether the experiences of those traveling to battlefields strongly associated with nation building legends and stories resemble those of diasporic tourists in seeking to return to their homeland. Emerging from the analysis, the
confines of the blurred boundary between diaspora tourism and battlefield tourism is discussed in detail and an associated research agenda is proposed that aims to further clarify the scope of these concepts in relation to the broad spectrum of heritage tourism resources.
The Risky Business of Understanding: Philosophical Hermeneutics and the Knowing Subject in Worldmaking
Authors: Caton Kellee
Published: August 2013

In this critical commentary, Caton argues that since its introduction to the literature over the past decade by Hollinshead, the notion of "worldmaking" has risen to become an important organizing concept within tourism studies. Here, Caton deems worldmaking to be "a wonderfully holistic
notion," because it takes into account not only the interactions of the diverse agents, the structures, the ideologies, and the material conditions that make up what she sees as "our tourism world," but also the larger world beyond—of which the sphere of tourism is such a powerful part.
Yet Caton is concerned that, currently, the epistemological dimensions of worldmaking have not been rigorously or vigorously explored. In this review article, therefore, she explores how the seeds of the so-called worldmaking process (or ordinary worldmaking activity, in general) conceivably
begin at the level of the individual knowing mind. Her critical commentary thereby seeks to remind readers of Tourism Analysis of the work of the great 20th-century philosopher, Hans-Georg Gadamer, specifically with regard to his development of the position called "philosophical hermeneutics."
Caton argues here that Gadamerian philosophical hermeneutics can indeed stand as a/or the epistemological foundation par excellence for "tourism" as may be seen and interpreted through worldmaking lenses. In this review piece, Caton maintains that pondering of and about Gadamer's work can
not only vitally help us all toward improved understanding of ourselves as "epistemic subjects" but lead us to become much more aware and reflective about the power we actually do hold in the production of our times. (Abstract by the Review's Editor)
Stability of SG1 nitroxide towards unprotected sugar and lithium salts: a preamble to cellulose modification by nitroxide-mediated graft polymerization
Authors: Moreira Guillaume , Charles Laurence , Major Mohamed , Vacandio Florence , Guillaneuf Yohann , Lefay Catherine , Gigmes Didier
Published: August 2013

The range of applications of cellulose, a glucose-based polysaccharide, is limited by its inherently poor mechanical properties. The grafting of synthetic polymer chains by, for example, a “grafting from” process may provide the means to broaden the range of applications. The nitroxide-mediated polymerization (NMP) method is a technique of choice to control the length, the composition and the architecture of the grafted copolymers. Nevertheless, cellulose is difficult to solubilize in organic media because of inter- and intramolecular hydrogen bonds. One possibility to circumvent this limitation is to solubilize cellulose in N,N-dimethylformamide (DMF) or N,N-dimethylacetamide (DMA) with 5 to 10 wt % of lithium salts (LiCl or LiBr), and carry out grafted polymerization in this medium. The stability of nitroxides such as SG1 has not been studied under these conditions yet, even though these parameters are of crucial importance to perform the graft modification of polysaccharide by NMP. The aim of this work is to offer a model study of the stability of the SG1 nitroxide in organic media in the presence of unprotected glucose or cellobiose (used as a model of cellulose) and in the presence of lithium salts (LiBr or LiCl) in DMF or DMA.

Contrary to TEMPO, SG1 proved to be stable in the presence of unprotected sugar, even with an excess of 100 molar equivalents of glucose. On the other hand, lithium salts in DMF or DMA clearly degrade SG1 nitroxide as proven by electron-spin resonance measurements. The instability of SG1 in these lithium-containing solvents may be explained by the acidification of the medium by the hydrolysis of DMA in the presence of LiCl. This, in turn, enables the disproportionation of the SG1 nitroxide into an unstable hydroxylamine and an oxoammonium ion.

Once the conditions to perform an SG1-based nitroxide-mediated graft polymerization from cellobiose have been established, the next stage of this work will be the modification of cellulose and cellulose derivatives by NMP.
Télé‑communs versus télé‑services publics : vers des services publics collaboratifs en ligne
Authors: Bourcier Danièle
Published: August 2013

Résumé Les télé‑communs sont des télé‑services qui sont issus de la coopération entre le secteur public et le secteur privé non marchand. Ces services sont nés du mouvement des communs et de l’explosion de l’ open data qui oblige l’administration à mettre à la disposition de tous les données publiques. Des groupes d’acteurs particuliers les communautés numériques vont donc devenir un nouveau partenaire dont l’administration devra tenir compte. Nous observerons leurs implications particulièrement dans le mouvement de l’ open data et comment ces communautés ont coopéré à certains services publics notamment en matière de santé, d’environnement, d’urbanisme et de transports publics. Nous ferons alors l’hypothèse que le e‑gouvernement a ouvert, de façon dynamique, de nouvelles façons de penser ce que serait un nouveau type de service public, à la fois pour le public et avec le public.
Le service public du nommage, consecration et limites
Authors: du Marais Bertrand
Published: August 2013

Résumé La loi du 22 mars 2011, et plus encore les décisions du Conseil d’Etat du 10 juin 2013, précisent le cadre juridique de la gestion du « .fr » sans fondamentalement en changer la nature et le régime de service public. Elles n’ont malheureusement pas non plus réduit les principales sources d’insécurité juridiques – absence de qualification juridique du nom de domaine, rareté des adresses – car les pouvoirs publics français restent contraints par la gouvernance internationale très particulière de cette activité.
Téléservices et confidentialités en matière de défense
Authors: Cammilleri‑Subrenat Anne
Published: August 2013

Résumé Le ministère de la défense est au cœur de l’État républicain. Comme les autres ministères, il contribue à l’essor des téléservices. Mais, il n’en demeure pas moins qu’il a une mission régalienne particulière de protection des secrets de la sécurité et de la défense nationale. Il doit assurer avec agilité un équilibre entre les développements des téléservices et le respect strict de toutes les formes du secret. Pour ce faire, à la rigidité de la maîtrise des systèmes d’information s’ajoute celle de l’existence « du besoin de connaître l’information » et des procédures d’habilitation des personnes.
Nouvelles technologies et fiscalite vers un « e‑contrat fiscal » ?
Authors: Boudet Jean-François
Published: August 2013

Résumé Le développement du commerce électronique a considérablement modifié l’appréhension des systèmes d’impositions et des modalités de paiement de l’impôt. Ce phénomène s’est d’autant plus amplifié que les États entendent user des nouvelles technologies de l’information et de la communication pour améliorer leurs relations avec les contribuables. Cette « nouvelle économie » bouleverse l’impôt dans sa nature et dans son régime juridique, de telle sorte que se dessinent une conception nouvelle de l’impôt formulée sur la méthode contractuelle.
Le vote des fonctionnaires en 2012 ou la crise de l'appareil d'état
Authors: Rouban Luc
Published: August 2013

Résumé L’analyse du vote des fonctionnaires lors de l’élection présidentielle de 2012 montre que les agents publics ont davantage voté contre Nicolas Sarkozy qu’ils n’ont soutenu François Hollande. Elle révèle également que deux évolutions touchent leurs comportements politiques et constituent les signes d’une crise d’identité. Au premier tour, les choix électoraux varient sensiblement selon la catégorie et le métier. La fonction publique apparaît ainsi éclatée en différents univers socio­politiques assez éloignés les uns des autres, notamment sous l’effet du niveau de diplôme. D’autre part, le vote en faveur de l’extrême-droite a beaucoup progressé.
Usage of Pre-Made Text-Modules and Peer-Groups for Mitigating Information Asymmetry in Social Lending
Authors: Frerichs Arne , Michaelis Christian , Wienekamp Marco , Plagge Jens , Schumann Matthias
Published: August 2013

Recently, several platforms for arranging credit mediation between borrowers and lenders without usage of a financial intermediary have emerged. Social lending has attracted the interest of researchers who analyzed the behavior of borrowers and lenders on these platforms. The authors examine the impact of pre-made text modules and usage of peer groups on the funding success of a credit request. Analyzing empirical data from the German social lending platform Smava, the authors find evidence that the use of pre-made text modules doesn’t influence lender decisions significantly. Additionally, the authors find that the usage of peer groups significantly influences funding success, if borrowers seek affiliation to groups with only few members.
Using Social Media for Service Innovations
Authors: Scupola Ada , Nicolajsen Hanne Westh
Published: August 2013

This article investigates how social software such as blogs can be used to collect ideas generated by the users in the service innovation process. After a theoretical discussion of user involvement and more specifically user involvement using social software and interactive web-tools, the article reports the results from a field experiment at a university library. In the experiment, a blog was established to collect ideas for service innovations from the library users. The experiment shows that blogs may generate a modest, but very useful amount of ideas. The experiment furthermore reveals that blogs might be useful to provide the institution with an image of openness and willingness to listen to customer input.
Functional Modelling and Analysis of IDM E-Tailer Platforms
Authors: Srinivasan Thomas , Pillai Prashant S. , Qadir Abdul , Sharma Ravi S.
Published: August 2013

The research described in this article is motivated by the need to provide models and frameworks that would guide online web-stores in their platform provisioning and customer retention. The authors propose the e-tailer Platform Functionality Model (ePFM) for modelling the requirements of business-to-consumer (B2C) online stores for Interactive Digital Media (IDM). Encompassing e-tailer strategy formulation and functional requirements of the web-store, a variation of the Empathic Design (ED) methodology was used in the field research for investigating the efficacy of the ePFM. The research suggests that incorporating multiple perspectives - namely transaction, marketing, and revenue functionalities - for an online business is a critical success factor. Secondly, development of an online business platform requires design that is aligned with customers’ expectations of each of the three functionalities. Finally, e-business managers and platform architects may need to pay special attention to strategies that advance value creation in order to retain competitive advantage. From the empirical results, the authors may conclude that while all three types of functionalities are required for market impact, there are also differences between hygiene and competitive factors that eventually differentiate between success and mediocrity.
Reviewing Business-IT Alignment Instruments Under SAM Dimensions
Authors: Belfo Fernando , Sousa Rui Dinis
Published: August 2013

Business-IT alignment has been on the top of the concerns of IT executives for many years and how to assess it has been under research. Among many proposals, one of the best known and cited in the literature, showing some relevant empirical work, is the Luftman’s Strategic Alignment Maturity (SAM) categories assessment. Taking it as a framework, seven other proposals are examined using SAM categories as dimensions of business-IT alignment: communications, competency/value measurements, governance, partnership, technology scope and skills. Except for one proposal revealing a tactical level approach, this review shows that business-IT alignment assessment has been studied essentially at the strategic level. Among the examined dimensions across the several proposals, governance is the best covered one while the human resource skills dimension is considerably neglected. Having still room for improvements, either in the governance or the technology scope dimensions, the SAM assessment seems a well balanced instrument. The empirical work already found on SAM provides a good starting point to get an acceptable validated instrument. However, if in terms of content validity, SAM is one of the most promising instruments, there is still much work to do on what concerns its operationalization. Future research should strive for a rigorous, strong instrument on every component of construct validity, namely, the convergent, discriminant and nomological components.
Retained-Key Encryption
Authors: Crowe David , Al-Hamdani Wasim
Published: August 2013

This paper presents a synchronous encryption key management model that does not require the sender to disclose the encryption key in order to effect decryption. This eliminates the need for key exchange mechanisms, giving the sender improved control over their keys. The retained-key model is presented as being a software application that handles the initiation of a secure communication channel between sender and receiver, and facilitates user authentication by a trusted third party—presumably, the software’s vendor. This model is not intended to replace public/private key-based mechanisms, as they serve an important role in message signing and authentication. Rather, it seeks to provide an alternative means of decrypting messages in a secure fashion while allowing the sender to avoid the need to disclose the message’s key.
A Formal Framework for Patch Management
Authors: Francia Guillermo A. , Kim Kihyun , Ahn Byungoh , Zhou Sen Xin
Published: August 2013

A patch management model provides a framework with which a system’s parameters and behavior can be tested and validated. The authors propose a formal framework that is based on the Continuous Time Markov Chain Model and validate the model using the SHARPE modeling tool. Furthermore, they perform sensitivity analyses to study the dynamic behavior of the proposed model with varying parameter values. A discussion on the results of our study and future research directions concludes the paper.
Mission Assurance Challenges within the Military Environment
Authors: Musman Scott , Grimaila Michael R.
Published: August 2013

Virtually all modern organizations have embedded information and communication technologies into their core processes as a means to increase operational efficiency, improve decision quality, and reduce operational costs. However, this dependence can place the organizational mission at risk when an incident occurs that compromises a cyber resource critical to the success of the organizational mission. In this paper, the authors examine the challenges of developing and maintaining a mission-wide understanding of organizational mission risk within military environments. Specifically, they examine the concept of mission assurance, discuss various factors which must be taken into account when describing military missions, analyze the four primary types of representations used to capture mission-to-cyber relationships, and highlight the complexities of documenting cyber dependencies for the purpose of achieving mission assurance.
Refactoring Flash Embedding Methods
Authors: Ying Ming , Miller James
Published: August 2013

Flash and Ajax are currently two popular Rich Internet Application (RIA) technologies, integrating Flash and Ajax will further enhance Internet users’ experiences. To communicate Flash written in ActionScript with Ajax written in JavaScript, the first step is to embed Flash content into a web page. Two methods can be used: markup-based Flash embedding methods and JavaScript-based Flash embedding methods. However, the drawbacks of markup-based Flash embedding methods make JavaScript-based Flash embedding methods a better solution. To automatically convert markup-based Flash embedding methods into a JavaScript-based method, this paper presents a refactoring tool, called FlashembedRT, to assist programmers with the transformation. This tool refactors the five different markup-based Flash embedding methods to the JavaScript-based Flash embedding method called flashembed.
Programmed Death-1 Is a Marker for Abnormal Distribution of Naive/Memory T Cell Subsets in HIV-1 Infection
Authors: Breton Gaëlle , Chomont Nicolas , Takata Hiroshi , Fromentin Rémi , Ahlers Jeffrey , Filali-Mouhim Abdelali , Riou Catherine , Boulassel Mohamed-Rachid , Routy Jean-Pierre , Yassine-Diab Bader , Sékaly Rafick-Pierre
Published: August 2013

Chronic activation of T cells is a hallmark of HIV-1 infection and plays an important role in disease progression. We previously showed that the engagement of the inhibitory receptor programmed death (PD)-1 on HIV-1–specific CD4+ and CD8+ T cells leads to their functional exhaustion in vitro. However, little is known about the impact of PD-1 expression on the turnover and maturation status of T cells during the course of the disease. In this study, we show that PD-1 is upregulated on all T cell subsets, including naive, central memory, and transitional memory T cells in HIV-1–infected subjects. PD-1 is expressed at similar levels on most CD4+ T cells during the acute and the chronic phase of disease and identifies cells that have recently entered the cell cycle. In contrast, PD-1 expression is dramatically increased in CD8+ T cells during the transition from acute to chronic infection, and this is associated with reduced levels of cell proliferation. The failure to downregulate expression of PD-1 in most T cells during chronic HIV-1 infection is associated with persistent alterations in the distribution of T cell subsets and is associated with impaired responses to IL-7. Our findings identify PD-1 as a marker for aberrant distribution of T cell subsets in HIV-1 infection.
Soluble CD80 Restores T Cell Activation and Overcomes Tumor Cell Programmed Death Ligand 1–Mediated Immune Suppression
Authors: Haile Samuel T. , Dalal Sonia P. , Clements Virginia , Tamada Koji , Ostrand-Rosenberg Suzanne
Published: August 2013

Many tumor cells escape anti-tumor immunity through their expression of programmed death ligand-1 (PDL1 or B7-H1), which interacts with T cell–expressed PD1 and results in T cell apoptosis. We previously reported that transfection of human tumor cells with a membrane-bound form of the human costimulatory molecule CD80 prevented PD1 binding and restored T cell activation. We now report that a membrane-bound form of murine CD80 similarly reduces PDL1–PD1-mediated suppression by mouse tumor cells and that a soluble protein consisting of the extracellular domains of human or mouse CD80 fused to the Fc domain of IgG1 (CD80-Fc) overcomes PDL1-mediated suppression by human and mouse tumor cells, respectively. T cell activation experiments with human and mouse tumor cells indicate that CD80-Fc facilitates T cell activation by binding to PDL1 to inhibit PDL1–PD1 interactions and by costimulating through CD28. CD80-Fc is more effective in preventing PD1–PDL1-mediated suppression and restoring T cell activation compared with treatment with mAb to either PD1 or PDL1. These studies identify CD80-Fc as an alternative and potentially more efficacious therapeutic agent for overcoming PDL1-induced immune suppression and facilitating tumor-specific immunity.
TWEAK Inhibits TRAF2-Mediated CD40 Signaling by Destabilization of CD40 Signaling Complexes
Authors: Salzmann Steffen , Lang Isabell , Rosenthal Alevtina , Schäfer Viktoria , Weisenberger Daniela , Carmona Arana José Antonio , Trebing Johannes , Siegmund Daniela , Neumann Manfred , Wajant Harald
Published: August 2013

We found recently that TNF-like weak inducer of apoptosis (TWEAK) and fibroblast growth factor–inducible-14 (Fn14) by virtue of their strong capability to reduce the freely available cytoplasmic pool of TNFR-associated factor (TRAF)2 and cellular inhibitors of apoptosis (cIAPs) antagonize the functions of these molecules in TNFR1 signaling, resulting in sensitization for apoptosis and inhibition of classical NF-κB signaling. In this study, we demonstrate that priming of cells with TWEAK also interferes with activation of the classical NF-κB pathway by CD40. Likewise, there was strong inhibition of CD40 ligand (CD40L)–induced activation of MAPKs in TWEAK-primed cells. FACS analysis and CD40L binding studies revealed unchanged CD40 expression and normal CD40L–CD40 interaction in TWEAK-primed cells. CD40L immunoprecipitates, however, showed severely reduced amounts of CD40 and CD40-associated proteins, indicating impaired formation or reduced stability of CD40L–CD40 signaling complexes. The previously described inhibitory effect of TWEAK on TNFR1 signaling has been traced back to reduced activity of the TNFR1-associated TRAF2–cIAP1/2 ubiquitinase complex and did not affect the stability of the immunoprecipitable TNFR1 receptor complex. Thus, the inhibitory effect of TWEAK on CD40 signaling must be based at least partly on other mechanisms. In line with this, signaling by the CD40-related TRAF2-interacting receptor TNFR2 was also attenuated but still immunoprecipitable in TWEAK-primed cells. Collectively, we show that Fn14 activation by soluble TWEAK impairs CD40L–CD40 signaling complex formation and inhibits CD40 signaling and thus identify the Fn14-TWEAK system as a potential novel regulator of CD40-related cellular functions.
Multistage T Cell–Dendritic Cell Interactions Control Optimal CD4 T Cell Activation through the ADAP-SKAP55–Signaling Module
Authors: Mitchell Jason S. , Burbach Brandon J. , Srivastava Rupa , Fife Brian T. , Shimizu Yoji
Published: August 2013

The Ag-specific interactions between T cells and dendritic cells progress through dynamic contact stages in vivo consisting of early long-term stable contacts and later confined, yet motile, short-lived contacts. The signaling pathways that control in vivo interaction dynamics between T cells and dendritic cells during priming remain undefined. Adhesion and degranulation promoting adapter protein (ADAP) is a multifunctional adapter that regulates “inside-out” signaling from the TCR to integrins. Using two-photon microscopy, we demonstrate that, in the absence of ADAP, CD4 T cells make fewer early-stage stable contacts with Ag-laden dendritic cells, and the interactions are characterized by brief repetitive contacts. Furthermore, ADAP-deficient T cells show reduced contacts at the late motile contact phase and display less confinement around dendritic cells. The altered T cell interaction dynamics in the absence of ADAP are associated with defective early proliferation and attenuated TCR signaling in vivo. Regulation of multistage contact behaviors and optimal T cell signaling involves the interaction of ADAP with the adapter src kinase–associated phosphoprotein of 55 kDa (SKAP55). Thus, integrin activation by the ADAP-SKAP55–signaling module controls the stability and duration of T cell–dendritic cell contacts during the progressive phases necessary for optimal T cell activation.
Negative Charges in the Flexible N-Terminal Domain of Rho GDP-Dissociation Inhibitors (RhoGDIs) Regulate the Targeting of the RhoGDI–Rac1 Complex to Membranes
Authors: Ueyama Takehiko , Son Jeonghyun , Kobayashi Takeshi , Hamada Takeshi , Nakamura Takashi , Sakaguchi Hirofumi , Shirafuji Toshihiko , Saito Naoaki
Published: August 2013

In its resting state, Rho GDP-dissociation inhibitor (RhoGDI) α forms a soluble cytoplasmic heterodimer with the GDP-bound form of Rac. Upon stimulation, the dissociation of RhoGDIα from the RhoGDIα–Rac complex is a mandatory step for Rac activation; however, this mechanism is poorly understood. In this study, we examined how the cytoplasm/membrane cycles of the RhoGDI–Rac complex are regulated, as well as where RhoGDI dissociates from the RhoGDI–Rac complex, during FcγR-mediated phagocytosis. The negatively charged and flexible N terminus (25 residues) of RhoGDIα, particularly its second negative amino acid cluster possessing five negatively charged amino acids, was a pivotal regulator in the cytoplasm/membrane cycles of the RhoGDI–Rac complex. We also found that RhoGDIα translocated to the phagosomes as a RhoGDIα–Rac1 complex, and this translocation was mediated by an interaction between the polybasic motif in the C terminus of Rac1 and anionic phospholipids produced on phagosomes, such as phosphatidic acid, that is, by a phagosome-targeting mechanism of Rac1. Thus, we demonstrated that the targeting/accumulation of the RhoGDIα–Rac1 complex to phagosomes is regulated by a balance between three factors: 1) the negatively charged and flexible N-terminal of RhoGDIα, 2) the binding affinity of RhoGDIα for Rac1, and 3) anionic phospholipids produced on phagosomes. Moreover, we demonstrated that the mechanism of targeting/accumulation of the RhoGDIα–Rac1 complex is also applicable for the RhoGDIβ-Rac1 complex.
Notch Signaling Regulates Follicular Helper T Cell Differentiation
Authors: Auderset Floriane , Schuster Steffen , Fasnacht Nicolas , Coutaz Manuel , Charmoy Mélanie , Koch Ute , Favre Stéphanie , Wilson Anne , Trottein François , Alexander James , Luther Sanjiv A. , MacDonald H. Robson , Radtke Freddy , Tacchini-Cottier Fabienne
Published: August 2013

Follicular helper T (TFH) cells are specialized in providing help for B cell differentiation and Ab secretion. Several positive and negative regulators of TFH cell differentiation have been described but their control is not fully understood. In this study, we show that Notch signaling in T cells is a major player in the development and function of TFH cells. T cell–specific gene ablation of Notch1 and Notch2 impaired differentiation of TFH cells in draining lymph nodes of mice immunized with T-dependent Ags or infected with parasites. Impaired TFH cell differentiation correlated with deficient germinal center development and the absence of high-affinity Abs. The impact of loss of Notch on TFH cell differentiation was largely independent of its effect on IL-4. These results show a previously unknown role for Notch in the regulation of TFH cell differentiation and function with implications for the control of this T cell population.
Peritoneal Cavity Regulatory B Cells (B10 Cells) Modulate IFN-γ+CD4+ T Cell Numbers during Colitis Development in Mice
Authors: Maseda Damian , Candando Kathleen M. , Smith Susan H. , Kalampokis Ioannis , Weaver Casey T. , Plevy Scott E. , Poe Jonathan C. , Tedder Thomas F.
Published: August 2013

The spleen regulatory B cell subset with the functional capacity to express IL-10 (B10 cells) modulates both immune responses and autoimmune disease severity. However, the peritoneal cavity also contains relatively high frequencies of functionally defined IL-10–competent B10 cells. In this study, peritoneal cavity B10 cells shared similar cell surface phenotypes with their spleen counterparts. However, peritoneal cavity B10 cells were 10-fold more frequent among B cells than occurred within the spleen, intestinal tract, or mesenteric lymph nodes and were present at higher proportions among the phenotypically defined peritoneal B1a > B1b > B2 cell subpopulations. The development or localization of B10 cells within the peritoneal cavity was not dependent on the presence of commensal microbiota, T cells, IL-10 or B10 cell IL-10 production, or differences between their fetal liver or adult bone marrow progenitor cell origins. The BCR repertoire of peritoneal cavity B10 cells was diverse, as occurs in the spleen, and predominantly included germline-encoded VH and VL regions commonly found in either the conventional or B1 B cell compartments. Thereby, the capacity to produce IL-10 appears to be an intrinsic functional property acquired by clonally diverse B cells. Importantly, IL-10 production by peritoneal cavity B cells significantly reduced disease severity in spontaneous and induced models of colitis by regulating neutrophil infiltration, colitogenic CD4+ T cell activation, and proinflammatory cytokine production during colitis onset. Thus, the numerically small B10 cell subset within the peritoneal cavity has regulatory function and is important for maintaining homeostasis within gastrointestinal tissues and the immune system.
Amplified NKG2C+ NK Cells in Cytomegalovirus (CMV) Infection Preferentially Express Killer Cell Ig-like Receptor 2DL: Functional Impact in Controlling CMV-Infected Dendritic Cells
Authors: Djaoud Zakia , David Gaëlle , Bressollette Céline , Willem Catherine , Rettman Pauline , Gagne Katia , Legrand Nolwenn , Mehlal Souad , Cesbron Anne , Imbert-Marcille Berthe-Marie , Retière Christelle
Published: August 2013

CMV infection represents a major complication in hematopoietic stem cell transplantation, which compromises graft outcome. Downregulation of HLA class I expression is one mechanism by which CMV evades T cell–mediated immune detection, rendering infected cells vulnerable to killer cell Ig-like receptor (KIR)+ NK cells. In this study, we observed that the amplified NKG2C+ NK cell population observed specifically in CMV seropositive individuals mainly expressed KIR2DL receptors. We have shown that HLA class I expression was downregulated on CMV-infected immature dendritic cells (iDCs), which escape to HLA-A2-pp65–specific T lymphocytes but strongly trigger the degranulation of KIR2D+ NK cells. CMV infection conferred a vulnerability of C2C2+ iDCs to educated KIR2DL1+ and KIR2DL3+ NK cell subsets. Alloreactivity of KIR2DL1+ NK cell subsets against C1C1+ iDCs was maintained independently of CMV infection. Unexpectedly, CMV-infected C1C1+ iDCs did not activate KIR2DL3+ NK cell reactivity, suggesting a potential CMV evasion to KIR2DL3 NK cell recognition. Altogether, the coexpression of KIR and NKG2C on expanded NK cell subsets could be related to a functional contribution of KIR in CMV infection and should be investigated in hematopoietic stem cell transplantation, in which the beneficial impact of CMV infection has been reported on the graft-versus-leukemia effect.
Rhabdomyolysis as a Presenting Manifestation of Very Long-Chain Acyl-Coenzyme a Dehydrogenase Deficiency
Authors: Oliveira Sara Freitas , Pinho Liliana , Rocha Hugo , Nogueira Célia , Vilarinho Laura , Dinis Maria José , Silva Conceição
Published: August 2013

Very long-chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency (MIM 201475) is a rare inherited disorder with three forms of clinical presentation: a severe early-onset form; an intermediate form with childhood onset; and an adult-onset form, of mild severity. During adolescence and adulthood, exercise intolerance, myalgia and recurrent episodes of rhabdomyolysis are the main clinical features. The authors present a case of a 13-year old female, with severe myalgia and dark urine after prolonged exercise. Analytical evaluation showed marked elevation plasma creatine kinase and myoglobin. The increased levels of tetradecenoyl carnitine in patient’s dried blood spot suggested a VLCAD deficiency, which was confirmed by molecular study. Family history is remarkable for first grade consanguinity of parents and a 19-year old brother with records of repeated similar episodes after moderate intensity physical efforts which was subsequently also diagnosed with VLCAD deficiency. This is one of the first cases of late-onset of disease diagnosed in Portugal.
The meaning of being young with dementia and living at home
Authors: Rostad Dag , Hellzén Ove , Enmarker Ingela
Published: August 2013

Studies that explore the subjective experiences of younger people with dementia living at home are rare. Therefore, the aim of this study was to gain an understanding of the lived experience of younger persons (<65 years) who lived at home and suffered from earlyonset dementia, and the meanings that might be found in those experiences. The researchers conducted a qualitative study using a phenomenological hermeneutic approach. Data were collected through narrative interviews with four informants. Two men and two women ages 55 to 62 participated. Three of the informants lived with their spouses, and one lived alone, close to his children. The informants’ subjective experiences revealed the following four key themes: entrapment by circumstances, loss of humanity, the preservation of hope and willpower, and the desire to ensure one’s quality of life. These themes provide a deeper understanding of the experiences of younger people with dementia who live at home. The theme of preserving hope and willpower rebuts prejudicial contentions that life with Alzheimer’s syndrome does not have anything more to offer and may be seen as diminishing a patient’s humanity. Patients’ autonomy and self-determination should not be ignored. In all phases of the progression of dementia, the person in charge of giving care to the relative with dementia should be ethically aware of and reflective to the progress of his/her illness.
Papillary squamotransitional cell carcinoma of the uterine cervix: A histomorphological and immunohistochemical study of nine cases
Authors: Anand Mani , Deshmukh Sanjay D. , Gulati Harveen K.
Published: August 2013

Background: Papillary squamotransitional cell carcinoma (PSCC) is a distinctive subcategory of squamous cell carcinoma of the uterine cervix. It has a propensity for local recurrence and late metastasis. Histologically, it can be misinterpreted as transitional cell carcinoma, or other papillary lesions of the cervix including squamous papilloma, verrucous carcinoma or cervical intraepithelial neoplasia grade 3 with papillary configuration. Materials and Methods: Nine cases of PSCC of the uterine cervix were diagnosed on a cervical biopsy specimen on routine hematoxylin and eosin (H and E) stained sections. Their clinic-morphological features were analyzed. The cases were further evaluated immunohistochemically by cytokeratin 7 (CK7), cytokeratin 20 (CK20), p53 and Ki-67. Results: The patients ranged in age from 35 years to 75 years; with abnormal uterine bleeding being the most common clinical presentation. All the cases showed papillary architecture with fibrovascular cores lined by multilayered atypical epithelium. Three cell types were observed: Clear, intermediate and basaloid. Stromal invasion was seen in five cases, whereas in the remaining four cases, the biopsy specimen was too superficial to definitely assess invasion. Immunohistochemically, eight cases were CK7 + /CK20 - and one case was CK7 - /CK20 - . All nine cases showed nuclear accumulation of mutant p53. Moderate and high proliferative activity was observed in two and seven cases, respectively. Five of patients for whom follow-up information was available underwent radical hysterectomy and two of them were disease free 18 months following treatment. Conclusion: PSCC of the uterine cervix are a clinicomorphologically distinct group of cervical lesions that display a morphologic spectrum. They are potentially aggressive malignant tumors that should be distinguished from transitional cell carcinoma and other papillary lesions of the uterine cervix.
Clinico-immunological response to intratumoral versus intravenous neoadjuvant chemotherapy in advanced pediatric solid malignancies
Authors: Kumar Vijayendra , Ramaswami Nandini , Pandey Anand , Shukla Ram Chandra , Sen Maloy Ranjan , Sharma Shiv Prasad , Gupta Dinesh Kumar , Gangopadhyay Ajay Narayan
Published: August 2013

Background: There is minimal literature on the use of intralesional chemotherapy in the pediatric age group. We undertook this present study to evaluate the two modalities (intratumoral and intravenous) of giving chemotherapy in terms of toxicity of chemotherapy, hematological parameters, efficacy of chemotherapy in reduction in volume of the tumor as well as resectability of tumor with special emphasis on immunological parameters. Materials and Methods: Advanced cases of Wilms′ tumor and Neuroblastoma were included in the study. Intratumoral chemotherapy was given through 25 G spinal needle under aseptic precautions and ultrasound guidance in the same dose as in systemic chemotherapy. Intravenous group was given chemotherapy in the usual way. Reassessment was carried out after every course of chemotherapy. Results: Group A included 16 cases of Wilms′ tumor and 6 cases of neuroblastoma. In group B, there were 14 cases of Wilms′ tumor and 8 of neuroblastoma. Vomiting, diarrhea, mucositis, and thrombophlebitis were more common in the intravenous group (P<0.05). The fall in Immunoglobulin A, Immunogloblulin G, Immunoglobulin M, and T-cell rosetting was more common in the intravenous group (P<0.05). Seventy percent of patients had completely resectable tumor at the end of 6 doses of intratumoral chemotherapy as compared to 50% resectability in the intravenous group (P<0.05). Conclusion: Intratumoral chemotherapy, besides causing less of the adverse effects and increasing the resecability rate, also causes less suppression of the immune system. This may be offered as an alternative safe and effective modality of treatment for advanced solid tumors.
Review of clinical profile and bacterial spectrum and sensitivity patterns of pathogens in febrile neutropenic patients in hematological malignancies: A retrospective analysis from a single center
Authors: Karanwal Arun B. , Parikh Bharat J. , Goswami Parijat , Panchal Harsha P. , Parekh Bhavesh B. , Patel Kaushal B.
Published: August 2013

Background: The aim of this study was to study clinical profile with bacterial spectrum and susceptibility patterns of pathogens in culture positive febrile neutropenic (FN) patients of hematological malignancies. Materials and Methods: We retrospectively reviewed the medical records of 23 hematological malignancy patients admitted with chemotherapy induced febrile neutropenia with culture positive results, at our institute between June 2011 and December 2011. Results: A total of 23 patients were studied 12 males and 11 females, with a median age of 35 years. Most common diagnosis was acute leukemia (78%) with the majority of patients developing febrile neutropenia during the induction phase of treatment. Most common presenting symptoms were fever, cough, dyspnea, and diarrhea. Primary site of infection was not found in 47% of patients while the rest had lung, gastro-intestinal and skin/soft-tissue infection. Overall 23 organisms were isolated during the study period, from blood (56%), sputum (46%), stool (23%), and nasal swab from one patient. Gram negative bacteria accounted for 78% of organisms while gram positive organisms accounted for 22% of the total isolates. The most common organisms were: Escherichia coli (43%), Staphylococcus aureus (22%), Pseudomonas aeruginosa (17.4%) and Klebsiella pneumonia (17.4%). Antibiotic sensitivity patterns of these bacteria were studied. Gram negative bacterial infections were associated with higher mortality (89%). Conclusions: Induction phase of treatment in acute leukemia is the major cause of FN in hematological malignancies at our institute and gram negative organisms are the predominant organisms with E. coli as major isolate while S. aureus represents the most common gram positive organism. Amikacin and cefoperazone/sulbactum appears to be initial antibiotic appropriate to cover most gram negative pathogens while vancomycin to be added for suspected gram positive infections. FN represents a major cause of morbidity and mortality in hematological malignancy patients, high index of suspicion and early empirical antibiotics with supportive care are main interventions to reduce high mortality for these patients. Antibiotics should be modified according to culture sensitive report as soon as possible.