bluuebunny/crossref_metadata_2025 huggingface dataset:
An Analysis of Potential Economic Benefits of Turkey's Full EU Membership
Authors: Ay Hakan , Yilmaz Eren Alper
Published: April 2015

Even though Turkey has become the sixth largest economy in Europe, there are still hesitations and economic problems for the EU due to Turkey's rising population, low rate of GDP, budget deficit, migration, etc. In recent political history—before 2000s—Turkey failed in its economic liberalization policy. However, the country has seen a significant increase in the economy by developing a market economy and privatizations successfully in the last decade. There is no doubt that Europe would profit from the accession of Turkey to the EU in terms of internal market factors, agriculture, manufacturing industry, trade relations, tourism, and so on. For this reason, instead of looking for faults within the Turkish economy, the EU should try to see positive developments in the Turkish economic system and it should follow a policy that could overcome ongoing problems by mutual negotiations with Turkey. Approval of Turkey's membership to the EU would bring serious economic profits to Europe.
An Evaluation of Oral and Dental Health Services in Turkey and in the Member States of the EU in Terms of Economy
Authors: Işık Abdülkadir , Suat Seda , Yavuz Özge Selvi , Şeren Gamze Yıldız , Habiboğlu Berkay
Published: April 2015

Dental health expenditures are a big part of general health expenditures. In Turkey, oral health services are provided by both private practitioners and government sections. In 2012, approximately 7 million fillings were made by government clinics. According to Turkish Dental Association data, in the same year, the number of fillings that Turkish citizens needed was 247 million. Even if the entire budget of the Health Ministry of Turkey were spent for these fillings, it is impossible to handle this demand. In 2012, in the European Union with 24 member countries, dental health spending was close to 74 billion Euro. Because of this financial burden, Turkey and the other countries are trying to find cost-effective methods to minimize dental health spending. This chapter emphasizes dental health conditions of both Turkey and European Union, firstly, and then successful and cost-effective strategies are discussed.
The Sustainable Development Approach in the Economy-Ecology Dilemma
Authors: Tenikler Gökhan , Şeren Gamze Yıldız
Published: April 2015

The managerial model of cooperation and dialogue-driven, international, and supranational efforts during the past half-century form one of the most important topics within the “sustainable development” concept. Rapidly growing human population, together with the unsustainable pattern of consumption of renewable natural resources for future generations, also leads to the transfer of resources. The concept of development in keeping with ecological concerns about the impact of the dynamic approach should be reformulated. Faced with such dilemmas, these debates illustrate the need for a rational approach. Without jeopardizing the needs of future generations, to meet the demands of today's resource usage, the authors envision a sustainable development approach that seeks to balance protection and use. This approach should be addressed in the context of an understanding.
Economic Crisis and its Impact on Regionalism and Globalism
Authors: Kablamaci Baris , Gozgor Giray
Published: April 2015

This chapter reviews the financial crisis of 2008-09 and its impacts on the international trade in terms of regionalism and globalism. The chapter glances over different aspects of globalism and regionalism as well as looks on historical pattern and recent developments of regionalism and globalism. The data used in the chapter indicates that the financial crisis of 2008-09 negatively affected both globalization and regionalization trends. In addition, the EU has experienced an interesting transformation from regionalism to globalism. This chapter suggests that the issue is not only related with the great trade collapse of 2008-09 but also the sovereign debt crisis of 2010-12.
Natural Language Processing and Psychology in e-Government Services
Authors: Iriberri Alicia
Published: April 2015

Crime statistics from the US Bureau of Justice and the FBI Uniform Crime Report show a gap between reported and unreported crime. For police to effectively prevent and solve crime, they require accurate and complete information about incidents. This article describes the evaluation of a crime reporting and interviewing system that witnesses can use to report crime incidents or suspicious activities anonymously while ensuring the information received is of such quality that police can use it to begin an investigation process. The system emulates the tasks that a police investigator would perform by leveraging natural language processing technology and the interviewing techniques used in the Cognitive Interview. The system incorporates open-source code from the General Architecture for Text Engineering (GATE) program developed by researchers at the University of Sheffield, Web and database technology, and Java-based proprietary code developed by the author. Findings of this evaluation show that the system is capable of producing accurate and complete reports by enhancing witnesses' memory recall and that its efficacy approximates the efficacy of a human conducting a cognitive interview closer than existing alternatives. The system is introduced as the first computer application of the cognitive interview and proposed as a viable alternative to face-to-face investigative interviews.
The Influence of Social Networks on High School Students' Performance
Authors: Abu-Shanab Emad , Al-Tarawneh Heyam
Published: April 2015

Social networks are becoming an integral part of people's lives. Students are spending much time on social media and are considered the largest category that uses such application. This study tries to explore the influence of social media use, and especially Facebook, on high school students' performance. The study used the GPA of students in four courses and their responses regarding the use of social media. Statistical analysis is used to infer this relationship and its implications. Results indicated a support of this study aim and the relationship between the different dimensions of Facebook influence on students with respect to the time spent on the Internet and Facebook specifically. Conclusions and future work are stated at the end.
Analysis of the Perception of Students about Biometric Identification
Authors: Guillén-Gámez Francisco D. , García-Magariño Iván , Romero Sonia J.
Published: April 2015

Currently, there is a demand within distance education of control mechanisms for verifying the identity of students when conducting activities within virtual classrooms. Biometric authentication is one of the tools to meet this demand and prevent fraud. In this line of research, the present work is aimed at analyzing the perceptions of a group of distance students on the impact on the teaching-learning process of a technology of biometric authentication called Smowl. To meet this objective the authors design a quasi-experimental study with two groups of 50 students, one using Smowl technology and the other not. The results show a comparison of the perceptions of both groups, finding that students who have used Smowl are more favorable towards the use of such tools, except in matters relating to the impact on academic performance and ethical aspects of its use, in which no significant differences were found.
The Impacts of Distance Interactivity on Learners' Achievements in Online Mobile Language Learning
Authors: Mellati Morteza , Khademi Marzieh
Published: April 2015

The expansion of technological applications such as computers and mobile phones in the past three decades has impacted our life from different perspectives. Language teaching is no exception and like other fields of study, language teaching has also influenced by new language teaching sources and software. More recently, there has been a passionate debate about the usefulness of the smart-phones for educational purposes and their possible uses in English language instruction; therefore, the present study investigated the impacts of interactivity perceptions on EFL learners' achievements in Online Mobile Language Learning (OMLL) course. To conduct the present study, 68 Iranian intermediate EFL learners were chosen among which 43 participated in Online Mobile Language Learning (OMLL) course and 25 others participated in conventional language classrooms. The results of the study demonstrated that OMLL has significant effects on learners' achievements; however, there are some challenges in conducting online mobile language learning (OMLL) courses in Iranian EFL context.
E-Book Acceptance among Undergraduate Students
Authors: Ngafeeson Madison N. , Sun Jun
Published: April 2015

This paper utilizes the technology acceptance model (TAM) to uncover the moderating roles of technology innovativeness. A study of 158 undergraduate students revealed that the original TAM constructs and relationships were reliable, supported, and applicable in the measurement of e-book acceptance. Interestingly, personal technology innovativeness was found to moderate in a significant way, the relationship between behavioral intention to use e-book and actual usage of e-book. These findings suggest that while individuals who are more open to technology (adopters) as well as less technologically innovative individuals (late adopters and non-adopters) are likely to have the intention to use web-based instructional technologies like e-book, only highly innovative individuals, may actually translate intention into actual usage. These results have serious implications on adopters, implementers and users of instructional technologies who would need to factor into their decision-making the role of the individual technology innovativeness of its users.
What Influences the Market Outcome of Online P2P Lending Marketplace?
Authors: Xu Yun , Luo Chuan , Chen Dongyu , Zheng Haichao
Published: April 2015

Online Peer-to-Peer (P2P) lending marketplaces allow individuals to lend and borrow directly among each other without the mediation of a creditor bank institution. Prior literature has examined online P2P, but has largely been limited to the Western context. This paper thus explores how social capital and other factors influences online P2P lending in the U.S. and China. Based on the archival data of Prosper and PPDai, we compare market outcome of two online P2P lending marketplaces in the U.S. and China. The empirical results show that social capital is not equally important in different online communities. Social capital seems to be more influential for likelihood of getting funded in China than in the U.S. In contrast, social capital has influence on interest rate in the U.S. only. The authors' study thus extends current understanding about how social capital influences online communities to a global perspective.
Exploring Information Technology and Supply Chain Governance
Authors: Dolci Pietro Cunha , Maçada Antonio Carlos Gastaud , Grant Gerald G.
Published: April 2015

The aim of this study is to investigate how information technology (IT) investment supports and relates to SCG and its conceptions (transactional and relational. The authors conducted exploratory case studies in two large Brazilian companies and two major suppliers, interviewing top supply chain executives. In the first case, they identified a more relational type of governance that was mainly based on the company's relationship with its suppliers which was driven by the desire to achieve a greater market share. IT investments focused on sales and operations planning projects where all systems were being integrated. In the second case, they identified transactional governance as the predominant form. This reflects the presence of a great number of suppliers, low partnership and low supply on time delivery rate. IT investments are being made to achieve more relational governance through expenditure on e-procurement and greater integration with their suppliers using ERP.
High Mitochondrial Respiration and Glycolytic Capacity Represent a Metabolic Phenotype of Human Tolerogenic Dendritic Cells
Authors: Malinarich Frano , Duan Kaibo , Hamid Raudhah Abdull , Bijin Au , Lin Wu Xue , Poidinger Michael , Fairhurst Anna-Marie , Connolly John E.
Published: April 2015

Human dendritic cells (DCs) regulate the balance between immunity and tolerance through selective activation by environmental and pathogen-derived triggers. To characterize the rapid changes that occur during this process, we analyzed the underlying metabolic activity across a spectrum of functional DC activation states, from immunogenic to tolerogenic. We found that in contrast to the pronounced proinflammatory program of mature DCs, tolerogenic DCs displayed a markedly augmented catabolic pathway, related to oxidative phosphorylation, fatty acid metabolism, and glycolysis. Functionally, tolerogenic DCs demonstrated the highest mitochondrial oxidative activity, production of reactive oxygen species, superoxide, and increased spare respiratory capacity. Furthermore, assembled, electron transport chain complexes were significantly more abundant in tolerogenic DCs. At the level of glycolysis, tolerogenic and mature DCs showed similar glycolytic rates, but glycolytic capacity and reserve were more pronounced in tolerogenic DCs. The enhanced glycolytic reserve and respiratory capacity observed in these DCs were reflected in a higher metabolic plasticity to maintain intracellular ATP content. Interestingly, tolerogenic and mature DCs manifested substantially different expression of proteins involved in the fatty acid oxidation (FAO) pathway, and FAO activity was significantly higher in tolerogenic DCs. Inhibition of FAO prevented the function of tolerogenic DCs and partially restored T cell stimulatory capacity, demonstrating their dependence on this pathway. Overall, tolerogenic DCs show metabolic signatures of increased oxidative phosphorylation programing, a shift in redox state, and high plasticity for metabolic adaptation. These observations point to a mechanism for rapid genome-wide reprograming by modulation of underlying cellular metabolism during DC differentiation.
Differential Activation of Inflammatory Pathways in Testicular Macrophages Provides a Rationale for Their Subdued Inflammatory Capacity
Authors: Bhushan Sudhanshu , Tchatalbachev Svetlin , Lu Yongning , Fröhlich Suada , Fijak Monika , Vijayan Vijith , Chakraborty Trinad , Meinhardt Andreas
Published: April 2015

Spermatogenic cells express cell-specific molecules with the potential to be seen as “foreign” by the immune system. Owing to the time difference between their appearance in puberty and the editing of the lymphocyte repertoire around birth, local adaptations of the immune system coined immune privilege are required to confer protection from autoattack. Testicular macrophages (TM) play an important role in maintaining testicular immune privilege and display reduced proinflammatory capacity compared with other macrophages. However, the molecular mechanism underlying this macrophage phenotype remained elusive. We demonstrate that TM have a lower constitutive expression of TLR pathway–specific genes compared with peritoneal macrophages. Moreover, in TM stimulated with LPS, the NF-κB signaling pathway is blocked due to lack of IκBα ubiquitination and, hence, degradation. Instead, challenge of TM with LPS or polyinosinic-polycytidylic acid induces MAPK, AP-1, and CREB signaling pathways, which leads to production of proinflammatory cytokines such as TNF-α, although at much lower levels than in peritoneal macrophages. Pretreatment of TM with inhibitors for MAPKs p38 and ERK1/2 suppresses activation of AP-1 and CREB signaling pathways and attenuates LPS-induced TNF-α and IL-10 secretion. High levels of IL-10 production and activation of STAT3 by LPS stimulation in TM indicate a regulatory macrophage phenotype. Our results suggest that TM maintain testicular immune privilege by inhibiting NF-κB signaling through impairment of IκBα ubiquitination and a general reduction of TLR cascade gene expression. However, TM do maintain some capacity for innate immune responses through AP-1 and CREB signaling pathways.
The Tolerogenic Function of Annexins on Apoptotic Cells Is Mediated by the Annexin Core Domain
Authors: Linke Björn , Abeler-Dörner Lucie , Jahndel Veronika , Kurz Alexandra , Mahr Andrea , Pfrang Sandra , Linke Linda , Krammer Peter H. , Weyd Heiko
Published: April 2015

Immunological tolerance is constantly being maintained in the periphery by dendritic cells processing material from apoptotic cells (ACs) in the steady-state. Although research has focused on the uptake of ACs by phagocytes, tolerogenic signals exposed by the ACs are much less well defined. In this article, we show that the annexin (Anx) family members AnxA5 and AnxA13 translocate to the surface of ACs to function as redundant tolerogenic signals in vitro and in vivo. Exposure of bone marrow–derived dendritic cells to AnxA5 or AnxA13 in vitro resulted in the inhibition of both proinflammatory cytokine secretion and the upregulation of costimulatory molecules upon TLR stimulation. The highly conserved Anx core domain was sufficient to mediate these effects, whereas recognition by N-formyl peptide receptor family members was dispensable. In vivo, coinjection of OVA-expressing and Anx-expressing ACs prevented induction of Ag-specific CD8+ T cells. Moreover, mice immunized with Anx-expressing ACs became refractory to an antigenic challenge. These results suggest that several Anxs contribute to AC-induced suppression of dendritic cell activation. Therefore, manipulating Anx-mediated immunosuppression may prove beneficial for patients with cancer or autoimmune diseases and chronic inflammatory disorders.
IL-37 Alleviates Rheumatoid Arthritis by Suppressing IL-17 and IL-17–Triggering Cytokine Production and Limiting Th17 Cell Proliferation
Authors: Ye Liang , Jiang Bo , Deng Jun , Du Jing , Xiong Wen , Guan Youfei , Wen Zhongyang , Huang Kunzhao , Huang Zhong
Published: April 2015

IL-37, a new member of the IL-1 cytokine family, is a natural inhibitor of innate immunity associated with autoimmune diseases. This study was undertaken to evaluate whether IL-37 has antiarthritic effects in patients with rheumatoid arthritis (RA) and in mice with collagen-induced arthritis (CIA). In this study, we analyzed the expression of IL-37 in PBMCs, serum, and lymphocytes from RA patients as well as CD4+ T cells polarized under Th1/Th2/Th17 conditions. The role of IL-37 was assessed by investigating the effects of recombinant human (rh)IL-37 and an adenovirus encoding human IL-37 (Ad–IL-37) on Th17 cells and Th17-related cytokines in RA patients and CIA mice. We found that active RA patients showed higher IL-37 levels compared with patients with inactive RA and healthy controls. Upregulated IL-37 expression also was found in CD3+ T cells and CD4+ T cells from RA patients and in Th1/Th17-differentiation conditions. rhIL-37 markedly decreased IL-17 expression and Th17 cell frequency in PBMCs and CD4+ T cells from RA patients. Furthermore, IL-37 exerted a more suppressive effect on Th17 cell proliferation, whereas it had little or no effect on Th17 cell differentiation. IL-17 and IL-17–driving cytokine production were significantly reduced in synovium and joint cells from CIA mice receiving injections of Ad–IL-37. Our findings indicate that IL-37 plays a potent immunosuppressive role in the pathogenesis of human RA and CIA models via the downregulation of IL-17 and IL-17–triggering cytokine production and the curbing of Th17 cell proliferation.
Critical Role of Mast Cells and Peroxisome Proliferator–Activated Receptor γ in the Induction of Myeloid-Derived Suppressor Cells by Marijuana Cannabidiol In Vivo
Authors: Hegde Venkatesh L. , Singh Udai P. , Nagarkatti Prakash S. , Nagarkatti Mitzi
Published: April 2015

Cannabidiol (CBD) is a natural nonpsychotropic cannabinoid from marijuana (Cannabis sativa) with anti-epileptic and anti-inflammatory properties. Effect of CBD on naive immune system is not precisely understood. In this study, we observed that administering CBD into naive mice triggers robust induction of CD11b+Gr-1+ myeloid-derived suppressor cells (MDSC) in the peritoneum, which expressed functional arginase 1, and potently suppressed T cell proliferation ex vivo. Furthermore, CBD-MDSC suppressed LPS-induced acute inflammatory response upon adoptive transfer in vivo. CBD-induced suppressor cells were comprised of CD11b+Ly6-G+Ly6-C+ granulocytic and CD11b+Ly6-G−Ly6-C+ monocytic subtypes, with monocytic MDSC exhibiting higher T cell–suppressive function. Induction of MDSC by CBD was markedly attenuated in Kit-mutant (KitW/W-v) mast cell–deficient mice. MDSC response was reconstituted upon transfer of wild-type bone marrow–derived mast cells in KitW/W-v mice, suggesting the key role of cKit (CD117) as well as mast cells. Moreover, mast cell activator compound 48/80 induced significant levels of MDSC in vivo. CBD administration in mice induced G-CSF, CXCL1, and M-CSF, but not GM-CSF. G-CSF was found to play a key role in MDSC mobilization inasmuch as neutralizing G-CSF caused a significant decrease in MDSC. Lastly, CBD enhanced the transcriptional activity of peroxisome proliferator-activated receptor γ in luciferase reporter assay, and PPAR-γ selective antagonist completely inhibited MDSC induction in vivo, suggesting its critical role. Together, the results suggest that CBD may induce activation of PPAR-γ in mast cells leading to secretion of G-CSF and consequent MDSC mobilization. CBD being a major component of Cannabis, our study indicates that marijuana may modulate or dysregulate the immune system by mobilizing MDSC.
MicroRNA-125a Inhibits Autophagy Activation and Antimicrobial Responses during Mycobacterial Infection
Authors: Kim Jin Kyung , Yuk Jae-Min , Kim Soo Yeon , Kim Tae Sung , Jin Hyo Sun , Yang Chul-Su , Jo Eun-Kyeong
Published: April 2015

MicroRNAs (miRNAs) are small noncoding nucleotides that play critical roles in the regulation of diverse biological functions, including the response of host immune cells. Autophagy plays a key role in activating the antimicrobial host defense against Mycobacterium tuberculosis. Although the pathways associated with autophagy must be tightly regulated at a posttranscriptional level, the contribution of miRNAs and whether they specifically influence the activation of macrophage autophagy during M. tuberculosis infection are largely unknown. In this study, we demonstrate that M. tuberculosis infection of macrophages leads to increased expression of miRNA-125a-3p (miR-125a), which targets UV radiation resistance-associated gene (UVRAG), to inhibit autophagy activation and antimicrobial responses to M. tuberculosis. Forced expression of miR-125a significantly blocked M. tuberculosis–induced activation of autophagy and phagosomal maturation in macrophages, and inhibitors of miR-125a counteracted these effects. Both TLR2 and MyD88 were required for biogenesis of miR-125a during M. tuberculosis infection. Notably, activation of the AMP-activated protein kinase significantly inhibited the expression of miR-125a in M. tuberculosis–infected macrophages. Moreover, either overexpression of miR-125a or silencing of UVRAG significantly attenuated the antimicrobial effects of macrophages against M. tuberculosis. Taken together, these data indicate that miR-125a regulates the innate host defense by inhibiting the activation of autophagy and antimicrobial effects against M. tuberculosis through targeting UVRAG.
Mechanistic Assessment of PD-1H Coinhibitory Receptor–Induced T Cell Tolerance to Allogeneic Antigens
Authors: Flies Dallas B. , Higuchi Tomoe , Chen Lieping
Published: April 2015

PD-1H is a recently identified cell surface coinhibitory molecule of the B7/CD28 immune modulatory gene family. We showed previously that single injection of a PD-1H agonistic mAb protected mice from graft-versus-host disease (GVHD). In this study, we report two distinct mechanisms operate in PD-1H–induced T cell tolerance. First, signaling via PD-1H coinhibitory receptor potently arrests alloreactive donor T cells from activation and expansion in the initiation phase. Second, donor regulatory T cells are subsequently expanded to maintain long-term tolerance and GVHD suppression. Our study reveals the crucial function of PD-1H as a coinhibitory receptor on alloreactive T cells and its function in the regulation of T cell tolerance. Therefore, PD-1H may be a target for the modulation of alloreactive T cells in GVHD and transplantation.
The Processed Amino-Terminal Fragment of Human TLR7 Acts as a Chaperone To Direct Human TLR7 into Endosomes
Authors: Hipp Madeleine M. , Shepherd Dawn , Booth Sarah , Waithe Dominic , Reis e Sousa Caetano , Cerundolo Vincenzo
Published: April 2015

TLR7 mediates innate immune responses to viral RNA in endocytic compartments. Mouse and human (h)TLR7 undergo proteolytic cleavage, resulting in the generation of a C-terminal fragment that accumulates in endosomes and associates with the signaling adaptor MyD88 upon receptor triggering by TLR7 agonists. Although mouse TLR7 is cleaved in endosomes by acidic proteases, hTLR7 processing can occur at neutral pH throughout the secretory pathway through the activity of furin-like proprotein convertases. However, the mechanisms by which cleaved hTLR7 reaches the endosomal compartment remain unclear. In this study, we demonstrate that, after hTLR7 proteolytic processing, the liberated amino (N)-terminal fragment remains bound to the C terminus through disulfide bonds and provides key trafficking information that ensures correct delivery of the complex to endosomal compartments. In the absence of the N-terminal fragment, the C-terminal fragment is redirected to the cell surface, where it is functionally inactive. Our data reveal a novel role for the N terminus of hTLR7 as a molecular chaperone that provides processed hTLR7 with the correct targeting instructions to reach the endosomal compartment, hence ensuring its biological activity and preventing inadvertent cell surface responses to self-RNA.
Upregulation of the N-Formyl Peptide Receptors in Scleroderma Fibroblasts Fosters the Switch to Myofibroblasts
Authors: Rossi Francesca Wanda , Napolitano Filomena , Pesapane Ada , Mascolo Massimo , Staibano Stefania , Matucci-Cerinic Marco , Guiducci Serena , Ragno Pia , di Spigna Gaetano , Postiglione Loredana , Marone Gianni , Montuori Nunzia , de Paulis Amato
Published: April 2015

Systemic sclerosis (SSc) is characterized by chronic inflammation and fibrosis. N-Formyl peptide (fMLF) receptors (FPRs) are chemotactic receptors involved in inflammation. Three FPRs have been identified: FPR1, FPR2, and FPR3. We have examined, by RT-PCR, Western blot and immunohistochemistry, FPRs expression in skin fibroblasts from 10 normal subjects and 10 SSc patients, showing increased expression in SSc fibroblasts. Several functions of FPRs occur through the interaction with a region of the urokinase-type plasminogen activator receptor (uPAR88–92), able to interact with FPRs and to mediate urokinase (uPA) or fMLF-dependent cell migration. Soluble uPAR84–95 peptide can act as a direct ligand of FPRs. Furthermore, uPA or its aminoterminal fragment (ATF) can promote the exposure of the uPAR88–92 region. The WKYMVm peptide is a FPRs pan-agonist. We investigated the functional effects of these agonists on normal and SSc fibroblasts. ATF, uPAR84–95, and WKYMVm regulated adhesion, migration, and proliferation of normal fibroblasts. Despite FPR overexpression, the response of SSc fibroblasts to the same agonists was greatly reduced, except for the proliferative response to ATF. SSc fibroblasts showed increased α-smooth muscle actin expression and improved capability to induce wound closure. Indeed, they overexpressed a cleaved uPAR form, exposing the uPAR88–92 region, and vitronectin, both involved in fibrosis and in the fibroblast-to-myofibroblast transition. FPR stimulation promoted α-smooth muscle actin expression in normal fibroblasts as well as motility, matrix deposition, αvβ5 integrin expression, and radical oxygen species generation in normal and SSc fibroblasts. This study provides evidence that FPRs may play a role in fibrosis and in the fibroblast-to-myofibroblast transition.
Allogeneic Mature Human Dendritic Cells Generate Superior Alloreactive Regulatory T Cells in the Presence of IL-15
Authors: Litjens Nicolle H. R. , Boer Karin , Zuijderwijk Joke M. , Klepper Mariska , Peeters Annemiek M. A. , Prens Errol P. , Verschoor Wenda , Kraaijeveld Rens , Ozgur Zeliha , van den Hout-van Vroonhoven Mirjam C. , van IJcken Wilfred F. J. , Baan Carla C. , Betjes Michiel G. H.
Published: April 2015

Expansion of Ag-specific naturally occurring regulatory T cells (nTregs) is required to obtain sufficient numbers of cells for cellular immunotherapy. In this study, different allogeneic stimuli were studied for their capacity to generate functional alloantigen-specific nTregs. A highly enriched nTreg fraction (CD4+CD25brightCD127− T cells) was alloantigen-specific expanded using HLA-mismatched immature, mature monocyte-derived dendritic cells (moDCs), or PBMCs. The allogeneic mature moDC-expanded nTregs were fully characterized by analysis of the demethylation status within the Treg-specific demethylation region of the FOXP3 gene and the expression of both protein and mRNA of FOXP3, HELIOS, CTLA4, and cytokines. In addition, the Ag-specific suppressive capacity of these expanded nTregs was tested. Allogeneic mature moDCs and skin-derived DCs were superior in inducing nTreg expansion compared with immature moDCs or PBMCs in an HLA-DR– and CD80/CD86-dependent way. Remarkably, the presence of exogenous IL-15 without IL-2 could facilitate optimal mature moDC-induced nTreg expansion. Allogeneic mature moDC-expanded nTregs were at low ratios (<1:320), potent suppressors of alloantigen-induced proliferation without significant suppression of completely HLA-mismatched, Ag-induced proliferation. Mature moDC-expanded nTregs were highly demethylated at the Treg-specific demethylation region within the FOXP3 gene and highly expressed of FOXP3, HELIOS, and CTLA4. A minority of the expanded nTregs produced IL-10, IL-2, IFN-γ, and TNF-α, but few IL-17–producing nTregs were found. Next-generation sequencing of mRNA of moDC-expanded nTregs revealed a strong induction of Treg-associated mRNAs. Human allogeneic mature moDCs are highly efficient stimulator cells, in the presence of exogenous IL-15, for expansion of stable alloantigen-specific nTregs with superior suppressive function.
C-Reactive Protein Directly Suppresses Th1 Cell Differentiation and Alleviates Experimental Autoimmune Encephalomyelitis
Authors: Zhang Lin , Liu Shan-Hui , Wright Tyler T. , Shen Zhi-Yuan , Li Hai-Yun , Zhu Wei , Potempa Lawrence A. , Ji Shang-Rong , Szalai Alexander J. , Wu Yi
Published: April 2015

Human C-reactive protein (CRP) is a serum-soluble pattern recognition receptor that serves as a marker of inflammation and directly contributes to innate immunity. In this study, we show that human CRP also directly contributes to adaptive immunity, that is, native CRP binds specifically to human Jurkat T cells and to mouse naive CD4+ T cells and modulates their Th1 and Th2 responses. In vitro both exogenously added (purified) and endogenously expressed (via transfection) human CRP inhibited Th1 differentiation and augmented Th2 differentiation of naive CD4+ T cells. In vivo for human CRP transgenic compared with wild-type mice, a lesser proportion of the T cells recovered from the spleens of healthy animals were Th1 cells. Moreover, in both CRP transgenic mice and in wild-type mice treated with human CRP, during myelin oligodendrocyte glycoprotein peptide–induced experimental autoimmune encephalomyelitis both the Th1 cell response and disease severity were inhibited. These pattern recognition–independent actions of CRP directly on T cells highlights the potential for this soluble pattern recognition receptor to act as a tonic regulator of immunity, shaping global adaptive immune responses during both homeostasis and disease.
A New Approach for the Treatment of Arthritis in Mice with a Novel Conjugate of an Anti-C5aR1 Antibody and C5 Small Interfering RNA
Authors: Mehta Gaurav , Scheinman Robert I. , Holers V. Michael , Banda Nirmal K.
Published: April 2015

Rheumatoid arthritis (RA) is an inflammatory autoimmune joint disease in which the complement system plays an important role. Of the several components of complement, current evidence points to C5 as the most important inducer of inflammation. Several groups generated Abs or small interfering RNAs (siRNAs) or small molecule inhibitors against C5 and C5aR1 (CD88) that have showed some efficacy in RA in animal models. However, none of these candidate therapeutics has moved from bench to bedside. In this study, we test in collagen Ab-induced arthritis (CAIA) a new therapeutic strategy using a novel anti–C5ab-C5 siRNA conjugate. We first demonstrate that although C5aR2 or C5L2 (GPR77) plays no role in CAIA, C5aR1 contributes to pathogenesis. We demonstrate that injection of siRNAs blocking C5, C5aR1, or the combination decreased clinical disease activity in mice with CAIA by 45%, 51%, and 58%, respectively. Anti-C5 Ab (BB5.1) has only limited efficacy, but significantly reduced arthritis up to 66%. We then generated a novel anti-C5aR1 Ab–protamine–C5 siRNA conjugate. To our knowledge, we show for the first time that whereas unconjugated Ab plus siRNAs reduce arthritis by 19%, our anti-C5aR1 Ab–protamine–C5 siRNA conjugate was effective in reducing arthritis by 83% along with a parallel decrease in histopathology, C3 deposition, neutrophils, and macrophages in the joints of mice with CAIA. These data suggest that by targeting anti-C5 siRNAs to the receptor for its C5a activation fragment (C5aR1), a striking clinical effect can be realized.
Graphs and two-step nilpotent Lie algebras
Authors: Mainkar Meera G.
Published: April 2015

We consider a method popular in the literature of associating a two-step nilpotent Lie algebra with a finite simple graph. We prove that the two-step nilpotent Lie algebras associated with two graphs are Lie isomorphic if and only if the graphs from which they arise are isomorphic.
Dynamics on the PSL(2, $\mathbb C$)-character variety of a twisted $I$-bundle
Authors: Lee Michelle
Published: April 2015

Let

M

be a twisted interval bundle over a closed nonorientable hyperbolizable surface. Let

\mathcal{X}(M)

be the PSL(2,

\mathbb C

)-character variety of

\pi_1(M)

. We examine the dynamics of the action of Out

(\pi_1(M))

on

\mathcal{X}(M),

and in particular, we find an open set on which the action is properly discontinuous that is strictly larger than the interior of the deformation space of marked hyperbolic

3

-manifolds homotopy equivalent to

M

. Furthermore, we identify which discrete and faithful representations can lie in a domain of discontinuity for the action of Out

(\pi_1(M))

on

\mathcal{X}(M)

.
Stability in orbit equivalence for Baumslag–Solitar groups and Vaes groups
Authors: Kida Yoshikata
Published: April 2015

A measure-preserving action of a discrete countable group on a standard probability space is called stable if the associated equivalence relation is isomorphic to its direct product with the ergodic hyperfinite equivalence relation of type

\mathrm {II}_1

. We show that any Baumslag–Solitar group has such an ergodic, free and stable action. It follows that any Baumslag–Solitar group is measure equivalent to its direct product with any amenable group. The same property is obtained for the inner amenable groups of Vaes.
Right-angled Artin groups and Out($\mathbb F_n$) – I. Quasi-isometric embeddings
Authors: Taylor Samuel J.
Published: April 2015

We construct quasi-isometric embeddings from right-angled Artin groups into the outer automorphism group of a free group. These homomorphisms are modeled on the homomorphisms into the mapping class group constructed by Clay, Leininger, and Mangahas. Toward this goal, we develop tools in the free group setting that mirror those for surface groups and discuss various analogs of subsurface projection.
Thompson's group $F$ is not SCY
Authors: Friedl Stefan , Vidussi Stefano
Published: April 2015

In this note we prove that Thompson's group

F

cannot be the fundamental group of a symplectic 4-manifold with canonical class

K = 0 \in H^{2}(M)

by showing that its Hausmann–Weinberger invariant

q(F)

is strictly positive.
Neurological Sequelae of Hospitalized Japanese Encephalitis Cases in Gansu Province, China
Authors: Yin Zundong , Wang Xuxia , Li Li , Li Hui , Zhang Xiaoshu , Li Junhong , Ning Guijun , Li Fengqin , Liang Xuefeng , Gao Li , Liang Xiaofeng , Li Yixing
Published: April 2015

We conducted a follow-up survey for 55 Japanese encephalitis (JE) cases 1–2 years after hospital discharge in Gansu province, China. Community-, education-, and gender-matched healthy individuals without history of neurologic disease were selected as the comparison group. All subjects received neurological examination, intelligence quotient (IQ) measurement, adaptive behavior measurement, and Wechsler memory scale (WMS) assessment. We found 43.6% JE cases had at least one nervous system sequelae compared with 3.6% healthy individuals. Among JE cases, 22.4% had subnormal IQ, 18.4% subnormal verbal IQ (VIQ), 20.4% subnormal performance IQ (PIQ), and 78.4% had subnormal memory quotient (MQ). Among healthy individuals, 2.0% had subnormal IQ, VIQ, or PIQ and 8.1% had subnormal MQ. Among adult JE cases, 47.8% and 39.1% had adaptive behavior impairments and intellectual disability, respectively, compared with 18.8% and 9.7% among young cases, respectively. The results showed both adult and young surviving JE cases had significant neurological sequelae and mental disability 1–2 years after discharged.
Histoplasmosis in Israeli Travelers
Authors: Segel Michael J. , Rozenman Judith , Lindsley Mark D. , Lachish Tamar , Berkman Neville , Neuberger Ami , Schwartz Eli
Published: April 2015

Histoplasmosis is a common endemic human mycoses acquired mostly in the Americas. We reviewed 23 cases of histoplasmosis in Israeli travelers; 22 had traveled to Central or South America and one to North America. Fourteen cases had been exposed to bat habitats and were symptomatic, presenting ≤ 3 months after their return. Asymptomatic patients (N = 9) were diagnosed during the evaluation of incidental radiological findings or because a travel partner had been suspected of Histoplasma infection, 16–120 months after their return. Serological testing was positive in 75% of symptomatic cases but only 22% of asymptomatic cases. Histoplasmosis should be considered in travelers returning from the Americas with respiratory or febrile illness within weeks of return, particularly if exposed to bat habitats. Travel history is essential in patients presenting with pulmonary nodules, even years after travel to endemic countries.
Polymorphisms in the K13-Propeller Gene in Artemisinin-Susceptible Plasmodium falciparum Parasites from Bougoula-Hameau and Bandiagara, Mali
Authors: Ouattara Amed , Kone Aminatou , Adams Matthew , Fofana Bakary , Maiga Amelia Walling , Hampton Shay , Coulibaly Drissa , Thera Mahamadou A. , Diallo Nouhoum , Dara Antoine , Sagara Issaka , Gil Jose Pedro , Bjorkman Anders , Takala-Harrison Shannon , Doumbo Ogobara K. , Plowe Christopher V. , Djimde Abdoulaye A.
Published: April 2015

Artemisinin-resistant Plasmodium falciparum malaria has been documented in southeast Asia and may already be spreading in that region. Molecular markers are important tools for monitoring the spread of antimalarial drug resistance. Recently, single-nucleotide polymorphisms (SNPs) in the PF3D7_1343700 kelch propeller (K13-propeller) domain were shown to be associated with artemisinin resistance in vivo and in vitro. The prevalence and role of K13-propeller mutations are poorly known in sub-Saharan Africa. K13-propeller mutations were genotyped by direct sequencing of nested polymerase chain reaction (PCR) amplicons from dried blood spots of pre-treatment falciparum malaria infections collected before and after the use of artemisinin-based combination therapy (ACT) as first-line therapy in Mali. Although K13-propeller mutations previously associated with delayed parasite clearance in Cambodia were not identified, 26 K13-propeller mutations were identified in both recent samples and pre-ACT infections. Parasite clearance time was comparable between infections with non-synonymous K13-propeller mutations and infections with the reference allele. These findings suggest that K13-propeller mutations are present in artemisinin-sensitive parasites and that they preceded the wide use of ACTs in Mali.
Factors Determining Water Treatment Behavior for the Prevention of Cholera in Chad
Authors: Lilje Jonathan , Kessely Hamit , Mosler Hans-Joachim
Published: April 2015

Cholera is a well-known and feared disease in developing countries, and is linked to high rates of morbidity and mortality. Contaminated drinking water and the lack of sufficient treatment are two of the key causes of high transmission rates. This article presents a representative health survey performed in Chad to inform future intervention strategies in the prevention and control of cholera. To identify critical psychological factors for behavior change, structured household interviews were administered to N = 1,017 primary caregivers, assessing their thoughts and attitudes toward household water treatment according to the Risk, Attitude, Norm, Ability, and Self-regulation model. The intervention potential for each factor was estimated by analyzing differences in means between groups of current performers and nonperformers of water treatment. Personal risk evaluation for diarrheal diseases and particularly for cholera was very low among the study population. Likewise, the perception of social norms was found to be rather unfavorable for water treatment behaviors. In addition, self-reported ability estimates (self-efficacy) revealed some potential for intervention. A mass radio campaign is proposed, using information and normative behavior change techniques, in combination with community meetings focused on targeting abilities and personal commitment to water treatment.
Community Prevalence of Fever and Relationship with Malaria Among Infants and Children in Low-Resource Areas
Authors: Prasad Namrata , Sharples Katrina J. , Murdoch David R. , Crump John A.
Published: April 2015

We used Demographic and Health Survey data to describe the 2-week period prevalence of fever, cough, and diarrhea among children aged < 5 years in low-resources areas. We then explored the relationship between prevalence of isolated fever and national malaria risk. Fever and isolated fever occurred in 26.7% and 7.0% of children, respectively, and was not fully explained by malaria.
Geophagy is Associated with Environmental Enteropathy and Stunting in Children in Rural Bangladesh
Authors: George Christine Marie , Oldja Lauren , Biswas Shwapon , Perin Jamie , Lee Gwenyth O. , Kosek Margaret , Sack R. Bradley , Ahmed Shahnawaz , Haque Rashidul , Parvin Tahmina , Azmi Ishrat J. , Bhuyian Sazzadul Islam , Talukder Kaisar A. , Mohammad Shahnaij , Faruque Abu G.
Published: April 2015

There is a growing body of literature indicating an association between stunting and environmental enteropathy (EE), a disorder thought to be caused by repeated exposures to enteric pathogens. To investigate the relationship between exposure to enteric pathogens through geophagy, consumption of soil, EE, and stunting, we conducted a prospective cohort study of 216 children under 5 years of age in rural Bangladesh. Geophagy was assessed at baseline using 5 hour structured observation and caregiver reports. Stool was analyzed for fecal markers of intestinal inflammation: alpha-1-antitrypsin, myeloperoxidase, neopterin (all three combined to form an EE disease activity score), and calprotectin. Eighteen percent of children had observed geophagy events by structured observation and 28% had caregiver reported events in the past week. Nearly all households had Escherichia coli (97%) in soil, and 14% had diarrheagenic E. coli. Children with caregiver-reported geophagy had significantly higher EE scores (0.72 point difference, 95% confidence interval [CI]: 0.01, 1.42) and calprotectin concentrations (237.38 μg/g, 95% CI: 12.77, 462.00). Furthermore, at the 9-month follow-up the odds of being stunted (height-for-age z-score < −2) was double for children with caregiver-reported geophagy (odds ratio [OR]: 2.27, 95% CI: 1.14, 4.51). These findings suggest that geophagy in young children may be an important unrecognized risk factor for EE and stunting.
Diagnosis of Schistosoma haematobium Infection with a Mobile Phone-Mounted Foldscope and a Reversed-Lens CellScope in Ghana
Authors: Ephraim Richard K. D. , Duah Evans , Cybulski James S. , Prakash Manu , D'Ambrosio Michael V. , Fletcher Daniel A. , Keiser Jennifer , Andrews Jason R. , Bogoch Isaac I.
Published: April 2015

We evaluated two novel, portable microscopes and locally acquired, single-ply, paper towels as filter paper for the diagnosis of Schistosoma haematobium infection. The mobile phone-mounted Foldscope and reversed-lens CellScope had sensitivities of 55.9% and 67.6%, and specificities of 93.3% and 100.0%, respectively, compared with conventional light microscopy for diagnosing S. haematobium infection. With conventional light microscopy, urine filtration using single-ply paper towels as filter paper showed a sensitivity of 67.6% and specificity of 80.0% compared with centrifugation for the diagnosis of S. haematobium infection. With future improvements to diagnostic sensitivity, newer generation handheld and mobile phone microscopes may be valuable tools for global health applications.
Thyroid Cancer in Patients with Hyperthyroidism
Authors: Tastan Baki , Dogu Alper , Sevim Yusuf
Published: April 2015

Background and objective

Malignant tumors of the thyroid gland are the most common of the endocrine malignancies. Although, patients with thyroid cancer have high 5 years survival rate, thyroid cancer is the most seen cause of mortality among cancers of the endocrine organs. The incidence of thyroid cancer in hyperthyroid patients varies from 0.1 to 21% in the literature. We aimed in this study to analyze the frequency of coexisting thyroid cancer and hyperthyroidism in our experience.

Results

Total 230 patients, who were operated for hyperthyroidism without the suspicion of thyroid malignancy between January 2005 and September 2010 were included in our study. Toxic multinodular goiter, toxic adenoma and Graves’ disease were diagnosed preoperatively in 187, 16 and 27 patients respectively. Histopathological thyroid malignancy was detected in 13 patients (5.7%).

Conclusion

Thyroid cancer with variable incidence up to 21% should be remembered in differential diagnosis of hyperthyroid patients.

How to cite this article

Tastan B, Dogu A, Sevim Y. Thyroid Cancer in Patients with Hyperthyroidism. World J Endoc Surg 2015;7(2):29-32.