bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidemiological study of shigellosis in an urban area of Argentina
Authors: Rolfo Florencia , Marin Gustavo Horacio , Silberman Martin , Pattin Jorgelina , Giugnio Silvina , Gatti Blanca , Bettiol Marisa , Rigoni Ana
Published: April 2012

Introduction: Shigellosis represents one of the main causes of bloody diarrhoea in South America. This study aimed to establish the incidence of shigellosis in an urban zone of Buenos Aires, Argentina, by examining the type of Shigella and living conditions associated with this infection. Methodology: Between January 2009 and December 2010 we analyzed shigellosis in children admitted to the public health service with bloody diarrhoea from La Plata, the capital of Buenos Aires, Argentina. A total of 372 children under 15 years old with Shigella present in their stool samples were admitted to the study. Variables studied were patient age, type of Shigella, family economic status, and access to sewage services and safe drinking water. Results: Shigella flexneri was found to be present in 66.8% of the cases. Incidence was 187 cases/year/100,000 children under 15 years old. Cases were mainly observed during the summer (38.5%) in the population of under 5 years old (69.1% of all cases). The risk of shigellosis increased 12 times in those children who lacked safe drinking water and this risk increased 1.5 times in the population without sewage services. Fewer cases of shigellosis were noted in downtown areas, while hot spots were identified in the suburbs. Treating one case of shigellosis has a local cost of US $976 while assuring safe drinking water and sewage services for one family costs US $634.  Conclusion: Incidence of shigellosis in urban areas is associated with quality of water and sewage services. Policies aimed at providing education and improving public utilities networks can help to reduce the incidence of shigellosis.
Diagnostic potential of nested PCR, galactomannan EIA, and Beta-D-glucan for invasive aspergillosis in pediatric patients
Authors: Badiee Parisa , Alborzi Abdolvahab , Karimi Mahammad , Pourabbas Bahman , Haddadi Pedram , Mardaneh Jalal , Moieni Mahsa
Published: April 2012

Introduction: Limited specific data and investigations are available for invasive aspergillosis (IA) in pediatric patients. We evaluated the diagnostic potential of three noninvasive tests including the Platelia Aspergillus EIA kit for using galactomannan antigen, (1,3)-β-D-glucan Detection Reagent Kit, and nested-PCR for Aspergillus DNA in sera. We evaluated the diagnostic potential of three noninvasive tests including EIA for galactomannan antigen  (Platelia Aspergillus), nested  PCR assay for Aspergillus DNA and test for  (1→3)-β-D-glucan (Glucatell assay Kit). Methodology: All pediatric patients treated at the hematology/oncology unit who were at increased risk of developing invasive aspergillosis were enrolled. Clinical samples were examined for Aspergillus infections by mycological methods. Serial blood samples were collected twice weekly and evaluated by noninvasive tests. Results: We analyzed 230 consecutive blood samples from 62 pediatric patients. The incidence rate of invasive aspergillosis in the patients was found to be 27.4%, and the etiologic agents were Aspergillus flavus, Aspergillus fumigatus, and Aspergillus spp.  The sensitivity, specificity, positive and negative predictive values, and likelihood ratios for positive and negative results of galactomannan in patients with proven and probable IA were 90%, 92%, 81.8%, 96%, 11.25, and 0.1; for beta-D-glucan they were 50%, 46%, 26%, 70.6%, 0.9, 0.9; and for nested-PCR they were 80%, 96.2%, 88.9%, 92.6%, 21, and 0.2, respectively. Conclusions: The conventional methods are not able to detect IA, due to the lack of valid and proper sampling. Galactomannan and nested-PCR tests in serum, with enough accuracy and reliability, can serve as noninvasive methods for the detection of IA in pediatric patients. However, the beta-D-glucan test cannot serve as an efficient diagnostic tool in those with hematologic disorders.
First isolation in Argentina of a highly virulent Shiga toxin-producing Escherichia coli O145:NM from a domestic cat
Authors: Rumi María Valeria , Irino Kinue , Deza Natalia , Huguet Miguel J , Bentancor Adriana B
Published: April 2012

Introduction: Hemolytic uremic syndrome (HUS) is distributed worldwide. In Argentina, more than 450 cases of HUS, mostly sporadic, are reported annually. The main serotype isolated is O157:H7, and among non-O157 STEC, O145:NM is the most frequent strain. We studied the relationship of companion animals living in contact with a child with sporadic HUS, as carriers of Shiga toxin-producing Escherichia coli (STEC) strains. Methodology: Duplicate rectal swab samples were taken weekly from the household cat and dog at the home of a patient with HUS. Samples were plated on MacConkey and sorbitol MacConkey-CT agar. Confluent growth from each plate was screened for the presence of stx1, stx2 and rfbO157 gene by PCR assays. Up to 300 individual colonies taken from positive plates at screening were retested by PCR. Results: The strain from the cat belonged to the highly virulent serotype O145:NM. Although this strain differed antigenically from the strain isolated from a child with HUS living in the same house, both carried the stx2, eae and ehxA virulence genes. The strain isolated from the dog belonged to the serotype O178:H19. Conclusions: An asymptomatic household cat may harbour the high virulent STEC strain, such as O145:NM, the second most frequently STEC serotype associated with HUS in Argentina. Companion animals are probably exposed to the same sources as the humans. More studies are needed to establish dogs and cats as sources of infection in the epidemiological cycle of infections caused by STEC strains, and to develop effective control strategies for this pathogen.
OXA-type carbapenemases in Acinetobacter baumannii in South America
Authors: Opazo Andrés , Domínguez Mariana , Bello Helia , Amyes Sebastian G.B. , González-Rocha Gerardo
Published: April 2012

Acinetobacter baumannii is an opportunistic pathogen that is frequently involved in outbreaks of infection, occurring mostly in intensive care units. The increasing incidence of carbapenem resistance in A. baumannii worldwide is a concern since it limits drastically the range of therapeutic alternatives. The most important mechanism of carbapenem resistance is the enzymatic hydrolysis mediated by carbapenemases. In A. baumannii these enzymes are usually OXA-type carbapenemases, and belong to class D according to the classification of Ambler. The OXA-type carbapenemases are divided into five subgroups, four of which correspond to acquired carbapenemases, which accounts for the distribution of genes blaOXA in different geographic areas. In this work we review the different types of OXA-type carbapenemases present in A. baumannii, emphasizing the current situation in South America with special mention to the findings in Chile.
Spontaneous splenic rupture in dengue fever with non-fatal outcome in an adult
Authors: Bhaskar Emmanuel , Moorthy Swathy
Published: April 2012

A 26-year-old male presented with fever for five days and abdominal pain for 24 hours. System examination identified a soft abdomen with diffuse tenderness. CT-abdomen findings were consistent with splenic rupture with intra and peri-splenic hematoma. Laboratory investigations showed a platelet count of 40,000 per mm3. In due course he developed hypotension and underwent splenectomy. Non-structural protein 1 (NS1) dengue antigen was positive in the admission sample and IgM dengue antibodies were detected in the follow-up sample. Histopathology of the spleen showed normal architecture with no evidence of hyperplasia, cellular infiltrates or haematological malignancy. Splenic rupture is a rare, but potentially fatal complication of dengue fever and severe dengue which should be suspected when a patient presents with abdominal pain and hypotension. Our case highlights the occurrence of splenic rupture in the viremic phase of dengue illness before the development of IgM antibodies.
Delayed Presentation of Traumatic Dislocation of a Visian Implantable Collamer Lens
Authors: Schmitz Joseph W. , McEwan Gavin C. , Hofmeister Elizabeth M.
Published: April 2012

PURPOSE:

To report traumatic dislocation of a Visian Implantable Collamer Lens (ICL, STAAR Surgical Co) discovered on routine examination.

METHODS:

A 26-year-old man was found to have ICL subluxation into the anterior chamber with pupillary capture on routine screening examination. The patient reported being punched near the left eye 2 weeks earlier. He noted mild blurry vision, no pain, and uncorrected distance visual acuity (UDVA) was 20/30, which was decreased from his baseline of 20/20 in the affected eye.

RESULTS:

Surgical repositioning was performed under pupillary dilation without complication. Postoperatively, UDVA was 20/20
−2
. Persistent pigment on the ICL, slight pupillary margin peaking, and anterior chamber inflammation were noted.

CONCLUSIONS:

Traumatic ICL dislocation may occur with minimal signs and symptoms. Education of patients about the necessity for examination after ocular trauma and need to wear eye protection during activities at high risk of ocular trauma are important.
Conception de leçons multimédia : liberté ou guidage ?
Authors: Bertin Jean-Claude
Published: April 2012

La conception de matériaux multimédia par tous les formateurs est maintenant chose possible grâce à de nouveaux systèmes-auteurs dont l’ergonomie limite au maximum le recours aux connaissances informatiques. La liberté de création ainsi offerte permet de répondre de manière plus appropriée aux besoins de tous les apprenants. Lors d’une récente enquête, l’auteur a pu dégager une corrélation entre le niveau de compétence linguistique des apprenants et leur attente en matière d’autonomie dans les didacticiels. Ceci pose le problème de l’organisation de la navigation au sein de ces didacticiels. Cette communication se propose d’exposer les résultats de cette enquête et de suggérer différentes manières d’adapter un même contenu pédagogique à des apprenants aux attentes différentes.
Service Composition Based Software Solution Design
Authors: Mo Tong , Xu Jingmin , Wang Zhongjie , Ma Yufei , Huang Heyuan , Wang Yuan , Liu Ying , Zhu Jun , Xu Xiaofei
Published: April 2012

Service composition and Web mash-up are promising for meeting specific business requirements by integrating multiple distributed services and SaaS (Software as a Service) has become a popular way of software development and delivery paradigm. An application that meets the business challenges the customer faces in managing its supply chain by integrating two existing SaaS offerings into a newly developed technology presented to validate the service composition technologies. This paper contributes with a practice of a light weight approach of the problems that are inevitable in SaaS integration such as data synchronization, process control, and identification. The purpose of this paper tries to provide a reference for researchers and engineers in this domain.
An Ideation Framework for Service Process Improvement
Authors: Kaner Maya , Karni Reuven
Published: April 2012

Service delivery processes play a key role in the competitiveness of modern organizations. Their effectiveness and efficiency are a consequence of successful design of new processes and improvement of existing processes. Improvement methodologies commonly focus on generic steps serving as a road map for moving a process from its current state along a guided path to better performance. However, these methodologies ignore the crucial step of methods for modifying processes, which often necessitate the generation of new improvement alternatives; generally based on “randomized” brainstorming rather than on systematic triggering of new ideas and reusing past improvements. The authors’ framework comprises and integrates 21 goal determinants to be achieved through process redesign, 32 best practices describing possible process modifications, 40 TRIZ inventive principles for generating new improvement ideas, and case-based reasoning (CBR) for retaining and reusing past improvements. This paper illustrates the application of the proposed methodology using an example of an inbound telesales process.
Peer-to-Peer Overlay for the IP Multimedia Subsystem
Authors: Lin Ling , Liotta Antonio
Published: April 2012

The growth of the Internet and its popular services are forcing telecom operators to provide advanced services to their subscribers, as traditional voice services are no longer enough to attract more customers. To enable more innovative and value-added IP services and take advantage of the services that the Internet provides, the IP Multimedia Subsystem (IMS) is introduced. The IMS provides a complete access-agnostic architecture and framework that facilitates the convergence of the mobile network, removing the gap between the two most successful communication networks: cellular and Internet network. The harmonized All-IP platform has the potential to provide all Internet services with a more cost-effective and more efficient architecture than the circuit-switched networks do. However, by merging two of the most successful networks, the integration of two network models with different concerns and motivations is not without its problems, among which, the scalability issue is the most essential when supporting content delivery services. The purpose of this chapter is to study and design a new content delivery network infrastructure, PeerMob, merging the Peer-to-Peer technology with the IMS framework, which benefits IMS with scalability, reliability, and efficiency features coming with decentralized P2P architecture. The chapter also puts this P2P IMS paradigm under realistic network conditions and strenuous simulation to evaluate the performance of the P2P IMS system.
Recent Advances in Peer-to-Peer Video Streaming by Using Scalable Video Coding
Authors: Grois Dan , Hadar Ofer
Published: April 2012

Scalable Video Coding provides important functionalities, such as the spatial, temporal, and SNR (quality) scalability, thereby significantly improving coding efficiency over prior standards such as the H.264/AVC and enabling the power adaptation. In turn, these functionalities lead to the enhancement of the video streaming over Peer-to-Peer networks, thereby providing a powerful platform for a variety of multimedia streaming applications, such as video-on-demand, video conferencing, live broadcasting, and many others. P2P systems are considered to be extremely cost-effective, since they utilize resources of the peer machines (e.g., CPU resources, memory resources, and bandwidth). However, since bandwidth is usually not constant and also since Peer-to-Peer networks suffer from the packet loss, there is no guarantee for the end-user video presentation quality. In addition, due to different server and end-user hardware configurations, it will be useful to specify the quality of the media (e.g., the bit-rate, spatial/temporal resolution, and the like). As a result, the Scalable Video Coding approach is an excellent choice, since the media streaming can be adjusted to a suitable stream to fit a particular Peer-to-Peer network and particular end-user requirements.
Genomics Perspectives of Bioethanol Producing Zymomonas Mobilis
Authors: Asraf S. Sheik , Rajnish K.N. , Gunasekaran P.
Published: April 2012

In recent years, there has been continuous increase in demand for fossil fuels that has led to the need for new potential fuel sources. Biofuels, in particular ethanol, are of high interest because of dwindling fossil fuels. Among the ethanol producers, Zymomonas mobilis has acquired greater interest because it is a renewable source of bioethanol. Zymomonas mobilis is an aerotolerant, gram-negative, ethanol producing bacterium that shows high ethanol yield, tolerance, and greater productivity. This chapter focuses on recent efforts made to engineer Z. mobilis, transcriptomic, genome-based metabolomic studies, and bioinformatics exploitation of the available genomic data for the production of bioethanol. Recently, several bioinformatics tools have been used to predict the functional properties of the carbohydrate active ethanologenic enzymes in Z. mobilis. A number of processes were used to study the functional properties of the ethanologenic enzymes of Z. mobilis. Thus, functional genomics seeks to apply technologies that would help to improve the production of bioethanol by Z. mobilis.
Interactive Diagram Layout
Authors: Maier Sonja , Minas Mark
Published: April 2012

The authors also describe a framework that enables the creation of a layout engine, which satisfies the user demands identified in a user study. The approach is capable of defining layout behavior for various visual languages like graphs, class diagrams, mindmaps, business process models, or even GUI forms. The framework enables the combination of different layout approaches and provides the possibility to reuse already defined layout behavior.
Availability Analysis of IaaS Cloud Using Analytic Models
Authors: Longo Francesco , Ghosh Rahul , Naik Vijay K. , Trivedi Kishor S.
Published: April 2012

Cloud based systems are inherently large scale. Failures in such a large distributed environment are quite common phenomena. To reduce the overall Cloud downtime and to provide a seamless service, providers need to assess the availability characteristics of their data centers. Such assessments can be done through controlled experimentations, large scale simulations and via analytic models. In the scale of Cloud, conducting repetitive experimentations or simulations might be costly and time consuming. Analytic models, on the other hand, can be used as a complement to small scale measurements and simulations since the analytic results can be obtained quickly. However, accurate analytic modeling requires dealing with large number of system states, leading to state-space explosion problem. To reduce the complexity of analysis, novel analytic methods are required. This chapter introduces the reader to a novel approach using interacting analytic sub-models and shows how such approach can deal with large scale Cloud availability analysis. The chapter puts the work in perspective of other existing and ongoing research in this area, describe how such approach can be useful to Cloud providers, especially in the case of federated scenarios, and summarize the open research questions that are yet to be solved.
Monitoring Services in a Federated Cloud
Authors: Clayman Stuart , Toffetti Giovanni , Galis Alex , Chapman Clovis
Published: April 2012

This chapter presents the need, the requirements, and the design for a monitoring system that is suitable for supporting the operations and management of a Federated Cloud environment. The chapter discusses these issues within the context of the RESERVOIR Service Cloud computing project. It first presents the RESERVOIR architecture itself, then introduces the issues of service monitoring in a federated environment, together with the specific solutions that have been devised for RESERVOIR. It ends with a review of the authors’ experience in this area by showing a use-case application executing on RESERVOIR, which is responsible for the computational prediction of organic crystal structures.
Designing Multiplayer Online Games Using the Real-Time Framework
Authors: Gorlatch Sergei , Glinka Frank , Ploss Alexander , Meiländer Dominik
Published: April 2012

This chapter describes a novel, high-level approach to designing and executing online computer games. The approach is based on our Real-Time Framework (RTF) and suits a wide spectrum of online games including Massively Multiplayer Online Games (MMOG) and First-Person Shooters (FPS). The authors address major design issues like data structures and Area of Interest (AoI), with a special focus on the scalability of games implemented on multiple servers, including distribution of the game state, inter-server communication, object serialization and migration, etc. The chapter illustrates the approach with two case studies: the design of a new multi-player online game and bringing the single-server commercial game Quake 3 to multiple servers in order to increase the number of simultaneous players. The authors show the place of their approach in the taxonomy of game development approaches, and they report experimental results on the performance of games developed using RTF.
Low Cost Immersive VR Solutions for Serious Gaming
Authors: Sandaruwan Damitha , Kodikara Nihal , Keppitiyagama Chamath , Rosa Rexy , Dias Kapila , Senadheera Ranjith , Manamperi Kanchana
Published: April 2012

Games are used for other purposes than providing entertainment. This chapter is particularly interested in serious games, also known as simulators, with immersive virtual reality environments that are used for training and teaching purposes. These simulators have very stringent requirements and as a result, they are expensive to build. However, the authors managed to develop a ship handling simulator for the Sri Lanka Navy, at a cost of less than $20,000, which is an order of magnitude less costly than the cheapest available ship handling simulators. The cost of the simulator was kept at a minimum by using Commodity-Off-The-Shelf (COTS) hardware, Free and Open Source Software (FOSS), and also by adopting a development strategy which kept the client involved in the complete life cycle of the development. The availability of the required manpower at a very low cost in Sri Lanka was also beneficial.
Enterprise System Development in Higher Education
Authors: Chae Bongsug , Poole Marshall Scott
Published: April 2012

This chapter reports a case in which a major university system in the US attempted to develop an in-house enterprise system. The system is currently used by over 4000 individual users in almost 20 universities and state agencies. This case offers a historical analysis of the design, implementation, and use of the system from its inception in the mid 1980s to the present. This case indicates that ES design and implementation in higher education is quite challenging and complex due to unique factors in the public sector—including state mandates/requirements, IT leadership/resources, value systems, and decentralized organizational structure, among other things—that must be taken into account in planning, designing, and implementing ES (Ernst, Katz, & Sack, 1994; Lerner, 1999; McCredie, 2000). This case highlights (1) the challenges and issues in the rationale behind “one system for everyone” and (2) some differences as well as similarities in IT management between the private and public sectors. It offers some unique opportunities to discuss issues, challenges, and potential solutions for the deployment of ES in the public arena, particularly in higher education.
Planning and Implementing Online Programs
Authors: Bishop Kay , Kroll Christine
Published: April 2012

This case study reviews the planning, development, and initial implementation of an online Master’s of Library Science (MLS) degree program at a large public research university. The development process will be presented from both a school-based and a department-based perspective. A review of the literature found articles and books that address online programs in education and library science; however, the majority of those publications focus on either the experiences of students or the concerns of faculty members who deliver courses through distance education technologies. Very few of the resources address the full spectrum of planning, developing, and implementing an online program. The authors found that the MLS program development process greatly benefited from existing school-based policies and procedures, while some barriers and challenges were also encountered in the context of customizing those policies and procedures for the Library and Information Studies (LIS) department. The authors believe these experiences will inform practices at other institutions and departments considering initiating online programs.
Lab Development for Delivering Information Systems Courses Online at Small Campuses
Authors: Chao Li
Published: April 2012

In this case study, you will encounter some of the issues of lab development for delivering lab-based information systems courses online. Many small campuses have very limited budget or no budget at all for the computer lab specifically designed for information systems majors. Sometimes, even with new computers purchased, very few people know how to set them up for lab-based information systems (IS) courses. What are the software and hardware requirements for getting the lab online? How much will it cost? Where can you find resources for the lab development? To ensure quality teaching on IS-related topics, you have to deal with these issues. This case study will discuss how to create a lab that allows students to get hands-on practice for courses such as network management or database processing online with a shoestring budget.
Recombinant Viral-Vectored Vaccines Expressing Plasmodium chabaudi AS Apical Membrane Antigen 1: Mechanisms of Vaccine-Induced Blood-Stage Protection
Authors: Biswas Sumi , Spencer Alexandra J. , Forbes Emily K. , Gilbert Sarah C. , Holder Anthony A. , Hill Adrian V. S. , Draper Simon J.
Published: April 2012

Apical membrane Ag 1 (AMA1) is one of the leading candidate Ags for inclusion in a subunit vaccine against blood-stage malaria. However, the efficacy of Ab-inducing recombinant AMA1 protein vaccines in phase IIa/b clinical trials remains disappointing. In this article, we describe the development of recombinant human adenovirus serotype 5 and modified vaccinia virus Ankara vectors encoding AMA1 from the Plasmodium chabaudi chabaudi strain AS. These vectors, when used in a heterologous prime-boost regimen in BALB/c mice, are capable of inducing strong transgene-specific humoral and cellular immune responses. We show that this vaccination regimen is protective against a nonlethal P. chabaudi chabaudi strain AS blood-stage challenge, resulting in reduced peak parasitemias. The role of vaccine-induced, AMA1-specific Abs and T cells in mediating the antiparasite effect was investigated by in vivo depletion of CD4+ T cells and adoptive-transfer studies into naive and immunodeficient mice. Depletion of CD4+ T cells led to a loss of vaccine-induced protection. Adoptive-transfer studies confirmed that efficacy is mediated by both CD4+ T cells and Abs functioning in the context of an intact immune system. Unlike previous studies, these results confirm that Ag-specific CD4+ T cells, induced by a clinically relevant vaccine-delivery platform, can make a significant contribution to vaccine blood-stage efficacy in the P. chabaudi model. Given that cell-mediated immunity may also contribute to parasite control in human malaria, these data support the clinical development of viral-vectored vaccines that induce both T cell and Abs against Plasmodium falciparum blood-stage malaria Ags like AMA1.
Genetic Variation at a Yin-Yang 1 Response Site Regulates the Transcription of Cyclin-Dependent Kinase Inhibitor p18INK4C Transcript in Lupus-Prone Mice
Authors: Potula Hari-Hara S. K. , Morel Laurence
Published: April 2012

We have previously shown that a novel −74 C-to-T mutation in the promoter of the cyclin-dependent kinase inhibitor p18Ink4c (p18) gene was associated with a reduced p18 expression in B cells from mice carrying the Sle2c1 lupus susceptibility locus. To determine the function of the −74 C/T single nucleotide polymorphism, we have characterized the proximal promoter of the mouse p18 gene. Functional analysis of the 5′ flanking region by sequential deletions revealed crucial elements between −300 and +1, confirming the in silico prediction that the −74 T allele created a novel Yin-Yang 1 (YY-1) binding site adjacent to an existing one common to both alleles. Moreover, we found that YY-1, E2F1, and Sp-1 can synergistically enhance the activity of the p18 promoter. Mutational inactivation revealed that YY-1 binding regulates the p18 activity in an allele-dependent fashion. EMSAs with splenic B cell extracts directly demonstrated that YY-1 binds to the p18 promoter with differences between the C and the T alleles. We also determined in vivo by chromatin immunoprecipitation that the T allele resulted in increased YY-1 and decreased Nrf-2 binding to the p18 promoter as compared with the C allele in B cells. Thus, YY-1 is a direct regulator of p18 gene expression in an allele-dependent fashion that is consistent with the lupus-associated T allele, inducing a lower p18 transcriptional activity by increasing YY-1 binding. These results establish the p18 −74 C/T mutation as the leading causal variant for the B1a cell expansion that characterizes the NZB and NZM2410 lupus-prone strains.
Mouse β-Defensin 14 (Defb14) Promotes Tumor Growth by Inducing Angiogenesis in a CCR6-Dependent Manner
Authors: Röhrl Johann , Huber Barbara , Koehl Gudrun E. , Geissler Edward K. , Hehlgans Thomas
Published: April 2012

β-defensins are known for their antimicrobial activity and belong to the molecular barrier of the innate immune system against invading pathogens. In addition, it has been shown that some members of the β-defensin superfamily have the capacity to promote local innate inflammatory and systemic adaptive immune responses, mediated in part by the interaction with CCR6. We found that mouse β-defensin 14 (mBD14, Defb14), a newly identified member of the mouse β-defensin superfamily, is expressed in mouse fibrosarcoma tumor tissue. Tumor cells overexpressing mBD14 demonstrated enhanced solid tumor growth in syngeneic C57BL/6 mice concomitant with increased vascularization of these tumors. Furthermore, mBD14-overexpressing tumors demonstrated increased expression of proangiogenic MIP-2 (CXCL2) ex vivo. In contrast, vascular endothelial growth factor expression was not affected. Cellular analysis of tumor-infiltrating leukocytes revealed a significant increase of CCR6+ B220+ lymphocytes in solid tumors derived from mBD14-overexpressing tumor cells. Enhanced tumor growth of mBD14-overexpressing fibrosarcomas was abolished in CCR6-deficient mice, which was paralleled by decreased infiltration of CCR6+ B220+ lymphocytes, indicating the requirement of CCR6 expression on host cells. Previously, the interaction of activated, LTαβ+, lymphocytes with lymphotoxin β-receptor–expressing fibrosarcoma tumor cells has been identified as a new CXCL2-dependent proangiogenic pathway. Coexpression of a soluble lymphotoxin β-receptor:Ig fusion protein, an inhibitor of CXCL2-dependent angiogenesis, in mBD14-overexpressing fibrosarcoma tumor cells abolished enhanced solid tumor growth. Thus, we conclude that mBD14 expression by tumor-infiltrating host cells results in the chemoattraction of CCR6+ B220+ lymphocytes, which in turn initiates a proangiogenic pathway leading to enhanced angiogenesis and organized tumor tissue development.
Cutting Edge: Neuronal Recognition by CD8 T Cells Elicits Central Diabetes Insipidus
Authors: Scheikl Tanja , Pignolet Béatrice , Dalard Cécile , Desbois Sabine , Raison Danièle , Yamazaki Masanori , Saoudi Abdelhadi , Bauer Jan , Lassmann Hans , Hardin-Pouzet Hélène , Liblau Roland S.
Published: April 2012

An increasing number of neurologic diseases is associated with autoimmunity. The immune effectors contributing to the pathogenesis of such diseases are often unclear. To explore whether self-reactive CD8 T cells could attack CNS neurons in vivo, we generated a mouse model in which the influenza virus hemagglutinin (HA) is expressed specifically in CNS neurons. Transfer of cytotoxic anti-HA CD8 T cells induced an acute but reversible encephalomyelitis in HA-expressing recipient mice. Unexpectedly, diabetes insipidus developed in surviving animals. This robust phenotype was associated with preferential accumulation of cytotoxic CD8 T cells in the hypothalamus, upregulation of MHC class I molecules, and destruction of vasopressin-expressing neurons. IFN-γ production by the pathogenic CD8 T cells was necessary for MHC class I upregulation by hypothalamic neurons and their destruction. This novel mouse model, in combination with related human data, supports the concept that autoreactive CD8 T cells can trigger central diabetes insipidus.
New Biomarkers with Relevance to Leprosy Diagnosis Applicable in Areas Hyperendemic for Leprosy
Authors: Geluk Annemieke , Bobosha Kidist , van der Ploeg-van Schip Jolien J. , Spencer John S. , Banu Sayera , V. S. B. Martins Marcia , Cho Sang-Nae , Franken Kees L. M. C. , Kim Hee Jin , Bekele Yonas , Uddin Mohammad K. M. , Abdul Hadi Sheikh , Aseffa Abraham , Pessolani Maria C. V. , Pereira Geraldo M. B. , Dockrell Hazel M. , Ottenhoff Tom H. M.
Published: April 2012

Leprosy is not eradicable with currently available diagnostics or interventions, as evidenced by its stable incidence. Early diagnosis of Mycobacterium leprae infection should therefore be emphasized in leprosy research. It remains challenging to develop tests based on immunological biomarkers that distinguish individuals controlling bacterial replication from those developing disease. To identify biomarkers for field-applicable diagnostics, we determined cytokines/chemokines induced by M. leprae proteins in blood of leprosy patients and endemic controls (EC) from high leprosy-prevalence areas (Bangladesh, Brazil, Ethiopia) and from South Korea, where leprosy is not endemic anymore. M. leprae-sonicate–induced IFN-γ was similar for all groups, excluding M. leprae/IFN-γ as a diagnostic readout. By contrast, ML2478 and ML0840 induced high IFN-γ concentrations in Bangladeshi EC, which were completely absent for South Korean controls. Importantly, ML2478/IFN-γ could indicate distinct degrees of M. leprae exposure, and thereby the risk of infection and transmission, in different parts of Brazilian and Ethiopian cities. Notwithstanding these discriminatory responses, M. leprae proteins did not distinguish patients from EC in one leprosy-endemic area based on IFN-γ. Analyses of additional cytokines/chemokines showed that M. leprae and ML2478 induced significantly higher concentrations of MCP-1, MIP-1β, and IL-1β in patients compared with EC, whereas IFN-inducible protein-10, like IFN-γ, differed between EC from areas with dissimilar leprosy prevalence. This study identifies M. leprae-unique Ags, particularly ML2478, as biomarker tools to measure M. leprae exposure using IFN-γ or IFN-inducible protein-10, and also shows that MCP-1, MIP-1β, and IL-1β can potentially distinguish pathogenic immune responses from those induced during asymptomatic exposure to M. leprae.
The Relative Roles of Factor H Binding Protein, Neisserial Surface Protein A, and Lipooligosaccharide Sialylation in Regulation of the Alternative Pathway of Complement on Meningococci
Authors: Lewis Lisa A. , Carter Matthew , Ram Sanjay
Published: April 2012

Neisseria meningitidis inhibits the alternative pathway (AP) of complement using diverse mechanisms, including expression of capsule (select serogroups), Neisserial surface protein A (NspA), factor H (fH) binding protein (fHbp), and lipooligosaccharide (LOS) sialylation. The contribution of the latter three molecules in AP regulation in encapsulated meningococci was studied using isogenic mutants. When LOS was unsialylated, deleting NspA alone from group A strain A2594 (low fHbp/high NspA) significantly increased AP-mediated C3 deposition. C3 deposition further increased ∼2-fold in a ΔfHbpΔNspA double mutant, indicating cooperative fHbp function. LOS sialylation of A2594 ΔfHbpΔNspA decreased the rate of C3 deposition, revealing AP inhibition by LOS sialic acid. Maximal C3 deposition on group B strain H44/76 (high fHbp/low NspA) occurred when all three molecules were absent; again, LOS sialylation attenuated the AP in the absence of both fHbp and NspA. When H44/76 LOS was unsialylated, both fHbp and NspA independently inhibited the AP. LOS sialylation enhanced binding of fH C-terminal domains 18–20 to C3 fragments deposited on bacteria. Interaction of meningococci with nonhuman complement is relevant for animal models and vaccine evaluation studies that use nonhuman complement. Consistent with their human-specific fH binding, neither fHbp nor NspA regulated the rat AP. However, LOS sialylation inhibited the rat AP and, as with human serum, enhanced binding of rat fH to surface-bound C3. These data highlight the cooperative roles of meningococcal NspA and fHbp in regulating the human AP and broaden the molecular basis for LOS sialylation in AP regulation on meningococci in more than one animal species.
Identification of a New Pathway for Th1 Cell Development Induced by Cooperative Stimulation with IL-4 and TGF-β
Authors: Tofukuji Soichi , Kuwahara Makoto , Suzuki Junpei , Ohara Osamu , Nakayama Toshinori , Yamashita Masakatsu
Published: April 2012

IL-4 plays an important role in the induction of Th2 and Th9 cells, as well as in the inhibition of Th1 cell generation. We show that a combination of IL-4 and TGF-β augments the development of Th1 cells that express CD103 (CD103+ Th1 cells) if IFN-γ is present. The T-box–containing transcription factor eomesodermin (Eomes) is preferentially expressed in CD103+ Th1 cells and is involved in IFN-γ production. The induction of T-bet during early T cell activation is essential for the formation of the active chromatin at both the Eomes and IFN-γ gene loci. TGF-β is required for the induction of Eomes and CD103, as well as the inhibition of Th2 cytokine expression. In addition, IL-4 induces Eomes transcription through activation of the Stat6-signaling pathway. IFN-γ–producing CD103+ Th1 cells are detected in the intraepithelial lymphocytes of normal mice, and their numbers significantly decrease in Tbet- and Stat6-deficient mice. To our knowledge, these results represent the first molecular mechanism of IL-4/TGF-β–dependent augmentation of Th1 cell generation and raise the possibility that IL-4 and TGF-β simultaneously enhance the Th1 cell-mediated immune responses under certain cytokine conditions.
Cutting Edge: mTORC1 in Intestinal CD11c+CD11b+ Dendritic Cells Regulates Intestinal Homeostasis by Promoting IL-10 Production
Authors: Ohtani Masashi , Hoshii Takayuki , Fujii Hideki , Koyasu Shigeo , Hirao Atsushi , Matsuda Satoshi
Published: April 2012

The mammalian target of rapamycin (mTOR) controls cell growth and survival through two distinct complexes called mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). Although several reports have suggested the involvement of mTORC1 in development and function of dendritic cells (DCs), its physiological roles remain obscure. We therefore established mTORC1 signal-deficient mice lacking Raptor, an essential component of mTORC1 signal, specifically in DC lineage (referred to here as RaptorDC−/−). RaptorDC−/− mice exhibited cell expansion in specific subsets of DCs such as splenic CD8+ DCs and intestinal CD11c+CD11b+ DCs. We also found that impaired mTORC1 signal resulted in the suppression of IL-10 production along with enhanced CD86 expression in intestinal CD11c+CD11b+ DCs and that RaptorDC−/− mice were highly susceptible to dextran sodium sulfate-induced colitis. Our results uncover mTORC1-mediated anti-inflammatory programs in intestinal CD11c+CD11b+ DCs to limit the intestinal inflammation.
Differential Requirements for IRF-2 in Generation of CD1d-Independent T Cells Bearing NK Cell Receptors
Authors: Notake Tsuyoshi , Horisawa Shin , Sanjo Hideki , Miyagawa Shin-ichi , Hida Shigeaki , Taki Shinsuke
Published: April 2012

NK cell receptors (NKRs) such as NK1.1, NKG2D, and Ly49s are expressed on subsets of CD1d-independent memory phenotype CD8+ and CD4–CD8– T cells. However, the mechanism for the generation and functions of these NKR+ T cells remained elusive. In this study, we found that CD1d-independent Ly49+ T cells were reduced severely in the spleen, bone marrow, and liver, but not thymus, in mice doubly deficient for IFN regulatory factor-2 (IRF-2) and CD1d, in which the overall memory phenotype T cell population was contrastingly enlarged. Because a large fraction of Ly49+ T cells coexpressed NK1.1 or NKG2D, the reduction of Ly49+ T cells resulted indirectly in underrepresentation of NK1.1+ or NKG2D+ cells. Ly49+ T cell deficiency was observed in IRF-2−/− mice additionally lacking IFN-α/βR α-chain (IFNAR1) as severely as in IRF-2−/− mice, arguing against the involvement of the accelerated IFN-α/β signals due to IRF-2 deficiency. Rather, mice lacking IFN-α/βR alone also exhibited relatively milder Ly49+ T cell reduction, and IL-2 could expand Ly49+ T cells from IFNAR1−/−, but not from IRF-2−/−, spleen cells in vitro. These results together indicated that IRF-2 acted in Ly49+ T cell development in a manner distinct from that of IFN-α/β signals. The influence of IRF-2 deficiency on Ly49+ memory phenotype T cells observed in this study suggested a unique transcriptional program for this T cell population among other NKR+ T and memory phenotype T cells.
B Cell-Specific S1PR1 Deficiency Blocks Prion Dissemination between Secondary Lymphoid Organs
Authors: Mok Simon W. F. , Proia Richard L. , Brinkmann Volker , Mabbott Neil A.
Published: April 2012

Many prion diseases are peripherally acquired (e.g., orally or via lesions to skin or mucous membranes). After peripheral exposure, prions replicate first upon follicular dendritic cells (FDC) in the draining lymphoid tissue before infecting the brain. However, after replication upon FDC within the draining lymphoid tissue, prions are subsequently propagated to most nondraining secondary lymphoid organs (SLO), including the spleen, by a previously underdetermined mechanism. The germinal centers in which FDC are situated produce a population of B cells that can recirculate between SLO. Therefore, we reasoned that B cells were ideal candidates by which prion dissemination between SLO may occur. Sphingosine 1-phosphate receptor (S1PR)1 stimulation controls the egress of T and B cells from SLO. S1PR1 signaling blockade sequesters lymphocytes within SLO, resulting in lymphopenia in the blood and lymph. We show that, in mice treated with the S1PR modulator FTY720 or with S1PR1 deficiency restricted to B cells, the dissemination of prions from the draining lymph node to nondraining SLO is blocked. These data suggest that B cells interacting with and acquiring surface proteins from FDC and recirculating between SLO via the blood and lymph mediate the initial propagation of prions from the draining lymphoid tissue to peripheral tissues.
Extreme Version of Projectivity for Normed Modules Over Sequence Algebras
Authors: Helemskii A. Ya.
Published: April 2012

We define and study the so-called extreme version of the notion of a projective normed module. The relevant definition takes into account the exact value of the norm of the module in question, in contrast with the standard known definition that is formulated in terms of normtopology.

After the discussion of the case where our normed algebra A is just C, we concentrate on the case of the next degree of complication, where A is a sequence algebra satisfying some natural conditions. The main results give a full characterization of extremely projective objects within the subcategory of the category of non-degenerate normed A-modules, consisting of the so-called homogeneous modules. We consider two cases, ‘non-complete’ and ‘complete’, and the respective answers turn out to be essentially different.

In particular, all Banach non-degenerate homogeneous modules consisting of sequences are extremely projective within the category of Banach non-degenerate homogeneous modules. However, neither of them, provided it is infinite-dimensional, is extremely projective within the category of all normed non-degenerate homogeneous modules. On the other hand, submodules of these modules consisting of finite sequences are extremely projective within the latter category.
Quasimap Floer Cohomology for Varying Symplectic Quotients
Authors: Wilson Glen , Woodward Christopher T.
Published: April 2012

We show that quasimap Floer cohomology for varying symplectic quotients resolves several puzzles regarding displaceability of toric moment fibers. For example, we present a compact Hamiltonian torus action containing an open subset of non-displaceable orbits and a codimension four singular set, partly answering a question of McDuff, and we determine displaceability for most of the moment fibers of a symplectic ellipsoid.
Weak Sequential Completeness of 𝑲(X,Y)
Authors: Bu Qingying
Published: April 2012

For Banach spaces X and Y, we show that if X* and Y are weakly sequentially complete and every weakly compact operator from X to Y is compact, then the space of all compact operators from X to Y is weakly sequentially complete. The converse is also true if, in addition, either X* or Y has the bounded compact approximation property.
The Effects of Zataria Multiflora Hydroalcoholic Extract on Some Liver Enzymes, Cholesterol, Triglyceride, HDL-Cholesterol, LDL-Cholesterol, Albumin and Total Protein in Rat
Authors: Ameneh Khoshvaghti  , Saeed Nazifi  , Seena Derakhshaniyan  , Bijan Akbarpour
Published: April 2012

Zataria multiflora is a valuable medicinal plant grown extensively in Iran, Pakistan and Afghanistan. The chemical compositions of their extracts have been extensively characterized in Iran and Pakistan. The present study was undertaken to investigate the effects of Zataria multiflora on some liver enzymes, triglyceride, cholesterol, HDL-cholesterol, LDL-cholesterol, albumin and total protein in rat. Sixty adult male Wistar rats weighing about 200 to 220 g were divided into six groups of ten. The control group (group 1) did not receive any drug. The sham group (group 2) received 2 cc of distilled water. The other four experimental groups (groups 3 to 6) including very low (100 mg/kg BW), low (200 mg/kg BW), medium (300 mg/kg BW) and maximum dose (400 mg/kg BW) received Zataria multiflora hydroalcoholic extract intraperitoneally daily for 28 days. After 28 days all animals in the different groups were weighed and blood samples were collected from heart vein. Serum biochemical parameters were measured using validated standard methods. The results of this study showed Zattaria multiflora hydroalcoholic extract analyses various lipids in lipid tissues and transfer to blood for elimination from body.
Design of Deadlock Prevention Supervisor in Waterway with Multiple Locks and Canals
Authors: Kezić Danko , Bogdan Stjepan , Kasum Josip
Published: April 2012

To avoid conflict and deadlock states in waterway with multiple locks and canals, a computer based traffic management system with proper control policy must be applied. The paper proposes a formal method for design of deadlock prevention supervisor by using discrete event theory, multiple reentrant flowlines class of Petri net and P-invariants control places calculation. By using and/or matrix algebra, authors analyze the structural characteristics of Petri net in order to find first and second level deadlocks. First level deadlocks are prevented by maintaining the number of vessels in the critical subsystems below the number of vessels in the critical circuits. A method for second level deadlock prevention, which is based on P-invariants, ensures that the key resources would not be the last available resources in the system. Functionality of the supervisor is verified by a computer simulation using Matlab software with Petri net toolbox and P-timed Petri net model of waterway.