bluuebunny/crossref_metadata_2025 huggingface dataset:
Conceptual Data Warehouse Design Methodology for Business Process Intelligence
Authors: Mansmann Svetlana , Neumuth Thomas , Burgert Oliver , Röger Matthias
Published: May 2010

The emerging area of business process intelligence aims at enhancing the analysis power of business process management systems by employing performance-oriented technologies of data warehousing and mining. However, the differences in the assumptions and objectives of the underlying models, namely the business process model and the multidimensional data model, aggravate straightforward and meaningful convergence of the two concepts. The authors present an approach to designing a data warehousing for enabling the multidimensional analysis of business processes and their execution. The aims of such analysis are manifold, from quantitative and qualitative assessment to process discovery, pattern recognition and mining. The authors demonstrate that business processes and workflows represent a non-conventional application scenario for the data warehousing approach and that multiple challenges arise at various design stages. They describe deficiencies of the conventional OLAP technology with respect to business process modeling and formulate the requirements for an adequate multidimensional presentation of process descriptions. Modeling extensions proposed at the conceptual level are verified by implementing them in a relational OLAP system, accessible via state-of-the-art visual frontend tools. The authors demonstrate the benefits of the proposed modeling framework by presenting relevant analysis tasks from the domain of medical engineering and showing the type of the decision support provided by our solution.
Data Warehouse Facilitating Evidence-Based Medicine
Authors: Stolba Nevena , Nguyen Tho Manh , Tjoa A Min
Published: May 2010

In the past, much effort of healthcare decision support systems were focused on the data acquisition and storage, in order to allow the use of this data at some later point in time. Medical data was used in static manner, for analytical purposes, in order to verify the undertaken decisions. Due to the immense volumes of medical data, the architecture of the future healthcare decision support systems focus more on interoperability than on integration. With the raising need for the creation of unified knowledge base, the federated approach to distributed data warehouses (DWH) is getting increasing attention. The exploitation of evidence-based guidelines becomes a priority concern, as the awareness of the importance of knowledge management rises. Consequently, interoperability between medical information systems is becoming a necessity in modern health care. Under strong security measures, health care organizations are striking to unite and share their (partly very high sensitive) data assets in order to achieve a wider knowledge base and to provide a matured decision support service for the decision makers. Ontological integration of the very complex and heterogeneous medical data structures is a challenging task. The authors’ objective is to point out the advantages of the deployment of a federated data warehouse approach for the integration of the wide range of different medical data sources and for distribution of evidence-based clinical knowledge, to support clinical decision makers, primarily clinicians at the point of care.
MOSAIC
Authors: Jiamthapthaksin Rachsuda , Choo Jiyeon , Chen Chun-sheng , Celepcikay Oner Ulvi , Giusti Christian , Eick Christoph F.
Published: May 2010

Strong theoretical foundation and low computational complexity make representative-based clustering one of the most popular approaches for a clustering problem. Despite those superiorities, it presents two main drawbacks: the shape of clusters obtained is limited to convex shapes, and its performance is highly dependent on seeds initialization. To address these problems, the authors introduce MOSAIC, a novel agglomerative clustering algorithm, which greedily merges neighboring clusters maximizing a plug-in fitness function. The key idea is that by considering neighboring relationship computed using Gabriel Graphs among cluster, MOSAIC can derive non-convex shapes as the unions of small clusters previously generated by a representative-based clustering algorithm. The authors evaluate MOSAIC for traditional unsupervised clustering with k-means and DBSCAN, and also for supervised clustering. The experimental results show that compared to k-means stand-alone, their proposed post-processing techniques obtain higher quality clusters, whereas compared to DBSCAN results, MOSAIC is capable of identifying comparable arbitrary shape clusters, given a suitable fitness function. In addition, MOSAIC can cope with problems of clustering on high dimensional data. The authors also claim that MOSAIC can be employed as an effective post-processing clustering algorithm to further improve the quality of clustering.
Ranking Gradients in Multi-Dimensional Spaces
Authors: Alves Ronnie , Ribeiro Joel , Belo Orlando , Han Jiawei
Published: May 2010

Business organizations must pay attention to interesting changes in customer behavior in order to anticipate their needs and act accordingly with appropriated business actions. Tracking customer’s commercial paths through the products they are interested in is an essential technique to improve business and increase customer satisfaction. Data warehousing (DW) allows us to do so, giving the basic means to record every customer transaction based on the different business strategies established. Although managing such huge amounts of records may imply business advantage, its exploration, especially in a multi-dimensional space (MDS), is a nontrivial task. The more dimensions we want to explore, the more are the computational costs involved in multi-dimensional data analysis (MDA). To make MDA practical in real world business problems, DW researchers have been working on combining data cubing and mining techniques to detect interesting changes in MDS. Such changes can also be detected through gradient queries. While those studies have provided the basis for future research in MDA, just few of them points to preference query selection in MDS. Thus, not only the exploration of changes in MDS is an essential task, but also even more important is ranking most interesting gradients. In this chapter, the authors investigate how to mine and rank the most interesting changes in a MDS applying a TOP-K gradient strategy. Additionally, the authors also propose a gradient-based cubing method to evaluate interesting gradient regions in MDS. So, the challenge is to find maximum gradient regions (MGRs) that maximize the task of raking gradients in a MDS. The authors’ evaluation study demonstrates that the proposed method presents a promising strategy for ranking gradients in MDS.
Learning Cost-Sensitive Decision Trees to Support Medical Diagnosis
Authors: Freitas Alberto , Costa-Pereira Altamiro
Published: May 2010

Classification plays an important role in medicine, especially for medical diagnosis. Real-world medical applications often require classifiers that minimize the total cost, including costs for wrong diagnosis (misclassifications costs) and diagnostic test costs (attribute costs). There are indeed many reasons for considering costs in medicine, as diagnostic tests are not free and health budgets are limited. In this chapter, the authors have defined strategies for cost-sensitive learning. They have developed an algorithm for decision tree induction that considers various types of costs, including test costs, delayed costs and costs associated with risk. Then they have applied their strategy to train and to evaluate cost-sensitive decision trees in medical data. Generated trees can be tested following some strategies, including group costs, common costs, and individual costs. Using the factor of “risk” it is possible to penalize invasive or delayed tests and obtain patient-friendly decision trees.
An Approximate Approach for Maintaining Recent Occurrences of Itemsets in a Sliding Window over Data Streams
Authors: Koh Jia-Ling , Shin Shu-Ning , Don Yuan-Bin
Published: May 2010

Recently, the data stream, which is an unbounded sequence of data elements generated at a rapid rate, provides a dynamic environment for collecting data sources. It is likely that the embedded knowledge in a data stream will change quickly as time goes by. Therefore, catching the recent trend of data is an important issue when mining frequent itemsets over data streams. Although the sliding window model proposed a good solution for this problem, the appearing information of patterns within a sliding window has to be maintained completely in the traditional approach. For estimating the approximate supports of patterns within a sliding window, the frequency changing point (FCP) method is proposed for monitoring the recent occurrences of itemsets over a data stream. In addition to a basic design proposed under the assumption that exact one transaction arrives at each time point, the FCP method is extended for maintaining recent patterns over a data stream where a block of various numbers of transactions (including zero or more transactions) is inputted within a fixed time unit. Accordingly, the recently frequent itemsets or representative patterns are discovered from the maintained structure approximately. Experimental studies demonstrate that the proposed algorithms achieve high true positive rates and guarantees no false dismissal to the results yielded. A theoretic analysis is provided for the guarantee. In addition, the authors’ approach outperforms the previously proposed method in terms of reducing the run-time memory usage significantly.
Exploring Calendar-Based Pattern Mining in Data Streams
Authors: Monteiro Rodrigo Salvador , Zimbrão Geraldo , Schwarz Holger , Mitschang Bernhard , Moreira de Souza Jano
Published: May 2010

Calendar-based pattern mining aims at identifying patterns on specific calendar partitions. Potential calendar partitions are for example: every Monday, every first working day of each month, every holiday. Providing flexible mining capabilities for calendar-based partitions is especially challenging in a data stream scenario. The calendar partitions of interest are not known a priori and at each point in time only a subset of the detailed data is available. The authors show how a data warehouse approach can be applied to this problem. The data warehouse that keeps track of frequent itemsets holding on different partitions of the original stream has low storage requirements. Nevertheless, it allows to derive sets of patterns that are complete and precise. Furthermore, the authors demonstrate the effectiveness of their approach by a series of experiments.
Using Bayesian Networks for Web Effort Estimation
Authors: Mendez Emilia
Published: May 2010

Web effort models and techniques provide the means for Web companies to formalise the way they estimate effort for their projects, and help in obtaining more accurate estimates. Accurate estimates are fundamental to help project managers allocate resources more adequately, thus supporting projects to be finished on time and within budget. The aim of this chapter is to introduce the concepts related to Web effort estimation and effort forecasting techniques, and to discuss effort prediction when the estimation technique used is Bayesian Networks.
Auto-Associative Neural Networks to Improve the Accuracy of Estimation Models
Authors: Sarcia Salvatore A. , Cantone Giovanni , Basili Victor R.
Published: May 2010

Prediction of software engineering variables with high accuracy is still an open problem. The primary reason for the lack of high accuracy in prediction might be because most models are linear in the parameters and so are not sufficiently flexible and suffer from redundancy. In this chapter, we focus on improving regression models by decreasing their redundancy and increasing their parsimony, i.e., we turn the model into a model with fewer variables than the former. We present an empirical auto-associative neural network-based strategy for model improvement, which implements a reduction technique called Curvilinear component analysis. The contribution of this chapter is to show how multi-layer feedforward neural networks can be a useful and practical mechanism for improving software engineering estimation models.
From Textual Scenarios to Message Sequence Charts
Authors: Kof Leonid
Published: May 2010

Requirements engineering, the first phase of any software development project, is the Achilles’ heel of the whole development process, as requirements documents are often inconsistent and incomplete. In industrial requirements documents natural language is the main presentation means. In such documents, the system behavior is specified in the form of use cases and their scenarios, written as a sequence of sentences in natural language. For the authors of requirements documents some facts are so obvious that they forget to mention them. This surely causes problems for the requirements analyst. By the very nature of omissions, they are difficult to detect by document reviews: Facts that are too obvious to be written down at the time of document writing, mostly remain obvious at the time of review. In such a way, omissions stay undetected. This book chapter presents an approach that analyzes textual scenarios with the means of computational linguistics, identifies where actors or whole actions are missing from the text, completes the missing information, and creates a message sequence chart (MSC) including the information missing from the textual scenario. Finally, this MSC is presented to the requirements analyst for validation. The book chapter presents also a case study where scenarios from a requirement document based on industrial specifications were translated to MSCs. The case study shows feasibility of the approach.
A Bayesian Network for Predicting the Need for a Requirements Review
Authors: del Sagrado Martinez Jose , del Aguila Cano Isabel Maria
Published: May 2010

One of the major problems when developing complex software systems is that of Requirement Engineering. The methodologies usually propose iterations in which requirements are to be reviewed and re-written until the final version is obtained. This chapter focuses on the construction of “Requisites”, a Bayesian network designed to be used as a predictor that tells us whether a requirements specification has enough quality to be considered as a baseline. Requisites have been defined using several information sources, such as standards and reports, and through interaction with experts, in order to structure and quantify the final model. This Bayesian network reflects the knowledge needed when assessing a requirements specification. The authors show how Requisites can be used through the study of some use cases. After the propagation over the network of information collected about the certainty of a subset of variables, the value predicted will determine if the requirements specification has to be revised.
Knowledge Engineering Support for Software Requirements, Architectures and Components
Authors: Ramachandran Muthu
Published: May 2010

The demands of SE imply a growing need for using AI to support all aspects of the software development process. This chapter provides insights into the application of knowledge based approaches to the development of agile software development, software product line, software components and architecture. In particular, it presents three research systems that demonstrate the potential benefits of utilising knowledge based approaches to support agile methods. The first system, called SoBA, supports the use of a story card for agile software development; the second system, called .NET designer, provides design rationale for choosing appropriate architectural solutions, and the third system, called RAIS, provides reuse assessment and improvement for designing reusable software components.
An Intelligent Computational Argumentation System for Supporting Collaborative Software Development Decision Making
Authors: Liu Xiaoqing , Khudkhudia Ekta , Wen Lei , Sajja Vamshi
Published: May 2010

Many design decisions need to be made in a software development process. The development process usually involves many participants from multiple perspectives, who may be in geographically dispersed locations. Existing argumentation based software design rationale capturing methods and systems can support software development decision making by documenting design rationale for critical decisions. However, their applications are very limited since their argumentation networks are usually very large and they are hard to comprehend and use for effective decision making. In this chapter, we present a web-based intelligent computational argumentation method for supporting collaborative software development decision making. It provides tools for argumentation reduction, assessment of impact of indirect arguments on design alternatives, and detection of self-conflicting arguments using fuzzy logic for supporting decisions in software development processes. A software application case study is provided to demonstrate the effectiveness of the proposed method and system.
Supporting Quality-Driven Software Design through Intellectual Assistants
Authors: Soria Alvaro , Diaz-Pace J. Andres , Bass Len , Bachmann Felix , Campo Marcelo
Published: May 2010

Software design decisions are usually made at early stages but have far-reaching effects regarding system organization, quality, and cost. When doing design, developers apply their technical knowledge to decide among multiple solutions, seeking a reasonable balance between functional and quality-attribute requirements. Due to the complexity of this exploration, the resulting solutions are often more a matter of developer’s experience than of systematic reasoning. It is argued that AI-based tools can assist developers to search the design space more effectively. In this chapter, the authors take a software design approach driven by quality attributes, and then present two tools that have been specifically developed to support that approach. The first tool is an assistant for exploring architectural models, while the second tool is an assistant for the refinement of architectural models into object-oriented models. Furthermore, the authors show an example of how these design assistants are combined in a tool chain, in order to ensure that the main quality attributes are preserved across the design process.
Mining Past-Time Temporal Rules
Authors: Lo David , Khoo Siau-Cheng , Liu Chao
Published: May 2010

Specification mining is a process of extracting specifications, often from program execution traces. These specifications can in turn be used to aid program understanding, monitoring and verification. There are a number of dynamic-analysis-based specification mining tools in the literature, however none so far extract past time temporal expressions in the form of rules stating: “whenever a series of events occur, previously another series of events happened before”. Rules of this format are commonly found in practice and useful for various purposes. Most rule-based specification mining tools only mine future-time temporal expression. Many past-time temporal rules like “whenever a resource is used, it was allocated before” are asymmetric as the other direction does not holds. Hence, there is a need to mine past-time temporal rules. In this chapter, the authors describe an approach to mine significant rules of the above format occurring above a certain statistical thresholds from program execution traces. The approach start from a set of traces, each being a sequence of events (i.e., method invocations) and resulting in a set of significant rules obeying minimum thresholds of support and confidence. A rule compaction mechanism is employed to reduce the number of reported rules significantly. Experiments on traces of JBoss Application Server and Jeti instant messaging application shows the utility of our approach in inferring interesting past-time temporal rules.
Artificial Intelligence in Software Engineering
Authors: Meziane Farid , Vadera Sunil
Published: May 2010

Artificial intelligences techniques such as knowledge based systems, neural networks, fuzzy logic and data mining have been advocated by many researchers and developers as the way to improve many of the software development activities. As with many other disciplines, software development quality improves with the experience, knowledge of the developers, past projects and expertise. Software also evolves as it operates in changing and volatile environments. Hence, there is significant potential for using AI for improving all phases of the software development life cycle. This chapter provides a survey on the use of AI for software engineering that covers the main software development phases and AI methods such as natural language processing techniques, neural networks, genetic algorithms, fuzzy logic, ant colony optimization, and planning methods.
Lyme borreliosis in Canada: biological diversity and diagnostic complexity from an entomological perspective
Authors: Sperling Janet L.H. , Sperling Felix A.H.
Published: May 2010

Lyme borreliosis (LB), also known as Lyme disease, is emerging as a serious tickborne illness across Canada. More than three decades of research on LB in North America and Europe have provided a large, complex body of research involving well-documented difficulties at several levels. However, entomologists are well situated to contribute to resolving some of these challenges. The central pathogen in LB, the spirocheteBorrelia burgdorferiJohnsonet al., includes numerous genospecies and strains that are associated with different disease symptoms and distributions. The primary vectors of LB are ticks of variousIxodesLatreille species (Acari: Ixodida: Ixodidae), but questions linger concerning the status of a number of other arthropods that may be infected withB. burgdorferibut do not transmit it biologically. A variety of vertebrates may serve as reservoirs for LB, but differences in their ability to transmit LB are not well understood at the community level. Persistent cystic forms of and immune system evasion byB. burgdorfericontribute to extraordinary challenges in diagnosing LB. Multiple trade-offs constrain the effectiveness of assays like ELISA, Western blot, polymerase chain reaction, and microscopic visualization of the spirochetes. Consequently, opportunities abound for entomologists to contribute to documenting the diversity of the players and their interactions in this devilishly complex disease.
Seasonal parasitism of hemlock looper (Lepidoptera: Geometridae) eggs in eastern Canada
Authors: Carleton Drew , Royer Lucie , Hébert Christian , Delisle Johanne , Berthiaume Richard , Bauce Eric , Quiring Dan
Published: May 2010

A 2-year field study was conducted using sentinel traps to determine the seasonal distribution of the egg parasitoid (Hymenoptera) complex attacking hemlock looper, Lambdina fiscellaria (Guenée), throughout eastern Quebec and western Newfoundland. Hemlock looper populations remained low in all areas over the course of the study. Parasitism of eggs in sentinel traps was generally lower in fall than in spring. Trichogramma Westwood (Trichogrammatidae) as well as Telenomus flavotibiae Pelletier and an unidentified species of Telenomus Haliday (Scelionidae) only parasitized eggs in the fall. Telenomus droozi Muesebeck only parasitized eggs in the spring, whereas T. coloradensis Crawford attacked eggs during both fall and spring. Telenomus coloradensis was the most abundant parasitoid species collected and was far more abundant in spring than in fall collections.
TLR Stimulation of Prostate Tumor Cells Induces Chemokine-Mediated Recruitment of Specific Immune Cell Types
Authors: Galli Roberta , Starace Donatella , Busà Roberta , Angelini Daniela F. , Paone Alessio , De Cesaris Paola , Filippini Antonio , Sette Claudio , Battistini Luca , Ziparo Elio , Riccioli Anna
Published: May 2010

TLRs boost antimicrobial response mechanisms by epithelial cells and represent the first line of defense at mucosal sites. In view of these immunomodulatory properties, TLR stimulation may represent a novel means to activate anticancer immune responses. In the present study, the ability of TLR ligands to affect the recruitment of different immune cell populations by human prostate cancer cell lines and the underlying mechanisms were investigated. We showed that LNCaP and DU-145 cells express functionally active TLR3 and TLR5. Treatment with their respective agonists, polyinosinic:polycytidylic acid and flagellin, rapidly triggered NF-κB–dependent upregulation of different inflammatory molecules, as assayed by microarray and ELISA. Furthermore, we demonstrated that conditioned media from polyinosinic:polycytidylic acid- and flagellin-treated LNCaP and DU-145 cells induced the recruitment of different leukocyte subpopulations, suggesting that TLR stimulation is able to activate the earliest step of immune response mediated by soluble factors. Interestingly, the more aggressive cancer cell line PC3 expressed TLR3 and TLR5 but failed to respond to TLR agonists in terms of NF-κB activation and the ability to attract immune effectors. Overall, these data show for the first time that TLR3 and TLR5 stimulation of human prostate cancer cells triggers the production of chemokines, which, in turn, favor the attraction of immune effectors, thereby representing a tool to enhance the efficacy of conventional therapies by stimulating anticancer immune responses.
Effects of Polyclonal IgG Derived from Patients with Different Clinical Types of the Antiphospholipid Syndrome on Monocyte Signaling Pathways
Authors: Lambrianides Anastasia , Carroll Christopher J. , Pierangeli Silvia S. , Pericleous Charis , Branch Ware , Rice Jurhee , Latchman David S. , Townsend Paul , Isenberg David A. , Rahman Anisur , Giles Ian P.
Published: May 2010

A major mechanism of hypercoagulability in the antiphospholipid syndrome (APS) is antiphospholipid Ab-mediated upregulation of tissue factor (TF) on monocytes via activation of TLRs, p38 MAPK, and NF-κB pathways. We examined whether monocyte signaling pathways are differentially activated by IgG from patients with vascular thrombosis (VT) alone compared with IgG from patients with pregnancy morbidity (PM) alone. We purified IgG from 49 subjects. A human monocyte cell line and ex vivo healthy monocytes were treated with 100 μg/ml IgG for 6 h, and cell extracts were examined by immunoblot using Abs to p38 MAPK and NF-κB. To further investigate intracellular signaling pathways induced by these IgGs, specific inhibitors of p38 MAPK, NF-κB, TLR4, and TLR2 were used to determine their effect on TF activity. Only IgG from patients with VT but no PM (VT+/PM−) caused phosphorylation of NF-κBand p38 MAPK and upregulation of TF activity in monocytes. These effects were not seen with IgG from patients with PM alone (VT−/PM+), anti-phospholipid Ab-positive patients without APS, or healthy controls. TF upregulation caused by the VT+/PM− samples was reduced by inhibitors of p38 MAPK, NF-κB, and TLR4. The effects of VT+/PM− IgG on signaling and TF upregulation were concentrated in the fraction that bound β-2-glycoprotein I. Our findings demonstrate that IgGs from patients with diverse clinical manifestations of APS have differential effects upon phosphorylation of NF-κB and p38 MAPK and TF activity that may be mediated by differential activation of TLR4.
Downregulation of Th17 Cells in the Small Intestine by Disruption of Gut Flora in the Absence of Retinoic Acid
Authors: Cha Hye-Ran , Chang Sun-Young , Chang Jae-Hoon , Kim Jae-Ouk , Yang Jin-Young , Kim Chang-Hoon , Kweon Mi-Na
Published: May 2010

Retinoic acid (RA), a well-known vitamin A metabolite, mediates inhibition of the IL-6-driven induction of proinflammatory Th17 cells and promotes anti-inflammatory regulatory T cell generation in the presence of TGF-β, which is mainly regulated by dendritic cells. To directly address the role of RA in Th17/regulatory T cell generation in vivo, we generated vitamin A-deficient (VAD) mice by continuous feeding of a VAD diet beginning in gestation. We found that a VAD diet resulted in significant inhibition of Th17 cell differentiation in the small intestine lamina propria by as early as age 5 wk. Furthermore, this diet resulted in low mRNA expression levels of IL-17, IFN regulatory factor 4, IL-21, IL-22, and IL-23 without alteration of other genes, such as RORγt, TGF-β, IL-6, IL-25, and IL-27 in the small intestine ileum. In vitro results of enhanced Th17 induction by VAD dendritic cells did not mirror in vivo results, suggesting the existence of other regulation factors. Interestingly, the VAD diet elicited high levels of mucin MUC2 by goblet cell hyperplasia and subsequently reduced gut microbiome, including segmented filamentous bacteria. Much like wild-type mice, the VAD diet-fed MyD88−/−TRIF−/− mice had significantly fewer IL-17–secreting CD4+ T cells than the control diet-fed MyD88−/−TRIF−/− mice. The results strongly suggest that RA deficiency altered gut microbiome, which in turn inhibited Th17 differentiation in the small intestine lamina propria.
Human CD34-Derived Myeloid Dendritic Cell Development Requires Intact Phosphatidylinositol 3-Kinase–Protein Kinase B–Mammalian Target of Rapamycin Signaling
Authors: van de Laar Lianne , Buitenhuis Miranda , Wensveen Felix M. , Janssen Harry L.A. , Coffer Paul J. , Woltman Andrea M.
Published: May 2010

Dendritic cells (DCs) are composed of different subsets that exhibit distinct functionality in the induction and regulation of immune responses. The myeloid DC subsets, including interstitial DCs and Langerhans cells (LCs), develop from CD34+ hematopoietic progenitors via direct DC precursors or monocytes. The molecular mechanisms regulating DC development are still largely unknown and mostly studied in mice. Phosphatidylinositol 3-kinase (PI3K) regulates multiple processes in myeloid cells. This study investigated the role of PI3K signaling in the development of human CD34-derived myeloid DCs. Pharmacologic inhibition of PI3K or one of its downstream targets mTOR reduced interstitial DC and LC numbers in vitro. Increased activity of this signaling module by introduction of constitutively active protein kinase B (PKB/c-Akt) increased the yields of human DC precursors in vitro as well as in transplanted β2-microglobulin−/− NOD/SCID mice in vivo. Signaling inhibition during differentiation did not affect the acquisition of a DC phenotype, whereas proliferation and survival strongly depended on intact PI3K–PKB–mTOR signaling. Interestingly, however, this pathway became redundant for survival regulation upon terminal differentiation, which was associated with an altered expression of apoptosis regulating genes. Although dispensable for costimulatory molecule expression, the PI3K–PKB–mTOR signaling module was required for other important processes associated with DC function, including Ag uptake, LPS-induced cytokine secretion, CCR7 expression, and T cell stimulation. Thus, PI3K–PKB–mTOR signaling plays a crucial role in the development of functional CD34-derived myeloid DCs. These findings could be used as a strategy to manipulate DC subset distribution and function to regulate immunity.
HIV-1 Nef Triggers Macrophage Fusion in a p61Hck- and Protease-Dependent Manner
Authors: Vérollet Christel , Zhang Yan Mei , Le Cabec Véronique , Mazzolini Julie , Charrière Guillaume , Labrousse Arnaud , Bouchet Jérôme , Medina Indira , Biessen Erik , Niedergang Florence , Bénichou Serge , Maridonneau-Parini Isabelle
Published: May 2010

Macrophages are a major target of HIV-1 infection. HIV-1–infected macrophages form multinucleated giant cells (MGCs) using poorly elucidated mechanisms. In this study, we show that MGC formation was reduced when human macrophages were infected with nef-deleted HIV-1. Moreover, expression of Nef, an HIV-1 protein required in several aspects of AIDS, was sufficient to trigger the formation of MGCs in RAW264.7 macrophages. Among Nef molecular determinants, myristoylation was dispensable, whereas the polyproline motif was instrumental for this phenomenon. Nef has been shown to activate hematopoietic cell kinase (Hck), a Src tyrosine kinase specifically expressed in phagocytes, through a well-described polyproline–SH3 interaction. Knockdown approaches showed that Hck is involved in Nef-induced MGC formation. Hck is expressed as two isoforms located in distinct subcellular compartments. Although both isoforms were activated by Nef, only p61Hck mediated the effect of Nef on macrophage fusion. This process was abolished in the presence of a p61Hck kinase-dead mutant or when p61Hck was redirected from the lysosome membrane to the cytosol. Finally, lysosomal proteins including vacuolar adenosine triphosphatase and proteases participated in Nef-induced giant macrophage formation. We conclude that Nef participates in HIV-1–induced MGC formation via a p61Hck- and lysosomal enzyme-dependent pathway. This work identifies for the first time actors of HIV-1–induced macrophage fusion, leading to the formation of MGCs commonly found in several organs of AIDS patients.
Immunosuppressive Effect of Quercetin on Dendritic Cell Activation and Function
Authors: Huang Ren-Yeong , Yu Yen-Ling , Cheng Wan-Chien , OuYang Chun-Nan , Fu Earl , Chu Ching-Liang
Published: May 2010

Dendritic cells (DCs) play a crucial role in linking innate and adaptive immunity. Thus, DCs have been regarded as a major target of immunosuppressants for the control of harmful immune responses. In this study, we examined the effect of quercetin, a natural flavonoid found in many vegetables and fruits, on the activation and function of mouse DCs. Quercetin effectively inhibited LPS-induced DC activation by reducing the production of proinflammatory cytokines/chemokines and the expression levels of MHC class II and costimulatory molecules. In addition, quercetin uniquely blocked endocytosis by DCs and the LPS-induced DC migration was diminished by quercetin treatment. Furthermore, quercetin abrogated the ability of LPS-stimulated DCs to induce Ag-specific T cell activation, both in vitro and in vivo. Remarkably, coadministration of quercetin with 2,4-dinitro-1-fluorobenzene prevented 2,4-dinitro-1-fluorobenzene–induced contact hypersensitivity, indicating the potential of quercetin for treating delayed-type hypersensitive diseases. Blockage of LPS-induced ERK, JNK, Akt, and NF-κB activation contributed to the inhibitory effect of quercetin on DCs. These results strongly suggest that quercetin may be a potent immunosuppressive agent and could be used in the prevention and therapy of chronic inflammation, autoimmunity, and transplantation via the abolishment of DC activation and function.
Loss of Naive T Cells and Repertoire Constriction Predict Poor Response to Vaccination in Old Primates
Authors: Čičin-Šain Luka , Smyk-Paerson Sue , Currier Noreen , Byrd Laura , Koudelka Caroline , Robinson Tammie , Swarbrick Gwendolyn , Tackitt Shane , Legasse Alfred , Fischer Miranda , Nikolich-Žugich Dragana , Park Byung , Hobbs Theodore , Doane Cynthia J. , Mori Motomi , Axthelm Michael T. , Lewinsohn Deborah A. , Nikolich-Žugich Janko
Published: May 2010

Aging is usually accompanied by diminished immune protection upon infection or vaccination. Although aging results in well-characterized changes in the T cell compartment of long-lived, outbred, and pathogen-exposed organisms, their relevance for primary Ag responses remain unclear. Therefore, it remains unclear whether and to what extent the loss of naive T cells, their partial replacement by oligoclonal memory populations, and the consequent constriction of TCR repertoire limit the Ag responses in aging primates. We show in this study that aging rhesus monkeys (Macaca mulatta) exhibit poor CD8 T cell and B cell responses in the blood and poor CD8 responses in the lungs upon vaccination with the modified vaccinia strain Ankara. The function of APCs appeared to be maintained in aging monkeys, suggesting that the poor response was likely intrinsic to lymphocytes. We found that the loss of naive CD4 and CD8 T cells, and the appearance of persisting T cell clonal expansions predicted poor CD8 responses in individual monkeys. There was strong correlation between early CD8 responses in the transitory CD28+ CD62L− CD8+ T cell compartment and the peak Ab titers upon boost in individual animals, as well as a correlation of both parameters of immune response to the frequency of naive CD8+ T cells in old but not in adult monkeys. Therefore, our results argue that T cell repertoire constriction and naive cell loss have prognostic value for global immune function in aging primates.
Expression of a Gene Encoding 34.9 kDa PPE Antigen ofMycobacterium aviumsubsp.paratuberculosisinE. coli
Authors: Deb Rajib , Goswami P. P.
Published: May 2010

Mycobacterium aviumsubsp.paratuberculosis(Map) contains PPE family antigens which are Proline and glutamic acid rich and may play important role as T cell antigens. Hence the identification and generation of antigens are necessary for immunological characterization. In the present study, the epitopic region of a unique PPE gene encoding 34.9 kDa protein from Map was amplified by polymerase chain reaction. The gene was cloned intoEscherichia colivector pQE30 UA. The recombinant plasmid designated as pQPPE was transformed intoE. coliM15 and induced with IPTG revealed the high level expression of 37.1 kDa His-fusion protein (34.9 kDa PPE and 2.2 kDa His-tag), which was confirmed by immunoblotting. Recombinant PPE protein was then purified by Ni-NTA agarose chromatography. The polyclonal antiserum raised against purified recombinant PPE protein reacted with expressed 37.1 kDa His-fusion protein as well as with Map sonicate. The protein elicited significant delayed type hypersensitivity (DTH) skin reaction in mice sensitized with Map. The results indicated that the recombinant PPE protein of Map was associated with cellular immune response.
Understanding non-compliance with WHO-multidrug therapy among leprosy patients in Assam, India
Authors: Kar Sumit , Pal Ranabir , Bharati Dharamvir Ranajan
Published: May 2010

Objectives: The study was undertaken to assess the adherence to World Health Organization (WHO)-multidrug therapy (MDT) and its successful completion by the leprosy patients and the extent of such defaulting, its correlates and reasons. Design: Retrograde cohort analysis was conducted during the fi rst quarter of 2007 from the cases registered for WHO-MDT treatment during 2002 to 2005 in Kamrup district of Assam, India. Results: A total of 254 leprosy cases refl ected the treatment seeking behavior of registered cases during the study period. Majority of the cases were from urban areas and defaulter rate higher in urban areas. The study group consisted of 60.63% males and 39.37% females. Both the compliance and default was higher in the age group of 16 to 30 years. Majority of defaulters (32.28%) had passed the high school leaving certifi cate examination had per capita monthly income between Rs 500 - 749 (30.71%) and belonged to social class IV (33.86%) and V (30.71%). Signifi cant statistical association was found between gender, literacy status, per capita income per month and socioeconomic status with treatment outcome. On analysis for the reasons of defaulting treatment; majority (33.07%) defaulted treatment due to loss of occupational hours when they come for receiving drugs at health center, 25.98% defaulted due to adverse reactions of drugs and 18.11% feared social stigma among major causes. Conclusions: The causes of defaulting treatment were related to gender, educational status, income as well as social class, or some combination of these. Recommendations, on strategic interventions to obviate the cause for noncompliance, were presented.
Inca - interparietal bones in neurocranium of human skulls in central India
Authors: Marathe RR , AS Yogesh , Pandit S V , Joshi M , Trivedi GN
Published: May 2010

Inca bones are accessory bones found in neurocranium of human skulls. Occurrence of Inca bones is rare as compared to other inter sutural bones such as wormian bones. These Inca ossicles are regarded as variants of the normal. The reporting of such occurrences is inadequate from Central India. Objectives: To fi nd the incidence of Inca variants in Central India. Materials and Methods: In the present study, 380 dried adult human skulls were examined. All specimen samples were procured from various Medical colleges of Central India. They were analyzed for gross incidence, sexual dimorphism and number of fragments of Inca bones. Results: Gross incidence of Inca bones was found to be 1.315 %. Incidence rate was higher in male skulls than female skulls (male: 1.428%; female: 1.176%). The Inca bones frequently occurred signally. Out of the fi ve observed Inca ossicles, two were fragmented. Conclusions: This data gives idea regarding gross incidence, sexual dimorphism and number of fragments of Inca bones in neurocranium of human skulls from Central India. The knowledge of this variable is useful for neurosurgeons, anthropologists and radiologists.
Penetrating craniofacial arrow injury
Authors: Jain DK , Aggarwal Gaurav , Lubana PS , Moses Sonia
Published: May 2010

Arrow injuries are an extinct form of injury in most parts of the developed world, but are still seen, albeit infrequently in developing countries. Reports of penetrating injuries of the craniofacial region secondary to projectiles are few and far between. The morbidity-free outcome of surgical removal, in case of penetrating arrow injuries, despite the delay in presentation and, moreover, in the emergency surgical practice, are the salient points to be remembered whilst managing such cases, for ‘what the mind knows is what the eyes see and what the eyes see is what can be practiced’. We report the case of a patient who was attacked by a projectile fired from a crossbow. Immediate surgery under general anesthesia was required to remove the arrow, with utmost care to avoid any neurovascular compromise to the facial nerve, as well as minimize postoperative complications such as otitis media and subsequent meningitis.
Penetrating head injury from angle grinder: A cautionary tale
Authors: Senthilkumaran S , Balamurgan N , Arthanari K , Thirumalaikolundusubramanian P
Published: May 2010

Penetrating cranial injury is a potentially life-threatening condition. Injuries resulting from the use of angle grinders are numerous and cause high-velocity penetrating cranial injuries. We present a series of two penetrating head injuries associated with improper use of angle grinder, which resulted in shattering of disc into high velocity missiles with reference to management and prevention. One of those hit on the forehead of the operator and the other on the occipital region of the co-worker at a distance of fi ve meters. The pathophysiological consequence of penetrating head injuries depends on the kinetic energy and trajectory of the object. In the nearby healthcare center the impacted broken disc was removed without realising the consequences and the wound was packed. As the conscious level declined in both, they were referred. CT brain revealed fracture in skull and changes in the brain in both. Expeditious removal of the penetrating foreign body and focal debridement of the scalp, skull, dura, and involved parenchyma and Watertight dural closure were carried out. The most important thing is not to remove the impacted foreign body at the site of accident. Craniectomy around the foreign body, debridement and removal of foreign body without zigzag motion are needed. Removal should be done following original direction of projectile injury. The neurological sequelae following the non missile penetrating head injuries are determined by the severity and location of initial injury as well as the rapidity of the exploration and fastidious debridement.
Back bugged: A case of sacral hydatid cyst
Authors: Patel Dipak , Shukla Dhaval
Published: May 2010

Hydatid cyst of bone constitutes only 0.5 - 2% of all hydatidoses. The thoracic spine is the most common site of spinal hydatidoses. Primary hydatid cyst of the sacral spinal canal is rare. A 23-year-old gentleman had back pain fi ve years ago. At that time he was evaluated and found to have a small cyst in S1 spinal canal, which was presumed to be a benign Tarlov’s cyst; and no treatment was off ered. He continued to have back pain and also developed sciatica on the right side. Neurological examination presently revealed right S1 radiculopathy. Magnetic resonance imaging (MRI) showed a large multiloculated cystic lesion extending from L5 to S2 spinal canal with bone erosion, both anteriorly and posteriorly. He underwent L5 to S2 laminectomy and excision of multiple cysts. The whole cyst was excised and cavity irrigated with sterilized formalin. A laparoscope was introduced in the cavity to look for extension into the pelvis and to confirm complete excision. Postoperatively, the patient received albendazole for two months. At 16 months follow-up the patient was asymptomatic. Hydatid cyst of sacrum is rare and can be missed at initial presentation. If the patient with a cystic lesion of sacral continues to have symptoms the diagnosis should be revaluated and prompt treatment should be off ered.
Biflatness and Pseudo-Amenability of Segal Algebras
Authors: Samei Ebrahim , Spronk Nico , Stokke Ross
Published: May 2010

We investigate generalized amenability and biflatness properties of various (operator) Segal algebras in both the group algebra,L1(G), and the Fourier algebra,A(G), of a locally compact groupG.
Estimation of net uptake and leakage rates of orthophosphate from 32P‐uptake kinetics by a linear force‐flow model
Authors: Istvánovics Vera , Herodek Sándor
Published: May 2010

32P‐uptake kinetics of extremely P‐deficient planktonic microorganisms were analyzed in shallow Lake Balaton by means of a conceptual model of P uptake. According to the model, net P uptake is a linear function of the driving force of the uptake and ceases below a substrate threshold for energetic reasons. We estimated net P‐uptake and P‐leakage rates from 32P‐uptake data. The study period (January–May 1992) covered development, steady state growth, and collapse of a typical spring diatom bloom. 32P incorporation of <3‐, 3–12‐, and > 12‐µm microorganisms was separated by postfiltration. On five occasions, net P‐uptake rates were simultaneously obtained from chemical measurements. Chemically measured net P‐uptake curves, 32P‐uptake curves, and size partitioning of 32P incorporation can be recalculated from the constants of the linear force‐flow model. The initial orthophosphate concentration fluctuated around 0.1 µg P liter−1. The community‐average P threshold exceeded the initial P concentration by a mean factor of 1.4, that of the > 12‐µm microorganisms by a mean factor of 3.9.

Small‐scale fluctuations of in situ P concentrations were necessary to maintain P uptake and growth of larger microorganisms. In a nonhomogeneous environment, sensitivity to the fluctuating nutrient concentrations, efficiency of leakage reduction, and lower maintenance cell quotas may provide a competitive advantage to more complex organisms.
Identification of marine invertebrate larvae by means of PCR‐RAPD species‐specific markers
Authors: Coffroth Mary Alice , Mulawka John M.
Published: May 2010

We used the polymerase chain reaction (PCR) to randomly amplify polymorphic DNA (RAPD) to identify species‐specific genetic markers for five species of gorgonian corals. Using PCR‐RAPDs, we can identify adult gorgonians as well as larvae collected in the field. This technique can be applied to any organism in which identification based on morphologic traits is difficult. Identification of larvae allows more detailed studies of early life histories of marine organisms and studies of the subsequent effects on the dynamics and genetic structure of adult populations.