bluuebunny/crossref_metadata_2025 huggingface dataset:
A systematic review of theory use in studies investigating the motivations of software engineers
Authors: Hall Tracy , Baddoo Nathan , Beecham Sarah , Robinson Hugh , Sharp Helen
Published: June 2009

Motivated software engineers make a critical contribution to delivering successful software systems. Understanding the motivations of software engineers and the impact of motivation on software engineering outcomes could significantly affect the industry's ability to deliver good quality software systems. Understanding the motivations of people generally in relation to their work is underpinned by eight classic motivation theories from the social sciences. We would expect these classic motivation theories to play an important role in developing a rigorous understanding of the specific motivations of software engineers. In this article we investigate how this theoretical basis has been exploited in previous studies of software engineering. We analyzed 92 studies of motivation in software engineering that were published in the literature between 1980 and 2006. Our main findings are that many studies of software engineers' motivations are not explicitly underpinned by reference to the classic motivation theories. Furthermore, the findings presented in these studies are often not explicitly interpreted in terms of those theories, despite the fact that in many cases there is a relationship between those findings and the theories. Our conclusion is that although there has been a great deal of previous work looking at motivation in software engineering, the lack of reference to classic theories of motivation means that the current body of work in the area is weakened and our understanding of motivation in software engineering is not as rigorous as it may at first appear. This weakness in the current state of knowledge highlights important areas for future researchers to contribute towards developing a rigorous and usable body of knowledge in motivating software engineers.
Tools and experiments supporting a testing-based theory of component composition
Authors: Hamlet Dick
Published: June 2009

Development of software using off-the-shelf components seems to offer a chance for improving product quality and developer productivity. This article reviews a foundational testing-based theory of component composition, describes tools that implement the theory, and presents experiments with functional and nonfunctional component/system properties that validate the theory and illuminate issues in component composition.

The context for this work is an ideal form of Component-Based Software Development (CBSD) supported by tools. Component developers describe their components by measuring approximations to functional and nonfunctional behavior on a finite collection of subdomains. Systems designers describe an application-system structure by the component connections that form it. From measured component descriptions and a system structure, a CAD tool synthesizes the system properties, predicting how the system will behave. The system is not built, nor are any test executions performed. Neither the component sources nor executables are needed by systems designers. From CAD calculations a designer can learn (approximately) anything that could be learned by testing an actual system implementation. The CAD tool is often more efficient than it would be to assemble and execute an actual system.

Using tools that support an ideal separation between component- and system development, experiments were conducted to investigate two related questions: (1) To what extent can unit (that is, component) testing replace system testing? (2) What properties of software and subdomains influence the quality of subdomain testing?
A Chinese-Japanese Lexical Machine Translation through a Pivot Language
Authors: Tsunakawa Takashi , Okazaki Naoaki , Liu Xiao , Tsujii Jun’ichi
Published: June 2009

The bilingual lexicon is an expensive but critical resource for multilingual applications in natural language processing. This article proposes an integrated framework for building a bilingual lexicon between the Chinese and Japanese languages. Since the language pair Chinese-Japanese does not include English, which is a central language of the world, few large-scale bilingual resources between Chinese and Japanese have been constructed. One solution to alleviate this problem is to build a Chinese-Japanese bilingual lexicon through English as the pivot language. In addition to the pivotal approach, we can make use of the characteristics of Chinese and Japanese languages that use Han characters. We incorporate a translation model obtained from a small Chinese-Japanese lexicon and use the similarity of the hanzi and kanji characters by using the log-linear model. Our experimental results show that the use of the pivotal approach can improve the translation performance over the translation model built from a small Chinese-Japanese lexicon. The results also demonstrate that the similarity between the hanzi and kanji characters provides a positive effect for translating technical terms.
A comparative evaluation of the Z, CSP, RSL, and VDM languages
Authors: Nami Mohammad Reza , Hassani Fatemeh
Published: June 2009

The software engineering process has been described in many ways. Today, few of these deal specifically with the use of formal methods in software engineering. New software engineering uses formal specification languages in system analysis, requirement analysis, and system design to develop software for critical-safety systems. Formal specification languages describe the system at a much higher level than a programming language. They are catego-rized into model-oriented, constructive, algebraic, process model, hybrid, and logical. This paper describes the properties and types of formal specification languages in software engineering. It then compares the Z, VDM, RSL, and CSP formal specification lan-guages from different point of views.
A discussion on security typing and measurement for SOA
Authors: Tsui Frank , Wang Andy , Qian Kai
Published: June 2009

In a service oriented environment, using SOA technologies, different business entities and services are combined together. Such an environment introduces various security vulnerabilities. This paper proposes an innovative approach to address SOA application security through security typing. We first define security typing concepts, its declaration and definition, with a simple security type, SST, as an example. We then explore various operations under this concept including type equivalence, type compatibility, and type inference. We show, through unary and binary operational examples, that measuring security characteristics requires a clear understanding of the metric scale level and that often times extending an ordinal scale metric to ratio level can be misleading. Our idea and approach to SST may be generalized in the future to more sophisticated security typing.
Simultaneous resource binding and interconnection optimization based on a distributed register-file microarchitecture
Authors: Cong Jason , Fan Yiping , Xu Junjuan
Published: June 2009

Behavior synthesis and optimization beyond the register-transfer level require an efficient utilization of the underlying platform features. This article presents a platform-based resource binding approach based on a
Distributed Register-File Microarchitecture (DRFM)
, which makes efficient use of distributed embedded memory blocks as register files in modern FPGAs. DRFM contains multiple islands, each having a local register file, a functional unit pool, and data-routing logic. Compared to the traditional discrete-register counterpart, a DRFM allows use of the platform-featured on-chip memory or register-file IP blocks to implement its local register files, and this results in a substantial saving of multiplexing logic and global interconnects. DRFM provides a useful architectural template and a direct optimization objective for minimizing interisland connections for synthesis algorithms. Given the scheduling solution and resource (functional units) constraints, two novel algorithms in the resource binding stage are developed based on DRFM: (i) a simultaneous DRFM clustering and binding algorithm, which decides the configuration of DRFM and the assignment of operations into islands with the focus on optimizing global connections; (ii) a data-forwarding scheduling algorithm, which takes advantage of the operation slacks to handle the read-port restriction of register files. On the Xilinx Virtex4 FPGA platform, experimental results with a set of real-life test cases show a 50% logic area reduction achieved by applying our approach, with a 14.6% performance improvement, compared to the traditional discrete-register-based approach. Also, experiments on small-size designs show that our algorithm produces the same number of total connections and at most one more maximum feeding-in connection compared to optimal solutions generated by ILP.
Allocating power ground vias in 3D ICs for simultaneous power and thermal integrity
Authors: Yu Hao , Ho Joanna , He Lei
Published: June 2009

The existing work on via allocation in 3D ICs ignores power/ground vias' ability to simultaneously reduce voltage bounce and remove heat. This article develops the first in-depth study on the allocation of power/ground vias in 3D ICs with simultaneous consideration of power and thermal integrity. By identifying principal ports and parameters, effective electrical and thermal macromodels are employed to provide dynamic power and thermal integrity as well as sensitivity with respect to via density. With the use of sensitivity, an efficient via allocation simultaneously driven by power and thermal integrity is developed. Experiments show that, compared to sequential power and thermal optimization using static integrity, sequential optimization using the dynamic integrity reduces nonsignal vias by up to 18%, and simultaneous optimization using dynamic integrity further reduces nonsignal vias by up to 45.5%.
Haskell session types with (almost) no class
Authors: Pucella Riccardo , Tov Jesse A.
Published: June 2009

We describe an implementation of session types in Haskell. Session types statically enforce that client-server communication proceeds according to protocols. They have been added to several concurrent calculi, but few implementations of session types are available.

Our embedding takes advantage of Haskell where appropriate, but we rely on no exotic features. Thus our approach translates with minimal modification to other polymorphic, typed languages such as ML and Java. Our implementation works with existing Haskell concurrency mechanisms, handles multiple communication channels and recursive session types, and infers protocols automatically.

While our implementation uses unsafe operations in Haskell, it does not violate Haskell's safety guarantees. We formalize this claim in a concurrent calculus with unsafe communication primitives over which we layer our implementation of session types, and we prove that the session types layer is safe. In particular, it enforces that channel-based communication follows consistent protocols.
Smallcheck and lazy smallcheck
Authors: Runciman Colin , Naylor Matthew , Lindblad Fredrik
Published: June 2009

This paper describes two Haskell libraries for property-based testing. Following the lead of QuickCheck, these testing libraries SmallCheck and Lazy SmallCheck also use type-based generators to obtain test-sets of finite values for which properties are checked, and report any counter-examples found. But instead of using a sample of randomly generated values they test properties for all values up to some limiting depth, progressively increasing this limit. The paper explains the design and implementation of both libraries and evaluates them in comparison with each other and with QuickCheck.
Yi
Authors: Bernardy Jean-Philippe
Published: June 2009

Yi is a text editor written in Haskell and extensible in Haskell. We take advantage of Haskell's expressive power to define embedded DSLs that form the foundation of the editor. In turn, these DSLs provide a flexible mechanism to create extended versions of the editor. Yi also provides some support for editing Haskell code.
Clase
Authors: Allwood Tristan O.R. , Eisenbach Susan
Published: June 2009

The zipper is a well known design pattern for providing a cursor-like interface to a data structure. However, the classic treatise by Huet (1) only scratches the surface of some of the potential applications of the zipper. In this work we have taken inspiration from Huet, and built a library suitable as an underpinning for a structured editor for programming languages. We consider a zipper structure that is suitable for traversing heterogeneous data types, encoding routes to other places in the tree (for bookmark or quick-jump functionality), expressing lexically bound information using contexts, and traversals for rendering a program indicating where the cursor is currently focused in the whole.
Without a License, or Accidents Waiting to Happen
Authors: Geiduschek E. Peter
Published: June 2009

This is a memoir of circumstances that have shaped my life as a scientist, some of the questions that have excited my interest, and some of the people with whom I have shared that pursuit. I was introduced to transcription soon after the discovery of RNA polymerase and have been fascinated by questions relating to gene regulation since that time. My account touches on early experiments dealing with the ability of RNA polymerase to selectively transcribe its DNA template. Temporal programs of transcription that control the multiplication cycles of viruses (phages) and the precise mechanisms generating this regulation have been a continuing source of fascination and new challenges. A longtime interest in eukaryotic RNA polymerase III has centered on yeast and on the enumeration and properties of its transcription initiation factors, the architecture of its promoter complexes, and the mechanism of transcriptional initiation. These areas of research are widely regarded as separate, but to my thinking they have posed similar questions, and I have been unwilling or unable to abandon either one for the other. An additional interest in archaeal transcription can be seen as stemming naturally from this point of view.
Single-Molecule Studies of the Neuronal SNARE Fusion Machinery
Authors: Brunger Axel T. , Weninger Keith , Bowen Mark , Chu Steven
Published: June 2009

SNAREs are essential components of the machinery for Ca2+-triggered fusion of synaptic vesicles with the plasma membrane, resulting in neurotransmitter release into the synaptic cleft. Although much is known about their biophysical and structural properties and their interactions with accessory proteins such as the Ca2+ sensor synaptotagmin, their precise role in membrane fusion remains an enigma. Ensemble studies of liposomes with reconstituted SNAREs have demonstrated that SNAREs and accessory proteins can trigger lipid mixing/fusion, but the inability to study individual fusion events has precluded molecular insights into the fusion process. Thus, this field is ripe for studies with single-molecule methodology. In this review, we discuss applications of single-molecule approaches to observe reconstituted SNAREs, their complexes, associated proteins, and their effect on biological membranes. Some of the findings are provocative, such as the possibility of parallel and antiparallel SNARE complexes or of vesicle docking with only syntaxin and synaptobrevin, but have been confirmed by other experiments.
The Role of Ubiquitin in NF-κB Regulatory Pathways
Authors: Skaug Brian , Jiang Xiaomo , Chen Zhijian J.
Published: June 2009

Nuclear factor kappa enhancer binding protein (NF-κB) regulates diverse biological processes including immunity, inflammation, and apoptosis. A vast array of cellular stimuli converges on NF-κB, and ubiquitination plays an essential role in the coordination of these signals to regulate NF-κB activity. At least three steps in NF-κB activation directly involve ubiquitination: proteasomal degradation of inhibitor of NF-κB (IκB), processing of NF-κB precursors, and activation of the transforming growth factor (TGF)-β-activated kinase (TAK1) and IκB kinase (IKK) complexes. In this review, we discuss recent advances in the identification and characterization of ubiquitination and deubiquitination machinery that regulate NF-κB. Particular emphasis is given to proteasome-independent functions of ubiquitin, specifically its role in the activation of protein kinase complexes and in coordination of cell survival and apoptosis signals downstream of tumor necrosis factor α (TNFα).
Large-Scale Structural Biology of the Human Proteome
Authors: Edwards Aled
Published: June 2009

The large-scale structural biology projects that target human proteins focus predominantly on the catalytic domains of potential therapeutic targets and the domains of human proteins that mediate protein-protein and protein-small-molecule interactions. Their main scientific objective is to elucidate the molecular basis for specificity and selectivity of function within large protein families of therapeutic interest, such as kinases, phosphatases, and proteins involved in epigenetic regulation. Half of the unique human protein structures determined in the past three years derive from these initiatives.
Genetic and Biochemical Analysis of Non-Vesicular Lipid Traffic
Authors: Voelker Dennis R.
Published: June 2009

Robust lipid traffic within and among membranes is essential for cell growth and membrane biogenesis. Many of these transport reactions occur by nonvesicular pathways, and the genetic and biochemical details of these processes are now beginning to emerge. Intramembrane lipid transport reactions utilize P-type ATPases, ABC transporters, scramblases, and Niemann-Pick type C (NPC) family proteins. The intramembrane processes regulate the establishment and elimination of membrane lipid asymmetry, the cellular influx and efflux of sterols and phospholipids, and the egress of lysosomally deposited lipids. The intermembrane lipid transport processes play important roles in membrane biogenesis, sterol sequestration, and steroid hormone formation. The roles of soluble lipid carriers and membrane-bound lipid-transporting complexes, as well as the mechanisms for regulation of their targeting and assembly, are now becoming apparent. Elucidation of the details of these systems is providing new perspectives on the regulation of lipid traffic within cells.
Adipose triacylglycerol lipase deletion alters whole body energy metabolism and impairs exercise performance in mice
Authors: Huijsman Elisabeth , van de Par Caro , Economou Catherine , van der Poel Chris , Lynch Gordon S. , Schoiswohl Gabriele , Haemmerle Gunter , Zechner Rudolf , Watt Matthew J.
Published: June 2009

Adipose triacylglycerol lipase (ATGL) and hormone-sensitive lipase (HSL) are essential for efficient lipolysis in adipose tissue and skeletal muscle. Herein, we utilized whole body knockout mice to address the importance of ATGL and HSL for metabolic function and exercise performance. ATGL deletion severely disrupts whole-body substrate partitioning at rest; reducing plasma free fatty acid (FFA) availability (WT: 0.49 ± 0.06 vs. ATGL−/− 0.34 ± 0.03 mM), which in turn enhances carbohydrate oxidation during fasting (mean RER, WT: 0.86 ± 0.02, ATGL−/− 0.90 ± 0.01) and is associated with depleted muscle and liver glycogen stores. While plasma FFA was modestly reduced (23%) and whole body carbohydrate metabolism increased in HSL−/− mice, resting glycogen storage was not compromised. Studies in isolated muscles revealed that the capacity of ATGL and HSL−/− muscle to transport exogenous fatty acids is not compromised and the capacity to oxidize fatty acids is actually increased (3.7- and 1.3-fold above WT for ATGL and HSL). The exercise-induced increase in plasma FFA and glycerol was blunted with ATGL or HSL deletion, demonstrating an impaired capacity for exercise-induced lipolysis in these mice. Carbohydrate oxidation was increased concomitantly during exercise in ATGL−/− and HSL−/− mice, resulting in more muscle and liver glycogen depletion. Maximal running velocity and endurance capacity were reduced by 42% and 46% in ATGL−/− mice, but not in HSL−/− mice. The reduction in performance in ATGL−/− mice was not due to defective muscle contractile performance. These results demonstrate an essential role for both ATGL and HSL in maintaining adequate FFA supply to sustain normal substrate metabolism at rest and during exercise.
Recurrent Villous Adenoma with High-Grade Dysplasia Arising in a Urethral Diverticulum
Authors: Zarineh Alireza , Bulakhtina Elena , Olson Peter R. , Silverman Jan F.
Published: June 2009

Villous adenomas of the urinary tract are an uncommon, well-recognized entity, described in different locations. However, the occurrence of this lesion in the female urethral diverticulum is very unusual. We present the first case of a recurrent villous adenoma with high-grade dysplasia unassociated with adenocarcinoma, arising from a urethral diverticulum. A 75-year-old African-American female presented with urethral prolapse complaining of mild voiding difficulty, stress incontinence, and mild spotting of blood. Histological examination revealed a papillary lesion with finger-like processes lined by pseudostratified columnar epithelium with abundant goblet cells. There were focal areas with stratification to the luminal surface and loss of nuclear polarity and atypical mitoses, interpreted as villous adenoma with high-grade dysplasia. The lesion recurred at one year without evidence of malignant transformation. We also present a brief literature review of urothelial villous adenomas.
Vibration of Slender Structures Subjected to Axial Flow or Axially Towed in Quiescent Fluid
Authors: Wang L. , Ni Q.
Published: June 2009

The vibrations and stability of slender structures subjected to axial flow or axially towed in quiescent fluid are discussed in this paper. A selective review of the research undertaken on it is presented. It is endeavoured to show that slender structures subjected to axial flow or axially towed in quiescent fluid are capable of displaying rich dynamical behavior. The basic dynamics of straight and curved pipes conveying fluid (with or without motion constraints), carbon nanotubes conveying fluid, tubular beams subjected to both internal and external flows in axial direction, slender structures in axial flow or axially towed in quiescent fluid, cylindrical shells conveying or immersed in axial flow, solitary plate or parallel‐plate assembly in axial flow; linear, nonlinear, and chaotic dynamics; these and many more are some of the aspects of the problem considered.
Development of Transgenic Rice Expressing Mite Antigen for a New Concept of Immunotherapy
Authors: Suzuki Kazuya , Kaminuma Osamu , Yang Lijun , Motoi Yuji , Takai Toshiro , Ichikawa Saori , Okumura Ko , Ogawa Hideoki , Mori Akio , Takaiwa Fumio , Hiroi Takachika
Published: June 2009

Background: To elucidate the usefulness of antigen-specific immunotherapy based on oral vaccination with an edible part of the plant, we examined the effect of transgenic (Tg) rice seeds expressing an immunodominant fragment of the group 1 antigen of Dermatophagoides pteronyssinus (Der p 1) on a murine model of asthma. Methods: Mice were orally vaccinated with the Tg or non-Tg rice seeds for 2 weeks, then they were immunized with recombinant Der p 1 (rDer p 1) and alum intraperitoneally. Antigen-induced immune responses, such as proliferation and cytokine production of CD4+ T cells, antigen-specific serum IgE and IgG, and infiltration of inflammatory cells into the airways were investigated in those mice. Results: The proliferation and Th2 cytokine production of CD4+ T cells in vitro, antigen-specific IgE and IgG synthesis as well as accumulation of eosinophils and lymphocytes into the airways in vivo were significantly inhibited by administration of the Tg rice. Conclusions: These results suggest that the edible vaccines using Tg rice seeds are useful for the treatment of allergic disorders including bronchial asthma.
Upregulation of Lung Dendritic Cell Functions in Elastase-Induced Emphysema
Authors: Harada Hiroaki , Imamura Mitsuru , Okunishi Katsuhide , Nakagome Kazuyuki , Matsumoto Taku , Sasaki Oh , Tanaka Ryoichi , Yamamoto Kazuhiko , Dohi Makoto
Published: June 2009

Background: Chronic obstructive pulmonary disease (COPD) is now considered a chronic inflammatory disease. Although dendritic cells (DCs) are thought to play a key role in immune responses, studies investigating the role of DCs in COPD are quite limited. Methods: Porcine pancreas elastase was intratracheally administered to C57BL/6J mice on day 0. On days 2, 7 and 14, emphysema formation was evaluated by pressure-volume relationships and microscopic findings, including measurement of the mean linear intercept. Lung DCs were isolated on day 2, and their ability to stimulate allogeneic T cells and to produce cytokines was examined. Results: Pathologic emphysematous change was observed on day 2 and a significant increase in lung volume was observed on day 14. Lung DC function, such as the induction of T-cell proliferation and IL-10 production, was upregulated. Conclusions: Upregulation of DC function was observed in elastase-induced emphysema. Further investigation on the contribution to emphysema formation may provide a useful target for future therapy.
Amphiregulin Production by Human Eosinophils
Authors: Matsumoto Kenji , Fukuda Shuhei , Nakamura Yuri , Saito Hirohisa
Published: June 2009

Background: Amphiregulin (AREG) plays critical roles in mammary gland development, immune responses against nematode infection, and mucous production in the lung. Since remarkable eosinophil infiltration has been shown at all of these tissue sites, we examined AREG production by human eosinophils in vitro. Methods: Using Ficoll and antibody-coated immunomagnetic beads, eosinophils and other blood cells were purified from peripheral blood samples obtained from normal or mild allergic patients. Eosinophils were cultured in the presence of 10 ng/ml of granulocyte-macrophage colony-stimulating factor (GM-CSF), 10 ng/ml of IL-5, 100 ng/ml of IFN-γ or immobilized secretory IgA. Total mRNA was extracted after 6 h of culture, and mRNA expression was measured using a microarray and RT-PCR. The AREG concentration in the supernatant and cell lysate after 48 h of culture was measured using ELISA. Results: AREG mRNA was constitutively expressed in fresh eosinophils, and the expression level in the eosinophils was higher than that in other types of blood cells. AREG mRNA increased significantly upon stimulation with GM-CSF and IL-5 but not with IFN-γ. AREG mRNA expression in GM-CSF-stimulated eosinophils was enhanced by dexamethasone. Fresh eosinophils did not contain AREG protein. AREG was significantly released into the supernatant when the eosinophils were stimulated with GM-CSF, but not with IFN-γ or immobilized secretory IgA. Conclusion: Our data suggested that eosinophils produce and release AREG, and participate in some physiological and pathological conditions in vivo.
Intracellular Protein Phosphorylation in Eosinophils and the Functional Relevance in Cytokine Production
Authors: Yamamura Koichi , Adachi Tetsuya , Masuda Tomoko , Kojima Yasuhiro , Hara Asae , Toda Takako , Nagase Hiroyuki , Ohta Ken
Published: June 2009

Background: Eosinophils play a pivotal role in the pathogenesis of asthma. Thus, it is of paramount importance to investigate the mechanism of eosinophil activation. Although a number of factors including cytokines/chemokines activate eosinophils, the potency of each stimulus to phosphorylate intracellular molecules and activate eosinophils remains to be elucidated. In the present study, we performed inclusive analyses of protein phosphorylation in eosinophils and studied the functional relevance of such phosphorylation in cytokine production. Methods: Blood eosinophils were purified using Percoll and anti-CD16 antibody-coated magnetic beads. Purified eosinophils were stimulated with various stimuli. The eosinophil lysates were subjected to phosphoprotein analysis using the Luminex system. In some of these experiments, we studied the effect of a few signaling inhibitors on cytokine production from eosinophils. Results: We found that several factors such as IL-5, eotaxin, platelet-activating factor (PAF), and PGD2 phosphorylated Akt, ERK1/2, p38 MAPK, and glycogen synthase kinase-3 (GSK-3) in the eosinophils. Because eotaxin most potently induced the production of various cytokines, we performed the inhibition study using eotaxin-stimulated eosinophils. Eotaxin-induced production of IL-1β, IL-6, and MIP-1β was significantly reduced by the MEK inhibitor PD98059, p38 MAPK inhibitor SB203580, or PI3K inhibitor LY294002. In contrast, the GSK-3 inhibitor SB216763 blocked only IL-1β production from the eosinophils. Conclusions: In terms of the phosphorylation of intracellular signaling molecules, we could quantify the potency of various stimuli that activate eosinophils. We are the first to demonstrate the role of GSK-3 in cytokine production from eosinophils. The Luminex system aids in examining the mechanism of eosinophil activation.
Regulation of Peroxisome Proliferator-Activated Receptor-γ Expression in Human Eosinophils by Estradiol
Authors: Ueki Shigeharu , Oguma Mariko , Usami Atsuko , Kamada Yumiko , Kato Hikari , Kamada Rie , Takeda Masahide , Ito Wataru , Tanigai Tomomi , Kayaba Hiroyuki , Chihara Junichi
Published: June 2009

Background: Peroxisome proliferator-activated receptor-γ (PPARγ) is a nuclear receptor that regulates not only adipogenesis but also immune reaction. We previously demonstrated that human eosinophils expressed functional PPARγ, although the modulator of PPARγ expression is less well understood. Because clinical studies have shown that the efficacy of PPARγ agonists as insulin sensitizers is stronger in women than in men, we investigated whether sex hormones caused any changes in eosinophil PPARγ expression levels. Methods: First, purified human peripheral blood eosinophils were cultured with 17β-estradiol for 24 h, followed by PPARγ measurement using a flow cytometer. Next, eosinophil PPARγ expression and serum estradiol were studied in 10 healthy women during the menstrual and follicular phases to identify the physiological significance of estradiol. Eosinophil PPARγ expression was also compared in 22 men, 21 non-pregnant women, and 15 pregnant women. Results: We observed that PPARγ protein expression in eosinophils was significantly enhanced by 10–6M 17β-estradiol. Although serum estradiol concentration was increased during the follicular phase, PPARγ expression levels were not affected by the menstrual cycle. In addition, no significant differences in PPARγ expression were observed in terms of sex and pregnancy. Conclusions: These findings suggest that estradiol potentially upregulates eosinophil PPARγ expression in vitro, although some other mechanisms might be involved in its regulation in vivo.
Effects of Nickel on Eosinophil Survival
Authors: Ishihara Kenji , Goi Yoshiaki , Hong Jang Ja , Seyama Toshio , Ohtsu Hiroshi , Wada Hiroshi , Ohuchi Kazuo , Hirasawa Noriyasu
Published: June 2009

Background: Accessories, watches, coins and other items containing metal sometimes cause contact dermatitis and metal allergy. Among metals, nickel in alloys is ionized by sweat on the surface of the skin and exhibits particularly marked irritancy and allergenicity. Although eosinophils play important roles in allergy, the effects of nickel on eosinophils have not been elucidated. Methods: Eosinophils were prepared from the peritoneal cavity in rats immunized with Ascaris suum extract. Purified rat eosinophils were incubated in the presence of various kinds of metals including nickel. The viability of eosinophils was analyzed using a flow cytometer. Results: When rat eosinophils were incubated for 3 days in the presence of nickel chloride at 30–1,000 μM, the viability of eosinophils was decreased in a concentration-dependent manner. Nickel chloride at 300 μM significantly increased the percentage of annexin V+ PI– eosinophils. The population of annexin V+ PI– eosinophils was also increased by nickel sulfate, cobalt chloride and zinc sulfate. The binding of nickel ions to eosinophils was detected by flow cytometer. Conclusions: Nickel ions bind to eosinophils and decrease the viability of eosinophils through the induction of apoptosis. Nickel ions may exhibit activity which modifies the function of eosinophils in allergy.
Proteomic Approach to FcεRI Aggregation-Initiated Signal Transduction Cascade in Human Mast Cells
Authors: Yamaoka Kazuko , Okayama Yoshimichi , Kaminuma Osamu , Katayama Kazufumi , Mori Akio , Tatsumi Hideki , Nemoto Sohichi , Hiroi Takachika
Published: June 2009

Background: Mast cells (MCs) play a central role in allergic reactions through high-affinity IgE receptor (FcεRI)-mediated responses. Many attempts have been performed to investigate MC functions, though molecular bases of the intracellular signaling cascade through FcεRI, especially in human MCs, remain scant and unexplored. Methods: Human MCs were differentiated from CD34+ cells by culture with stem cell factor, IL-6 and IL-3. The differential phosphorylation profiles of protein tyrosine residues in the resulting MCs with or without FcεRI aggregation were examined by two-dimensional gel electrophoresis. The candidate phosphoproteins of interest were picked, in-gel digested and mass spectrometry fingerprinted. Results: Approximately 40 proteins in MCs were phosphorylated on their tyrosine residues in response to activation and some of them were identified. Particularly IL-31 receptor α, solute carrier family 39, syntaxin 5 and heterogeneous nuclear ribonucleoprotein are newly identified as phosphoproteins that are potentially involved in the MC signaling cascade through FcεRI. Conclusion: Our present phosphoproteome data may provide the clue to understand the molecular mechanisms for the activation of human MCs.
15-Deoxy-Δ12,14-Prostaglandin J2 Induces IL-8 and GM-CSF in a Human Airway Epithelial Cell Line (NCI-H292)
Authors: Chiba Takahito , Ueki Shigeharu , Ito Wataru , Kato Hikari , Takeda Masahide , Kayaba Hiroyuki , Furue Masutaka , Chihara Junichi
Published: June 2009

Background: 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), a major prostanoid metabolized from prostaglandin D2 (PGD2), plays an important role in various biological processes including inflammatory responses. 15d-PGJ2 exerts its effects through two major receptors, chemoattractant receptor- homologous molecule expressed on Th2 cells (CRTH2) and peroxisome proliferator-activated receptor-γ (PPARγ). The 15d-PGJ2/PPARγ system, in particular, regulates numerous biological processes including adipogenesis, apoptosis, and inflammation. Although our studies have shown that PGD2 (metabolic precursor of 15d-PGJ2) induces IL-8 and GM-CSF production, the role of 15d-PGJ2 (metabolite of PGD2) is unknown in human bronchial epithelial cells. In this study, we investigated the function of 15d-PGJ2 on a human airway epithelial cell line: NCI-H292. Method: NCI-H292 cells were cultured in the presence of various stimulants. The resulting supernatants were used for ELISA analysis. Results: We demonstrated that 15d-PGJ2 induced production of IL-8 and GM-CSF from NCI-H292. 13,14-Dihydro-15-keto-PGD2 (DK-PGD2) (CRTH2 agonist) and troglitazone (PPARγ agonist) failed to increase the production of these cytokines. Pretreatment with ramatroban (CRTH2 antagonist) and GW9662 (PPARγ antagonist) did not reduce the production of these cytokines. 15d-PGJ2 activated the ERK1/2 signaling pathway in a time-dependent manner. Conclusion: These data showed that 15d-PGJ2 is a potent inducer of IL-8 and GM-CSF production through ERK1/2 kinase activation, but this is independent of CRTH2 or PPARγ activation.
Neutrophilic Inflammation and CXC Chemokines in Patients with Refractory Asthma
Authors: Kikuchi Shinya , Kikuchi Izumi , Takaku Yotaro , Kobayashi Takehito , Hagiwara Koichi , Kanazawa Minoru , Nagata Makoto
Published: June 2009

Background: There is evidence that eosinophils and neutrophils are simultaneously increased in the airways of some patients with chronic refractory asthma. The mechanisms by which neutrophils accumulate in the airways of asthmatics remain to be elucidated, however, chemoattractants for neutrophils such as CXC chemokines may affect either the accumulation or functional status of neutrophils in such patients. The objective of the present study was to identify the CXC chemokine responsible for the neutrophilic and possibly eosinophilic inflammation observed in the airways of patients with refractory asthma. Methods: Following the inhalation of hypertonic saline, induced sputum was obtained from 14 healthy controls, 16 patients with mild well-controlled nonrefractory asthma, and 14 patients with refractory asthma. Concentrations of CXC chemokines and differential inflammatory cell counts were determined. Results: The percentages of induced sputum eosinophils were significantly higher both in patients with nonrefractory asthma and in patients with refractory asthma. On the other hand, the percentages of neutrophils were increased only in sputum from patients with refractory asthma. The concentration of IL-8, but not ENA-78 or GRO-α, was also significantly increased in induced sputum from patients with refractory asthma. The concentration of IL-8 correlated significantly with the percentages of neutrophils. Conclusions: The results of the present study suggest that IL-8, but not ENA-78 or GRO-α, may contribute to the observation of neutrophilic inflammation in patients with refractory asthma.
A Case of Eosinophilic Pneumonia Successfully Treated with Suplatast Tosilate Alone
Authors: Watanabe Naoto , Hirata Akira , Makino Sohei , Fukuda Takeshi
Published: June 2009

We report a case of eosinophilic pneumonia that was successfully treated with suplatast tosilate. A 72-year-old woman with hypertension and diabetes, who did not smoke and did not have pets, consulted a physician with the chief complaints of cough, sputum, and slight fever. Chest X-ray films revealed a permeation shadow in the bilateral upper lobes. She visited a hospital because her symptoms did not improve. Pulmonary tuberculosis was suspected because of an elevated inflammatory reaction, and anti-tuberculosis treatment was started. Afterwards, eosinophilia appeared in the peripheral blood. Although daily drugs (nicardipine hydrochloride, pentoxifylline, and ticlopidine hydrochloride) were stopped, eosinophilia did not improve and was detected in a sputum sample. She was diagnosed with pulmonary infiltration with eosinophilia syndrome and hospitalized. Physical examination revealed neither rhonchus nor cardiac murmurs on auscultation. Laboratory findings showed a leukocyte count of 21,300/μl, with eosinophils accounting for 66.3% of cells. A diagnosis of eosinophilic pneumonia was made after a lung biopsy specimen was examined under a bronchial fiberscope. After suspension of anti-tuberculosis drugs and administration of suplatast tosilate 300 mg/day for 4 weeks, symptoms subsided, eosinophilia improved to within normal ranges, eosinophils in sputum disappeared, and the permeation shadow disappeared on chest X-ray films.
Role of IL-23-Th17 Cell Axis in Allergic Airway Inflammation
Authors: Wakashin Hidefumi , Hirose Koichi , Iwamoto Itsuo , Nakajima Hiroshi
Published: June 2009

Asthma is characterized by chronic airway inflammation with intense eosinophil and lymphocyte infiltration, mucus hyperproduction, and airway hyperresponsiveness to a variety of stimuli. It is now generally accepted that antigen-specific Th2 cells and their cytokines orchestrate these pathognomonic features of asthma. On the other hand, Th17 cells and IL-23, a cytokine that preferentially expands Th17 cells, play a significant role in the development of chronic inflammatory diseases, including autoimmune diseases. Recently, we have shown that IL-23 and Th17 cells enhance not only neutrophilic airway inflammation but also Th2 cell-mediated eosinophilic airway inflammation in a murine asthma model. In this review, we will discuss the roles of IL-23 and Th17 cells in airway inflammation in asthma.
Does the Type of Resuscitative Fluid Affect Healing of Colonic Anastomosis in Experimentally Induced Hemorrhagic Shock in Rats?
Authors: Harlak Ali , Can Mehmet Fatih , Mentes Oner , Ersoz Nail , Kurt Bulent , Turker Turker , Yagci Gokhan , Tufan Turgut
Published: June 2009

Objective: The aim of the study was to investigate the effects of different resuscitative fluids on the healing of intestinal anastomosis in a hemorrhagic-shock rat model. Materials and Methods: Closed-colony Wistar male rats (n = 40; 8 rats per group) were subjected to volume-controlled hemorrhagic shock, followed by a 30-min shock phase. The animals were then resuscitated with one of the following fluids (which also corresponds to their respective groups): lactated Ringer’s solution (LR), hydroxyethyl starch (HES), 7.5% hypertonic saline (HS) and autologous blood (AB). There was also a control group (CL), which did not experience hemorrhagic shock or receive any resuscitative fluids. All rats underwent laparotomy, segmental resection and anastomosis of the left colon. Five days later, a 2nd laparotomy was performed and the anastomotic bursting pressure was measured in vivo. Thereafter, the anastomosed segment was resected to measure the tissue hydroxyproline level and the grade of anastomotic fibrosis. Results: All experimental groups (LR, HES, HS and AB) exhibited lower anastomotic bursting pressures than the CL group; however, nointergroup differences achieved statistical significance. The mean tissue hydroxyproline level and fibrosis grade also were similar across all 5 groups. Conclusion: In traumatic hemorrhagic shock, anastomosis safety does not appear to be affected by the type of fluid used for resuscitation. Moreover, LR, HES and HS all seemed to reinforce healing as effectively as transfused blood.
Antinociceptive and Anti-Inflammatory Effects of Stachytarpheta jamaicensis (L.) Vahl (Verbenaceae)in Experimental Animal Models
Authors: Sulaiman M.R. , Zakaria Z.A. , Chiong H.S. , Lai S.K. , Israf D.A. , Azam Shah T.M.
Published: June 2009

Objective: The present study was carried out to explore the antinociceptive as well as the anti-inflammatory effects of an ethanol extract of Stachytarpheta jamaicensis (L.) Vahl (EESJ) using 3 models of nociception and 2 models of inflammation in experimental animals. Materials and Methods: EESJ was prepared by overnight soaking of the oven-dried (50°C; 72 h) ground leaves (500 g) in 80% ethanol (1:5; w/v). The filtrate was evaporated to dryness (50°C), resuspended in distilled water at concentrations to provide the desired doses of 50, 100 and 150 mg/kg. For antinociceptive effects, 3 models were used: acetic acid-induced abdominal writhing, hot-plate- and formalin-induced paw-licking tests; for anti-inflammatory effects, 2 models were used – carrageenan-induced paw edema and cotton-pellet-induced granuloma tests. Appropriate doses were administered intraperitoneally (i.p.) to mice/rats prior to each test. The mechanisms of antinociceptive action of the extract were also investigated by pretreatment with naloxone (5 mg/kg, i.p.). Results: The extract exhibited significant (p < 0.05) antinociceptive activity in all nociceptive models tested with dose-dependent activity observed using the abdominal writhing and formalin tests. Pretreatment with naloxone partially, but significantly (p < 0.05) reversed the antinociceptive activity of the extract when assessed using the abdominal-writhing- and formalin-induced paw-licking tests, and completely inhibited its activity when the hot-plate test was used. The extract also showed significant (p < 0.05) anti-inflammatory activity in both the acute (carrageenan-induced paw edema test) and the chronic (cotton-pellet granuloma test) tests. Conclusion: This study showed the potential of EESJ to exert antinociceptive and anti-inflammatory activities, the former being modulated via peripheral and central mechanisms and involving, in part, activation of the opioid receptor system.
Corticosteroids Reduce Glial Fibrillary Acidic Protein Expression in Response to Spinal Cord Injury in a Fetal Rat Model of Dysraphism
Authors: Melo-Filho Antônio Aldo , Weber Guimarães Barreto Maria , Capelli Nassr Azize Cristina , Rogério Fábio , Langone Francesco , Pereira Luis Antonio Violin , Sbragia Lourenço
Published: June 2009

Background: Exposure of the spinal cord in myelomeningocele (MM) throughout gestation increases spinal injury. Astrocyte activation evidenced by glial fibrillary acidic proteins (GFAP) indicates the extent of injury. Corticosteroids modulate GFAP synthesis, but their effect in MM is unclear. The purpose of this study was to evaluate the GFAP expression in a fetal rat model of dysraphism and the effect of corticosteroid treatment on this marker and on clinical neurological disabilities. Methods: Dysraphism was surgically created in 2 groups of 48 rat fetuses; group 1: control, and group 2: treated with corticosteroid. Each group was subdivided into fetuses with surgically created MM, controls and shams on day 18.5 of gestation (term = 22 days). Fetuses were harvested on day 21.5, examined for evidence of neurological deficits, and the following clinical parameters were registered: kyphosis, tail deformities, leg deformities, leg paralysis or paresis and pain perception. The fetuses were fixed for GFAP immunostaining. Results: All fetuses with MM in group 1 presented neurological deficits and glial reactions with GFAP expression, as opposed to controls and shams. In group 2, corticosteroid treatment prevented some neurological deficits (18–25%), reducing glial response and GFAP expression. Conclusions: Experimentally induced dysraphism in the rat fetus is related to glial response and increased GFAP expression in the spinal cord. Corticoid treatment clinically improved nerve injury in some fetuses. It reduced glial reaction and GFAP expression.
Significant Pediatric Morbidity and Mortality from Intracranial Ballistic Injuries Caused by Nonpowder Gunshot Wounds
Authors: O’Neill Patrick J. , Lumpkin Mary Foster , Clapp Benjamin , Kopelman Tammy R. , Matthews Marc R. , Cox Jordy C. , Caruso Daniel M. , Feiz-Erfan Iman
Published: June 2009

Nonpowder (ball-bearing and pellet) weapons derive their source of energy from compressed air or carbon dioxide. Such weapons are dangerous toys that cause serious injuries and even death to children and adolescents. A retrospective chart review study was undertaken to describe nonpowder gun injuries at a southwestern US urban level I adult and pediatric trauma center. Specific emphasis was placed on intracranial injuries. Over the past 6 years, a total of 29 pediatric and 7 adult patients were identified as having nonpowder firearm injuries. The patient population was overwhelmingly male (89.7%; mean age, 11 years). Overall, 17 out of 29 pediatric patients (56.8%) sustained serious injury. Nine patients (30.0%) required operation, 6 (20.7%) sustained significant morbidity, and there were 2 deaths (6.9%). Injuries to the brain, eye, head, and neck were the most common sites of injury (65.6%). Specific intracranial injuries in 3 pediatric patients are described that resulted in the death of 2 children. We suggest that age warning should be adjusted to 18 years or older for unsupervised use to be considered safe of these potentially lethal weapons.