254 research outputs found

    Architecting in global software engineering

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    Cataloged from PDF version of article.This paper summarizes the results of the First Workshop on Architecting in Global Software Engineering (GSE), which was organized in conjunction with the 6th International Conference on Global Software Engineering (ICGSE 2011). The workshop aimed to bring together researchers and practitioners for defining and advancing the state-of-the-art and state-of-the practice in architecture design of global software development systems

    Roles of Fukutin, the Gene Responsible for Fukuyama-Type Congenital Muscular Dystrophy, in Neurons: Possible Involvement in Synaptic Function and Neuronal Migration

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    Fukutin is a gene responsible for Fukuyama-type congenital muscular dystrophy (FCMD), accompanying ocular and brain malformations represented by cobblestone lissencephaly. Fukutin is related to basement membrane formation via the glycosylation of α-dystoglycan (α-DG), and astrocytes play a crucial role in the pathogenesis of the brain lesion. On the other hand, its precise function in neurons is unknown. In this experiment, the roles of fukutin in mature and immature neurons were examined using brains from control subjects and FCMD patients and cultured neuronal cell lines. In quantitative PCR, the expression level of fukutin looked different depending on the region of the brain examined. A similar tendency in DG expression appears to indicate a relation between fukutin and α-DG in mature neurons. An increase of DG mRNA and core α-DG in the FCMD cerebrum also supports the relation. In immunohistochemistry, dot-like positive reactions for VIA4-1, one of the antibodies detecting the glycosylated α-DG, in Purkinje cells suggest that fukutin is related to at least a post-synaptic function via the glycosylation of α-DG. As for immature neurons, VIA4-1 was predominantly positive in cells before and during migration with expression of fukutin, which suggest a participation of fukutin in neuronal migration via the glycosylation of α-DG. Moreover, fukutin may prevent neuronal differentiation, because its expression was significantly lower in the adult cerebrum and in differentiated cultured cells. A knockdown of fukutin was considered to induce differentiation in cultured cells. Fukutin seems to be necessary to keep migrating neurons immature during migration, and also to support migration via α-DG

    Effect of Cu impurities on wet etching of Si(110): formation of trapezoidal hillocks

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    We simulate the formation of experimentally observed trapezoidal hillocks on etched Si(110) surfaces, describing their generic geometrical shape and analyzing the relative stability and/or reactivity of the key surface sites. In our model, the hillocks are stabilized by Cu impurities in the etchant adsorbing on the surface and acting as pinning agents. A model of random adsorptions will not result in hillock formation since a single impurity is easily removed from the surface. Instead a whole cluster of Cu atoms is needed as a mask to stabilize a hillock. Therefore we propose and analyze mechanisms that drive correlated adsorptions and lead to stable Cu clusters.Peer reviewe

    Rapid Change in Articulatory Lip Movement Induced by Preceding Auditory Feedback during Production of Bilabial Plosives

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    BACKGROUND: There has been plentiful evidence of kinesthetically induced rapid compensation for unanticipated perturbation in speech articulatory movements. However, the role of auditory information in stabilizing articulation has been little studied except for the control of voice fundamental frequency, voice amplitude and vowel formant frequencies. Although the influence of auditory information on the articulatory control process is evident in unintended speech errors caused by delayed auditory feedback, the direct and immediate effect of auditory alteration on the movements of articulators has not been clarified. METHODOLOGY/PRINCIPAL FINDINGS: This work examined whether temporal changes in the auditory feedback of bilabial plosives immediately affects the subsequent lip movement. We conducted experiments with an auditory feedback alteration system that enabled us to replace or block speech sounds in real time. Participants were asked to produce the syllable /pa/ repeatedly at a constant rate. During the repetition, normal auditory feedback was interrupted, and one of three pre-recorded syllables /pa/, /Φa/, or /pi/, spoken by the same participant, was presented once at a different timing from the anticipated production onset, while no feedback was presented for subsequent repetitions. Comparisons of the labial distance trajectories under altered and normal feedback conditions indicated that the movement quickened during the short period immediately after the alteration onset, when /pa/ was presented 50 ms before the expected timing. Such change was not significant under other feedback conditions we tested. CONCLUSIONS/SIGNIFICANCE: The earlier articulation rapidly induced by the progressive auditory input suggests that a compensatory mechanism helps to maintain a constant speech rate by detecting errors between the internally predicted and actually provided auditory information associated with self movement. The timing- and context-dependent effects of feedback alteration suggest that the sensory error detection works in a temporally asymmetric window where acoustic features of the syllable to be produced may be coded

    Dual oscillator model of the respiratory neuronal network generating quantal slowing of respiratory rhythm

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    We developed a dual oscillator model to facilitate the understanding of dynamic interactions between the parafacial respiratory group (pFRG) and the preBötzinger complex (preBötC) neurons in the respiratory rhythm generation. Both neuronal groups were modeled as groups of 81 interconnected pacemaker neurons; the bursting cell model described by Butera and others [model 1 in Butera et al. (J Neurophysiol 81:382–397, 1999a)] were used to model the pacemaker neurons. We assumed (1) both pFRG and preBötC networks are rhythm generators, (2) preBötC receives excitatory inputs from pFRG, and pFRG receives inhibitory inputs from preBötC, and (3) persistent Na+ current conductance and synaptic current conductances are randomly distributed within each population. Our model could reproduce 1:1 coupling of bursting rhythms between pFRG and preBötC with the characteristic biphasic firing pattern of pFRG neurons, i.e., firings during pre-inspiratory and post-inspiratory phases. Compatible with experimental results, the model predicted the changes in firing pattern of pFRG neurons from biphasic expiratory to monophasic inspiratory, synchronous with preBötC neurons. Quantal slowing, a phenomena of prolonged respiratory period that jumps non-deterministically to integer multiples of the control period, was observed when the excitability of preBötC network decreased while strengths of synaptic connections between the two groups remained unchanged, suggesting that, in contrast to the earlier suggestions (Mellen et al., Neuron 37:821–826, 2003; Wittmeier et al., Proc Natl Acad Sci USA 105(46):18000–18005, 2008), quantal slowing could occur without suppressed or stochastic excitatory synaptic transmission. With a reduced excitability of preBötC network, the breakdown of synchronous bursting of preBötC neurons was predicted by simulation. We suggest that quantal slowing could result from a breakdown of synchronized bursting within the preBötC

    TLR7 single-nucleotide polymorphisms in the 3' untranslated region and intron 2 independently contribute to systemic lupus erythematosus in Japanese women: a case-control association study

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    IntroductionThe Toll-like receptor 7 (TLR7) gene, encoded on human chromosome Xp22.3, is crucial for type I interferon production. A recent multicenter study in East Asian populations, comprising Chinese, Korean and Japanese participants, identified an association of a TLR7 single-nucleotide polymorphism (SNP) located in the 3\u27 untranslated region (3\u27 UTR), rs3853839, with systemic lupus erythematosus (SLE), especially in males, although some difference was observed among the tested populations. To test whether additional polymorphisms contribute to SLE in Japanese, we systematically analyzed the association of TLR7 with SLE in a Japanese female population.MethodsA case-control association study was conducted on eight tag SNPs in the TLR7 region, including rs3853839, in 344 Japanese females with SLE and 274 healthy female controls.ResultsIn addition to rs3853839, two SNPs in intron 2, rs179019 and rs179010, which were in moderate linkage disequilibrium with each other (r2 = 0.53), showed an association with SLE (rs179019: P = 0.016, odds ratio (OR) 2.02, 95% confidence interval (95% CI) 1.15 to 3.54; rs179010: P = 0.018, OR 1.75, 95% CI 1.10 to 2.80 (both under the recessive model)). Conditional logistic regression analysis revealed that the association of the intronic SNPs and the 3\u27 UTR SNP remained significant after we adjusted them for each other. When only the patients and controls carrying the risk genotypes at the 3\u27 UTR SNPpositionwere analyzed, the risk of SLE was significantly increased when the individuals also carried the risk genotypes at both of the intronic SNPs (P = 0.0043, OR 2.45, 95% CI 1.31 to 4.60). Furthermore, the haplotype containing the intronic risk alleles in addition to the 3\u27 UTR risk allele was associated with SLE under the recessive model (P = 0.016, OR 2.37, 95% CI 1.17 to 4.80), but other haplotypes were not associated with SLE.ConclusionsThe TLR7 intronic SNPs rs179019 and rs179010 are associated with SLE independently of the 3\u27 UTR SNP rs3853839 in Japanese women. Our findings support a role of TLR7 in predisposition for SLE in Asian populations

    Methamphetamine induces endoplasmic reticulum stress related gene CHOP/Gadd153/ddit3 in dopaminergic cells

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    We examined the toxicity of methamphetamine and dopamine in CATH.a cells, which were derived from mouse dopamine-producing neural cells in the central nervous system. Use of the quantitative real-time polymerase chain reaction revealed that transcripts of the endoplasmic reticulum stress related gene (CHOP/Gadd153/ddit3) were considerably induced at 24–48 h after methamphetamine administration (but only under apoptotic conditions), whereas dopamine slightly induced CHOP/Gadd153/ddit3 transcripts at an early stage. We also found that dopamine and methamphetamine weakly induced transcripts for the glucose-regulated protein 78 gene (Grp78/Bip) at the early stage. Analysis by immunofluorescence microscopy demonstrated an increase of CHOP/Gadd153/ddit3 and Grp78/Bip proteins at 24 h after methamphetamine administration. Treatment of CATH.a cells with methamphetamine caused a re-distribution of dopamine inside the cells, which mimicked the presynaptic activity of neurons with cell bodies located in the ventral tegmental area or the substantia nigra. Thus, we have demonstrated the existence of endoplasmic reticulum stress in a model of presynaptic dopaminergic neurons for the first time. Together with the recent evidence suggesting the importance of presynaptic toxicity, our findings provide new insights into the mechanisms of dopamine toxicity, which might represent one of the most important mechanisms of methamphetamine toxicity and addiction

    In Orbit Timing Calibration of the Hard X-Ray Detector on Board Suzaku

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    The hard X-ray detector (HXD) on board the X-ray satellite Suzaku is designed to have a good timing capability with a 61 μ\mus time resolution. In addition to detailed descriptions of the HXD timing system, results of in-orbit timing calibration and performance of the HXD are summarized. The relative accuracy of time measurements of the HXD event was confirmed to have an accuracy of 1.9×1091.9\times 10^{-9} s s1^{-1} per day, and the absolute timing was confirmed to be accurate to 360 μ\mus or better. The results were achieved mainly through observations of the Crab pulsar, including simultaneous ones with RXTE, INTEGRAL, and Swift.Comment: Accepted for publication on PASJ Vol.60, SP-1, 200

    Small primary adenocarcinoma in adenomyosis with nodal metastasis: a case report

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    <p>Abstract</p> <p>Background</p> <p>Malignant transformation of adenomyosis is a very rare event. Only about 30 cases of this occurrence have been documented till now.</p> <p>Case presentation</p> <p>The patient was a 57-year-old woman with a slightly enlarged uterus, who underwent total hysterectomy and unilateral adnexectomy. On gross inspection, the uterine wall displayed a single nodule measuring 5 cm and several small gelatinous lesions. Microscopic examination revealed a common leiomyoma and multiple adenomyotic foci. A few of these glands were transformed into a moderately differentiated adenocarcinoma. The endometrium was completely examined and tumor free. The carcinoma was, therefore, considered to be an endometrioid adenocarcinoma arising from adenomyosis. Four months later, an ultrasound scan revealed enlarged pelvic lymph nodes: a cytological diagnosis of metastatic adenocarcinoma was made.</p> <p>Immunohistochemical studies showed an enhanced positivity of the tumor site together with the neighbouring adenomyotic foci for estrogen receptors, aromatase, p53 and COX-2 expression when compared to the distant adenomyotic glands and the endometrium. We therefore postulate that the neoplastic transformation of adenomyosis implies an early carcinogenic event involving p53 and COX-2; further tumor growth is sustained by an autocrine-paracrine loop, based on a modulation of hormone receptors as well as aromatase and COX-2 local expression.</p> <p>Conclusion</p> <p>Adenocarcinoma in adenomyosis may be affected by local hormonal influence and, despite its small size, may metastasize.</p
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