144 research outputs found

    The Guardian, April 9, 1982

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    Eight page issue of The Guardian, the official student-run newspaper for Wright State University. The Guardian has been published regularly since March of 1965.https://corescholar.libraries.wright.edu/guardian/1998/thumbnail.jp

    Made in Amsterdam : a 1771 cittern by Benoit Joseph Boussu

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    Cittern-family instruments enjoyed popularity in the second half of the 18th century, most notably in the British Isles and France. Many such instruments from these countries have survived in museums and private collections. This ‘guittar’ fashion also took root in the Netherlands, although very few Dutch-made, late 18th-century citterns have survived. The recent rediscovery of an Amsterdam-made cittern by Benoit Joseph Boussu, previously only known about from written sources, adds another example to this small but important group of Dutch-made instruments. In this article, the Boussu cittern is comprehensively described, based on visual observations, endoscopy and CT-scanning, techniques that also enable a detailed analysis of its inner construction. The instrument’s provenance and the biography of its maker are also discussed. These analyses lead to the conclusion that a cittern, of equal quality and appearance to British and French instruments, had already been built in the Netherlands as early as 1771, and included in its design an innovative watch-key tuning mechanism

    Early clearance of Chikungunya virus in children is associated with a strong innate immune response

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    Chikungunya fever (CHIKF) is a global infectious disease which can affect a wide range of age groups. The pathological and immunological response upon Chikungunya virus (CHIKV) infection have been reported over the last few years. However, the clinical profile and immune response upon CHIKV infection in children remain largely unknown. In this study, we analyzed the clinical and immunological response, focusing on the cytokine/chemokine profile in a CHIKV-infected pediatric cohort from Sarawak, Malaysia. Unique immune mediators triggered upon CHIKV infection were identified through meta-analysis of the immune signatures between this pediatric group and cohorts from previous outbreaks. The data generated from this study revealed that a broad spectrum of cytokines/chemokines is up-regulated in a sub-group of virus-infected children stratified according to their viremic status during hospitalization. Furthermore, different immune mediator profiles (the levels of pro-inflammatory cytokines, chemokines and growth and other factors) were observed between children and adults. This study gives an important insight to understand the immune response of CHIKV infection in children and would aid in the development of better prognostics and clinical management for children

    Backbone and side-chain 1H, 13C and 15N assignments of the ubiquitin-associated domain of human X-linked inhibitor of apoptosis protein

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    X-linked inhibitor of apoptosis protein (XIAP), a leading member of the family of inhibitor of apoptosis (IAP) proteins, is considered as the most potent and versatile inhibitor of caspases and apoptosis. It has been reported that XIAP is frequently overexpressed in cancer and its expression level is implicated in contributing to tumorigenesis, disease progression, chemoresistance and poor patient-survival. Therefore, XIAP is one of the leading targets in drug development for cancer therapy. Recently, based on bioinformatics study, a previously unrecognized but evolutionarily conserved ubiquitin-associated (UBA) domain in IAPs was identified. The UBA domain is found to be essential for the oncogenic potential of IAP, to maintain endothelial cell survival and to protect cells from TNF-α-induced apoptosis. Moreover, the UBA domain is required for XIAP to activate NF-κB. In the present study, we report the near complete resonance assignments of the UBA domain-containing region of human XIAP protein. Secondary structure prediction based on chemical shift index (CSI) analysis reveals that the protein is predominately α-helical, which is consistent with the structures of known UBA proteins

    C-Terminal Binding Protein 2 Is a Novel Tumor Suppressor Targeting the Myc-Irf4 axis in Multiple Myeloma

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    Multiple myeloma (MM) cells are addicted to MYC and its direct transactivation targets IRF4 for proliferation and survival. MYC and IRF4 are still considered undruggable, as most small-molecule inhibitors suffer from low potency, suboptimal pharmacokinetic properties, and undesirable off-target effects. Indirect inhibition of MYC/IRF4 emerges as a therapeutic vulnerability in MM. Here, we uncovered an unappreciated tumor-suppressive role of C-terminal binding protein 2 (CTBP2) in MM via strong inhibition of the MYC-IRF4 axis. In contrast to epithelial cancers, CTBP2 is frequently downregulated in MM, in association with shortened survival, hyperproliferative features, and adverse clinical outcomes. Restoration of CTBP2 exhibited potent antitumor effects against MM in vitro and in vivo, with marked repression of the MYC-IRF4 network genes. Mechanistically, CTBP2 impeded the transcription of MYC and IRF4 by histone H3 lysine 27 deacetylation (H3K27ac) and indirectly via activation of the MYC repressor IFIT3. In addition, activation of the interferon gene signature by CTBP2 suggested its concomitant immunomodulatory role in MM. Epigenetic studies have revealed the contribution of polycomb-mediated silencing and DNA methylation to CTBP2 inactivation in MM. Notably, inhibitors of Enhance of zeste homolog 2, histone deacetylase, and DNA methyltransferase, currently under evaluation in clinical trials, were effective in restoring CTBP2 expression in MM. Our findings indicated that the loss of CTBP2 plays an essential role in myelomagenesis and deciphers an additional mechanistic link to MYC-IRF4 dysregulation in MM. We envision that the identification of novel critical regulators will facilitate the development of selective and effective approaches for treating this MYC/IRF4-addicted malignancy

    Clonazepam Treatment of Pathologic Childhood Aerophagia with Psychological Stresses

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    The treatment of pathologic aerophagia has rarely been discussed in the literature. In this retrospective study, the authors investigated the effects of clonazepam on the management of pathologic childhood aerophagia (PCA) with psychological stresses (PS), but not with mental retardation. Data from 22 consecutive PCA patients with PS (aged 2 to 10 yr), who had been followed up for over 1 yr, were reviewed. On the basis of videolaryngoscopic views, the authors observed that the pathologyof aerophagia was the result of reflex-induced swallowing with paroxysmal openings of the upper esophageal sphincter due to unknown factors and also observed that these reflex-induced openings were subsided after intravenous low dose benzodiazepine administration. Hence, clonazepam was administered to treat paroxysmal openings in these PCA patients with PS. Remission positivity was defined as symptom-free for a consecutive 1 month within 6 months of treatment. The results of treatment in 22 PCA patients with PS were analyzed. A remission positive state was documented in 14.3% of PCA patients managed by reassurance, and in 66.7% of PCA patients treated with clonazepam (p=0.032). Thus, clonazepam may produce positive results in PCA with PS. Future studies by randomized and placebo-controlled trials are needed to confirm the favorable effect of clonazepam in PCA

    The Significance of Gastric Juice Analysis for a Positive Challenge by a Standard Oral Challenge Test in Typical Cow's Milk Protein-Induced Enterocolitis

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    This study was performed to investigate the significance of gastric juice analysis (GJA) as a diagnostic criterion of a positive challenge in a standard oral cow's milk challenge (OCC) to confirm typical cow's milk protein-induced enterocolitis (CMPIE). Data from 16 CMPIE patients (aged 14 to 44 days) were analyzed. A standard OCC was openly executed using 0.15 g/kg of protein. Three symptoms (vomiting, lethargy, and bloody or pus-like stool), and four laboratory findings (GJA [3 hr], changes in peripheral blood absolute neutrophil count [ANC] [6 hr], C-reactive protein [6 hr], and stool smear test for occult blood or leukocytes) were observed after OCC. Before OCC, baseline studies were conducted; a stool smear test, blood sampling, and GJA. Positive OCC results were; vomiting (87.5%) (observed 1-3 hr after OCC), lethargy (62.5%) (1-3 hr), bloody or pus-like stool (43.8%) (6-10 hr), abnormal GJA (93.8%), an ANC rise >3,500 cells/µL (93.8%), and an abnormal stool smear test (75.0%). A single GJA test after a standard OCC is a sensitive diagnostic criterion of a positive challenge, and may provide an early confirmatory diagnosis of CMPIE. An investigation of positive OCC outcomes helps to find out a diagnostic algorithm of criteria of a positive challenge in CMPIE

    GABA-enriched Oolong Tea: Reducing Stress in a Student Cohort May Involve More than Just GABA

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    We have previously shown that the consumption of GABA-enriched oolong tea is effective in reducing stress in a student cohort. However, key constituent content has not been previously investigated, especially as applied to a standard cup of tea. Further, it has not been substantiated whether it is the suggested GABA content or other constituents that lead to these observed changes in stress behaviour. Using reverse-phase HPLC, we determined the actual content of four chemicals known to influence stress in 200 mL cups of regular or GABA-enriched oolong tea brewed to manufacturer’s instructions. We found eight times as much γ-aminobutyric acid (GABA) and 1.5 times as much caffeine in GABA-enriched oolong tea as in regular oolong tea. In contrast, there was 10 times less epigallocatechin gallate (EGCG), and half as much theanine in the GABA-enriched tea. Thus, there are changes in multiple constituents in GABA-enriched oolong tea that may contribute to the biological effects we observed in students consuming these teas
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