Miracle-dz/UniFAR-FTUs huggingface dataset:
ASC is essential for LPS‐induced activation of procaspase‐1 independently of TLR‐associated signal adaptor molecules

Toll‐like receptors (TLRs) initiate a signalling cascade via association with an adaptor molecule, myeloid differentiation factor 88 (MyD88) and/or TIR domain‐containing adaptor inducing‐IFN‐β (Trif), to induce various pro‐inflammatory cytokines for microbial eradication. After stimulation of TLR4 with lipopolysaccharide (LPS), both IL‐1β and IL‐18 are processed, depending on the activation of caspase‐1, although its mechanism remains unclear. ASC is an adapter protein possibly involved in the activation of procaspase‐1. To unravel the requirement of ASC, we generated Asc−/– mice. Upon stimulation with LPS, Asc−/– macrophages failed in the processing of procaspase‐1 and maturation of pro‐IL‐1β and pro‐IL‐18, but normally produced other pro‐inflammatory cytokines including TNF‐α and IL‐6. MyD88−/– and Trif−/– macrophages showed normal activation of caspase‐1, demonstrating a dispensable role for MyD88 and Trif. After, LPS‐challenged Asc−/– mice lacked serum elevation of IL‐1β and IL‐18. Moreover, the Asc−/– mice exhibited neither acute liver injury nor lethal shock. These results demonstrate critical roles for ASC in the release of IL‐1β/IL‐18 via activation of caspase‐1 and provide new insights into the inflammatory responses for host defence and diseases.
Spectrum of corrugated and periodically loaded waveguides from classical matrix eigenvalues

The paper presents a rigorous full-wave analysis of propagation in corrugated and periodically loaded waveguides. The propagation constants are determined from the classical eigenvalues of a canonical matrix eigenvalue problem instead of a determinant. The entries of the matrix are computed only once per frequency point. The entire k/sub 0/-/spl beta/ diagram of a corrugated circular waveguide, a circular waveguide periodically loaded with dielectric disks, and a rectangular waveguide periodically loaded with capacitive irises are determined and compared with results of other researchers. Excellent agreement is documented in each case.
An Extended-Strategic Alignment Model for technical information system alignment

Information systems (ISs) are the cornerstone of manufacturing companies. These rely on technical ISs that enable the integration between the infrastructures and the support of design and production management activities. For them, ‘strategic alignment’ is crucial for business performance. It exists when the ISs and business goals and activities are in concordance. In the literature, it is often approached from a top managerial point of view, whereas it had also to be managed at an operational level through integration into the upstream phases of the ISs design and development. To succeed in, we propose the Extended-Strategic Alignment Model and an exploitation process. They support the systematic study of the mutual influences between business, information technology and product design or manufacturing. The propositions are illustrated on the part monitoring module of the manufacturing workshop from a real small and medium enterprise.
High Molecular Weight Microtubule-associated Proteins Contain O-Linked N-Acetylglucosamine (*)

We have examined the post-translational modification of high molecular weight microtubule-associated proteins (MAPs) and have shown that MAP1, MAP2, and MAP4 are glycosylated. The presence of carbohydrate residues on these proteins was indicated by labeling with biotin hydrazide following periodate oxidation, a specific and well established method for detecting saccharide moieties on proteins. Both MAP2 and MAP4 were also labeled in vitro by UDP-[H]galactose in the presence of galactosyltransferase. Labeling by galactosyltransferase indicated that MAP2 and MAP4 contained terminal nonreducing GlcNAc residues, and they appeared to be O-linked to the proteins as shown by their sensitivity to β-elimination. Chromatographic analysis showed that the GlcNAc residues were directly linked to the proteins as monosaccharides. Thus, we have added MAP2 and MAP4 to the list of intracellular O-GlcNAc-modified proteins, which includes other cytoskeletal proteins such as cytokeratins 8, 13, and 18 and neurofilament proteins NF-L and NF-M. We further characterized the O-GlcNAc modification of MAP2, and stoichiometric analysis indicated that nearly 10% of the MAP2 isolated from rat brain is modified by O-GlcNAc. However, this estimate is thought to reflect the minimal level of O-GlcNAc modification present on MAP2. We have also shown that both the O-GlcNAc and biotin hydrazide-reactive carbohydrate moieties are located on the projection domain of MAP2. Three O-GlcNAc-containing peaks were observed following fast protein liquid chromatography of a tryptic digest of MAP2, suggesting that multiple modification sites exist. The specific modification sites and functional significance of the O-GlcNAc glycosylation on the high M MAPs remain to be determined.
FRAXA and FRAXE: the results of a five year survey

We report the results of a five year survey of FRAXA and FRAXE mutations among boys aged 5 to 18 with special educational needs (SEN) related to learning disability. We tested their mothers using the X chromosome not transmitted to the son as a control chromosome, and the X chromosome inherited by the son to provide information on stability of transmission. We tested 3738 boys and 2968 mothers and found 20 FRAXA and one FRAXE full mutations among the boys and none among the mothers. This gives an estimated prevalence of full mutations in males of 1 in 5530 for FRAXA and 1 in 23 423 for FRAXE. We found an excess of intermediate and premutation alleles for both FRAXA and FRAXE. For FRAXA this was significant at the 0.001 level but the excess for FRAXE was significant only at the 0.03 level. We conclude that the excess of intermediate and premutation sized alleles for FRAXA may well be a contributing factor to the boys' mental impairment, while that for FRAXE may be a chance finding. We studied approximately 3000 transmissions from mother to son and found five instabilities of FRAXA in the common or intermediate range and three instabilities of FRAXE in the intermediate range. Thus instabilities in trinucleotide repeat size for FRAXA and FRAXE are rare, especially among alleles in the common size range.
Different frequencies of Streptococcus anginosus infection in oral cancer and esophageal cancer

Multiple cancers frequently occur in the upper aerodigestive tract. The high incidence rate of multiple carcinomas in this region is often explained in terms of involvement of the same underlying risk factors. It has been reported that the oral bacterium Streptococcus anginosus (S. anginosus) is associated with esophageal, gastric, and pharyngeal cancer tissues. In this study, a highly specific quantification method for S. anginosus DNA using real‐time PCR was established. We employed this assay to determine whether S. anginosus is also associated with oral cancer tissues. This precise quantification method revealed different degrees of infection with S. anginosus in esophageal cancer and oral cancer. We assayed 10 ng of genomic DNA from cancer tissues, and found that eight of 18 samples (44%) from the esophagus contained a detectable level (>10 fg) of S. anginosus DNA, whereas this was the case for only five of 38 samples (13%) of oral cancer. The quantity of S. anginosus DNA in the esophageal cancer tissues was significantly higher than in oral cancer. The maximum amount of S. anginosus DNA was approximately ten times higher in esophageal than in oral cancer tissues. In addition, none of the five different oral cancer sites (floor of the mouth, mandibular gingival, maxillary gingival, buccal mucosal, and tongue) showed significant signs of S. anginosus infection. On the other hand, most non‐cancerous tissues of the esophagus and tongue showed an undetectable level of S. anginosus. These results suggest that S. anginosus is associated with esophageal cancer, but is not closely related with oral cancer.
Partnership Building and Implementation of an Integrated Healthy-Aging Program

Background: Evidence-based interventions exist for prevention of chronic disease in older adults. Partnering with community organizations may provide a mechanism for disseminating these interventions.Objective: To describe the partnership and program implementation by the Arthritis Foundation (AF) and the University of Pittsburgh.Methods: The AF Exercise Program (AFEP; an existing evidence-based program) was enhanced with the “10 Keys”™ to Healthy Aging (a prevention-focused program bundling the most common risk factors for chronic disease and disability in older adults and applies behavior change strategies to enhance prevention). The program was delivered in 20 sessions over 10 weeks by community health workers in a cluster-randomized trial.Lessons Learned: Partnering with an organization having an existing infrastructure supports program delivery at the community level. This partnership provided programming in 54 sites across Pittsburgh and surrounding communities.Conclusions: This collaborative partnership created a productive synergy maximizing strengths in both research and program delivery.
UvA-DARE ( Digital Academic Repository ) Path-metadynamics : A computational study of conformational transitions in proteins

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Wavelet-based Bayesian nonlinear regression for the air pollution effects on clinic visits in small areas of Taiwan

ABSTRACT We revisit the complete clinic visit records and environmental monitoring data at 50 townships and city districts of Taiwan. Extending the earlier analyses, here we consider a Bayesian analysis using Daubechies wavelet. Appropriate model selection is also considered using Bayesian model averaging. Temperature, dew point, and NO2 and CO of the current day and the previous day are identified as the pollutants in different areas of the island following some spatial pattern.
Serum cytokine profiles in patients with adult onset Still's disease.

OBJECTIVE Adult onset Still's disease (AOSD) is a systemic inflammatory disorder characterized by fever, arthritis, and rash. Although the pathogenesis is not known, immunologically mediated inflammation occurs in active AOSD. To evaluate the pathogenesis and disease activity of AOSD, we measured serial serum concentrations of several cytokines in patients with active and inactive disease. METHODS Seventeen patients diagnosed as having AOSD were enrolled. We analyzed clinical and laboratory findings retrospectively. Serial serum samples were obtained from 14 patients with active and inactive AOSD. Interleukin 18 (IL-18), soluble IL-2 receptor (sIL-2R), IL-6, interferon-g (IFN-g), and IL-8 were determined by ELISA. RESULTS Serum levels of IL-18, IFN-g, and IL-8 were significantly higher in patients with AOSD than in healthy controls (p < 0.01), but there were no significant differences between patients with active and inactive AOSD. Serum sIL-2R levels tended to be higher in the active state than in healthy controls, but there was no statistically significant difference between the 2 groups. Serum sIL-2R levels decreased significantly with antiinflammatory therapy (p < 0.05). Serum IL-18 and sIL-2R levels correlated significantly with serum ferritin levels in the active AOSD group (p < 0.05). CONCLUSION Overproduction of IL-18 may contribute to the pathogenic mechanism of AOSD, and serum sIL-2R levels may be used as a marker for monitoring disease activity in AOSD.
Anticancer efficacy of deguelin in human prostate cancer cells targeting glycogen synthase kinase‐3 β/β‐catenin pathway

Activation of survival pathways has been associated with chemoresistance and progression of androgen independence which places a major obstacle to successful treatment of metastatic prostate cancer. Deguelin, a rotenoid isolated from Mundulea sericea, has an anticancer effect against several types of cancers; however, the mechanism of its antitumor effects on prostate cancer is not well understood. The aim of our study was to elucidate the effect of deguelin on the growth of prostate cancer cells and its putative mechanism of action. Deguelin decreased the viability of both androgen‐dependent and ‐independent prostate cancer cells but not normal prostate epithelial cells. Downregulation of phosphorylated Akt and GSK‐3β by deguelin promoted proteosomal degradation of β‐catenin that resulted in decreased nuclear accumulation and inhibited transactivation of β‐catenin‐responsive genes. Deguelin‐induced downregulation of proliferative (cyclin D1 and c‐myc) and antiapoptotic proteins (Mcl‐1, Bcl‐xL and survivin) in prostate cancer cells culminated in the induction of apoptosis, inhibition of DNA synthesis and cell growth, altered membrane integrity, marked reduction of invasiveness, inhibition of anchorage‐dependent and ‐independent colony formation. Our data demonstrated for the first time that deguelin inhibits the growth and survival of human androgen‐independent prostate cancer cells, and its anticancer and antimetastatic activity occurs, at least in part through downregulating GSK‐3β/β‐catenin signaling pathway and antiapoptotic survival proteins. Taken together our study indicates that deguelin may have translational potential as therapeutic agent for advanced or metastatic prostate cancer.
Seroprevalence of Helicobacter pylori in South Korea

Background: Helicobacter pylori‐associated gastrointestinal diseases have been widely recognized. The aims of this study were to investigate the interval change of seropositivity of H. pylori between 1998 and 2005 in Korean adult population and to find the factors related to H. pylori infection.
Platelets: A New Target for Gene Therapy of Haemophilia B

Much progress has been made in developing gene therapy approaches for treating haemophilia B since the method was first tested in mice over a decade ago (1). However, achieving sustained therapeutic levels of factor IX has proven difficult. In this issue of Thrombosis and Haemostasis Rodriguez et al. report the results of pilot experiments to test the feasibility of utilizing platelets to deliver factor IX directly to the site of tissue damage.
Association of Matrix Metalloproteinase-7 (-181A>G) Polymorphism with Risk of Esophageal Squamous Cell Carcinoma in Kashmir Valley

Background/Aim: Degradation of the basement membrane and extracellular matrix by matrix metalloproteinases (MMPs) is believed to be an essential step in the complicated process of hematogenous metastasis. Matrix metalloproteinase-7 (MMP-7) is a small secreted proteolytic enzyme with a broad substrate specificity, and its expression has been shown to be associated with tumor invasion and metastasis for various cancers. Patients and Methods: To document the role of MMP-7 polymorphism in esophageal carcinogenesis, a case-control study was performed comprising 135 patients with esophageal cancer (EC) and 195 healthy controls. Genotyping was done by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Data were statistically analyzed using χ2 - test and logistic regression models. Results: Carriers for the MMP-7 (-181A>G) GG were associated with an increased risk for EC [odds ratio (OR = 2.17; 95% confidence interval (CI) = 1.21-3.92; P = 0.010; P-trend = 0.04]. Also, in a recessive model, our results showed that MMP-7 (-181A>G) GG allele conferred significantly higher risk for EC (OR =2.16; 95% CI = 1.31-3.54; P = 0.003). The high risk due to MMP-7 (-181GG) genotype was limited to squamous cell histology of EC (OR = 2.41; 95% CI = 1.27-4.56; P = 0.007). Although smoking (Hukka) and high consumption of salted tea are independent risk factors for EC, the interaction of MMP-7 (-181A>G) genotypes with these factors did not further modulate the risk of EC. Conclusions: In conclusion, our results show that MMP-7 (-181A>G) GG carriers are at a higher risk of esophageal squamous cell carcinoma in Kashmir valley.
Transient molecular visualization of ocular dominance columns (ODCs) in normal adult marmosets despite the desegregated termination of the retino‐geniculo‐cortical pathways

The activity‐dependent immediate early gene protein Krox‐24, expressed in the neocortex at high basal levels, decreases rapidly upon neuronal deactivation (Chaudhuri et al. [1995] Vis. Neurosci. 12:35–50). In infant marmosets, as in most primates, the geniculo‐cortical terminations segregate into eye‐specific anatomical ocular dominance columns (ODCs), which disappear, however, during adolescence (Spatz [1989] Brain Res. 488:376–380), resulting in balanced inputs from the two eyes (Sengpiel et al. [1996] Vis. Neurosci. 13:145–160). Nevertheless, we found, in adult marmosets, 24 hours after monocular retinal activity blockade by tetrodotoxin, distinct alternating compartments of potentiated and depressed Krox‐24‐like immunoreactivity (Krox‐IR) in layer IV of area 17. This pattern of Krox‐IR disappeared at 10 days of retinal silencing, but was still present at this survival time in stains for cytochrome oxidase or NADPH‐diaphorase. After 20 days of retinal silencing, the pattern was not demonstrable with any of the three stains. We term these compartments physiological ODCs, in contrast to the anatomical ODCs of most primates. If the anatomical ODCs of infant marmosets disappear by collateral sprouting into the inappropriate ODCs, then the collateral geniculo‐cortical synapses might differ slightly in their properties from the original ones. We silenced the sets of original and collateral synapses of the one ocularity. This apparently transiently initiated, at the synapses driven by the intact eye, two different complex processes leading to molecular potentiation at the original synapses and to molecular depression at the collateral synapses. J. Comp. Neurol. 393:118–134, 1998. © 1998 Wiley‐Liss, Inc.
Factors Characterising High Prevalence Rates of Urinary Schistosomiasis in Mufumbwe District, North Western Province of Zambia

This study investigated prevalence of Urinary Schistosomiasis in Mufumbwe district of Zambia. It identified risk factors responsible and suggested possible ameliorating measures. Objectives were to; 1) determine prevalence rates, 2) identify and document risk factors responsible for the infection and spread of the disease, 3) determine affected gender and age groups among primary school children, and 4) identify indigenous control measures used and their efficacy. Questionnaires and field observations were used on pupils and teachers. Blood samples were collected from pupils and examined for Schistosoma haematobium ova. Results showed a high prevalence rate of urinary bilharzia (56.7%) in male age groups of 11-15 years with prevalence of 60.7%. Five water contact activities were responsible for transmission. Remedies used to treat bilharzia included; Mitragyna stipulosa, Ricinus communis, Steganotaenia araliacea, Capsicum roots and Mangifera indica, but these were not effective, and more research is required to determine their efficacy.
The use of a standardized language assessment tool to measure the language development of urban Aboriginal preschoolers

Abstract The use of standardized language assessment tools with Australian Indigenous children has been criticized for language and cultural reasons; however, this has not been tested in an urban context. The aim of the study was to explore the language performance of a small sample of urban Aboriginal preschoolers on a standardized language tool compared with a conversational sample. Fifteen participants (drawn from a birth cohort study of over 150 Aboriginal infants born at a metropolitan hospital) completed the Clinical Evaluation of Language Fundamentals–Preschool Edition, Second Edition (CELF-P2) and generated a 30-minute conversational language sample. Descriptive data are reported, and five case studies are explored in detail to compare results of the CELF-P2 and the language sample analysis. Grammatical features of Aboriginal English are also investigated. There was a diverse range of responses to standardized assessment and language sampling, with some samples reflective of CELF-P2 results. Two or more grammatical features of Aboriginal English were identified in 13 of the language samples. The results suggest the CELF-P2 is an appropriate tool to use to assess the language development of the children in the study when used in conjunction with analysis of language samples obtained using culturally appropriate methods.
Association of functional gene variants in the regulatory regions of COX‐2 gene (PTGS2) with nonmelanoma skin cancer after organ transplantation

Summary Background Overexpression of cyclooxygenase‐2 (COX‐2), resulting in excessive prostaglandin production, has been observed in human epidermal keratinocytes after ultraviolet B injury, in squamous cell skin carcinoma (SCC), in actinic keratoses, and in the early stages of carcinogenesis in a wide variety of tissues. The dysregulation of COX‐2 expression can in part be due to functional changes affecting regulatory elements in the promoter or 3′ untranslated region (UTR) of the gene. Two common polymorphisms (–765G→C, and –1195A→G) in the promoter region of the COX‐2 gene (now PTGS2), and one common polymorphism in the 3′ UTR (8473T→C) have been described, and reported as associated with various malignancies.
Effect of the kinase inhibitor, H-7, on stress, crossbridge phosphorylation, muscle shortening and inositol phosphate production in rabbit arteries.

Smooth muscle contractile agents cause large increases in crossbridge phosphorylation (Mp) and cycling rates resulting in the rapid development of stress (force/muscle cross-sectional area). Despite temporal declines in Mp and cycling during continued activation, stress is maintained at high levels. This observation led to several different hypotheses describing the regulation of steady-state stress. One proposal is that protein kinase C regulates stress maintenance, whereas another invokes a steady-state dependence on Ca+(+)-calmodulin-dependent myosin light chain kinase. The aim of this study was to investigate the mechanism of stress-maintenance by analyzing the inhibitory efficacy of a protein kinase C inhibitor, H-7 [1-(5-isoquinolinesulfonyl)-2-methylpiperizine], on steady-state values of stress, Mp and crossbridge cycling in rabbit renal and femoral arteries. H-7 effectively inhibited steady-state stress produced by KCl (IC50 = 3.7-4.4 microM) and phenylephrine (PhE) (IC50 = 10.6-15.2 microM). Likewise, increases in the level of Mp and the rate of crossbridge cycling induced by both KCl and PhE were significantly reduced by 10 microM H-7. H-7 did not reduce inositol phosphate production stimulated by PhE, but did reduce early stress development thought to be mediated by inositol phosphate-induced mobilization of intracellular calcium. Calcium-induced increases in stress and Mp produced in saponin-skinned artery strips were reduced by less than 50% by 320 microM H-7. (ABSTRACT TRUNCATED AT 250 WORDS)