Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of VanYn, a novel D,D‐peptidase/D,D‐carboxypeptidase involved in glycopeptide antibiotic resistance in Nonomuraea sp. ATCC 39727

VanYn is a novel protein involved in the mechanism of self‐resistance in Nonomuraea sp. ATCC 39727, which produces the glycopeptide antibiotic A40926, the precursor of the second‐generation dalbavancin, which is in phase III of clinical development. VanYn (196 residues) is encoded by the dbv7 gene within the dbv biosynthetic cluster devoted to A40926 production. C‐terminal His6‐tagged VanYn was successfully expressed as a soluble and active protein in Escherichia coli. The analysis of the sequence suggests the presence of a hydrophobic transmembrane portion and two conserved sequences (SxHxxGxAxD and ExxH) in the extracytoplasmic domain that are potentially involved in coordination of Zn2+ and catalytic activity. The presence of these conserved sequences indicates a similar mechanism of action and substrate binding in VanYn as in VanY, VanX and VanXY Zn2+‐dependent d,d‐carboxypeptidases and d‐Ala‐d‐Ala dipeptidases acting on peptidoglycan maturation and involved in glycopeptide resistance in pathogens. On substrates mimicking peptidoglycan precursors, VanYn shows d,d‐carboxypeptidase and d,d‐dipeptidase activity, but lacks d,d‐carboxyesterase ability on d‐Ala‐d‐Lac‐terminating peptides. VanYn belongs to the metallo‐d,d‐carboxypeptidase family, but it is inhibited by β‐lactams. Its characterization provides new insights into the evolution and transfer of resistance determinants from environmental glycopeptide‐producing actinomycetes (such as Nonomuraea sp.) to glycopeptide‐resistant pathogens (enterococci and staphylococci). It may also contribute to an early warning system for emerging resistance mechanisms following the introduction into clinics of a second‐generation glycopeptide such as dalbavancin.
Quantitation of Human Metallothionein Isoforms: A Family of Small, Highly Conserved, Cysteine-rich Proteins*

Human metallothioneins (MTs) are important regulators of metal homeostasis and protectors against oxidative damage. Their altered mRNA expression has been correlated with metal toxicity and a variety of cancers. Current immunodetection methods lack the specificity to distinguish all 12 human isoforms. Each, however, can be distinguished by the mass of its acetylated, cysteine-rich, hydrophilic N-terminal tryptic peptides. These properties were exploited to develop a bottom-up MALDI-TOF/TOF-MS-based method for their simultaneous quantitation. Key features included enrichment of N-terminal acetylated peptides by strong cation exchange chromatography, optimization of C18 reversed-phase chromatography, and control of methionine oxidation. Combinations of nine isoforms were identified in seven cell lines and two tissues. Relative quantitation was accomplished by comparing peak intensities of peptides generated from pooled cytosolic proteins alkylated with 14N- or 15N-iodoacetamide. Absolute quantitation was achieved using 15N-iodoacetamide-labeled synthetic peptides as internal standards. The method was applied to the cadmium induction of MTs in human kidney HK-2 epithelial cells expressing recombinant MT-3. Seven isoforms were detected with abundances spanning almost 2 orders of magnitude and inductions up to 12-fold. The protein-to-mRNA ratio for MT-1E was one-tenth that of other MTs, suggesting isoform-specific differences in protein expression efficiency. Differential expression of MT-1G1 and MT-1G2 suggested tissue- and cell-specific alternative splicing for the MT-1G isoform. Protein expression of MT isoforms was also evaluated in human breast epithelial cancer cell lines. Estrogen-receptor-positive cell lines expressed only MT-2 and MT-1X, whereas estrogen-receptor-negative cell lines additionally expressed MT-1E. The combined expression of MT isoforms was 38-fold greater in estrogen-receptor-negative cell lines than in estrogen-receptor-positive cells. These findings demonstrate that individual human MT isoforms can be accurately quantified in cells and tissues at the protein level, complementing and expanding mRNA measurement as a means for evaluating MTs as potential biomarkers for cancers or heavy metal toxicity.
Effects of Mn nanoparticles on wettability and intermetallic compounds in between Sn-3.8Ag-0.7Cu and Cu substrate during multiple reflow

In this research, the effects of Mn nanoparticles on wettability and interfacial intermetallic compounds in between Sn-3.8Ag-0.7Cu (SAC) solder and copper (Cu) substrate was investigated. The nanocomposite solders were fabricated by mechanical mixing of SAC solder paste with Mn nanoparticles. The melting characteristic of the solders was characterized by differential scanning calorimeter (DSC). The solder pastes were reflowed in a reflow oven at 250°C for 60 seconds. The spreading rate and contact angle of the solders was calculated to measure the wettability. The solder joints were characterized by field emission scanning electron microscope (FESEM) and energy dispersive X-Ray (EDX). It was found that with the addition of Mn nanoparticles the total IMC thickness decreased after first and six times reflow. The Cu3Sn layer was not affected with the addition of Mn nanoparticles. However, some probable mechanism is suggested to explain the effect of Mn nanoparticles on SAC solder.
Glutamine Modulates Sepsis-Induced Changes to Intestinal Intraepithelial &ggr;&dgr;T Lymphocyte Expression in Mice

ABSTRACT This study investigated the effect of glutamine (GLN) on intestinal intraepithelial lymphocyte (IEL) &ggr;&dgr;T-cell cytokines and immune regulatory factor gene expressions in a mouse model of polymicrobial sepsis. Mice were randomly assigned to a normal group, a sepsis with saline (SS) group, or a sepsis with GLN (SG) group. All mice were fed a chow diet. Sepsis was induced by cecal ligation and puncture (CLP). The SS group was injected with saline, and the SG group was given 0.75 g GLN/kg body weight once via a tail vein 1 h after CLP. Septic mice were killed 12 h after CLP, and IEL &ggr;&dgr;T cells of the animals were isolated for further analysis. Results showed that compared with normal mice, sepsis resulted in lower IEL &ggr;&dgr;T-cell percentage and higher messenger RNA expressions of interferon &ggr;, tumor necrosis factor &agr;, interleukin 4 (IL-4), IL-13, IL-17, retinoid acid receptor–related orphan receptor &ggr;t, and complement 5a receptor by IEL &ggr;&dgr;T cells. These immunomodulatory mediator genes exhibited decreases, whereas IL-7 receptor expression increased in IEL &ggr;&dgr;T cells in septic mice with GLN administration. Annexin V/7-amino-actinomycin D stain revealed significantly lower rates of apoptosis, and IEL &ggr;&dgr;T-cell percentage was higher in the SG group. The histological findings also showed that damage to intestinal epithelial cells was less severe in the SG group. These results indicated that a single dose of GLN administered as treatment after the initiation of sepsis prevented apoptosis of IEL &ggr;&dgr;T cells and downregulated &ggr;&dgr;T cell–expressed inflammatory mediators that may consequently ameliorate the severity of sepsis-induced intestinal epithelial injury.
Reliability of Self-Report Measures of Drug Use in Prevention Research: Evaluation of the Project Smart Questionnaire via the Test-Retest Reliability Matrix

The present article describes an evaluation of a self-report questionnaire administered to whole classrooms of 7th graders. Using the test-retest reliability matrix (based on concepts of Cronbach [1] and Campbell and Fiske [2]), eight of nine drug-use indices appeared to have acceptable to good reliability. The three measures included in the test-retest reliability matrix provide stronger evidence for good reliability than could any single measure.
1 Entrepreneurship and Regional Development

This chapter offers a review on modern entrepreneurship analysis, against the background of regional development. After a conceptual discussion on the importance and the measurement of entrepreneurship, the contribution discusses success factors and determinants of entrepreneurships. Next, focus is laid on the geography of entrepreneurship, while also due attention is paid to the relevance of networks for modern entrepreneurship. The chapter concludes with some retrospective and prospective remarks.
Stimulation of Osteoblastic Cell Differentiation by Notch

Notch is a transmembrane protein that plays a critical role in the determination of cellular differentiation pathways. Although its importance in the development of mesenchymal tissues has been suggested, its role in skeletal tissues has not been well investigated. Northern blot experiments showed the expression of Notch1 in MC3T3‐E1 osteoblastic cells at early differentiation stages. When a Notch1 cytoplasmic domain (Notch‐IC [NIC]) delivered by an adenovirus vector was expressed in osteoblastic MC3T3‐E1 cells, a significant increase in calcified nodule formation was observed in long‐term cultures. Activation of endogenous Notch in MC3T3‐E1 by coculturing them with Delta‐like‐1 (Dll1)‐expressing myeloma cells also resulted in a stimulation of calcified nodule formation. Not only affecting nodule formation, Notch activation also had effects on osteoblastic differentiation of multipotent mesenchymal cells. Osteoblastic differentiation of C3H10T1/2 cells induced by bone morphogenetic protein 2 (BMP‐2) was significantly stimulated, whereas adipogenic differentiation was suppressed strongly, resulting in a dominant differentiation of osteoblastic cells. NIC expression in primary human bone marrow mesenchymal stem cells (hMSCs) also induced both spontaneous and stimulated osteoblastic cell differentiation. These observations suggest that osteoblastic cell differentiation is regulated positively by Notch and that Notch could be a unique and interesting target molecule for the treatment of osteoporosis.
Profile of periodontal conditions in a Brazilian adult population.

PURPOSE To evaluate the periodontal condition of adult patients attending public health centres in the city of Recife, Brazil, and to investigate whether periodontal conditions are associated with socioeconomic and demographic variables. MATERIALS AND METHODS This cross-sectional study included 13 randomly selected public health centres. Sample size was calculated using 5.0% standard error and a confidence interval of 95%. The minimum sample size was 461 subjects, and a total of 505 subjects participated in this study. Each participant completed a questionnaire and underwent periodontal examination. Periodontal conditions were based on the Community Periodontal Index (CPI). Bivariate analysis of frequencies and means was performed with SPSS, version 11.0. The chi-square and likelihood ratio statistical tests were used to calculate the level of statistical significance of the associations tested. The level of statistical significance was set at P < 0.05. RESULTS Calculus was the highest CPI score in 61.8% of the subjects, and shallow pockets (4-5 mm) were the highest score in 15.2% of them. A healthy periodontium was observed in 10.7%, while gingival bleeding and deep pockets (> or = 6 mm) were found as the highest CPI score in 10.3% and 2.0% of the sample, respectively. Periodontal conditions showed significant association with the socioeconomic and demographic variables analysed (P < 0.05). CONCLUSIONS Findings indicate a high prevalence of periodontal alterations in the sample. Periodontal conditions were worse in men, married individuals, older subjects and individuals with low socioeconomic class and poor education.
GM2 gangliosidosis in Saudi Arabia: Multiple mutations and considerations for future carrier screening

The GM2 gangliosidose, Tay–Sachs and Sandhoff diseases, are a class of lysosomal storage diseases in which relentless neurodegeneration results in devastating neurological disability and premature death. Primary prevention is the most effective intervention since no effective therapy is currently available. An extremely successful model for the prevention of GM2 gangliosidosis in the Ashkenazi Jewish community is largely attributable to the very limited number of founder mutations in that population. Consistent with our previous observation of allelic heterogeneity in consanguineous populations, we show here that these diseases are largely caused by private mutations which present a major obstacle in replicating the Ashkenazi success story. Alternative solutions are proposed which can also be implemented for other autosomal recessive diseases in our population. © 2011 Wiley‐Liss, Inc.
Interaction of Vinyl Chloride Monomer Exposure and Hepatitis B Viral Infection on Liver Cancer

Learning ObjectivesIdentify previously reported findings relating occupational vinyl chloride monomer (VCM) exposure to liver disease.Relate how - and to what extent - hepatitis B surface antigen (HBsAg) status and particular job-related tasks interact to increase the risk of hepatocellular carcinoma in workers exposed to VCM.Explain postulated mechanisms by which hepatitis B virus infection and VCM exposure may interact to cause liver cancer. Vinyl-chloride monomer (VCM), a human carcinogen, has caused angiosarcoma of the liver. Recent studies have shown that VCM exposure is associated with hepatocellular cancer. In Taiwanese studies, the majority of VCM-exposed workers with liver cancer had history of hepatitis B virus (HBV) infection. To determine the role of HBV on the development of liver cancer in the VCM-exposed workers, we conducted a case-control study from a previously established polyvinyl chloride (PVC) cohort consisting of 4096 male workers from six PVC polymerization plants. A total of 18 patients with liver cancer, and 68 control subjects matched for age and specific plant of employment were selected. Detailed history of the participants that included alcohol consumption status, cigarette use, occupation, and family history of chronic liver disease were obtained using an interviewer-administered questionnaire. When the HBV surface antigen (HBsAg)-negative subjects without history of tank-cleaning were used as the reference, the HBsAg-negative subjects with history of tank-cleaning demonstrated a 4.0-fold greater risk of liver cancer (95% confidence interval: 95% CI = 0.2–69.1). The HBsAg carriers without history of tank-cleaning revealed a 25.7-fold greater risk of liver cancer (95% CI = 2.9–229.4). Whereas the HBsAg carriers with history of tank-cleaning revealed the greatest risk (matched odds ratio (ORm) 396.0, 95% CI = 22.6–∞) of developing liver cancer among subjects with different VCM-exposure status and HBsAg status categories. Further analysis showed the interaction term was significant (P < .01). Therefore, our results suggest an interaction between occupational VCM exposure and HBV infection for the development of liver cancer.
Treatment of Alcohol Withdrawal Syndrome with Gabapentin

Four in-patients with moderate alcohol-withdrawal syndromes benefited from treatment with gabapentin administered in an add-on fashion to clomethiazole. In comparison with the amount of clomethiazole required as estimated using a specially developed score during previous detoxifications of these patients at our hospital, gabapentin (400 mg q.i.d.) clearly reduced the amount of clomethiazole needed now Gabapentin, an anticonvulsant with favorable pharmacokinetic properties and tolerability, and with no known risk of dependence, may therefore be a useful new drug in the treatment of alcohol withdrawal. We believe that the potential value of gabapentin in alcohol withdrawal deserves further controlled studies.
Multivariate Behavioral Genetic Analysis of Parenting in Early Childhood

SYNOPSIS Objective. Caregivers play an important role in child development; in addition to instilling their norms and values in their children through socialization, caregivers modify their parenting practices in response to children’s characteristics. Previous studies have documented child genetic effects on parenting behaviors, but multivariate behavioral genetic examinations of parenting are scarce. Design. The current study examined the multivariate structure of child genetic and environmental influences on parenting in a sample of 236 individual twins aged 0–5 years, providing a total of 542 observations. Results. “Shared environments” (between-family environmental differences that are shared by twins reared in the same home, including parental characteristics, family socioeconomic status, and neighborhood characteristics) account for the majority of variation in parenting practices, whereas child genetic effects are more modest and occur more on specific parenting practices. Conclusion. Caregivers generally engage in similar parenting across children reared together and, at the same time, adjust their broad parenting approach and particularly their specific practices in response to genetically driven child characteristics. Future research may benefit from using a multidimensional framework to examine the different components and age-related transformations in these parent-driven and child-driven processes.
Metallothionein Immunolocalization in Actinic Skin Nonmelanoma Carcinomas

Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most frequent skin cancer. Its pathogeny is linked to genotoxic effects of actinic radiation exposure, especially to ultraviolet wavelength. Metallothionein (MT) is a low-molecular weight protein with high affinity for heavy metal. Its intracellular function has been related to heavy metals and free-radical detoxification, although many studies linked MT to protective action against actinic mutagenesis. In other way, overexpression in malignant tumors has been related to worse prognosis. We aimed to evaluate MT immunohistochemical expression in skin cancer associated to actinic radiation. Twenty-six BCC cases, 20 SCC, and 6 normal skin fragments were investigated. Immunohistochemical assay were performed by streptavidin-biotin-peroxidase technique with standard monoclonal antibody (E9). In normal skin, immunostaining was observed in basal layer of the epithelium. In the epithelium adjacent to tumors, suprabasal layer was also intensely labeled. Mean MT immunostaining indices were 18.5+21.2% for BCC and 69.1+14.4% for SCC. This difference was statistically significant. Higher MT expression in SCC as compared with BCC suggests association with tumoral aggressiveness.
Do Frequency Representations Eliminate Conjunction Effects? An Exercise in Adversarial Collaboration

The present article offers an approach to scientific debate called adversarial collaboration. The approach requires both parties to agree on empirical tests for resolving a dispute and to conduct these tests with the help of an arbiter. In dispute were Hertwig's claims that frequency formats eliminate conjunction effects and that the conjunction effects previously reported by Kahneman and Tversky occurred because some participants interpreted the word “and” in “bank tellers and feminists” as a union operator. Hertwig proposed two new conjunction phrases, “and are” and “who are,” that would eliminate the ambiguity. Kahneman disagreed with Hertwig's predictions for “and are,” but agreed with his predictions for “who are. ” Mellers served as arbiter. Frequency formats by themselves did not eliminate conjunction effects with any of the phrases, but when filler items were removed, conjunction effects disappeared with Hertwig's phrases. Kahneman and Hertwig offer different interpretations of the findings. We discuss the benefits of adversarial collaboration over replies and rejoinders, and present a suggested protocol for adversarial collaboration.
The work conditions of allied health professionals : the impact on satisfaction, commitment and psychological distress

The present study investigated the extent to which the Demand-Control-Support (DCS) model, in combination with organizational justice variables, predicts the employee-level outcomes of allied health professionals'. Allied health professionals from an Australian healthcare organization were surveyed, with 113 participating (52,6%). Multiple regression analyses revealed that the DCS model predicted all the outcome variables of job satisfaction, organizational commitment and psychological distress. Conversely, significant contributions of the organizational justice variables were limited to organizational commitment and psychological distress. The results of the study provide practical implications for the job conditions of allied health professionals, in particular, the delivery of support and maintaining high levels of justice.
Prosodic marking and predictability in lexical self-repair

This paper reports on an investigation of lexical selfrepair in Dutch spontaneous dialogue. Lexical selfrepairs, in which one word is rejected for another, can be produced with or without notable ̳prosodic marking‘ of the second word. It remains unclear what motivates speakers‘ choices, but previous research has shown that the semantic distance between the two words is relevant. This study assesses the relevance of the words‘ predictability. Prosodic marking judgements are modelled using an established semantic classification and a range of probabilistic variables, including both frequencybased and cloze-based measures. Results suggest that probabilistic measures add little predictive power to the semantic classification, although informative data trends can be observed.
A fuzzy-rule-based image enhancement method for medical applications

Using fuzzy set theory, we develop a fuzzy rule-based system to perform some of the most common tasks of image enhancement: removing impulsive noise; smoothing nonimpulsive noise; and enhancing edges. Three different filters for each task and the selection criteria based on local information are derived. The selection criteria constitute the antecedent clauses of the fuzzy rules, and the corresponding filters constitute the consequent clauses of the fuzzy rules. The overall result of the fuzzy rule-based system is computed as the combination of the results of the individual filters, where each result contributes to the degree that the corresponding antecedent clause is satisfied. This approach gives us a powerful and flexible image enhancement paradigm. We present results on several types of images such as retinal and chromosome images. <<ETX>>
Guidelines for elective percutaneous coronary intervention in patients with stable coronary artery disease (JCS 2011) published in 2012--digest version.

Released online May 9, 2013 Mailing address: Scientific Committee of the Japanese Circulation Society, 8th Floor CUBE OIKE Bldg. , 599 Bano-cho, Karasuma Aneyakoji, Nakagyo-ku, Kyoto 604-8172, Japan. E-mail: meeting@j-circ.or. jp This English language document is a revised digest version of Guidelines on Indications of Elective Intervention (including CABG) in the Treatment of Coronary Artery Disease reported at the Japanese Circulation Society Joint Working Groups performed in 2010 (Website: http://www.j-circ.or.jp/guideline/pdf/JCS2011_fujiwara_d.pdf). Joint Working Groups: The Japanese Circulation Society, The Japanese Coronary Association, The Japanese Association for Coronary Artery Surgery, The Japanese Association for Thoracic Surgery, The Japanese Association of Cardiovascular Intervention and Therapeutics, The Japanese Society for Cardiovascular Surgery, The Japanese College of Cardiology, The Japan Diabetes Society ISSN-1346-9843 doi: 10.1253/circj.CJ-66-0065 All rights are reserved to the Japanese Circulation Society. For permissions, please e-mail: cj@j-circ.or. jp Guidelines for Elective Percutaneous Coronary Intervention in Patients With Stable Coronary Artery Disease (JCS 2011) Published in 2012