Miracle-dz/UniFAR-FTUs huggingface dataset:
Recombinant Expression and Characterization of the Major β-Lactamase of Mycobacterium tuberculosis

ABSTRACT New antibiotic regimens are needed for the treatment of multidrug-resistant tuberculosis. Mycobacterium tuberculosis has a thick peptidoglycan layer, and the penicillin-binding proteins involved in its biosynthesis are inhibited by clinically relevant concentrations of β-lactam antibiotics. β-Lactamase production appears to be the major mechanism by whichM. tuberculosis expresses β-lactam resistance. β-Lactamases from the broth supernatant of 3- to 4-week-old cultures of M. tuberculosis H37Ra were partially purified by sequential gel filtration chromatography and chromatofocusing. Three peaks of β-lactamase activity with pI values of 5.1, 4.9, and 4.5, respectively, and which accounted for 10, 78, and 12% of the total postchromatofocusing β-lactamase activity, respectively, were identified. The β-lactamases with pI values of 5.1 and 4.9 were kinetically indistinguishable and exhibited predominant penicillinase activity. In contrast, the β-lactamase with a pI value of 4.5 showed relatively greater cephalosporinase activity. An open reading frame in cosmid Y49 of the DNA library of M. tuberculosis H37Rv with homology to known class A β-lactamases was amplified from chromosomal DNA of M. tuberculosis H37Ra by PCR and was overexpressed in Escherichia coli. The recombinant enzyme was kinetically similar to the pI 5.1 and 4.9 enzymes purified directly from M. tuberculosis. It exhibited predominant penicillinase activity and was especially active against azlocillin. It was inhibited by clavulanic acid andm-aminophenylboronic acid but not by EDTA. We conclude that the major β-lactamase of M. tuberculosis is a class A β-lactamase with predominant penicillinase activity. A second, minor β-lactamase with relatively greater cephalosporinase activity is also present.
The Structure of Commitment in Exchange

Commitment is an essential part of successful long-term relationships. Whereas commitments by both parties in an exchange can provide the foundation for development of relational social norms, disproportionate commitments can lead to opportunism by the less committed partner. The authors study the effect of the credibility and proportionality of commitment inputs in an exchange upon the development of relational social norms, opportunism, and long-term commitment intentions. They also investigate longitudinal effects of the credibility of long-term commitment intentions, relational social norms, and opportunism in one time period on commitment inputs and long-term commitment intentions in later periods. Data gathered from a behavioral simulation suggest that (1) the credibility of commitment inputs in exchange is positively related to the development of relational social norms, (2) and is positively related to long-term commitment intentions in the same time period, (3) relational social norms may be undermined by opportunistic conduct, and (4) the presence of relational social norms in one time period is positively related to commitment inputs and long-term commitment intentions in later periods.
Diversity and evolution of drug resistance mechanisms in Mycobacterium tuberculosis

Despite the efficacy of antibiotics to protect humankind against many deadly pathogens, such as Mycobacterium tuberculosis, nothing can prevent the emergence of drug-resistant strains. Several mechanisms facilitate drug resistance in M. tuberculosis including compensatory evolution, epistasis, clonal interference, cell wall integrity, efflux pumps, and target mimicry. In this study, we present recent findings relevant to these mechanisms, which can enable the discovery of new drug targets and subsequent development of novel drugs for treatment of drug-resistant M. tuberculosis.
Introduction to Toxicology

Toxicology can be defined as that branch of science that deals with poisons, and a poison can be defined as any substance that causes a harmful effect when administered, either by accident or design, to a living organism. By convention, toxicology also includes the study of harmful effects caused by physical phenomena, such as radiation of various kinds and noise. In practice, however, many complications exist beyond these simple definitions, both in bringing more precise meaning to what constitutes a poison and to the measurement of toxic effects. Broader definitions of toxicology, such as “the study of the detection, occurrence, properties, effects, and regulation of toxic substances,” although more descriptive, do not resolve the difficulties. Toxicity itself can rarely, if ever, be defined as a single molecular event but is, rather, a cascade of events starting with exposure, proceeding through distribution and metabolism, and ending with interaction with cellular macromolecules (usually DNA or protein) and the expression of a toxic end point. This sequence may be mitigated by excretion and repair. It is to the complications, and to the science behind them and their resolution, that this textbook is dedicated, particularly to the how and why certain substances cause disruptions in biologic systems that result in toxic effects. Taken together, these difficulties and their resolution circumscribe the perimeter of the science of toxicology. The study of toxicology serves society in many ways, not only to protect humans and the environment from the deleterious effects of toxicants but also to facilitate the development of more selective toxicants such as anticancer and other clinical drugs and pesticides. Poison is a quantitative concept, almost any substance being harmful at some doses but, at the same time, being without harmful effect at some lower dose. Between these two limits there is a range of possible effects, from subtle long-term chronic toxicity to immediate lethality. Vinyl chloride may be taken as an example. It is a potent hepatotoxicant at high doses, a carcinogen with a long latent period at lower
Hereditary Early-Onset Parkinson's Disease Caused by Mutations in PINK1

Parkinson's disease (PD) is a neurodegenerative disorder characterized by degeneration of dopaminergic neurons in the substantia nigra. We previously mapped a locus for a rare familial form of PD to chromosome 1p36 (PARK6). Here we show that mutations in PINK1 (PTEN-induced kinase 1) are associated with PARK6. We have identified two homozygous mutations affecting the PINK1 kinase domain in three consanguineous PARK6 families: a truncating nonsense mutation and a missense mutation at a highly conserved amino acid. Cell culture studies suggest that PINK1 is mitochondrially located and may exert a protective effect on the cell that is abrogated by the mutations, resulting in increased susceptibility to cellular stress. These data provide a direct molecular link between mitochondria and the pathogenesis of PD.
A novel floorplan representation with random contour corner selecting scheme

Floorplanning has played a crucial role in the VLSI physical design process, while a lot of focus has been put on the representation methodologies for the floorplan optimization in the recent researches. In this work, we propose an efficient P-admissible representation, called random contour corner (RCC), for non-slicing floorplans. It depends on a two-section random code, representing the sequence and location of the blocks respectively. The objective is to improve both area and wire length. For the optimization procedure, we apply a simulated annealing (SA) algorithm. The method is quite simple and time efficient for implementation even on large-scale integration floorplans, and the run time complexity for the algorithm is O(nlogn). The experimental results show that our proposed method achieves promising results by comparing with some other representations (O-tree, B*-tree and TCG) on basic MCNC benchmark circuits.
Effect of environmental dynamism on relational governance in manufacturer-supplier relationships: A contingency framework and an empirical test

The effect of dynamism in the downstream (i.e., customer and competitive) environment on the manner in which manufacturers manage their upstream (i.e., supplier) relationships is not well understood in the literature. While some prior studies suggest that manufacturers will adopt relational governance with suppliers in response to dynamism in the downstream environment, other studies suggest that manufacturers will avoid relational governance with suppliers when faced with environmental dynamism. Drawing from the literature on interparty learning, the authors develop a conceptual framework wherein the validating conditions for each conclusion are identified. Results from a survey of 221 manufacturing organizations show that in dynamic environments, manufacturers adopt (avoid) relational governance with suppliers under two conditions: (1) when manufacturer collaborative belief is high (low) and (2) when supplier knowledge is high (low). The results are discussed in terms of their managerial and future research implications.
Systemic Issues for Commonwealth Small States in the Current Functioning of the WTO

Small states face significant hurdles in securing the potential benefits of trade to their economies and in protecting themselves against trade practices and rules that harm their interests. This study explores the systemic issues and challenges confronted by Commonwealth small states in the multilateral trading system, and identifies two sets of priorities for these countries. First, the substantive content of trade agreements must account for the particular needs, constraints and vulnerabilities of small states. Second, WTO members need to address the systemic issues facing the WTO in ways that ensure small states can use and benefit from all of the functions the multilateral trading system offers. To help enable Commonwealth small states to participate meaningfully in debates on WTO reform, the paper highlights areas of particular importance and sets forth options and proposals they could consider advancing.
Nestin is expressed in basal-like and triple negative breast cancers

Aims: To analyse the distribution of nestin expression in different breast tumours and to determine the prognostic impact of nestin expression. Methods: Nestin expression was immunohistochemically analysed in a cohort of 245 invasive breast cancer patients treated with therapeutic surgery followed by anthracycline-based chemotherapy using a semi-quantitative scoring system. Results: Nestin was exclusively expressed in grade III breast carcinoma and preferentially expressed in basal-like and triple negative cancers. Nestin-positive tumours displayed high proliferation rates and p53 nuclear expression. Lymph-node positive patients with nestin-positive cancers had a shorter breast cancer specific survival; however nestin was not an independent prognostic factor on multivariate analysis. Conclusions: Nestin expression is preferentially found in basal-like and triple negative breast carcinomas. Further studies are warranted to define the biological role played by nestin in these subgroups of breast cancers.
Developing assessments to measure barriers to treatment entry: A critical step towards dissemination

Relationship functioning has important implications for numerous life domains, including physical health, psychological health, and social and work functioning (e.g., (Kiecolt-Glaser & Newton, 2001; Whisman & Uebelacker, 2006; Whisman, Uebelacker, & Settles, 2010). Indeed, marital distress is an important predictor of overall life satisfaction, accounting for more variability in life satisfaction than finances, health, and work (Fleeson, 2004), and there is an overall mental health advantage for those who are married versus those who are divorced (e.g., Kim & McKenry, 2002; Strohschein, McDonough, Monette, & Shao, 2005; Williams, 2003). Fortunately, there is empirical support that couples treatments can effectively address relationship distress (e.g., (Christensen, Atkins, Baucom, & Yi, 2010; Dunn & Schwebel, 1995), and can help to ameliorate individual psychiatric disorders occurring within the couple context (e.g., Baucom, Shoham, Mueser, Daiuto, & Stickle, 1998).
Green IS Research: A Modernity Perspective

Over the past two decades, the information systems community has become engaged in improving the environmental effects of information systems and technologies, which has given rise to the green IS field. Despite increasing interest, some have suggested that progress toward meaningful solutions for sustainability has been too slow. Responding to these concerns, we examine the development of green IS research using the modernity perspective to understand green IS’s evolution and to present alternative perspectives to motivate future research. From a sample of over 80 green IS papers published over a 15-year period, we identify four main patterns of modernity that are manifest in green IS research. These patterns include the importance of the individual in solving environmental problems; science as the main source of solutions; and the emergence of an artificial science approach, reliance on technology, and growth as businesses’ ultimate goals. Further, our analysis reveals that green IS research has started to demonstrate elements of a hyper-modernity perspective that emphasizes reflexivity. We argue that future green IS research should continue on this path and propose a conceptual framework inspired by hyper-modernity and centered on reflexivity that could serve as a guide for future research.
Incidence and tumor characteristics of breast cancer diagnosed before and after implementation of a population-based screening-program

Background. Randomized controlled trials and service screening programs have shown that breast cancer screening reduces the mortality from the disease. Several years of monitoring are needed to prove such an effect. In the meantime attention should be paid to early surrogate measures, such as histopathological tumor characteristics. The Norwegian Breast Cancer Screening Program started November 1995. This study compares incidence, prognostic tumor characteristics and surgical treatment in breast cancer cases diagnosed in the pre-screening (1987–1995, n=2 618) and screening period (1996–2004, n=5 417), in women aged 50–69 years, residing in the first four counties implementing the screening program. The screening period is divided into those invited versus those not invited to the screening program, and those exposed (participants) versus those not exposed to the program (non-participants). Results. The incidence of invasive breast cancer rose from 170 per 100 000 women years (wy) in 1987 to 355 per 100 000 wy in 1997. The proportion of DCIS was 5% in the pre-screening period, and 14% in the screening period. Tumors 20 mm or less were diagnosed in 56% of the invasive cases in the pre-screening period, in 74% of the invited, and in 77% of the exposed women. The relative risk of diagnosing breast cancer with metastases was 0.85 (95% CI 0.84–0.87) for invited and 0.82 (95% CI 0.81–0.84) for exposed women, relative to those diagnosed in the pre-screening period. Ablation was performed in 85% of the invasive cases diagnosed in the pre-screening period, and in 45% of the cases in the screening period. Conclusion. Breast cancer diagnosed in the screening period had prognostically favorable tumor characteristics compared to breast cancer diagnosed in the pre-screening period. Implementation of organized population based screening and the time trend are considered possible reasons.
The Impact of Consumer Ethnocentrism, Product Involvement, and Product Knowledge on Country of Origin Effects: An Empirical Analysis on Turkish Consumers’ Product Evaluation

ABSTRACT The purpose of this study is to explore whether, in which ways, and to what extent country-of-origin (COO) information affects the product-evaluation process in Turkey as a less-developed country. Moderating effects of consumer ethnocentrism (CE), product involvement, and product knowledge were also explored. Findings showed that COO cues have a significant main effect on the product-evaluation process. Although moderator variables (CE, product involvement, and product knowledge) do not have a significant effect alone on the product-evaluation process, they negatively moderate the relationship between COO cues and product evaluation. As far as we are aware, the roles of COO, CE product involvement, and product knowledge on product evaluation have not been simultaneously included in the same research model in previous empirical studies. So, as the original contribution of this article, this study investigates the interaction effects of CE, product involvement, and product knowledge on the relationship between COO cues and product evaluation in an emerging market.
Underestimation of risk of a BRCA1 or BRCA2 mutation in women with high-grade serous ovarian cancer by BRCAPRO: a multi-institution study.

PURPOSE Identification of the 10% to 15% of patients with ovarian cancer who have germline BRCA1 or BRCA2 mutations is important for management of both patients and relatives. The BRCAPRO model, which estimates mutation likelihood based on personal and family cancer history, can inform genetic testing decisions. This study's purpose was to assess the accuracy of BRCAPRO in women with ovarian cancer. METHODS BRCAPRO scores were calculated for 589 patients with ovarian cancer referred for genetic counseling at three institutions. Observed mutations were compared with those predicted by BRCAPRO. Analysis of variance was used to assess factors impacting BRCAPRO accuracy. RESULTS One hundred eighty (31%) of 589 patients with ovarian cancer tested positive. At BRCAPRO scores less than 40%, more mutations were observed than expected (93 mutations observed v 34.1 mutations expected; P < .001). If patients with BRCAPRO scores less than 10% had not been tested, 51 (28%) of 180 mutations would have been missed. BRCAPRO underestimated the risk for high-grade serous ovarian cancers but overestimated the risk for other histologies (P < .001), underestimation increased as age at diagnosis decreased (P = .02), and model performance varied by institution (P = .02). CONCLUSION Patients with ovarian cancer classified as low risk by BRCAPRO are more likely to test positive than predicted. The risk of a mutation in patients with low BRCAPRO scores is high enough to warrant genetic testing. This study demonstrates that assessment of family history by a validated model cannot effectively target testing to a high-risk ovarian cancer patient population, which strongly supports the recommendation to offer BRCA1/BRCA2 genetic testing to all patients with high-grade serous ovarian cancer regardless of family history.
A COMPENSATORY INFERENCE SYSTEM

This paper aims to introduce a new and useful inference system based on CFL. It will be called Compensatory Inference System (CIS). It is a generalization of the deduction like in mathematical logic, with one implication operator found in the literature. It is an octet (L,Ax,R,c,d,o,n,→), where c, d, o and n are the operators of the Compensatory Logic on Geometric Mean, L is the set of formulas of the propositional calculus in this CFL, Ax is the Kleene’s logical axioms, R is the modus ponens rule and → is the Reichenbach implication. This combination maximizes the validity of the Kleene’s axioms, as it will be exposed through this chapter. Therefore, it is an inference system with easy application and logically rigorous.
Safety of home parenteral nutrition in patients with amyotrophic lateral sclerosis: A French national survey

Abstract We carried out a retrospective multicentre study to assess the safety of home parenteral nutrition (HPN) in patients with ALS. We reviewed the case records of patients from French ALS centres treated with HPN by central venous catheter (CVC) using an implantable port between January 2005 and October 2009. Seventy-three patients received HPN for a total of 11,908 catheter days. Twenty-seven patients experienced a total of 37 CVC related complications resulting in an incidence rate of 3.11 CVC complications/1000 catheter days, including 1.93 septic complications and 1.09 mechanical complications/1000 catheter days. Metabolic complications were frequent but without serious consequences on mortality. The use of the catheter for intravenous therapies in addition to HPN was identified as a septicaemia's risk factor (relative risk (RR) = 2.54, confidence interval (CI) 1.56–4.14, p = 0.04). In conclusion, HPN is an alternative procedure to PEG in advanced ALS patients. The incidence of complications appears to be comparable to data from the literature on HPN in other diseases. A prospective study comparing HPN and radiologic inserted gastrostomy (RIG) would allow comparison of the relative risk-benefit and survival of these procedures. The relation of CVC and RIG placement timing and the complications’ occurrence should also be investigated.
Feature extraction through generalization of histogram refinement technique for local region‐based object attributes

Content based image retrieval (CBIR) is used to retrieve digital images from large databases. However, the problem of retrieving images on the basis of the contents remains largely unsolved. The proposed method of image retrieval is based on the information provided by histogram analysis of the intensity or grayscale values of images. Some additional properties are also calculated and used that are based on regional characteristics of various objects in the image. The need to retrieve the additional regional properties arises due to the fact that the standard histograms are insensitive to small changes in images. Many images of different types can have similar histograms, because, histograms provide only a coarse characterization of an image. This is the main disadvantage of using histograms. This research is based on the concept of Histogram Refinement (Pass and Zabih, IEEE Workshop Appl Comput Vision ( 1996 ), 96–102). Distributing the grayscale image intensities by splitting the pixels using their intensity values into several classes just like the histogram refinement method can provide an estimate of the object characteristics present in an image. After the calculation of clusters using a color refinement method, the inherent features of each of the clusters is calculated based on the regional properties of the clusters. These additional region based features expound some structural information of the image. Finally, all of these features are used for image retrieval. © 2011 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 21, 298–306, 2011;
An EM algorithm for maximum likelihood estimation of Barndorff-Nielsen's generalized hyperbolic distribution

We present an EM algorithm for Maximum Likelihood (ML) estimation of the location, structure matrix, skew or drift, and shape parameters of Barndorff-Nielsen's Generalized Hyperbolic distribution, which is the Gaussian Location Scale mixture (or Normal Variance Mean Mixture) with Generalized Inverse Gaussian (GIG) scale mixing distribution. We use the GLSM representation along with the closed form posterior expectations possible with the GIG distribution to derive an EM algorithm for computing ML parameter estimates.