Miracle-dz/UniFAR-FTUs huggingface dataset:
Detection of cfxA2, cfxA3, and cfxA6 genes in beta-lactamase producing oral anaerobes

ABSTRACT Purpose The aim of this study was to identify β-lactamase-producing oral anaerobic bacteria and screen them for the presence of cfxA and BlaTEM genes that are responsible for β-lactamase production and resistance to β-lactam antibiotics. Material and Methods Periodontal pocket debris samples were collected from 48 patients with chronic periodontitis and anaerobically cultured on blood agar plates with and without β-lactam antibiotics. Presumptive β-lactamase-producing isolates were evaluated for definite β-lactamase production using the nitrocefin slide method and identified using the API Rapid 32A system. Antimicrobial susceptibility was performed using disc diffusion and microbroth dilution tests as described by CLSI Methods. Isolates were screened for the presence of the β-lactamase-TEM (BlaTEM) and β-lactamase-cfxA genes using Polymerase Chain Reaction (PCR). Amplified PCR products were sequenced and the cfxA gene was characterized using Genbank databases. Results Seventy five percent of patients carried two species of β-lactamase-producing anaerobic bacteria that comprised 9.4% of the total number of cultivable bacteria. Fifty one percent of β-lactamase-producing strains mainly Prevotella, Porphyromonas, and Bacteroides carried the cfxA gene, whereas none of them carried blaTEM. Further characterization of the cfxA gene showed that 76.7% of these strains carried the cfxA2 gene, 14% carried cfxA3, and 9.3% carried cfxA6. The cfxA6 gene was present in three Prevotella spp. and in one Porphyromonas spp. Strains containing cfxA genes (56%) were resistant to the β-lactam antibiotics. Conclusion This study indicates that there is a high prevalence of the cfxA gene in β-lactamase-producing anaerobic oral bacteria, which may lead to drug resistance and treatment failure.
Gallstone Disease Does Not Predict Liver Histology in Nonalcoholic Fatty Liver Disease

Background/Aims We sought to examine whether the presence of gallstone disease (GD) in patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD) is associated with liver fibrosis and histological nonalcoholic steatohepatitis (NASH) score. Methods We included 441 Turkish patients with biopsy-proven NAFLD. GD was diagnosed in the presence of sonographic evidence of gallstones, echogenic material within the gallbladder with constant shadowing and little or no visualization of the gallbladder or absence of gallbladder at ultrasonography, coupled with a history of cholecystectomy. Results Fifty-four patients (12.2%) had GD (GD+ subjects). Compared with the GD- subjects, GD+ patients were older, had a higher body mass index and were more likely to be female and have metabolic syndrome. However, GD+ patients did not have a higher risk of advanced fibrosis or definite NASH on histology. After adjustment for potential confounding variables, the prevalence of GD in NAFLD patients was not associated with significant fibrosis (≥2) (odds ratio [OR], 1.06; 95% confidence interval [CI], 0.53 to 2.21; p=0.68) or definite NASH (OR, 1.03; 95% CI, 0.495 to 2.12; p=0.84). Conclusions The presence of GD is not independently associated with advanced fibrosis and definite NASH in adult Turkish patients with biopsy-proven NAFLD.
Effect of weight loss on cardiac synchronization and proinflammatory cytokines in premenopausal obese women.

OBJECTIVE Obesity is an important risk factor for heart failure in both women and men. Dyssynchrony between right and left ventricular contraction and relaxation has been identified as an independent predictor of heart failure. We examined the relationship of ventricular synchronization abnormalities with the concentration of proinflammatory cytokines in obese women at baseline and after sustained weight loss. RESEARCH DESIGN AND METHODS Echocardiographic parameters of ventricular dyssynchrony, circulating levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-18, and C-reactive protein (CRP) were investigated in 67 healthy, premenopausal obese women and 40 age-matched normal-weight women. RESULTS Compared with nonobese women, obese women had increased concentrations of CRP (P < 0.01), TNF-alpha (P < 0.01), IL-6 (P < 0.01), and IL-18 (P < 0.01). Moreover, obese women had a higher myocardial performance index (P < 0.02) and lower transmitral Doppler flow (P < 0.05), pulmonary venous flow analysis (P < 0.02), and ejection fraction (P < 0.05), indicating ventricular dyssynchrony. Concentrations of CRP, TNF-alpha, and IL-6 were related to anthropometric indexes of obesity and to echocardiographic parameters of ventricular dyssynchrony. After 1 year of a multidisciplinary program of weight reduction, obese women lost at least 10% of their original weight. This was associated with reduction of cytokine (P < 0.01) and CRP (P < 0.02) concentrations and with improvement of echocardiographic parameters of ventricular dyssynchrony, which correlated with changes in adiposity, particularly visceral adiposity. CONCLUSIONS In obese women, ventricular dyssynchrony correlates with body fat, possibly through inappropriate secretion of cytokines. Weight loss represents a safe method for downregulating the inflammatory state and ameliorating cardiac function in obese women.
Tractional force generation by porcine Müller cells: stimulation by growth factors in human vitreous.

PURPOSE To examine the levels of Müller cell contraction-stimulating activity in human vitreous, correlate these levels with clinical presentation, and identify, the causative growth factors. METHODS Human vitreous was collected from patients undergoing pars plana vitrectomy (n = 84). Müller cells were isolated from porcine retina and maintained in tissue culture. Tractional forces generated by cells incubated on three-dimensional collagen gels were measured as changes in gel thickness. Contraction-stimulating activity in vitreous (VA) was calculated from the close-response profiles of gel contraction to vitreous protein. The contributions of individual growth factors to vitreous activity (n = 10) were assessed by inhibition with specific neutralizing antibodies. RESULTS The mean VA of patients with retinal detachment (3.65) and proliferative vitreoretinopathy stages A, B, and C (2.06) were elevated above that of patients without retinal pathology (vitreous activity = 0.23) or retinal defects alone (0.57). Mean activities in patients with epimacular proliferation (1.22) and vitreous hemorrhage (1.40) were also significantly elevated. The percentage of this activity attributable to insulin-like growth factor 1 (IGF-1) varied from 9.2% to 84.5% with a mean of 61.3%. Similarly, the percent contribution of platelet-derived growth factor (PDGF) ranged from 6.8% to 49.0% with a mean of 26.5%. CONCLUSIONS The vitreous of patients with retinal detachment, proliferative retinal disease, and vitreous hemorrhage contain varying amounts of growth factors that stimulate tractional force generation by Müller cells. The majority of the activity can be attributed to IGF-1 and a smaller proportion to PDGF.
Dendritic cell exosomes directly kill tumor cells and activate natural killer cells via TNF superfamily ligands

Autocrine and paracrine cell communication can be conveyed by multiple mediators, including membrane-associate proteins, secreted proteins and exosomes. Exosomes are 30–100 nm endosome-derived vesicles consisting in cytosolic material surrounded by a lipid bilayer containing transmembrane proteins. We have previously shown that dendritic cells (DCs) express on their surface multiple TNF superfamily ligands (TNFSFLs), by which they can induce the apoptotic demise of tumor cells as well as the activation of natural killer (NK) cells. In the present study, we demonstrate that, similar to DCs, DC-derived exosomes (DCex) express on their surface TNF, FasL and TRAIL, by which they can trigger caspase activation and apoptosis in tumor cells. We also show that DCex activate NK cells and stimulate them to secrete interferonγ (IFNγ) upon the interaction of DCex TNF with NK-cell TNF receptors. These data demonstrate that DCex can mediate essential innate immune functions that were previously ascribed to DCs.
Long-Term Diversity and Genome Adaptation of Acinetobacter baylyi in a Minimal-Medium Chemostat

Laboratory-based evolution experiments on microorganisms that do not recombine frequently show two distinct phases: an initial rapid increase in fitness followed by a slower regime. To explore the population structure and the evolutionary tree in the later stages of adaptation, we evolved a very large population (∼3 × 10) of Acinetobacter baylyi bacteria for approximately 2,800 generations from a single clone. The population was maintained in a chemostat at a high dilution rate. Nitrate in limiting amount and as the sole nitrogen source was used as a selection pressure. Analysis via resequencing of genomes extracted from populations at different generations provides evidence that long-term diversity can be established in the chemostat in a very simple medium. To find out which biological parameters were targeted by adaptation, we measured the maximum growth rate, the nitrate uptake, and the resistance to starvation. Overall, we find that maximum growth rate could be a reasonably good proxy for fitness. The late slow adaptation is compatible with selection coefficients spanning a typical range of 10–10 per generation as estimated by resequencing, pointing to a possible subpopulations structuring.
Exploiting Web matrix permutations to speedup PageRank computation

Recently, the research community has devoted an increased attention to reduce the computational time needed by Web ranking algorithms. In particular, we saw many proposals to speed up the well-known PageRank algorithm used by Google . This interest is motivated by two dominant factors: (1) the Web Graph has huge dimensions and it is subject to dramatic updates in term of nodes and links - therefore PageRank assignment tends to became obsolete very soon; (2) many PageRank vectors need to be computed according to diﬀerent personalization vectors chosen. In the present paper, we address this problem from a numerical point of view. First, we show how to treat dangling nodes in a way which naturally adapts to the random surfer model and preserves the sparsity of the Web Graph. This result allows to consider the PageRank computation as a sparse linear system in alternative to the commonly adopted eigenpairs interpretation. Second, we exploit the Web Matrix reducibility and compose oppor-tunely some Web matrix permutation to speed up the PageRank computation. We tested our approaches on a Web Graphs crawled from the net. The largest one account about 24 millions nodes and more than 100 million links. Upon this Web Graph, the cost for computing the PageRank is reduced of 58% in terms of Mﬂops and of 89% in terms of time respect to the Power method commonly used.
Coprime Factorization and Optimal Control on the Doubly Infinite Discrete Time Axis

We study the problem of strongly coprime factorization over H-infinity of the unit disc. We give a necessary and sufficient condition for the existence of such a coprime factorization in terms of an optimal control problem over the doubly infinite discrete-time axis. In particular, we show that an equivalent condition for the existence of such a coprime factorization is that both the control and filter algebraic Riccati equation (of an arbitrary realization) have a solution (in general unbounded and even nondensely defined) and that a coupling condition involving these solutions is satisfied.
Product-Line Competition: Customization vs. Proliferation

We study a market with customers who have heterogeneous preferences for product attributes. We consider two types of firms that compete on price and product variety: A traditional firm, which chooses a limited set of product configurations, and a customizing firm, which can produce any configuration to order. The traditional firm carries product inventories and experiences a lead-time delay. The customizing firm does not carry inventory, and its customers incur waiting costs until they receive their orders. We assume that the customizing firm has limited capacity in the short run (e.g., when it does not outsource production to high-volume manufacturers). We derive the equilibrium for a duopoly competition between the customizing firm and the traditional firm, study its characteristics, and compare it to a monopoly. We characterize conditions that favor customization under competition. We find that the customizing firm's profit is not monotone in the market size and its ease of customization. Similarly, a decline in the traditional firm's holding cost may increase or decrease its profit. We show that the unit cost differential between the firms crucially affects the customizing firm's ideal market size, its returns from expanding capacity, its product variety, and the way operational improvements affect its performance.
Histone Deacetylase Inhibitors and 15-Deoxy-Δ12,14-Prostaglandin J2 Synergistically Induce Apoptosis

Purpose: The clinically relevant histone deacetylase inhibitors (HDI) valproic acid (VPA) and suberoylanilide hydroxamic acid exert variable antitumor activities but increase therapeutic efficacy when combined with other agents. The natural endogenous ligand of peroxisome proliferator–activated receptor γ 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is a potent antineoplastic agent. Therefore, we investigated whether these HDIs in combination with 15d-PGJ2 could show synergistic antitumor activity in colon cancer DLD-1 cells. Experimental Design: Cell viability was determined using a Cell Counting Kit-8 assay. Apoptosis and reactive oxygen species (ROS) generation were determined using flow cytometry analysis. Western blotting and real-time reverse transcription-PCR analysis were carried out to investigate the expression of apoptosis-related molecules. Mice bearing DLD-1 xenograft were divided into four groups (n = 5) and injected everyday (i.p.) with diluent, VPA (100 mg/kg), 15d-PGJ2 (5 mg/kg), or a combination for 25 days. Results: HDI/15d-PGJ2 cotreatments synergistically induced cell death through caspase-dependent apoptosis in DLD-1 cells. Moreover, HDIs/15d-PGJ2 caused histone deacetylase inhibition, leading to subsequent ROS generation and endoplasmic reticulum stress to decrease the expression of antiapoptotic molecules Bcl-XL and XIAP and to increase that of proapoptotic molecules CAAT/enhancer binding protein homologous protein and death receptor 5. Additionally, VPA/15d-PGJ2 cotreatment induced ROS-dependent apoptosis in other malignant tumor cells and was more effective than a VPA or 15d-PGJ2 monotherapy in vivo. Conclusions: Cotreatments with the clinically relevant HDIs and the endogenous peroxisome proliferator–activated receptor γ ligand 15d-PGJ2 are promising for the treatment of a broad spectrum of malignant tumors. Clin Cancer Res; 16(8); 2320–32. ©2010 AACR.
Airways: Optimization-Based Planning of Quadrotor Trajectories according to High-Level User Goals

In this paper we propose a computational design tool that allows end-users to create advanced quadrotor trajectories with a variety of application scenarios in mind. Our algorithm allows novice users to create quadrotor based use-cases without requiring deep knowledge in either quadrotor control or the underlying constraints of the target domain. To achieve this goal we propose an optimization-based method that generates feasible trajectories which can be flown in the real world. Furthermore, the method incorporates high-level human objectives into the planning of flight trajectories. An easy to use 3D design tool allows for quick specification and editing of trajectories as well as for intuitive exploration of the resulting solution space. We demonstrate the utility of our approach in several real-world application scenarios, including aerial-videography, robotic light-painting and drone racing.
Ovarian hormones ameliorate memory impairment, cholinergic deficit, neuronal apoptosis and astrogliosis in a rat model of Alzheimer's disease

Ovarian hormones, including progesterone (P4) and 17 β-estradiol (E2), have been shown to affect memory functions; however, the underlying mechanism whereby ovarian hormone replacement therapy may decrease the risk of Alzheimer's disease (AD) is currently unclear. The present study aimed to investigate the effects of P4 and E2 on spatial and learning memory in an ovariectomized rat model of AD. β-amyloid (Aβ) or saline were stereotaxically injected into the hippocampus of the rats and, after 1 day, ovariectomy or sham operations were performed. Subsequently, the rats were treated with P4 alone, E2 alone, or a combination of P4 and E2. Treatment with E2 and/or P4 was shown to improve the learning and memory functions of the rats, as demonstrated by the Morris water maze test. In addition, treatment with E2 and P4 was associated with increased expression levels of choline acetyltransferase and 5-hydroxytryptamine receptor 2A (5-HT2A), and decreased expression levels of the glial fibrillary acidic protein in the hippocampus of the rats. Furthermore, E2 and P4 treatment significantly attenuated neuronal cell apoptosis, as demonstrated by terminal deoxynucleotidyl transferase dUTP nick end labeling assays; thus suggesting that the ovarian hormones were able to protect against Aβ-induced neuronal cell toxicity. The results of the present study suggested that the neuroprotective effects of P4 and E2 were associated with amelioration of the cholinergic deficit, suppression of apoptotic signals and astrogliosis, and upregulation of 5-HT2A expression levels. Therefore, hormone replacement therapy may be considered an effective strategy for the treatment of patients with cognitive disorders and neurodegenerative diseases.
Trichothiodystrophy Reveals Cancer Predisposition Mouse Model for the Dna Repair/basal Transcription Disorder Updated Version Cited Articles Citing Articles E-mail Alerts Mouse Model for the Dna Repair/basal Transcription Disorder Trichothiodystrophy Reveals Cancer Predisposition

Patients with the nucleotide excision repair (NER) disorder xeroderma pigmentosum (XP) are highly predisposed to develop sunlight-induced skin cancer, in remarkable contrast to photosensitive NER-deficient tri-chothiodystrophy (TTD) patients carrying mutations in the same XPD gene. XPD encodes a helicase subunit of the dually functional DNA repair/basal transcription complex TFIIH. The pleiotropic disease phenotype is hypothesized to be, in part, derived from a repair defect causing UV sensitivity and, in part, from a subtle, viable basal transcription deficiency accounting for the cutaneous, developmental, and the typical brittle hair features of TTD. To understand the relationship between deficient NER and tumor susceptibility, we used a mouse model for TTD that mimics an XPD point mutation of a TTD patient in the mouse germline. Like the fibroblasts from the patient, mouse cells exhibit a partial NER defect, evident from the reduced UV-induced DNA repair synthesis (residual repair capacity ϳ25%), limited recovery of RNA synthesis after UV exposure, and a relatively mild hypersensitivity to cell killing by UV or 7,12-dimethylbenz[a]anthracene. In accordance with the cellular studies, TTD mice exhibit a modestly increased sensitivity to UV-induced inflammation and hyperplasia of the skin. In striking contrast to the human syndrome, TTD mice manifest a clear susceptibility to UV-and 7,12-dimethylbenz[a]anthracene-induced skin carcinogenesis, albeit not as pronounced as the totally NER-deficient XPA mice. These findings open up the possibility that TTD is associated with a so far unnoticed cancer predisposition and support the notion that a NER deficiency enhances cancer susceptibility. These findings have important implications for the etiology of the human disorder and for the impact of NER on carcinogenesis.
Estimating the Smoking Ban Effects on Smoking Prevalence, Quitting and Cigarette Consumption in a Population Study of Apprentices in Italy

Objectives: We evaluated the effects of the Italian 2005 smoking ban in public places on the prevalence of smoking, quitting and cigarette consumption of young workers. Data and Methods: The dataset was obtained from non-computerized registers of medical examinations for a population of workers with apprenticeship contracts residing in the province of Viterbo, Italy, in the period 1996–2007. To estimate the effects of the ban, a segmented regression approach was used, exploiting the discontinuity introduced by the application of the law on apprentices’ smoking behavior. Results: It is estimated that the Italian smoking ban generally had no effect on smoking prevalence, quitting ratio, or cigarette consumption of apprentices. However, when the estimates were applied to subpopulations, significant effects were found: −1% in smoking prevalence, +2% in quitting, and −3% in smoking intensity of apprentices with at least a diploma.
Word Sense Disambiguation Improves Statistical Machine Translation

Recent research presents conflicting evidence on whether word sense disambiguation (WSD) systems can help to improve the performance of statistical machine translation (MT) systems. In this paper, we successfully integrate a state-of-the-art WSD system into a state-of-the-art hierarchical phrase-based MT system, Hiero. We show for the first time that integrating a WSD system improves the performance of a state-ofthe-art statistical MT system on an actual translation task. Furthermore, the improvement is statistically significant.
Why Do HIV-1 and HIV-2 Use Different Pathways to Develop AZT Resistance?

The human immunodeficiency virus type 1 (HIV-1) develops resistance to all available drugs, including the nucleoside analog reverse transcriptase inhibitors (NRTIs) such as AZT. ATP-mediated excision underlies the most common form of HIV-1 resistance to AZT. However, clinical data suggest that when HIV-2 is challenged with AZT, it usually accumulates resistance mutations that cause AZT resistance by reduced incorporation of AZTTP rather than selective excision of AZTMP. We compared the properties of HIV-1 and HIV-2 reverse transcriptase (RT) in vitro. Although both RTs have similar levels of polymerase activity, HIV-1 RT more readily incorporates, and is more susceptible to, inhibition by AZTTP than is HIV-2 RT. Differences in the region around the polymerase active site could explain why HIV-2 RT incorporates AZTTP less efficiently than HIV-1 RT. HIV-1 RT is markedly more efficient at carrying out the excision reaction with ATP as the pyrophosphate donor than is HIV-2 RT. This suggests that HIV-1 RT has a better nascent ATP binding site than HIV-2 RT, making it easier for HIV-1 RT to develop a more effective ATP binding site by mutation. A comparison of HIV-1 and HIV-2 RT shows that there are numerous differences in the putative ATP binding sites that could explain why HIV-1 RT binds ATP more effectively. HIV-1 RT incorporates AZTTP more efficiently than does HIV-2 RT. However, HIV-1 RT is more efficient at ATP-mediated excision of AZTMP than is HIV-2 RT. Mutations in HIV-1 RT conferring AZT resistance tend to increase the efficiency of the ATP-mediated excision pathway, while mutations in HIV-2 RT conferring AZT resistance tend to increase the level of AZTTP exclusion from the polymerase active site. Thus, each RT usually chooses the pathway best suited to extend the properties of the respective wild-type enzymes.
Machine Learning versus Knowledge Based Classification of Legal Texts

This paper presents results of an experiment in which we used machine learning (ML) techniques to classify sentences in Dutch legislation. These results are compared to the results of a pattern-based classifier. Overall, the ML classifier performs as accurate (>90%) as the pattern based one, but seems to generalize worse to new laws. Given these results, the pattern based approach is to be preferred since its reasons for classification are clear and can be used for further modelling of the content of the sentences.