Miracle-dz/UniFAR-FTUs huggingface dataset:
Newly identified bacteriolytic enzymes that target a wide range of clinical isolates of Clostridium difficile

Clostridium difficile has emerged as a major cause of infectious diarrhea in hospitalized patients, with increasing mortality rate and annual healthcare costs exceeding $3 billion. Since C. difficile infections are associated with the use of antibiotics, there is an urgent need to develop treatments that can inactivate the bacterium selectively without affecting commensal microflora. Lytic enzymes from bacteria and bacteriophages show promise as highly selective and effective antimicrobial agents. These enzymes often have a modular structure, consisting of a catalytic domain and a binding domain. In the current work, using consensus catalytic domain and cell‐wall binding domain sequences as probes, we analyzed in silico the genome of C. difficile, as well as phages infecting C. difficile. We identified two genes encoding cell lytic enzymes with possible activity against C. difficile. We cloned the genes in a suitable expression vector, expressed and purified the protein products, and tested enzyme activity in vitro. These newly identified enzymes were found to be active against C. difficile cells in a dose‐dependent manner. We achieved a more than 4‐log reduction in the number of viable bacteria within 5 h of application. Moreover, we found that the enzymes were active against a wide range of C. difficile clinical isolates. We also characterized the biocatalytic mechanism by identifying the specific bonds cleaved by these enzymes within the cell wall peptidoglycan. These results suggest a new approach to combating the growing healthcare problem associated with C. difficile infections. Biotechnol. Bioeng. 2016;113: 2568–2576. © 2016 Wiley Periodicals, Inc.
Police Reform in the Commonwealth Caribbean

This paper will try to make a case for police reform, sketch the broad outlines of the programmatic options for reform, and finally, discuss some of the process issues, that is, how best to approach the business of getting a programme of change accepted by the police services and ultimately institutionalized. The paper aims not to be too detailed or too definitive, but rather to pitch the discussion at a fairly general level.
Inpatients' willingness to recommend: a multilevel analysis.

BACKGROUND Satisfaction with health care is one of the most widely assessed measures of hospital care quality, yet studies that account for clustering effects are uncommon. We constructed a multilevel model to identify predictors of willingness to recommend while controlling for clustering effects due to hospital and care unit. We also examined differences in predictors by care unit. PURPOSE The aim of this study was to identify factors that both influence patient perceptions of care and are potentially modifiable by the hospital delivering care. METHODOLOGY Our sample includes Hospital Consumer Assessment of Healthcare Providers and Systems survey data collected between July 1, 2007, and June 30, 2008, for 131 hospitals and 33,445 patients. The primary outcome was willingness to recommend the hospital to family and friends. Variables were collected at three levels: patient (Hospital Consumer Assessment of Healthcare Providers and Systems survey item responses and demographics), care unit, and hospital. Data were analyzed using multilevel modeling. We also ran a series of two-level models to explore differences in predictors by care type. FINDINGS The strongest predictors of willingness to recommend, controlling for clustering effects, were items that generally reflected interpersonal aspects of care such as nursing and physician behaviors. In the two-level models, predictors of willingness to recommend overlapped across care units, but important differences were noted. PRACTICE IMPLICATIONS Our results suggest that hospitals that wish to improve their performance would benefit most from focusing on interpersonal aspects of care. Hospitals that focus resources on improving in these areas, that assess care units separately, and that investigate the meaning and context of survey responses will be most likely to see improvements in satisfaction scores.
The effect of information on oversight: the European Parliament’s response to increasing information on comitology decision-making

The European Parliament, like any parliament, needs information for scrutinizing executive decision-making. But how does it process this information in practice? This article focuses on the European Parliament’s increasing grip on ‘comitology’ decision-making: committees composed of national civil servants, producing executive measures that are adopted by the European Commission. Two types of changes are addressed: organizational changes and changes in working methods of EP staff. The analysis shows that the European Parliament has effectively built up a system of decentralized police-patrol oversight, but not following more information rights as such but rather as a result of its increasing political powers. The article concludes that information only affects the behaviour of the European Parliament in combination with very specific as opposed to quite general or diffuse political rights. Points for practitioners This article traces the effects of information on the functioning of the European Parliament as an accountability forum. It concludes that information only makes a difference when coupled with very specific as opposed to very general or diffuse political rights.
MicroRNA-155 as a proinflammatory regulator in clinical and experimental arthritis

MicroRNA (miRNA) species (miR) regulate mRNA translation and are implicated as mediators of disease pathology via coordinated regulation of molecular effector pathways. Unraveling miR disease-related activities will facilitate future therapeutic interventions. miR-155 recently has been identified with critical immune regulatory functions. Although detected in articular tissues, the functional role of miR-155 in inflammatory arthritis has not been defined. We report here that miR-155 is up-regulated in synovial membrane and synovial fluid (SF) macrophages from patients with rheumatoid arthritis (RA). The increased expression of miR-155 in SF CD14+ cells was associated with lower expression of the miR-155 target, Src homology 2-containing inositol phosphatase-1 (SHIP-1), an inhibitor of inflammation. Similarly, SHIP-1 expression was decreased in CD68+ cells in the synovial lining layer in RA patients as compared with osteoarthritis patients. Overexpression of miR-155 in PB CD14+ cells led to down-regulation of SHIP-1 and an increase in the production of proinflammatory cytokines. Conversely, inhibition of miR-155 in RA synovial CD14+ cells reduced TNF-α production. Finally, miR-155–deficient mice are resistant to collagen-induced arthritis, with profound suppression of antigen-specific Th17 cell and autoantibody responses and markedly reduced articular inflammation. Our data therefore identify a role of miR-155 in clinical and experimental arthritis and suggest that miR-155 may be an intriguing therapeutic target.
Notes for a Contingent Claims Theory of Limit Order Markets

This paper provides a road map for building a contingent claims theory of limit order markets grounded in a simple observation: limit orders are equivalent to a portfolio of cash-or-nothing and asset-or-nothing digital options on market order flow. However, limit orders are not conventional derivative securities: order flow is an endogenous, non-price state variable; the underlying asset value is a construct, the value of the security in different order flow states; and arbitrage trading or hedging of limit orders is not feasible. Fortunately, none of these problems is fatal since options on order flow can be conceptualized as bets implicit in limit orders, arbitrage trading can be replaced by limit order substitution, and plausible assumptions can be made about the endogeneity of order flow states and their associated asset values. The analysis yields two main results: Arrow-Debreu prices for order flow %u2018%u2018states%u2019%u2019 are proportional to the slope of the limit order book and the limit order book at one time proves to be identical to that at an earlier time adjusted for the net order flow since that time when all information arrives via trades.
Framing climate vulnerability and adaptation at multiple levels: Addressing climate risks or institutional barriers in Lesotho?

Adaptation to climate change occurs largely through action at the local level, which is influenced by international and national levels of political and social organization. This article explores the impact of discourse at the international level on adaptation policy at the national and local level. Discourse defines which knowledge claims, methods and rationalities are accepted and reproduced by actors as a basis for policy development and implementation; this is called ‘framing’. Scientific literature defines adaptation and vulnerability in a general way and so accommodates different framings. This article reviews the history of the concepts of adaptation and vulnerability in the literature and their relation to development. Evidence is presented for the presence of two framings of CCIAV in the literature: the ‘decision-analytic’ and the ‘institutional-analytic’. Wetlands and climate-related projects in Lesotho are analysed and evidence is presented for the reproduction of the two framings. A decision-analytic framing favours projects focusing on technological solutions and reducing projected impacts. Conversely, institutional-analytic framing tends to produce projects that more explicitly include governance issues. It is concluded that framings exert a significant influence on policy when linked to, for example, sources of funding for adaptation. It is argued that methods linked to the ‘decision-analytic’ framing risk limiting the scope of effective adaptations.
Co-treatment with heat shock protein 90 inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin (DMAG) and vorinostat: a highly active combination against human Mantle Cell Lymphoma (MCL) cells

Heat shock protein (hsp) 90 inhibitors promote proteasomal degradation of pro-growth and pro- survival hsp90 client proteins, including CDK4, c-RAF and AKT, and induce apoptosis of human lymphoma cells. The pan-histone deacetylase inhibitor vorinostat has also been shown to induce growth arrest and apoptosis of lymphoma cells. Here, we determined the effects of the more soluble, orally bio-available, geldanamycin analogue 17-NN-dimethyl ethylenediamine geldanamycin (DMAG, Kosan Biosciences Inc) and/or vorinostat in cultured and primary human MCL cells. While vorinostat induced accumulation in the G1 phase, treatment with DMAG arrested MCL cells in the G2/M phase of the cell cycle. Both agents dose-dependently induced apoptosis of MCL cells. Vorinostat also induced hyperacetylation of hsp90 and disrupted the association of hsp90 with its co-chaperones p23 and cdc37, as well as with its client proteins CDK4 and c-RAF. Treatment of MCL cells with vorinostat or 17-DMAG was associated with the induction of p21 and p27, as well as with depletion of c-Myc, c-RAF, AKT and CDK4. Compared to treatment with either agent alone, co-treatment with DMAG and vorinostat markedly attenuated the levels of cyclin D1 and CDK4, as well as of c-Myc, c-RAF and AKT. Combined treatment with DMAG and vorinostat synergistically induced apoptosis of the cultured MCL cells, as well as induced more apoptosis of primary MCL cells than either agent alone. Therefore, these findings support the rationale to determine the in vivo efficacy of co- treatment with vorinostat and DMAG against human MCL cells.
Hippo Pathway Gene Mutations in Malignant Mesothelioma: Revealed by RNA and Targeted Exon Sequencing

Introduction: Malignant mesothelioma (MM) is an aggressive neoplasm causatively associated with exposure to asbestos. MM is rarely responsive to conventional cytotoxic drugs, and the outcome remains dismal. It is, therefore, necessary to identify the signaling pathways that drive MM and to develop new therapeutics specifically targeting the molecules involved. Methods: We performed comprehensive RNA sequencing of 12 MM cell lines and four clinical samples using so-called next-generation sequencers. Results: We found 15 novel fusion transcripts including one derived from chromosomal translocation between the large tumor suppressor 1 (LATS1) and presenilin-1 (PSEN1) genes. LATS1 is one of the central players of the emerging Hippo signaling pathway. The LATS1–PSEN1 fusion gene product lacked the ability to phosphorylate yes-associated protein and to suppress the growth of a MM cell line. The wild-type LATS1 allele was undetectable in this cell line, indicating two-hit genetic inactivation of its tumor suppressor function. Using pathway-targeted exon sequencing, we further identified a total of 11 somatic mutations in four Hippo pathway genes (neurofibromatosis type 2 [NF2], LATS2, RASSF1, and SAV1) in 35% (8 of 23) of clinical samples. Nuclear staining of yes-associated protein was detected in 55% (24 of 44) of the clinical samples. Expression and/or phosphorylation of the Hippo signaling proteins, RASSF1, Merlin (NF2), LATS1, and LATS2, was frequently absent. Conclusions: The frequent alterations of Hippo pathway molecules found in this study indicate the therapeutic feasibility of targeting this pathway in patients with MM.
Using Proxies for the Short Rate: When Are Three Months Like an Instant?

The dynamics of the unobservable short rate are frequently estimated directly using a proxy. We examine the biases resulting from this practice (the 'proxy problem'). Analytic results show that the proxy problem is not economically significant for single-factor affine models. In the two-factor affine model of Longstaff and Schwartz (1992), the proxy problem is only economically significant for pricing discount bonds with maturities of more than five years. We also describe two different numerical procedures for assessing the magnitude of the proxy problem in a general interest rate model. When applied to a nonlinear single-factor model, they suggest that the proxy problem can be economically significant. Article published by Oxford University Press on behalf of the Society for Financial Studies in its journal, The Review of Financial Studies.
The Na+/K+‐Pump Protects Muscle Excitability and Contractility during Exercise

&NA; NIELSEN, O.B. , and T. CLAUSEN. The Na+/K+‐pump protects muscle excitability and contractility during exercise. Exerc. Sport. Sci. Rev., Vol. 28, No. 4, pp 159‐164, 2000. In skeletal muscle, the concentration of Na+/K+‐pumps is high and increases through training. In isolated muscles, contractile endurance depends in part on Na+/K+‐pump concentration. Exercise leads to rundown of Na+/K+‐gradients, compound action potentials, and force. Early and efficient activation of the Na+/K+‐pump, however, protects excitability and contractility.
The travel behaviours of international students

International students represent a large and potentially lucrative market for various sectors of the tourism industry. Although previous empirical studies have examined this topic, most treated the market as homogeneous and small sample sizes have been the norm. The present Australia-based study represents the first large-scale investigation of the travel activities of international students. The large sample size (N = 4633) has allowed the researchers to identify nationality-based differences between international student travel behaviours and the factors that constrain their travel. The approach that has been adopted extends theoretical and applied understanding of this important tourism market and informs how tourism industry leaders may capitalise on the opportunities by undertaking initiatives, such as innovative tourism marketing, product development and packaging initiatives.
ATP13A2 variants in early‐onset Parkinson's disease patients and controls

Four genes responsible for recessively inherited forms of Parkinson's disease (PD) have been identified, including the recently discovered ATP13A2 (PARK9) gene. Our objective was to investigate the role of this gene in a large cohort of PD patients and controls. We extensively screened all 29 exons of the ATP13A2 coding region in 112 patients with early‐onset PD (EOPD; <40 years) of mostly European ethnic origin and of 55 controls. We identified four carriers (3.6%) of novel single heterozygous ATP13A2 missense changes that were absent in controls. Interestingly, the carrier of one of these variants also harbored two mutations in the Parkin gene. None of the carriers had atypical features previously described in patients with two mutated ATP13A2 alleles (Kufor–Rakeb syndrome). Our data suggest that two mutated ATP13A2 alleles are not a common cause of PD. Although heterozygous variants are present in a considerable number of patients, they are—based on this relatively small sample—not significantly more frequent in patients compared to controls. © 2009 Movement Disorder Society
Spatial duopoly with triangular markets

This article develops a duopoly model in which consumers are uniformly distributed along three sides (streets) of a triangular park and each consumer walks across the park in the shortest way to the lowest-price firm to buy one unit of a product. Two important findings emerge from our analysis. First, both firms choose location adjustment rather than price-cutting as a competition strategy to pursue their maximum profit. Second, asymmetric triangular markets provide more advantage to the firms than do symmetric ones. The intuition of this result is that each firm's monopoly power increases as the degree of asymmetry increases; firms can therefore raise their product prices in order to increase their profit. Copyright RSAI 2005.
SCube: A Tool for Segregation Discovery

Segregation discovery consists of finding contexts of segregation of social groups distributed across units or communities. The SCube system implements an approach for segregation discovery on top of frequent itemset mining, by offering to the analyst a multi-dimensional (segregation) data cube for exploratory data analysis. The demonstration first guides the audience through the social science concepts, then describes the architecture of the SCube system and how it is able to deal with both relational data and with attributed graph data modeling social networks. Finally, we go through two running case studies in the context of occupational segregation in the boards of company directors using a 2012 snaphost of the Italian companies, and a 20-year long dataset of Estonian companies.
BLAST : Target frequencies and information content

BLAST has two components: a fast heuristic for searching for similar sequences and a statistical framework for evaluating the results of the search. In previous lectures we discussed the search heuristic. Here, we discuss (1) the statistical significance of finding a match with score S, and (2) properties of sequence statistics and substitution matrices that influence the specificity and sensitivity of database searches.
Efficacy of a training program for long-term disease- free cancer survivors as health partners: a randomized controlled trial in Korea.

BACKGROUND To determine whether the Health Partner Program is effective in training long-term cancer survivors to be health coaches. MATERIALS AND METHODS We randomly assigned cancer survivors who were selected through a rigorous screening process to either the Health Partner Program or the waiting-list control group. The program consisted of 8 weeks of training in health management, leadership, and coaching. At baseline, 8, and 16 weeks, we measured primary outcomes using the Seven Habit Profile (SHP), the Korean Leadership Coaching Competency Inventory (KCCI), Ed Diner's Satisfaction with Life Scale (SWLS), and the Posttraumatic Growth inventory (PTGI) and secondary outcomes using the Hospital Anxiety and Depression Scale (HADS), the Impact of Event Scale-Revised (IES-R), and the Medical Outcomes Study (MOS) short form 36-item questionnaire (SF- 36). RESULTS We recruited 70 subjects and randomly assigned 34 to the intervention group. The Sharpen the Saw habit of the SHP increased significantly more in intervention group than in the control group (p = 0.049), as did most PTGI factors. The intervention group also showed a significantly greater enhancement of vitality (p = 0.015) and mental health (p = 0.049) SF-36 scores but no improvement in KCCI, SWLS, HADS, or IES-R scores. The intervention group also showed a greater clinically meaningful improvement in the "Think Win-Win" of SHP (p = 0.043) and in the personal strength score (p = 0.025) and total score (p = 0.015) of the PTGI. CONCLUSIONS Long-term cancer survivors can benefit from the Health Partner Program to become health coaches.
Extraction and amplification of mitochondrial DNA from formalin-fixed deep-sea mollusks.

This work was supported by the Arthritis Foundation post doctoral fellowship (to K.S.V.), a GAANN training grant (to B.M.J.) and National Institutes of Health Grant No. R29 CA58947 (David Skalnik). We would like to thank Drs. David Skalnik, Diana Carlone and Diana Catt for helpful discussions. Address correspondence to Kui Shin Voo, Wells Center for Pediatric Research, Indiana University School of Medicine, 1044 W. Walnut Street, Cancer Research Building, Indianapolis, IN 46202-5225, USA. Internet: kvoo@iupui.edu
A Trading Strategy to Profit from Overly Aggressive Downward Earnings Guidance

The empirical evidence presented in this article suggested that it is potentially possible for an informed trader in after-hours trading to earn abnormal returns from identifying and investing in stocks with a positive earnings surprise. The strategy is based on a simple (naïve) moving average time series forecast of earnings, conditional on the moving average forecast and the last analyst s forecast both being positive, and with the former being larger than the latter. These are likely firms that have been either subject to aggressive downward earning guidance or just firms for which analysts have become less favorably inclined about earnings prospects. These findings should prove useful to informed investors who trade or construct portfolios based on the information in earnings surprises.
Peaks and valleys : Price discovery in experimental asset markets with non-monotonic fundamentals

Purpose - This paper aims to study how the trajectory of fundamental values affects price discovery in an experimental asset market. Design/methodology/approach - An experiment is conducted with two treatments, in which the time path of fundamentals differs between treatments. In the peak treatment, fundamentals first rise and then fall, while in the valley treatment fundamentals first fall and then recover. The experiment allows market prices to be compared to fundamental values. Findings - Both peak and valley treatments experience bubbles when traders are inexperienced. However, price discovery is more rapid and complete in the peak than in the valley treatment. In the peak treatment, prices track the value, the direction of the trend, and changes in trend, more closely than in the valley treatment. Originality/value - This paper documents the first experimental results regarding pricing behavior in markets with non-monotonic fundamentals. It creates an environment (the valley treatment) in which convergence to close to fundamentals does not occur even with repetition of the market under identical conditions. The results demonstrate that the likelihood that an asset market tracks fundamentals depends on the time path of fundamentals.