Miracle-dz/UniFAR-FTUs huggingface dataset:
The ESAT‐6/CFP‐10 secretion system of Mycobacterium marinum modulates phagosome maturation

Virulence of Mycobacterium tuberculosis and related pathogenic mycobacteria requires the secretion of early secretory antigenic 6 kDa (ESAT‐6) and culture filtrate protein 10 (CFP‐10), two small proteins that lack traditional signal sequences and are exported through an alternative secretion pathway encoded primarily by the RD1 genetic locus. Mutations affecting the synthesis or secretion of ESAT‐6 or CFP‐10 attenuate the virulence of M. tuberculosis in murine models of infection. However, the specific functions of these proteins and of their secretion system are currently unclear. In this study, we isolated a mutant of Mycobacterium marinum defective in the secretion of ESAT‐6 and CFP‐10. The mutation was localized within MM5446, which is orthologous to Rv3871 of M. tuberculosis H37Rv and encodes an ATPase that is a component of the ESAT‐6/CFP‐10 secretion system. The mutant bacteria were unable to replicate within J774 macrophages although their growth in 7H9 medium was equivalent to the parental strain. Phagosome maturation and acidification were analysed in infected macrophages by confocal and electron microscopy using the late endosome/lysosome marker LAMP‐1, along with various fluid‐phase markers such as rhodamine‐dextran and ferritin and the acidotropic dye LysoTracker Red. These studies demonstrated that while the wild‐type parental strain of M. marinum primarily resides in a poorly acidified, non‐lysosomal compartment, a significantly higher percentage of the MM5446 mutant organisms are in acidified compartments. These results suggest that the ESAT‐6/CFP‐10 secretion system plays a role in preventing phagolysosomal fusion, a novel function that accounts for the ability of bacteria to survive inside host cells. This finding provides a mechanism by which the ESAT‐6/CFP‐10 secretion system potentiates the virulence of pathogenic mycobacteria.
Relative Contributions of Complications and Failure to Rescue on Mortality in Older Patients Undergoing Pancreatectomy

Background:For pancreatectomy patients, mortality increases with increasing age. Our study evaluated the relative contribution of overall postoperative complications and failure to rescue rates on the observed increased mortality in older patients undergoing pancreatic resection at specialized centers. Methods:We identified 2694 patients who underwent pancreatic resection from the American College of Surgeons’ National Surgical Quality Improvement Pancreatectomy Demonstration Project at 37 high-volume centers. Overall morbidity and in-hospital mortality were determined in patients younger than 80 years (N = 2496) and 80 years or older (N = 198). Failure to rescue was the number of deaths in patients with complications divided by the total number of patients with postoperative complications. Results:No significant differences were observed between patients younger than 80 years and those 80 years or older in the rates of overall complications (41.4% vs 39.4%, P = 0.58). In-hospital mortality increased in patients 80 years or older compared to patients younger than 80 years (3.0% vs 1.1%, P = 0.02). Failures to rescue rates were higher in patients 80 years or older (7.7% vs 2.7%, P = 0.01). Across 37 high-volume centers, unadjusted complication rates ranged from 25.0% to 72.2% and failure to rescue rates ranged from 0.0% to 25.0%. Among patients with postoperative complications, comorbidities associated with failure to rescue were ascites, chronic obstructive pulmonary disease, and diabetes. Complications associated with failure to rescue included acute renal failure, septic shock, and postoperative pulmonary complications. Conclusions:In experienced hands, the rates of complications after pancreatectomy in patients 80 years or older compared to patients younger than 80 years were similar. However, when complications occurred, older patients were more likely to die. Interventions to identify and aggressively treat complications are necessary to decrease mortality in vulnerable older patients.
The continuous evolution of the Greenlight laser; the XPS generator and the MoXy laser fiber, expanding the indications for photoselective vaporization of the prostate.

OBJECTIVE To report our early experience with new GreenLight XPS™ generator using the new MoXy laser fiber, examining its efficacy and safety and also its ability to effectively treat the larger prostate gland. PATIENTS AND METHODS From July 2010 until August 2012, 131 patients, with an average age of 72.6 years (range 49-92), were treated using the XPS/MoXy system in a single U.K. center on a day-case basis. Data were prospectively collected. Evaluation of outcome was assessed at 3 months postoperatively comparing both subjective (international prostate symptom score [IPSS]) and objective (Q-max, postvoiding residual [PVR] and prostate volume) parameters to the preoperative data and classified into three groups according to the preoperative prostate size (<40 cc, 40-80 cc, and >80 cc). RESULTS More than one quarter of patients had a prostate volume >80 cc. Overall significant improvement in IPSS (mean reduction by 9.9) and Q-max (mean increase 10.26 mL/sec) are observed and were similar across the three groups. Average volume reduction was (51.2%, 49.8%, & 48.1%) for the three groups, respectively. No significant intraoperative or early postoperative complications were reported. CONCLUSION Early data confirm that in treating men with symptomatic benign prostate disease, the Greenlight XPS generator and MoXy laser fiber are able to achieve challenging results in terms of clinical outcome and prostate volume reduction irrespective of baseline prostate volume.
Multiple myeloma: patient outcomes in real‐world practice

With increasing number of therapies available for the treatment of multiple myeloma, it is timely to examine the course of patients' journeys. We investigated patient characteristics, treatment durations and outcomes, and symptom burden across the treatment pathway in Belgium, France, Germany, Italy, Spain, Switzerland and the UK. In total, 435 physicians retrospectively reviewed 4997 patient charts. Profiles of patients diagnosed with multiple myeloma during the last 12 months were similar across countries; bone pain was the most common presentation. Median duration of first‐line therapy was 6 months, followed by a median treatment‐free interval of 10 months; both these decreased with increasing lines of therapy, as did time to progression. Depth of response, as assessed by the treating physician, also decreased with each additional line of therapy: 74% of patients achieved at least a very good partial response at first line, compared with only 11% at fifth line. Deeper responses were associated with longer time to progression, although these were physician‐judged. Toxicities and co‐morbidities increased with later treatment lines, and were more likely to have led to discontinuation of treatment. These real‐world data provide an insight into patient outcomes and treatment decisions being made in clinical practice.
Sovereign Default Risk, Fiscal Adjustment, and Debt Renegotiation

This paper studies the effects of government capital accumulation on sovereign debt default risk and debt restructuring renegotiation outcomes when government has limited ability to extract revenues from households. We develop a quantitative dynamic stochastic general equilibrium model of sovereign default, debt renegotiation, and fiscal policies, where government chooses between the fiscal instruments of government consumption and government investment. Government capital provides an additional means of adjustment in the face of a bad productivity shock. It also affects government's incentive to re-access the international credit market when a country chooses to default. We implement fiscal policies and rules that restrict foreign debt, especially focusing on how fiscal rules affect government spending dynamics. The model delivers three key predictions. (1) A higher level of government capital implies less risky sovereign debt and higher recovery rates when the government chooses to default. (2) A high debt to output ratio is possible with a sufficient level of government capital. (3) Fiscal adjustment that reduces public investment may be self-defeating.
Role of chemotaxis in the association of motile bacteria with intestinal mucosa: in vitro studies

Various Sephadex G-15 fractions of pepsin-digested mucosal extract inhibited the in vitro association of cholera vibrios with mucosal slices. Inhibitory activity paralleled the taxin activity of the fractions for these bacteria. This supports the theory that inhibition of mucosal association by pepsin-digested mucosal scrapings was due to the blocking of taxin receptors on the bacterial surface. Nonchemotactic mutants were significantly less efficient than the chemotactic parent or revertant strains in associating with mucosal slices in vitro. Control experiments in which filter paper disks replaced the mucosal slices showed a comparable extent of association of chemotactic and nonchemotactic vibrios with this material. Histological studies indicated that vibrios associated predominantly with the mucus gel of the intestinal slices rather than with the mucosal epithelium or the serosal surface. Intestinal slices attracted chemotactic vibrios even after prolonged washing, suggesting continuous production of the taxin by the tissue. Inert polystyrene particles 1.1 micrometers in diameter penetrated the mucus gel of intestinal slices very poorly, but nevertheless could be detected in low numbers in the deep intervillous spaces within 15 min. In contrast, chemotactic vibrios reached the deep intervillous spaces in significantly higher numbers, whereas motile, non-chemotactic vibrios reacted like the inert particles. It is concluded that mucus gel represents a partial barrier to the penetration of particles of bacterial size and that this barrier can be invaded efficiently by motile bacteria, but only when their locomotion is guided by chemotactic stimuli.
The relationship between the government debt and GDP growth: evidence of the Euro area countries

This paper investigates the average impact of government debt on GDP growth in the Euro area countries using data from the period 1981-2014. The empirical results suggest that the impact of debt on economic growth is positive and statistically highly significant. In our estimation of the growth equation the author also includes some other control variables such as: 1) the variables capturing the impact of inflation, 2) the indicators of the openness of the economy and the external competitiveness, and 3) other control variables related to the demographic characteristics of the economy as well as indicators that expected to influence the future investments.
Interproximal Papilla Stability Around CAD/CAM and Stock Abutments in Anterior Regions: A 2-Year Prospective Multicenter Cohort Study.

The aim of this study was to compare the interproximal papilla stability of restorations supported by computer-aided design/computer-assisted manufacture (CAD/CAM) abutments to those supported by prefabricated stock abutments in anterior areas over a 2-year follow-up. Abutments were selected depending on implant inclination and thickness of buccal peri-implant soft tissues from the following: zirconia stock, titanium stock, zirconia CAD/CAM and titanium CAD/CAM. Differences between the height of the papilla tip were measured (REC). RESULTS REC values of titanium and zirconia CAD/CAM abutments were significantly lower than those of titanium and zirconia stock. The use of titanium and zirconia CAD/CAM abutments is related to better interproximal papillae stability.
Gene cassettes: a new class of mobile element.

Gene cassettes form a diverse group of small mobile elements that already includes over 40 members. Usually, each cassette contains only a single gene and a specific recombination site. At present, the genes found in cassettes are mostly antibiotic-resistance genes, but it is likely that gene cassettes represent a more general modular gene-packaging mechanism. These gene cassettes are normally found integrated at a specific site in an integron, where they are often part of multi-cassette arrays. Three classes of integron are currently known, all of which appear to be able to integrate the same set of cassettes. However, cassettes are also found rarely at non-specific sites. They move by conservative site-specific recombination catalysed by an integrase encoded by the recipient integron, and thus form a family of mobile elements that are more akin to integrating phage and plasmids than to transposons. Cassettes do not, in general, include a promoter and are transcribed from a promoter in the integron. The multi-component cassette-integron system is thus a natural cloning and expression system.
Closed for Business: The value of open innovation in developing countries

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Controlling Cu electroplating to prevent sporadic voiding in Cu3Sn

One reliability concern, when soldering to a Cu surface finish, is the sporadic mechanical degradation of solder joints due to the formation and growth of voids within the interfacial Cu3Sn intermetallic compound (IMC) layer and at its interface with the Cu pad structure. Excess organic impurity incorporation during Cu electroplating has been shown to cause this problem. The level of impurity incorporation is found to depend greatly on interactions between the plating additive chemistry and the plating process parameters. A general picture has been developed, based upon the parabolic adsorption behavior of organic molecules on metal electrodes in aqueous plating solutions as a function of the applied potential. Thus the propensity for voiding, in soldering and subsequent thermal aging, can be manipulated by varying a range of plating parameters. The mechanistic understanding required to devise practical control is outlined. Any remaining research required for the formulation of step-by-step process guidelines is identified.
Green supply chain management: an empirical investigation on the construction sector

Purpose Curtailing the adverse environmental impacts of the construction sector is one the major challenges of the twenty-first century. However, despite the significance of this problem, the limited efforts so far to tackle the negative impacts associated with this particular sector have been largely fragmented and disjointed. Given that the net green outcome of a construction project is the sum total of the efforts undertaken at the various supply chain stages (from the initial design to the end-of-life demolition) by different stakeholders, the green supply chain management (GSCM) approach is seen as a way forward toward streamlining the fragmented efforts at greening the sector. This forms the motivation of the present work, and this paper aims to develop, validate and apply a multi-dimensional GSCM framework for the construction sector. Design/methodology/approach A comprehensive GSCM assessment framework consisting of nine constructs (external and internal drivers; external and internal barriers; core and facilitating GSCM practices; economic, environmental and organizational performance implications) and their underlying factors was developed through an extensive literature review. Using data collected through a structured questionnaire, the framework was validated, and the relevance/appropriateness of each construct and its underlying factors, along with the hypothesized relationships between the constructs, were assessed separately for each supply chain stakeholder. Findings The findings confirm the validity and reliability of the constructs and their underlying factors as well as the assessment framework. In general, the implementation of green practices has had a positive impact on the environmental, economic and organizational performance for all stakeholders, while the extent of the green practices implemented depends on the relative strength of the drivers and barriers. Research limitations/implications This study fills a gap in the literature about applying/implementing GSCM in the construction sector. Practical implications The findings provide practitioners, policy makers and organizations associated with the UAE construction sector, as well as the construction sector in general, insight into all key aspects of GSCM. Originality/value A comprehensive survey-based assessment of GSCM for the construction sector has not been previously attempted and constitutes the novelty of this work.
Prediction of response to paroxetine and venlafaxine by serotonin-related genes in obsessive-compulsive disorder in a randomized, double-blind trial.

OBJECTIVE Serotonin reuptake inhibitors (SRIs) are the most effective pharmacologic treatment currently available for patients with obsessive-compulsive disorder (OCD). Still, up to 40% to 60% of OCD patients do not respond to SRI treatment. The purpose of the present study was to determine whether polymorphisms of the serotonin transporter (5-HTT), 5-HT1B, and 5-HT2A receptor genes affect the efficacy of SRI treatment in OCD. METHOD 91 outpatients with OCD according to DSM-IV criteria consented to the study and were randomly assigned in a 12-week, double-blind trial to receive dosages titrated upward to 300 mg/day of venlafaxine or 60 mg/day of paroxetine. Primary efficacy was assessed by the change from baseline on the Yale-Brown Obsessive Compulsive Scale (YBOCS), and response was defined as a > or = 25% reduction on the YBOCS. Responders and nonresponders were stratified according to 5-HTT, 5-HT1B, and 5-HT2A genotypes and differentiated in paroxetine-or venlafaxine-treated groups. The study was conducted from August 1998 to July 2002. RESULTS In the whole group, 64% of responders carried the S/L genotype of the 5-HTTLPR polymorphism (chi2 = 7.17, df = 2, p = .028). In the paroxetine-treated patients, the majority of responders carried the G/G genotype of the 5-HT2A polymorphism (chi2 = 8.66, df = 2, p = .013), whereas in the venlafaxine-treated patients, the majority of responders carried the S/L genotype of the 5-HTTLPR polymorphism (chi2 = 9.72, df = 2, p = .008). CONCLUSIONS The results of this study suggest that response in venlafaxine-treated OCD patients is associated with the S/L genotype of the 5-HTTLPR polymorphism and in paroxetine-treated OCD patients with the G/G genotype of the 5-HT2A polymorphism.
Optimal error Estimates for the Stokes and Navier–Stokes equations with slip–boundary condition

We consider a finite element discretization by the Taylor–Hood element for the stationary Stokes and Navier–Stokes equations with slip boundary condition. The slip boundary condition is enforced pointwise for nodal values of the velocity in boundary nodes. We prove optimal error estimates in the H 1 and L 2 norms for the velocity and pressure respectively.
Close Encounters of the Virtual Kind: Agents Simulating Copresence

ABSTRACT Results of a field study of an open-access collaborative virtual environment in actual use suggested that awareness of others significantly increases the level of presence experienced by participants. Given the importance of copresence, this paper argues that, in the absence of other human collaborators in a collaborative virtual environment, copresence can potentially be simulated using agent technology. A controlled experiment deploying a prototype embodied conversational agent was conducted to investigate the potential of such agents to simulate copresence. This paper briefly introduces the concepts of presence and copresence, summarizes experiences drawn from the field study, reports on the controlled experiment, and discusses its results. Results suggest that even limited copresence as provided by the current prototype agent is sufficient to help users feel presence in the environment.
Entrepreneurial behaviour and firm performance of ethiopian tour operators

In developing countries, entrepreneurship is often seen as one of the solutions for economic development through job creation in the private sector, particularly in resource constrained contexts such as sub-Saharan Africa. This PhD study focuses on the entrepreneurial behaviour of small business owners in their pursuit of profitable opportunities and its eventual implications on firm performance. The findings of this PhD thesis are based on primary data collected from 220 respondents who own and manage tour operating firms in Ethiopia where the entrepreneurial context is uncertain and dynamic. Based on the findings described and analysed in four empirical chapters, discovery and creation behaviour are dichotomous constructs, even though creation is the predominantly applied behaviour. Besides, creation and effectual behaviour have a positive impact on financial performance measures contributing to personal wealth creation, whereas causation behaviour is positively related to an increase in employment size contributing to job creation. This PhD study makes more contributions, from both a practical and theoretical perspective, to the field of entrepreneurship. The findings can also be applied in other African countries with similar cultural conditions and business environments to promote tourism development and success in Africa.
Procedural Tree Modeling with Guiding Vectors

We propose guiding vectors to augment graph‐based tree synthesis, in which trees are collections of least‐cost paths in a graph. Each node has an associated guiding vector; edges parallel to the guiding vector are cheap, but edges are more expensive when their orientation differs from the guiding vector. We further propose an incremental method for assigning guiding vectors over the graph, in which a node's guiding vector is an incremental rotation of that of its parent. We present a complete procedural system for tree modeling; our use of guiding vectors enables the graph‐based method to produce high‐quality tree models resembling a variety of real‐world tree species.
Complete Genome Sequence of a Mammalian Species-Infectious and -Pathogenic H6N5 Avian Influenza Virus without Evidence of Adaptation

ABSTRACT An H6N5 avian influenza virus (AIV) strain, designated A/aquatic bird/Korea/CN5/2009 (H6N5), was isolated from fecal swabs of aquatic birds in 2009, and surprisingly, it showed infectivity and pathogenicity in mammalian species without evidence of adaptation. In this study, we report the first complete genome sequence containing 3′ and 5′ noncoding regions (NCRs) of a mammalian species-infectious and pathogenic H6N5 AIV, which will help provide important insights into the molecular basis of pathogenesis, transmission, and evolution of AIV.