Miracle-dz/UniFAR-FTUs huggingface dataset:
Understanding efflux in Gram-negative bacteria: opportunities for drug discovery

Introduction: Bacteria evolved an arsenal of mechanisms to deal with toxic compounds and metabolic stresses, including antimicrobial agents. Efflux pumps are major players in the multidrug resistance of Gram-negative bacteria and pose major hurdles in the drug discovery process. However, recent advances in our understanding of efflux in these bacteria provide opportunities and assets for drug discovery. Areas covered: This review provides an overview of drug efflux in Gram-negative bacteria and its role in antimicrobial resistance, stress responses and other biological processes such as biofilm formation, and virulence. The discussion includes comments on the significance of synergy between a low-permeability outer membrane and efflux, notably the role of porins and lipopolysaccharide. The author then summarizes efforts aimed at inhibiting efflux pumps as a means to extend the utility of clinically useful antibiotics. This includes highlights of identification and characterization of small molecule efflux pump inhibitors (EPIs) from natural and synthetic sources, as well as novel strategies such as gene silencing and inhibitory antibodies. Expert opinion: Options for treating infections caused by multidrug-resistant bacteria are limited. Given the attractiveness of the therapeutic potential of efflux pump inhibition, further studies exploring novel strategies to interfere with efflux pump expression and function are warranted. This includes rational EPI design facilitated by pump structure information, exploitation of genetically defined efflux-proficient and efflux-compromised strain panels and non-traditional approaches such as pump inhibition by gene silencing, antibodies and perhaps even phage.
Efficient coordinations of large-scale elastic loads with MCP and PSP auction mechanisms

In this paper, we propose a distributed method to coordinate large-scale elastic load units with auction mechanisms which have been widely applied in resource allocation problems. Distinct from the progressive second price (PSP) auction mechanism, under the market clearing price (MCP) auction mechanism, the incentive compatibility does not hold in general but holds with respect to the efficient bid profiles of other agents. We observe that the difference between the payments under PSP and MCP mechanisms vanishes as the population size goes to infinity and consequently show that the efficient bid strategy is an epsilon-Nash equilibrium in MCP auction games with epsilon converges to zero as the population size goes to infinity. As another key result developed in the paper we further show that the efficient bid strategy is an epsilon-Nash equilibrium of auction game systems with epsilon is on the second order of the second derivative of the generation cost which goes to zero as the population size goes to infinity in scalable systems.
Education for strategic environmental behavior

This article reviews four bodies of research that shed light on how to promote active care for the environment in children and youth: research on sources of proenvironmental behavior, socialization for democratic skills and values, the development of a personal sense of competence, and the development of collective competence. The article begins with an overview of studies of formative childhood experiences reported by environmental activists and educators, followed by correlational and experimental studies with young people regarding factors associated with their taking action for the environment. Because behaviors with the largest potential benefits for the environment require political engagement, the article also reviews experiences associated with young people’s interest and engagement in public issues. Action for the environment in the home or in public arena like schools and communities requires a personal sense of competence and a sense of collective competence, or confidence in one’s ability to achieve goals by working with a group. Therefore experiences that promote the development of these assets are summarized as well. The conclusion compares major findings in these different fields and discusses implications for environmental educators.
Early Detection and Successful Treatment of Drug-Induced Pneumonitis with Corticosteroids

A 69-year-old patient with non-small cell lung cancer developed pneumonitis with the use of the chemotherapeutic drugs gemcitabine, paclitaxel, and vinorelbine. He developed progressively worsening dyspnea, fevers, chills, and night sweats three weeks after initiation of chemotherapy treatment with no improvement with antibiotics. Bronchoscopic lung biopsy and endotracheal cultures were negative. Four weeks after the onset of symptoms, chest computed tomography scan showed a ground glass appearance of the lung parenchyma bilaterally consistent with pneumonitis. Gemcitabine is a nucleoside analog with activity against solid tumors, including breast and non-small cell lung cancers. Pneumonitis is a rare and potentially deadly complication of gemcitabine. Early treatment with corticosteroids leads to a complete resolution of this patients pneumonitis. Gemcitabine was discontinued and his chemotherapeutic regimen was changed to include paclitaxel, vinorelbine, and topotecan with no recurrence of pneumonitis. Pneumonitis should be included in the differential diagnosis of dyspnea in patients undergoing gemcitabine-based chemotherapy.
An investigation into the suitability of a commercial real-time PCR assay to screen for Taylorella equigenitalis in routine prebreeding equine genital swabs.

REASONS FOR PERFORMING STUDY Standard bacteriological methods for identifying Taylorella equigenitalis in cervical smears are time consuming. Therefore, a more rapid real-time PCR assay was evaluated for its suitability in screening swabs. OBJECTIVE To compare the results of a commercially available real-time PCR assay with routine microbiological culture for the identification of T. equigenitalis, the causative organism of contagious equine metritis, in equine genital swab samples, under 'field trial' conditions. MATERIALS AND METHODS Routine prebreeding genital swabs (n=2072) collected from Thoroughbred mares and stallions during 2009 were examined together with stored T. equigenitalis positive material. Swabs were cultured for T. equigenitalis using standard microbiological techniques. Bacterial lysates were isolated from the swabs and examined for the presence of a 16S DNA fragment of T. equigenitalis, using a commercial multiplex real-time PCR assay system. RESULTS There was complete concordance between positive and negative results obtained by the 2 methods. Real-time PCR also detected T. equigenitalis DNA from swabs that were negative using standard microbiological culture after 6 months' storage at +4 degrees C but from which T. equigenitalis had been isolated following collection. The sensitivities of real-time PCR and bacterial culture were both 10(-3) (equivalent to 3 colony-forming units). CONCLUSION AND CLINICAL RELEVANCE Routine bacterial culture of T. equigenitalis requires an incubation period of not less than 7 days before a conclusive negative result can be obtained, whereas bacterial extraction and real-time PCR assay can be completed in less than 6 h. The commercially-available PCR assay tested provided a rapid and reliable method for the identification of T. equigenitalis from equine genital swabs and could be usefully employed for the screening of mares and stallions for preseason Horserace Betting Levy Board (HBLB) Code of Practice and in other situations such as for bloodstock sales screening requirements, overcoming the current delays imposed by bacterial culture requirements. Its use could be quality assured by the existing HBLB biannual testing scheme for designated laboratories.
A Two Sector Endogenous Growth Model with Two Accumulating Factors- Implementing Trade

This paper is about trade in an endogenous growth model with accumulation of physical and human capital. The convergence to the ray of steady states is proved for two different development stages of similar small countries. Free trade benefits the education sector of a relatively less developed country and thus stimulates the human capital accumulation. Whereas a technological more developed country declines in favour of the world market. \\ Only if the small country is relatively less developed then there is a convergence to the balanced growth path of the world market and the country improves its situation. Without any trade policy a less developed country will lose necessary factors of production. A more developed country deals with stagnation or even fluctuation of its development stage.
An optimal control approach to clock synchronization

Algorithms following the peer-to-peer Precision Time Protocol (PTP) specified by the IEEE 1588 standard achieve synchronization of distributed clocks by propagating the timing information of a preselected master clock throughout the entire network. Based on this noisy timing information, each slave clock tries to follow as closely as possible the master time. In this work we formulate clock synchronization as a stochastic estimation-control problem. A two dimensional LQG controller is derived which produces an optimal reconstruction of the master time at each slave in the sense of minimizing the mean square error of the estimated master counter and frequency. Owing to its specific structure, the LQG controller does not violate the transparent clock concept. The performance of the proposed controller is verified by simulations.
Purification of a calf thymus DNA-dependent adenosinetriphosphatase that prefers a primer-template junction effector.

A purification procedure has been developed that resolves four chromatographically distinct DNA-dependent ATPase activities from calf thymus tissue. One of these activities has been purified to a nearly homogeneous protein, as judged by polyacrylamide gel electrophoresis. This protein has a specific activity of 18 mumol of ATP hydrolyzed per minute per milligram of protein and is active only in the presence of a DNA effector. The DNA-dependent ATPase activity is greatest in the presence of DNA containing a 3'-hydroxyl primer-template junction with a segment of adjacent single strand, i.e., a DNA polymerase substrate. Primer-template effectors that have had the 3'-hydroxyl group eliminated by the addition of a dideoxyribonucleotide are less active as cofactors for ATP hydrolysis than effectors which retain the 3'-hydroxyl group. Other DNAs can serve as cofactors, but with a reduced rate of ATP hydrolysis. DNA cofactors which are single stranded are much more effective at promoting ATPase activity than completely double-stranded cofactors, although the effectiveness of single-stranded DNA decreases as the length of the oligonucleotide decreases. An RNA/DNA hybrid does not promote ATPase activity. These data suggest that ATPase A may be involved in the recognition of primer-template junctions and the elongation phase of DNA synthesis.
Do hospital treatments represent a ‘teachable moment’ for quitting smoking? A study from a stage-theoretical perspective

Hospital treatments are assumed to be a ‘teachable moment’. This phenomenon, however, is only poorly conceptualised and untested. A stage-theoretical perspective implies that a cueing event such as hospital treatments is a teachable moment if a stage progression, change of cognitions, or both occur. This concept is examined in a cross-sectional study by comparing smokers in two treatment settings, an emergency department (ED) and inpatient treatment after elective surgery, with smokers in a control setting. Setting differences were hypothesised in stage distribution, and levels of and stage differences in social-cognitive factors under control for possible confounders. Stage, social-cognitive factors and possible confounders were assessed in 185 ED smokers, 193 inpatient smokers and 290 control smokers. Compared to control smokers, ED and inpatient smokers were in higher stages; they perceived fewer risks and cons; inpatient smokers reported more concrete plans. Stage differences in self-efficacy among ED and inpatient smokers differed from those among control smokers, but the former corresponded more strongly to the theoretical stage assumptions. The results suggest that hospital treatments lead to a stage progression and change of corresponding cognitions, and thus represent a ‘teachable moment’. Stage-matched interventions should be provided but consider differences in cognitions to be effective.
Technological aspects of hospital communication challenges: an observational study.

OBJECTIVE To gain insights into how technological communication tools impact effective communication among clinicians, which is critical for patient safety. DESIGN This multi-site observational study analyzes inter-clinician communication and interaction with information technology, with a focus on the critical process of patient transfer from the Emergency Department to General Internal Medicine. SETTING Mount Sinai Hospital, Sunnybrook Health Sciences Centre and Toronto General Hospital. PARTICIPANTS At least five ED and general internal medicine nurses and physicians directly involved in patient transfers were observed on separate occasions at each institution. INTERVENTIONS N/A. MAIN OUTCOME MEASURES N/A. RESULTS The study provides insight into clinician workflow, evaluates current hospital communication systems and identifies key issues affecting communication: interruptions, issues with numeric pagers, lack of integrated communication tools, lack of awareness of consultation status, inefficiencies related to the paper chart, unintuitive user interfaces, mixed use of electronic and paper systems and lack of up-to-date contact information. It also identifies design trade-offs to be negotiated: synchronous communication vs. reducing interruptions, notification of patient status vs. reducing interruptions and speed vs. quality of handovers. CONCLUSIONS The issues listed should be considered in the design of new technology for hospital communications.
Increased resistance of crosslinked cornea against enzymatic digestion

Purpose. Collagen-crosslinking using combined riboflavin/UVA treatment has been developed by us as a new treatment for keratoconus by stiffening the collagenous matrix. Recently, we have started to use the same method for the treatment of corneal ulcers. The aim of the present study was to evaluate the influence of the crosslinking treatment on the resistance of the cornea against enzymatic degradation. Methods. 60 enucleated porcine eyes were treated with the photosensitizer riboflavin and UVA-irradiation (370 nm; irradiance of 1, 2 or 3 mW/cm2) for 30 minutes and compared with 20 untreated control eyes. After crosslinking treatment, the corneal buttons were trephined and exposed to pepsin, trypsin and collagenase solutions. The extent of the corneal digestion was monitored daily. Selected cases were examined by light microscopy. Results. The corneal buttons crosslinked with riboflavin/UVA at 3 mW/cm2 were dissolved only by day 13 following pepsin digestion and by day 14 following collagenase treatment versus 6 days in the untreated control corneas. Digestion by trypsin was observed on day 5 in buttons crosslinked at 3 mW/cm2 compared to day 2 in the control corneas. Microscopically, a prolonged preservation especially of the anterior portion of the crosslinked corneas could be demonstrated. Conclusions. Photochemical crosslinking of the cornea using riboflavin and UVA results in a markedly increased resistance versus collagen digesting enzymes. The findings support the use of the new method in the treatment of corneal ulcers.
Determinants of level of cloud computing adoption in small and medium enterprises in Nairobi county, Kenya

Cloud computing offers a new way for business agility and supports a faster time to market by offering ready-to consume cloud-based IT services. However, in Kenya, despite of the government efforts at increasing the competitiveness of SMEs through ICT by enhancing internet infrastructure, lowering cost among others, and adoption of cloud computing has not been satisfactory among SMEs. The study purpose of the paper was to establish the determinants of cloud computing adoption. The Innovation Diffusion Theory provided a theoretical basis for the study. The study adopted explanatory research design. Cluster sampling was employed to select a sample of 398 Small Medium Enterprises in various industries within Nairobi County. A structured questionnaire was used to collect the data. Data was analyzed using multiple regression model with aid of Statistical Package for Social Science (SPSS) and included descriptive and inferential analysis. Results from regression model showed that technological context exhibited a positive and significant effect on the level of adoption of cloud computing (β1= 0.414, ρ<0.05) and organization context (β2= 0.262, ρ<0.05) had a positive and significant effect on the level of adoption of cloud computing. However, environmental context had no significant effect on the level of adoption of cloud computing (β3= -0.033, ρ>0.05. The main implication of the study offers great value to research community,
A pericyte‐derived angiopoietin‐1 multimeric complex induces occludin gene expression in brain capillary endothelial cells through Tie‐2 activation in vitro

Although tight‐junctions (TJs) at the blood–brain barrier (BBB) are important to prevent non‐specific entry of compounds into the CNS, molecular mechanisms regulating TJ maintenance remain still unclear. The purpose of this study was therefore to identify molecules, which regulate occludin expression, derived from astrocytes and pericytes that ensheathe brain microvessels by using conditionally immortalized adult rat brain capillary endothelial (TR‐BBB13), type II astrocyte (TR‐AST4) and brain pericyte (TR‐PCT1) cell lines. Transfilter co‐culture with TR‐AST4 cells, and exposure to conditioned medium of TR‐AST4 cells (AST‐CM) or TR‐PCT1 cells (PCT‐CM) increased occludin mRNA in TR‐BBB13 cells. PCT‐CM‐induced occludin up‐regulation was significantly inhibited by an angiopoietin‐1‐neutralizing antibody, whereas the up‐regulation by AST‐CM was not. Immunoprecipitation and western blot analyses confirmed that multimeric angiopoietin‐1 is secreted from TR‐PCT1 cells, and induces occludin mRNA, acting through tyrosine phosphorylation of Tie‐2 in TR‐BBB13 cells. A fractionated AST‐CM study revealed that factors in the molecular weight range of 30–100 kDa led to occludin induction. Conversely, occludin mRNA was reduced by transforming growth factor β1, the mRNA of which was up‐regulated in TR‐AST4 cells following hypoxic treatment. In conclusion, in vitro BBB model studies revealed that the pericyte‐derived multimeric angiopoietin‐1/Tie‐2 pathway induces occludin expression.
Services for Reducing the Duration of Hospital Care for Acute Stroke Patients

BACKGROUND Stroke patients conventionally receive a substantial part of their rehabilitation in hospital. Services have now been developed which offer patients in hospital an early discharge with rehabilitation at home (early supported discharge (ESD)). OBJECTIVES To establish the effects and costs of ESD services compared with conventional services. SEARCH STRATEGY We searched the Cochrane Stroke Group's trials register (last searched August 2004) and obtained further information from individual trialists. SELECTION CRITERIA Randomised controlled trials recruiting stroke patients in hospital to receive either conventional care or any service intervention which has provided rehabilitation and support in a community setting with an aim of reducing the duration of hospital care. DATA COLLECTION AND ANALYSIS Two reviewers scrutinised trials and categorised them on their eligibility. Standardised individual patient data was then sought from the primary trialists. Results were analysed for all trials and for subgroups of patients and services; in particular whether the intervention was provided by a co-ordinated multidisciplinary team (co-ordinated ESD team) or not. MAIN RESULTS Outcome data are currently available for 11 trials (1597 patients). Patients tended to be a selected elderly group with moderate disability. The ESD group showed significant reductions (P < 0.0001) in the length of hospital stay equivalent to approximately 8 days. Overall, the odds ratios (OR) (95% confidence interval (CI)) for death, death or institutionalisation, death or dependency at the end of scheduled follow up were OR 0.90, 95% CI 0.64 to 1.27, P = 0.56, OR 0.74, 95% CI 0.56 to 0.96, P = 0.02 and OR 0.79, 95% CI 0.64 to 0.97, P = 0.02, respectively. The greatest benefits were seen in the trials evaluating a co-ordinated ESD team and in stroke patients with mild-moderate disability. Improvements were also seen in patients' extended activities of daily living scores (standardised mean difference 0.12, 95% CI 0.00 to 0.25, P = 0.05) and satisfaction with services (OR 1.60, 95% CI 1.08 to 2.38, P = 0.02) but no statistically significant differences were seen in carers' subjective health status, mood or satisfaction with services. AUTHORS' CONCLUSIONS Appropriately resourced ESD services provided for a selected group of stroke patients can reduce long term dependency and admission to institutional care as well as reducing the length of hospital stay. No adverse impact was observed on the mood or subjective health status of patients or carers.
Excimer laser-induced hydroxyl radical formation and keratocyte death in vitro.

PURPOSE To characterize the type of reactive oxygen species (ROS) produced by excimer photoablation of aqueous solutions and to show the effects of ROS and antioxidants on corneal stromal cells in vitro. METHODS Electron spin-resonance spectroscopy was performed using the spin-trapping agent 5,5-dimethyl-1-pyrroline N-oxide (DMPO) for the detection of the superoxide anion and the hydroxyl radical in an acellular DMPO solution irradiated with the excimer laser. Hydroxyl radicals were produced by the Fenton reaction in vitro by the mixture of hydrogen peroxide and ferrous iron (Fe2+), and the effects on cultured corneal fibroblasts were observed by fluorescent microscopy using the cell death marker, propidium iodide (PI) and TdT-mediated dUTP nick-end labeling (TUNEL). RESULTS Excimer photoablation of a 1% DMPO solution produced a species-specific spin-trapping adduct for the hydroxyl radical ('OH), but not for the superoxide anion or other unidentified free radical. The signals were inhibited dose dependently by the hydroxyl radical scavenger dimethylsulfoxide (DMSO) and an L-ascorbic acid analogue, EPCK-1. The production of *OH in the supernatant of cultured rabbit corneal fibroblasts by the Fenton reaction caused an increase in PI (+) and TUNEL (+) cells by 90 minutes, which was significantly inhibited by the addition of DMSO. CONCLUSIONS Hydroxyl radicals may be partly responsible for stromal fibroblast cell apoptosis after excimer photoablation.