The yersiniabactin-associated ATP binding cassette proteins YbtP and YbtQ enhance Escherichia coli fitness during high-titer cystitis

The Yersinia high-pathogenicity island (HPI) is common to multiple virulence strategies used by Escherichia coli strains associated with urinary tract infection (UTI). Among the genes in this island are ybtP and ybtQ, encoding distinctive ATP binding cassette (ABC) proteins associated with iron(III)-yersiniabactin import in Yersinia pestis. In this study, we compared the impact of ybtPQ on a model E. coli cystitis strain during in vitro culture and experimental murine infections. A ybtPQ-null mutant exhibited no growth defect under standard culture conditions, consistent with nonessentiality in this background. A growth defect phenotype was observed and genetically complemented in vitro during iron(III)-yersiniabactin-dependent growth. Following inoculation into the bladders of C3H/HEN and C3H/HeOuJ mice, this strain exhibited a profound, 10(6)-fold competitive infection defect in the subgroup of mice that progressed to high-titer bladder infections. These results identify a virulence role for YbtPQ in the highly inflammatory microenvironment characteristic of high-titer cystitis. The profound competitive defect may relate to the apparent selection of Yersinia HPI-positive E. coli in uncomplicated clinical UTIs

Modeling Coastal and Estuarine Processes for Coastal Flood Management and Erosion Protection against Storms

Source: ICHE Conference Archive - https://mdi-de.baw.de/icheArchiv

Enterococcal biofilm formation and virulence in an optimized murine model of foreign body-associated urinary tract infections

Catheter-associated urinary tract infections (CAUTIs) constitute the majority of nosocomial UTIs and pose significant clinical challenges. Enterococcal species are among the predominant causative agents of CAUTIs. However, very little is known about the pathophysiology of Enterococcus-mediated UTIs. We optimized a murine model of foreign body-associated UTI in order to mimic conditions of indwelling catheters in patients. In this model, the presence of a foreign body elicits major histological changes and induces the expression of several proinflammatory cytokines in the bladder. In addition, in contrast to naïve mice, infection of catheter-implanted mice with Enterococcus faecalis induced the specific expression of interleukin 1β (IL-1β) and macrophage inflammatory protein 1α (MIP-1α) in the bladder. These responses resulted in a favorable niche for the development of persistent E. faecalis infections in the murine bladders and kidneys. Furthermore, biofilm formation on the catheter implant in vivo correlated with persistent infections. However, the enterococcal autolytic factors GelE and Atn (also known as AtlA), which are important in biofilm formation in vitro, are dispensable in vivo. In contrast, the housekeeping sortase A (SrtA) is critical for biofilm formation and virulence in CAUTIs. Overall, this murine model represents a significant advance in the understanding of CAUTIs and underscores the importance of urinary catheterization during E. faecalis uropathogenesis. This model is also a valuable tool for the identification of virulence determinants that can serve as potential antimicrobial targets for the treatment of enterococcal infections

Antipsychotic Prescribing Pathways, Polypharmacy, and Clozapine Use in Treatment of Schizophrenia

Objective To ensure optimal care for patients with schizophrenia, antipsychotic medications must be appropriately prescribed and used. Therefore, the primary objectives of this study were to identify and describe pathways for antipsychotic prescribing, assess the consistency of observed pathways with treatment guidelines, and describe variability across facilities. Methods Data from Veterans Affairs administrative data sets from fiscal year (FY) 2003 to FY 2007 were gathered for analysis in this retrospective cohort study of antipsychotic prescribing pathways among 13 facilities across two regional networks. Patients with a new episode of care for schizophrenia or schizoaffective disorder in FY 2005 were identified, and antipsychotic prescribing history was obtained for two years before and after the index diagnosis. Demographic characteristics and distribution of comorbidities were assessed. Median medical center rates of polypharmacy were calculated and compared with Fisher’s exact test. Results Of 1,923 patients with a new episode of schizophrenia care, 1,003 (52%) had complete data on prescribing pathways. A majority (74%) of patients were prescribed antipsychotic monotherapy, and 19% received antipsychotic polypharmacy. Of patients receiving antipsychotic polypharmacy, 65% began polypharmacy within 90 days of starting any antipsychotic treatment. There was a fourfold difference in polypharmacy across facilities. Antipsychotic polypharmacy was not associated with geographic location or medical center patient volume. Clozapine utilization was low (0%–2%). Conclusions Retrospective examination of longitudinal prescribing patterns identified multiple antipsychotic prescribing pathways. Although most patients received guideline-concordant care, antipsychotic polypharmacy was commonly used as initial treatment, and there was substantial variability among facilities. Study findings suggest the utility of secondary data to assess treatment adaptation or switching for practical clinical trials

Solutions to the R_b, R_c and alpha_s puzzles by Vector Fermions

We propose two minimal extensions of Standard Model, both of which can easily accommodate the recent puzzling observations about the excess in $R_b$, the deficit in $R_c$ and the discrepancy in the low energy and high energy determinations of $\alpha_{s}$. Each model requires three additional heavy vectorial fermions in order to resolve the puzzles. The current phenomenological constraints and the new potential phenomena are also discussed.Comment: 12 pages, in LaTeX, postscript file also appear http://www.uic.edu/~keung/pub/rbrc.p

Escherichia coli biofilms have an organized and complex extracellular matrix structure

Bacterial biofilms are ubiquitous in nature, and their resilience is derived in part from a complex extracellular matrix that can be tailored to meet environmental demands. Although common developmental stages leading to biofilm formation have been described, how the extracellular components are organized to allow three-dimensional biofilm development is not well understood. Here we show that uropathogenic Escherichia coli (UPEC) strains produce a biofilm with a highly ordered and complex extracellular matrix (ECM). We used electron microscopy (EM) techniques to image floating biofilms (pellicles) formed by UPEC. EM revealed intricately constructed substructures within the ECM that encase individual, spatially segregated bacteria with a distinctive morphology. Mutational and biochemical analyses of these biofilms confirmed curli as a major matrix component and revealed important roles for cellulose, flagella, and type 1 pili in pellicle integrity and ECM infrastructure. Collectively, the findings of this study elucidated that UPEC pellicles have a highly organized ultrastructure that varies spatially across the multicellular community

The StarCraft Multi-Agent Challenge

In the last few years, deep multi-agent reinforcement learning (RL) has become a highly active area of research. A particularly challenging class of problems in this area is partially observable, cooperative, multi-agent learning, in which teams of agents must learn to coordinate their behaviour while conditioning only on their private observations. This is an attractive research area since such problems are relevant to a large number of real-world systems and are also more amenable to evaluation than general-sum problems. Standardised environments such as the ALE and MuJoCo have allowed single-agent RL to move beyond toy domains, such as grid worlds. However, there is no comparable benchmark for cooperative multi-agent RL. As a result, most papers in this field use one-off toy problems, making it difficult to measure real progress. In this paper, we propose the StarCraft Multi-Agent Challenge (SMAC) as a benchmark problem to fill this gap. SMAC is based on the popular real-time strategy game StarCraft II and focuses on micromanagement challenges where each unit is controlled by an independent agent that must act based on local observations. We offer a diverse set of challenge maps and recommendations for best practices in benchmarking and evaluations. We also open-source a deep multi-agent RL learning framework including state-of-the-art algorithms. We believe that SMAC can provide a standard benchmark environment for years to come. Videos of our best agents for several SMAC scenarios are available at: https://youtu.be/VZ7zmQ_obZ0

Binding Transition in Quantum Hall Edge States

We study a class of Abelian quantum Hall (QH) states which are topologically unstable (T-unstable). We find that the T-unstable QH states can have a phase transition on the edge which causes a binding between electrons and reduces the number of gapless edge branches. After the binding transition, the single-electron tunneling into the edge gains a finite energy gap, and only certain multi-electron co-tunneling (such as three-electron co-tunneling for $\nu=9/5$ edges) can be gapless. Similar phenomenon also appear for edge state on the boundary between certain QH states. For example edge on the boundary between $\nu=2$ and $\nu=1/5$ states only allow three-electron co-tunneling at low energies after the binding transition.Comment: 4 pages, RevTeX, 1 figur

Determination of band alignment in the single layer MoS2/WSe2 heterojunction

The emergence of transition metal dichalcogenides (TMDs) as 2D electronic materials has stimulated proposals of novel electronic and photonic devices based on TMD heterostructures. Here we report the determination of band offsets in TMD heterostructures by using microbeam X-ray photoelectron spectroscopy ({\mu}-XPS) and scanning tunneling microscopy/spectroscopy (STM/S). We determine a type-II alignment between $\textrm{MoS}_2$ and $\textrm{WSe}_2$ with a valence band offset (VBO) value of 0.83 eV and a conduction band offset (CBO) of 0.76 eV. First-principles calculations show that in this heterostructure with dissimilar chalcogen atoms, the electronic structures of $\textrm{WSe}_2$ and $\textrm{MoS}_2$ are well retained in their respective layers due to a weak interlayer coupling. Moreover, a VBO of 0.94 eV is obtained from density functional theory (DFT), consistent with the experimental determination.Comment: ^ These authors contributed equally. *Corresponding author E-mail: [email protected], [email protected] 20 pages, 4 figures in main tex

A new era for studies on cross-Strait relations: introduction

After more than half a century’s separation, interaction between China and Taiwan has increased and has progressively changed from a politico-economic interaction to a more civic interaction. Scholars working on cross-Strait relations have recently begun to pay attention to the civic influence of Taiwanese businesses on the relationship. Some emphasize the importance of sub-governmental interactions in the process of cross-Strait integration. Others assert that Taiwanese businesses can exercise economic leverage to constrain the Chinese government in cross-Strait policymaking. These scholars stress bottom–up processes by observing current phenomena, then deducing the emerging pattern of cross-Strait relations that may be influenced by business activities. Taking account of changing trends in scholarly discussions of the cross-Strait relationship, this special issue of China Information presents current research in this field. Unlike studies on top–down processes that affect political and economic interactions between China and Taiwan, several contributions in the special issue highlight bottom–up mechanisms affecting such interactions by examining the identity of Taiwanese businesspeople and migrants, as well as the activities and implications of Taiwanese charitable organizations operating in China. This issue focuses not only on the impact of China on Taiwan, but also the impact of Taiwanese investments, migrants, and exports on Chinese society