1,953 research outputs found

    Reputation in perturbed repeated games

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    The paper analyzes reputation effects in perturbed repeated games with discounting. If there is some positive prior probability that one of the players is committed to play the same (pure) action in every period, then this provides a lower bound for her equilibrium playoff in all Nash equilibria. This bound is tight and independent of what other types have positive probability. It is generally lower than Fudenberg and Levine's bound for games with a long-run player facing a sequence of short-run opponents. The bound cannot be improved by considering types playing finitely complicated history-dependent commitment strategies

    The Ebf1 knockout mouse and glomerular maturation

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    Mice deficient in the transcription factor early B-cell factor 1 (Ebf1) lack mature B lymphocytes but have additional phenotypes suggesting functions outside the hematopoietic system. Fretz et al. report that these mice also exhibit quantitative and qualitative developmental renal defects and develop progressive podocyte foot process effacement. The findings not only suggest that Ebf1 may be pivotal to the transcriptional podocyte network, but also illustrate the importance of distinguishing cell-autonomous and non-autonomous inputs to podocyte maturation and integrity

    Claudins in the renal collecting duct

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    The renal collecting duct fine-tunes urinary composition, and thereby, coordinates key physiological processes, such as volume/blood pressure regulation, electrolyte-free water reabsorption, and acid-base homeostasis. The collecting duct epithelium is comprised of a tight epithelial barrier resulting in a strict separation of intraluminal urine and the interstitium. Tight junctions are key players in enforcing this barrier and in regulating paracellular transport of solutes across the epithelium. The features of tight junctions across different epithelia are strongly determined by their molecular composition. Claudins are particularly important structural components of tight junctions because they confer barrier and transport properties. In the collecting duct, a specific set of claudins (Cldn-3, Cldn-4, Cldn-7, Cldn-8) is expressed, and each of these claudins has been implicated in mediating aspects of the specific properties of its tight junction. The functional disruption of individual claudins or of the overall barrier function results in defects of blood pressure and water homeostasis. In this concise review, we provide an overview of the current knowledge on the role of the collecting duct epithelial barrier and of claudins in collecting duct function and pathophysiology

    Assembling kidney tissues from cells: the long road from organoids to organs

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    The field of regenerative medicine has witnessed significant advances that can pave the way to creating de novo organs. Organoids of brain, heart, intestine, liver, lung and also kidney have been developed by directed differentiation of pluripotent stem cells. While the success in producing tissue-specific units and organoids has been remarkable, the maintenance of an aggregation of such units in vitro is still a major challenge. While cell cultures are maintained by diffusion of oxygen and nutrients, three- dimensional in vitro organoids are generally limited in lifespan, size, and maturation due to the lack of a vascular system. Several groups have attempted to improve vascularization of organoids. Upon transplantation into a host, ramification of blood supply of host origin was observed within these organoids. Moreover, sustained circulation allows cells of an in vitro established renal organoid to mature and gain functionality in terms of absorption, secretion and filtration. Thus, the coordination of tissue differentiation and vascularization within developing organoids is an impending necessity to ensure survival, maturation, and functionality in vitro and tissue integration in vivo. In this review, we inquire how the foundation of circulation is laid down during the course of organogenesis, with special focus on the kidney. We will discuss whether nature offers a clue to assist the generation of a nephro-vascular unit that can attain functionality even prior to receiving external blood supply from a host. We revisit the steps that have been taken to induce nephrons and provide vascularity in lab grown tissues. We also discuss the possibilities offered by advancements in the field of vascular biology and developmental nephrology in order to achieve the long-term goal of producing transplantable kidneys in vitro

    Relative Oscillation Theory, Weighted Zeros of the Wronskian, and the Spectral Shift Function

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    We develop an analog of classical oscillation theory for Sturm-Liouville operators which, rather than measuring the spectrum of one single operator, measures the difference between the spectra of two different operators. This is done by replacing zeros of solutions of one operator by weighted zeros of Wronskians of solutions of two different operators. In particular, we show that a Sturm-type comparison theorem still holds in this situation and demonstrate how this can be used to investigate the finiteness of eigenvalues in essential spectral gaps. Furthermore, the connection with Krein's spectral shift function is established.Comment: 26 page

    Psychological Health and Smoking in Young Adulthood

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    Introduction: Young adulthood is a critical time for the emergence of risk behaviors including smoking. Psychological health is associated with smoking, but studies rarely track both over time. We used longitudinal data to assess whether average patterns of psychological health influenced average patterns of smoking and whether short-term fluctuations in psychological health influenced fluctuations in smoking. Method: Young adults aged 18–30 from the Panel Study of Income Dynamics were followed from 2007 to 2013, and mean trajectories of smoking were modeled. Psychological health variables included ever having a mental health diagnosis and time-varying distress. Results: In regression models, individuals with poorer psychological health (higher distress or a diagnosis) were more likely to be smokers and to smoke greater number of cigarettes. The association of diagnosis with number of cigarettes smoked increased with age. Conclusions: Smoking-related interventions should target individuals with poorer psychological health, even if they have no formal mental health diagnosis

    General practitioners' views and experiences in caring for patients after sepsis:a qualitative interview study

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    Contains fulltext : 232438.pdf (Publisher’s version ) (Open Access)BACKGROUND: Patients surviving critical illnesses, such as sepsis, often suffer from long-term complications. After discharge from hospital, most patients are treated in primary care. Little is known how general practitioners (GPs) perform critical illness aftercare and how it can be improved. Within a randomised controlled trial, an outreach training programme has been developed and applied. OBJECTIVES: The aim of this study is to describe GPs' views and experiences of caring for postsepsis patients and of participating a specific outreach training. DESIGN: Semistructured qualitative interviews. SETTING: 14 primary care practices in the metropolitan area of Berlin, Germany. PARTICIPANTS: 14 GPs who had participated in a structured sepsis aftercare programme in primary care. RESULTS: Themes identified in sepsis aftercare were: continuity of care and good relationship with patients, GP's experiences during their patient's critical illness and impact of persisting symptoms. An outreach education as part of the intervention was considered by the GPs to be acceptable, helpful to improve knowledge of the management of postintensive care complications and useful for sepsis aftercare in daily practice. CONCLUSIONS: GPs provide continuity of care to patients surviving sepsis. Better communication at the intensive care unit-GP interface and training in management of long-term complications of sepsis may be helpful to improve sepsis aftercare. TRIAL REGISTRATION NUMBER: ISRCTN61744782

    Structural basis of gene regulation by the Grainyhead/CP2 transcription factor family

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    Grainyhead (Grh)/CP2 transcription factors are highly conserved in multicellular organisms as key regulators of epithelial differentiation, organ development and skin barrier formation. In addition, they have been implicated as being tumor suppressors in a variety of human cancers. Despite their physiological importance, little is known about their structure and DNA binding mode. Here, we report the first structural study of mammalian Grh/CP2 factors. Crystal structures of the DNA-binding domains of grainyhead-like (Grhl) 1 and Grhl2 reveal a closely similar conformation with immunoglobulin-like core. Both share a common fold with the tumor suppressor p53, but differ in important structural features. The Grhl1 DNA-binding domain binds duplex DNA containing the consensus recognition element in a dimeric arrangement, supporting parsimonious target-sequence selection through two conserved arginine residues. We elucidate the molecular basis of a cancer-related mutation in Grhl1 involving one of these arginines, which completely abrogates DNA binding in biochemical assays and transcriptional activation of a reporter gene in a human cell line. Thus, our studies establish the structural basis of DNA target-site recognition by Grh transcription factors and reveal how tumor-associated mutations inactivate Grhl proteins. They may serve as points of departure for the structure-based development of Grh/CP2 inhibitors for therapeutic applications

    Does Human Papillomavirus Affect Pregnancy Outcomes? An Analysis of Hospital Data 2012-2014

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    Objective: To estimate the rate of Human Papillomavirus among pregnant women and its impact on the pregnancy outcomes. Study design: This was a retrospective cohort study of women who sought prenatal care and later delivered at the Nebraska Medical Center from 2012-2014. Human Papillomavirus infection was based on a cytological cervicovaginal diagnosis (Pap test) report. Bivariate and multivariable analyzes were performed using SAS 9.3. Results: Of the total sample size of 4824 women, 221 (4.4%) were HPV-positive. Women with Human Papillomavirus infection had increased risk of preeclampsia (adjusted OR: 2.83 95% CI: 1.28-6.26) and were also 1.8 times more likely to deliver preterm compared to women with no Human Papillomavirus infection (adjusted OR: 1.8, 95% CI: 1.15-2.83). Additionally, Human Papillomavirus infection was found to be significantly associated with low birth weight (adjusted OR: 2.58; 95% CI: 1.56-4.27). Conclusions: Although the prevalence of Human Papillomavirus infection was relatively low in this sample, the study clearly indicated a positive association between Human Papillomavirus infection and adverse pregnancy outcomes. Further research is needed to understand the impact of Human Papillomavirus infection in a larger and diverse sample of women. Also, a closer follow-up of pregnant women affected by Human Papillomavirus infection may be warranted

    Outskirts of Distant Galaxies In Absorption

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    QSO absorption spectroscopy provides a sensitive probe of both the neutral medium and diffuse ionized gas in the distant Universe. It extends 21cm maps of gaseous structures around low-redshift galaxies both to lower gas column densities and to higher redshifts. Combining galaxy surveys with absorption-line observations of gas around galaxies enables comprehensive studies of baryon cycles in galaxy outskirts over cosmic time. This Chapter presents a review of the empirical understanding of the cosmic neutral gas reservoir from studies of damped Lya absorbers (DLAs). It describes the constraints on the star formation relation and chemical enrichment history in the outskirts of distant galaxies from DLA studies. A brief discussion of available constraints on the ionized circumgalactic gas from studies of lower column density Lya absorbers and associated ionic absorption transitions is presented at the end.Comment: 45 pages, 7 figures, invited review, Book chapter in "Outskirts of Galaxies", Eds. J. H. Knapen, J. C. Lee and A. Gil de Paz, Astrophysics and Space Science Library, Springer, in pres
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