University of Wisconsin-Madison

About: University of Wisconsin-Madison is a education organization based out in Madison, Wisconsin, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 108707 authors who have published 237594 publications receiving 11883575 citations.

Asymmetric and symmetric stem-cell divisions in development and cancer

Abstract: Much has been made of the idea that asymmetric cell division is a defining characteristic of stem cells that enables them to simultaneously perpetuate themselves (self-renew) and generate differentiated progeny. Yet many stem cells can divide symmetrically, particularly when they are expanding in number during development or after injury. Thus, asymmetric division is not necessary for stem-cell identity but rather is a tool that stem cells can use to maintain appropriate numbers of progeny. The facultative use of symmetric or asymmetric divisions by stem cells may be a key adaptation that is crucial for adult regenerative capacity.

Effects of Oral Tolvaptan in Patients Hospitalized for Worsening Heart Failure: The EVEREST Outcome Trial

Abstract: ContextVasopressin mediates fluid retention in heart failure. Tolvaptan, a vasopressin V2 receptor blocker, shows promise for management of heart failure.ObjectiveTo investigate the effects of tolvaptan initiated in patients hospitalized with heart failure.Design, Setting, and ParticipantsThe Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST), an event-driven, randomized, double-blind, placebo-controlled study. The outcome trial comprised 4133 patients within 2 short-term clinical status studies, who were hospitalized with heart failure, randomized at 359 North American, South American, and European sites between October 7, 2003, and February 3, 2006, and followed up during long-term treatment.InterventionWithin 48 hours of admission, patients were randomly assigned to receive oral tolvaptan, 30 mg once per day (n = 2072), or placebo (n = 2061) for a minimum of 60 days, in addition to standard therapy.Main Outcome MeasuresDual primary end points were all-cause mortality (superiority and noninferiority) and cardiovascular death or hospitalization for heart failure (superiority only). Secondary end points included changes in dyspnea, body weight, and edema.ResultsDuring a median follow-up of 9.9 months, 537 patients (25.9%) in the tolvaptan group and 543 (26.3%) in the placebo group died (hazard ratio, 0.98; 95% confidence interval [CI], 0.87-1.11; P = .68). The upper confidence limit for the mortality difference was within the prespecified noninferiority margin of 1.25 (P<.001). The composite of cardiovascular death or hospitalization for heart failure occurred in 871 tolvaptan group patients (42.0%) and 829 placebo group patients (40.2%; hazard ratio, 1.04; 95% CI, 0.95-1.14; P = .55). Secondary end points of cardiovascular mortality, cardiovascular death or hospitalization, and worsening heart failure were also not different. Tolvaptan significantly improved secondary end points of day 1 patient-assessed dyspnea, day 1 body weight, and day 7 edema. In patients with hyponatremia, serum sodium levels significantly increased. The Kansas City Cardiomyopathy Questionnaire overall summary score was not improved at outpatient week 1, but body weight and serum sodium effects persisted long after discharge. Tolvaptan caused increased thirst and dry mouth, but frequencies of major adverse events were similar in the 2 groups.ConclusionTolvaptan initiated for acute treatment of patients hospitalized with heart failure had no effect on long-term mortality or heart failure–related morbidity.Trial Registrationclinicaltrials.gov Identifier: NCT00071331Published online March 25, 2007 (doi:10.1001/jama.297.12.1319).

Discrete Choice with Social Interactions

Abstract: This paper provides an analysis of aggregate behavioural outcomes when individual utility exhibits social interaction effects. We study generalized logistic models of individual choice which incorporate terms reflecting the desire of individuals to conform to the behaviour of others in an environment of noncooperative decisionmaking. Laws of large numbers are generated in such environments. Multiplicity of equilibria in these models, which are equivalent to the existence of multiple self-consistent means for average choice behaviour, will exist when the social interactions exceed a particular threshold. Local stability of these multiple equilibria is also studied. The properties of the noncooperative economy are contrasted with the properties of an economy in which a social planner determines the set of individual choices. Finally, a likelihood function based on the theoretical model is given and conditions for the econometric identifiability of the model are established.

Coupling of local folding to site-specific binding of proteins to DNA

Abstract: Thermodynamic studies have demonstrated the central importance of a large negative heat capacity change (delta C degree assoc) in site-specific protein-DNA recognition. Dissection of the large negative delta C degree assoc and the entropy change of protein-ligand and protein-DNA complexation provide a thermodynamic signature identifying processes in which local folding is coupled to binding. Estimates of the number of residues that fold on binding obtained from this analysis agree with structural data. Structural comparisons indicate that these local folding transitions create key parts of the protein-DNA interface. The energetic implications of this "induced fit" model for DNA site recognition are considered.