Efficient use of single molecule time traces to resolve kinetic rates, models and uncertainties

Single molecule time traces reveal the time evolution of unsynchronized kinetic systems. Especially single molecule F\"orster resonance energy transfer (smFRET) provides access to enzymatically important timescales, combined with molecular distance resolution and minimal interference with the sample. Yet the kinetic analysis of smFRET time traces is complicated by experimental shortcomings - such as photo-bleaching and noise. Here we recapitulate the fundamental limits of single molecule fluorescence that render the classic, dwell-time based kinetic analysis unsuitable. In contrast, our Single Molecule Analysis of Complex Kinetic Sequences (SMACKS) considers every data point and combines the information of many short traces in one global kinetic rate model. We demonstrate the potential of SMACKS by resolving the small kinetic effects caused by different ionic strengths in the chaperone protein Hsp90. These results show an unexpected interrelation between conformational dynamics and ATPase activity in Hsp90.Comment: 17 pages, 6 figure

Experiment-friendly kinetic analysis of single molecule data in and out of equilibrium

We present a simple and robust technique to extract kinetic rate models and thermodynamic quantities from single molecule time traces. SMACKS (Single Molecule Analysis of Complex Kinetic Sequences) is a maximum likelihood approach that works equally well for long trajectories as for a set of short ones. It resolves all statistically relevant rates and also their uncertainties. This is achieved by optimizing one global kinetic model based on the complete dataset, while allowing for experimental variations between individual trajectories. In particular, neither a priori models nor equilibrium have to be assumed. The power of SMACKS is demonstrated on the kinetics of the multi-domain protein Hsp90 measured by smFRET (single molecule F\"orster resonance energy transfer). Experiments in and out of equilibrium are analyzed and compared to simulations, shedding new light on the role of Hsp90's ATPase function. SMACKS pushes the boundaries of single molecule kinetics far beyond current methods.Comment: 11 pages, 8 figure

Power at work: Linking objective power to psychological power

Experimental research conducted with student participants has documented that feeling powerful or powerless (psychological power) affects outcomes with high practical relevance for organizations. However, it is unclear how results from these studies can be generalized to organizational settings in which individuals have various roles that imply more or less objective power. To address this gap, we present a theoretical framework to aid in the understanding of how objective power in organizations affects psychological power. We assume that stable differences in organizational rank (i.e., structural power) determine the likelihood of interactions with superiors, subordinates, or peers. These interactions give rise to within-person variation in situational power which should lead to dynamic fluctuations of psychological power and eventually its outcomes. Results of a preregistered experiment (n = 190 participants) and a preregistered experience sampling study (n = 129 participants) conducted with working adults support our key predictions: Structural power was associated with the likelihood of being in a high power versus low power situation. Within-person differences in situational power were related to feelings of power such as judgments about (1) one's own ability to influence others in a given social situation (i.e., interpersonal power) and (2) one's own competence, agency, autonomy, and independence (i.e., personal power)

The known unknowns of the Hsp90 chaperone

Molecular chaperones are vital proteins that maintain protein homeostasis by assisting in protein folding, activation, degradation, and stress protection. Among them, heat-shock protein 90 (Hsp90) stands out as an essential proteostasis hub in eukaryotes, chaperoning hundreds of "clients" (substrates). After decades of research, several "known unknowns" about the molecular function of Hsp90 remain unanswered, hampering rational drug design for the treatment of cancers, neurodegenerative and other diseases. We highlight three fundamental open questions, reviewing the current state of the field for each, and discuss new opportunities, including single-molecule technologies, to answer the known unknowns of the Hsp90 chaperone.Comment: 29 pages, 4 figure

Voice Onset Time in multilingual speakers: Italian heritage speakers in Germany with L3 English

This study brings together two previously largely independent fields of multilingual language acquisition: heritage language and third language (L3) acquisition. We investigate the production of fortis and lenis stops in semi-naturalistic speech in the three languages of 20 heritage speakers (HSs) of Italian with German as a majority language and English as L3. The study aims to identify the extent to which the HSs produce distinct values across all three languages, or whether crosslinguistic influence (CLI) occurs. To this end, we compare the HSs’ voice onset time (VOT) values with those of L2 English speakers from Italy and Germany. The language triad exhibits overlapping and distinct VOT realizations, making VOT a potentially vulnerable category. Results indicate CLI from German into Italian, although a systemic difference is maintained. When speaking English, th

Predictors of readmission and health related quality of life in patients with chronic heart failure: a comparison of different psychosocial aspects

Psychological distress is common in patients with chronic heart failure. The impact of different psychological variables on prognosis has been shown but the comparative effects of these variables remain unclear. This study examines the impact of depression, anxiety, vital exhaustion, Type D personality, and social support on prognosis in chronic heart failure patients. One hundred eleven patients (mean age 57±14years) having participated in an exercise based ambulatory cardiac rehabilitation program were enrolled in a prospective cohort study. Psychological baseline data were assessed at program entry. Mortality, readmission, and health-related quality of life were assessed at follow up (mean 2.8±1.1years). After controlling for disease severity none of the psychological variables were associated with mortality, though severe anxiety predicted readmission [HR=3.21 (95% CI, 1.04-9.93; P=.042)]. Health-related quality of life was independently explained by vital exhaustion, anxiety and either body mass index (physical dimension) or sex (emotional dimension). As psychological variables have a strong impact on health-related quality of life they should be routinely assessed in chronic heart failure patients's treatmen

HaSpaD - Data Manual (September 2021)

Extensive harmonization of survey and especially biographical data has not been common in the social sciences. HaSpaD provides a tool for harmonizing and accumulating, and thus comprehensively analyzing, survey-based longitudinal data sets on partnership biographies. The following studies were harmonized and merged for a joint analysis for the third-party funded project "Harmonizing and synthesizing partnership histories from different research data infrastructures" (HaSpaD): the panel studies pairfam, SOEP and SHARE; the cross-section studies General German Social Survey, Mannheim Divorce Study and the Fertility and Family Survey; as well as the cross-section studies combined with partially repeated surveys Family Surveys, German Life History Studies and the Generations and Gender Surveys. The project provides syntax-based harmonization processes available through the HaSpaD Harmonization Wizard. The HaSpaD Harmonization Wizard enables a customized selection of survey programs and variables. After downloading the source data sets from their repositories, the HaSpaD syntax package enables to generate an individually customized and harmonized data set of the source datasets. In addition to biographical data on partnerships, the HaSpaD target dataset may include other variables such as age, gender, citizenship, and education level. If all surveys are selected, the target data set will contain approximately 182,000 partnership biographies