A two-state model for helicase translocation and unwinding of nucleic acids

Helicases are molecular motors that unwind double-stranded nucleic acids (dsNA), such as DNA and RNA). Typically a helicase translocates along one of the NA single strands while unwinding and uses adenosine triphosphate (ATP) hydrolysis as an energy source. Here we model of a helicase motor that can switch between two states, which could represent two different points in the ATP hydrolysis cycle. Our model is an extension of the earlier Betterton-J\"ulicher model of helicases to incorporate switching between two states. The main predictions of the model are the speed of unwinding of the dsNA and fluctuations around the average unwinding velocity. Motivated by a recent claim that the NS3 helicase of Hepatitis C virus follows a flashing ratchet mechanism, we have compared the experimental results for the NS3 helicase with a special limit of our model which corresponds to the flashing ratchet scenario. Our model accounts for one key feature of the experimental data on NS3 helicase. However, contradictory observations in experiments carried out under different conditions limit the ability to compare the model to experiments.Comment: minor modification

The model of dynamo with small number of modes and magnetic activity of T Tauri stars

The model that describes operation of dynamo in fully convective stars is presented. It is based on representation of stellar magnetic field as a superposition of finite number of poloidal and toroidal free damping modes. In the frame of adopted low of stellar differential rotation we estimated minimal value of dynamo number D, starting from which generation of cyclic magnetic field in stars without radiative core is possible. We also derived expression for period of the cycle. It was found that dynamo cycles of fully convective stars and stars with thin convective envelopes differ in a qualitative way: 1) distribution of spots over latitude during the cycle is different in these stars; 2) the model predicts that spot formation in fully convective stars should be strongly suppressed at some phases of the cycle. We have analyzed historical lightcurve of WTTS star V410 Tau and found that long term activity of the star is not periodic process. Rather one can speak about quasi cyclic activity with characteristic time of $\sim 4$ yr and chaotic component over imposed. We concluded also that redistribution of cool spots over longitude is the reason of long term variations of V410 Tau brightness. It means that one can not compare directly results of photometric observations with predictions of our axially symmetric (for simplicity) model which allows to investigate time evolution of spot's distribution over latitude. We then discuss what kind of observations and in which way could be used to check predictions of the dynamo theory.Comment: 18 pages, 5 figures, accepted to Astron. Let

Entrustable professional activities for residency in general internal medicine: a systematic review.

Entrustable Professional Activities (EPAs) are observable tasks that are regular parts of a physician's daily clinical work. Before being permitted to accomplish these tasks independently, trainees must gain their supervisors' trust. Defining the list of EPAs that should be mastered by the end of a residency is critical to setting clear expectations about autonomous practice. To collect all the lists of EPAs defined for residencies in general internal medicine and synthesise them into a reference work useful for developing new lists of EPAs or improving existing ones. This systematic review searched five databases and relevant grey literature using keywords related to EPAs and postgraduate education, from 2005, when the first article on EPAs was published, to April 2022. Inclusion criteria were the availability of an EPAs list and a focus on general internal medicine. Two reviewers independently selected the studies, extracted data and performed a quality assessment using QATSDD and AACODS tools. Mean values and inter-rater reliability were calculated. The review yielded 3292 records, with 16 articles meeting the inclusion criteria, mostly from North America. Synthesising their 16 lists generated 395 EPAs. The reviewers then inductively categoried those EPAs, 308 of which fell into 6 domains, 14 themes and 24 subthemes. The domains were: (1) care and management of the general adult population (n = 103 EPAs); (2) care and management of patients with specific needs (n = 67); (3) care coordination and communication (n = 52); (4) management and leadership (N = 21); (5) healthcare quality, education, and research (n = 41); and (6) miscellaneous (n = 24). The remaining 87 EPAs were disease-specific and did not fit into this categorisation. Categorising EPAs created a unique synthesis of the existing lists of EPAs for educating residents in general internal medicine. This synthesis could be used as a reference for anyone tasked with developing new lists of EPAs or improving existing ones

On The Power of Tree Projections: Structural Tractability of Enumerating CSP Solutions

The problem of deciding whether CSP instances admit solutions has been deeply studied in the literature, and several structural tractability results have been derived so far. However, constraint satisfaction comes in practice as a computation problem where the focus is either on finding one solution, or on enumerating all solutions, possibly projected to some given set of output variables. The paper investigates the structural tractability of the problem of enumerating (possibly projected) solutions, where tractability means here computable with polynomial delay (WPD), since in general exponentially many solutions may be computed. A general framework based on the notion of tree projection of hypergraphs is considered, which generalizes all known decomposition methods. Tractability results have been obtained both for classes of structures where output variables are part of their specification, and for classes of structures where computability WPD must be ensured for any possible set of output variables. These results are shown to be tight, by exhibiting dichotomies for classes of structures having bounded arity and where the tree decomposition method is considered

Variation in survival after diagnosis of breast cancer in Switzerland

Background: Survival after diagnosis of cancer is a key criterion for cancer control. Major survival differences between time periods and countries have been reported by the EUROCARE studies. We investigated whether similar differences by period and region existed in Switzerland. Methods: Survival of 11 376 cases of primary invasive female breast cancer diagnosed between 1988 and 1997 and registered in seven Swiss cancer registries covering a population of 3.5 million was analysed. Results: Comparing the two periods 1988-1992 and 1993-1997, age-standardized 5 year relative survival improved globally from 77% to 81%. Furthermore, multivariate analysis adjusting for age, tumour size and nodal involvement identified regional survival differences. Survival was lowest in the rural parts of German-speaking eastern Switzerland and highest in urbanised regions of the Latin- and German-speaking northwestern parts of the country. Conclusions: This study confirms that survival differences are present even in a small and affluent, but culturally diverse, country like Switzerland, raising the issue of heterogeneity in access to care and quality of treatmen

Unusual Case of Pump Thrombosis in LVAD Patient with COVID-19 — Diagnostic Challenges

We present the first reported case of left ventricular assist device (LVAD) pump thrombosis in the setting of the coronavirus pandemic. We describe the clinical features of the case which helped to differentiate coronavirus disease 19 (COVID-19) from LVAD pump thrombosis. The patient is 56-year-old female supported by destination LVAD therapy. She was originally implanted with a HeartMate II device in 2015 and underwent two pump exchanges in 2017 and 2019 for pump thrombosis, despite medication adherence. Shortly after routine lab work revealed near doubling of her lactate dehydrogenase (LDH) levels, she tested positive for COVID-19. She then developed power spikes and symptomatic heart failure, which prompted hospital admission. An initial computed tomography (CT) scan showed bilateral ground glass opacities, but repeat testing was negative for COVID-19. Her LVAD pump thrombosis was treated with aspirin, unfractionated heparin, and cangrelor, which was guided by thromboelastogram. Over several weeks, her LDH returned to baseline, and she was transitioned from cangrelor to ticagrelor and from heparin to warfarin. A repeat CT scan after several days of IV diuresis showed resolution of the ground glass opacities

Collective Decision Dynamics in the Presence of External Drivers

We develop a sequence of models describing information transmission and decision dynamics for a network of individual agents subject to multiple sources of influence. Our general framework is set in the context of an impending natural disaster, where individuals, represented by nodes on the network, must decide whether or not to evacuate. Sources of influence include a one-to-many externally driven global broadcast as well as pairwise interactions, across links in the network, in which agents transmit either continuous opinions or binary actions. We consider both uniform and variable threshold rules on the individual opinion as baseline models for decision-making. Our results indicate that 1) social networks lead to clustering and cohesive action among individuals, 2) binary information introduces high temporal variability and stagnation, and 3) information transmission over the network can either facilitate or hinder action adoption, depending on the influence of the global broadcast relative to the social network. Our framework highlights the essential role of local interactions between agents in predicting collective behavior of the population as a whole.Comment: 14 pages, 7 figure