Impact of Generalist Physician Initiatives on Residency Selection

Objective:To compare the residency selection choices of students who experienced courses resulting from generalist physician initiatives to choices made by students prior to the implementation of those courses and to describe the characteristics of students selecting primary care residencies. Background:In the fall of 1994 a first year Community Continuity Experience course was initiated and in the summer of 1995 a third year Multidisciplinary Ambulatory Clerkship was begun at the University of Texas Medical Branch in Galveston. These courses were inserted into the curriculum to enhance and promote primary care education. Design/Methods:We examined the residency selections of cohorts of graduating medical students before (1992-1996) and after (1997-1999) the implementation of the primary care courses. Survey information on career preferences at matriculation and in the fourth year of medical school were available for students graduating after the programs began. We compared the career preferences and characteristics of those students who selected a primary care residency to those who did not. Results:Prior to the implementation of the programs, 45%(425/950) of students graduating selected primary care residencies compared to 45% (210/465) of students participating in the programs (p=0.88). At matriculation, 45% of students had listed a primary care discipline as their first career choice. Among the students who had indicated this degree of primary care interest 61% ended up matching in a primary care discipline. At year 4, 31% of students indicated a primary care discipline as their first career choice and 92% of these students matched to a primary care residency. By univariate analysis, minority students (53%) were more likely to select a primary care residency than non-minority students (40%); students in the two lowest grade point average quartiles (55% and 50%) selected primary care residencies compared to 37% and 38% of students in the top 2 quartiles; and students who stated that income potential had little or no impact on their choice were more likely to select a primary care residency (48%) than those who said income potential was important (37%). Conclusions:We observed no significant trend towards higher proportions of graduating students selecting primary care discipline residencies as a result of implementing courses that emphasized primary care. Those students expressing an interest in a primary care discipline at their entrance into medical school were more likely to select a primary care residency. A more significant impact on graduating students interested in primary care may be made through the medical student selection process than by altering the curriculum

Heat-evoked activation of TRPV4 channels in an HEK-293 cell expression system and in native mouse aorta endothelial cells

Peer reviewe

A Word from the New Book Review Editors

Non peer reviewe

Pulsation period variations in the RRc Lyrae star KIC 5520878

Learned et. al. proposed that a sufficiently advanced extra-terrestrial civilization may tickle Cepheid and RR Lyrae variable stars with a neutrino beam at the right time, thus causing them to trigger early and jogging the otherwise very regular phase of their expansion and contraction. This would turn these stars into beacons to transmit information throughout the galaxy and beyond. The idea is to search for signs of phase modulation (in the regime of short pulse duration) and patterns, which could be indicative of intentional, omnidirectional signaling. We have performed such a search among variable stars using photometric data from the Kepler space telescope. In the RRc Lyrae star KIC 5520878, we have found two such regimes of long and short pulse durations. The sequence of period lengths, expressed as time series data, is strongly auto correlated, with correlation coefficients of prime numbers being significantly higher ($p=99.8$\%). Our analysis of this candidate star shows that the prime number oddity originates from two simultaneous pulsation periods and is likely of natural origin. Simple physical models elucidate the frequency content and asymmetries of the KIC 5520878 light curve. Despite this SETI null result, we encourage testing other archival and future time-series photometry for signs of modulated stars. This can be done as a by-product to the standard analysis, and even partly automated.Comment: Accepted for publication in ApJ. 49 pages, 16 figure

Nucleosome repositioning via loop formation

Active (catalysed) and passive (intrinsic) nucleosome repositioning is known to be a crucial event during the transcriptional activation of certain eucaryotic genes. Here we consider theoretically the intrinsic mechanism and study in detail the energetics and dynamics of DNA-loop-mediated nucleosome repositioning, as previously proposed by Schiessel et al. (H. Schiessel, J. Widom, R. F. Bruinsma, and W. M. Gelbart. 2001. {\it Phys. Rev. Lett.} 86:4414-4417). The surprising outcome of the present study is the inherent nonlocality of nucleosome motion within this model -- being a direct physical consequence of the loop mechanism. On long enough DNA templates the longer jumps dominate over the previously predicted local motion, a fact that contrasts simple diffusive mechanisms considered before. The possible experimental outcome resulting from the considered mechanism is predicted, discussed and compared to existing experimental findings

A stitch in time: Efficient computation of genomic DNA melting bubbles

Background: It is of biological interest to make genome-wide predictions of the locations of DNA melting bubbles using statistical mechanics models. Computationally, this poses the challenge that a generic search through all combinations of bubble starts and ends is quadratic. Results: An efficient algorithm is described, which shows that the time complexity of the task is O(NlogN) rather than quadratic. The algorithm exploits that bubble lengths may be limited, but without a prior assumption of a maximal bubble length. No approximations, such as windowing, have been introduced to reduce the time complexity. More than just finding the bubbles, the algorithm produces a stitch profile, which is a probabilistic graphical model of bubbles and helical regions. The algorithm applies a probability peak finding method based on a hierarchical analysis of the energy barriers in the Poland-Scheraga model. Conclusions: Exact and fast computation of genomic stitch profiles is thus feasible. Sequences of several megabases have been computed, only limited by computer memory. Possible applications are the genome-wide comparisons of bubbles with promotors, TSS, viral integration sites, and other melting-related regions.Comment: 16 pages, 10 figure

Theoretical Analysis of Competing Conformational Transitions in Superhelical DNA

We develop a statistical mechanical model to analyze the competitive behavior of transitions to multiple alternate conformations in a negatively supercoiled DNA molecule of kilobase length and specified base sequence. Since DNA superhelicity topologically couples together the transition behaviors of all base pairs, a unified model is required to analyze all the transitions to which the DNA sequence is susceptible. Here we present a first model of this type. Our numerical approach generalizes the strategy of previously developed algorithms, which studied superhelical transitions to a single alternate conformation. We apply our multi-state model to study the competition between strand separation and B-Z transitions in superhelical DNA. We show this competition to be highly sensitive to temperature and to the imposed level of supercoiling. Comparison of our results with experimental data shows that, when the energetics appropriate to the experimental conditions are used, the competition between these two transitions is accurately captured by our algorithm. We analyze the superhelical competition between B-Z transitions and denaturation around the c-myc oncogene, where both transitions are known to occur when this gene is transcribing. We apply our model to explore the correlation between stress-induced transitions and transcriptional activity in various organisms. In higher eukaryotes we find a strong enhancement of Z-forming regions immediately 5′ to their transcription start sites (TSS), and a depletion of strand separating sites in a broad region around the TSS. The opposite patterns occur around transcript end locations. We also show that susceptibility to each type of transition is different in eukaryotes and prokaryotes. By analyzing a set of untranscribed pseudogenes we show that the Z-susceptibility just downstream of the TSS is not preserved, suggesting it may be under selection pressure

Conformations of closed DNA

We examine the conformations of a model for a short segment of closed DNA. The molecule is represented as a cylindrically symmetric elastic rod with a constraint corresponding to a specification of the linking number. We obtain analytic expressions leading to the spatial configuration of a family of solutions representing distortions that interpolate between the circular form of DNA and a figure-eight form that represents the onset of interwinding. We are also able to generate knotted loops. We suggest ways to use our approach to produce other configurations relevant to studies of DNA structure. The stability of the distorted configurations is assessed, along with the effects of fluctuations on the free energy of the various configurations.Comment: 39 pages in REVTEX with 14 eps figures. Submitted to Phys. Rev. E. This manuscript updates, expands and revises, to a considerable extent, a previously posted manuscript, entitled "Conformations of Circular DNA," which appeared as cond-mat/970104

Theoretical Analysis of the Stress Induced B-Z Transition in Superhelical DNA

We present a method to calculate the propensities of regions within a DNA molecule to transition from B-form to Z-form under negative superhelical stresses. We use statistical mechanics to analyze the competition that occurs among all susceptible Z-forming regions at thermodynamic equilibrium in a superhelically stressed DNA of specified sequence. This method, which we call SIBZ, is similar to the SIDD algorithm that was previously developed to analyze superhelical duplex destabilization. A state of the system is determined by assigning to each base pair either the B- or the Z-conformation, accounting for the dinucleotide repeat unit of Z-DNA. The free energy of a state is comprised of the nucleation energy, the sequence-dependent B-Z transition energy, and the energy associated with the residual superhelicity remaining after the change of twist due to transition. Using this information, SIBZ calculates the equilibrium B-Z transition probability of each base pair in the sequence. This can be done at any physiologically reasonable level of negative superhelicity. We use SIBZ to analyze a variety of representative genomic DNA sequences. We show that the dominant Z-DNA forming regions in a sequence can compete in highly complex ways as the superhelicity level changes. Despite having no tunable parameters, the predictions of SIBZ agree precisely with experimental results, both for the onset of transition in plasmids containing introduced Z-forming sequences and for the locations of Z-forming regions in genomic sequences. We calculate the transition profiles of 5 kb regions taken from each of 12,841 mouse genes and centered on the transcription start site (TSS). We find a substantial increase in the frequency of Z-forming regions immediately upstream from the TSS. The approach developed here has the potential to illuminate the occurrence of Z-form regions in vivo, and the possible roles this transition may play in biological processes

The repertoire and features of human platelet microRNAs

Playing a central role in the maintenance of hemostasis as well as in thrombotic disorders, platelets contain a relatively diverse messenger RNA (mRNA) transcriptome as well as functional mRNA-regulatory microRNAs, suggesting that platelet mRNAs may be regulated by microRNAs. Here, we elucidated the complete repertoire and features of human platelet microRNAs by high-throughput sequencing. More than 492 different mature microRNAs were detected in human platelets, whereas the list of known human microRNAs was expanded further by the discovery of 40 novel microRNA sequences. As in nucleated cells, platelet microRNAs bear signs of post-transcriptional modifications, mainly terminal adenylation and uridylation. In vitro enzymatic assays demonstrated the ability of human platelets to uridylate microRNAs, which correlated with the presence of the uridyltransferase enzyme TUT4. We also detected numerous microRNA isoforms (isomiRs) resulting from imprecise Drosha and/or Dicer processing, in some cases more frequently than the reference microRNA sequence, including 5′ shifted isomiRs with redirected mRNA targeting abilities. This study unveils the existence of a relatively diverse and complex microRNA repertoire in human platelets, and represents a mandatory step towards elucidating the intraplatelet and extraplatelet role, function and importance of platelet microRNAs