Epistasis not needed to explain low dN/dS

An important question in molecular evolution is whether an amino acid that occurs at a given position makes an independent contribution to fitness, or whether its effect depends on the state of other loci in the organism's genome, a phenomenon known as epistasis. In a recent letter to Nature, Breen et al. (2012) argued that epistasis must be "pervasive throughout protein evolution" because the observed ratio between the per-site rates of non-synonymous and synonymous substitutions (dN/dS) is much lower than would be expected in the absence of epistasis. However, when calculating the expected dN/dS ratio in the absence of epistasis, Breen et al. assumed that all amino acids observed in a protein alignment at any particular position have equal fitness. Here, we relax this unrealistic assumption and show that any dN/dS value can in principle be achieved at a site, without epistasis. Furthermore, for all nuclear and chloroplast genes in the Breen et al. dataset, we show that the observed dN/dS values and the observed patterns of amino acid diversity at each site are jointly consistent with a non-epistatic model of protein evolution.Comment: This manuscript is in response to "Epistasis as the primary factor in molecular evolution" by Breen et al. Nature 490, 535-538 (2012

Multifrequency Strategies for the Identification of Gamma-Ray Sources

More than half the sources in the Third EGRET (3EG) catalog have no firmly established counterparts at other wavelengths and are unidentified. Some of these unidentified sources have remained a mystery since the first surveys of the gamma-ray sky with the COS-B satellite. The unidentified sources generally have large error circles, and finding counterparts has often been a challenging job. A multiwavelength approach, using X-ray, optical, and radio data, is often needed to understand the nature of these sources. This chapter reviews the technique of identification of EGRET sources using multiwavelength studies of the gamma-ray fields.Comment: 35 pages, 22 figures. Chapter prepared for the book "Cosmic Gamma-ray Sources", edited by K.S. Cheng and G.E. Romero, to be published by Kluwer Academic Press, 2004. For complete article and higher resolution figures, go to: http://www.astro.columbia.edu/~muk/mukherjee_multiwave.pd

A preliminary report of an educational intervention in practice management

BACKGROUND: Practice management education continues to evolve, and little information exists regarding its curriculum design and effectiveness for resident education. We report the results of an exploratory study of a practice management curriculum for primary care residents. METHODS: After performing a needs assessment with a group of primary care residents at Wright State University, we designed a monthly seminar series covering twelve practice management topics. The curriculum consisted of interactive lectures and practice-based application, whenever possible. We descriptively evaluated two cognitive components (practice management knowledge and skills) and the residents' evaluation of the curriculum. RESULTS: The mean correct on the knowledge test for this group of residents was 74% (n = 12) and 91% (n = 12) before and after the curriculum, respectively. The mean scores for the practice management skill assessments were 2.62 before (n = 12), and 3.65 after (n = 12) the curriculum (modified Likert, 1 = strongly disagree, 5 = strongly agree). The residents rated the curriculum consistently high. CONCLUSIONS: This exploratory study suggests that this curriculum may be useful in developing knowledge and skills in practice management for primary care residents. This study suggests further research into evaluation of this curriculum may be informative for practice-based education

Rectal Transmission of Transmitted/Founder HIV-1 Is Efficiently Prevented by Topical 1% Tenofovir in BLT Humanized Mice

Rectal microbicides are being developed to prevent new HIV infections in both men and women. We focused our in vivo preclinical efficacy study on rectally-applied tenofovir. BLT humanized mice (n = 43) were rectally inoculated with either the primary isolate HIV-1(JRCSF) or the MSM-derived transmitted/founder (T/F) virus HIV-1(THRO) within 30 minutes following treatment with topical 1% tenofovir or vehicle. Under our experimental conditions, in the absence of drug treatment we observed 50% and 60% rectal transmission by HIV-1(JRCSF) and HIV-1(THRO), respectively. Topical tenofovir reduced rectal transmission to 8% (1/12; log rank p = 0.03) for HIV-1(JRCSF) and 0% (0/6; log rank p = 0.02) for HIV-1(THRO). This is the first demonstration that any human T/F HIV-1 rectally infects humanized mice and that transmission of the T/F virus can be efficiently blocked by rectally applied 1% tenofovir. These results obtained in BLT mice, along with recent ex vivo, Phase 1 trial and non-human primate reports, provide a critically important step forward in the development of tenofovir-based rectal microbicides

Formation of regulatory modules by local sequence duplication

Turnover of regulatory sequence and function is an important part of molecular evolution. But what are the modes of sequence evolution leading to rapid formation and loss of regulatory sites? Here, we show that a large fraction of neighboring transcription factor binding sites in the fly genome have formed from a common sequence origin by local duplications. This mode of evolution is found to produce regulatory information: duplications can seed new sites in the neighborhood of existing sites. Duplicate seeds evolve subsequently by point mutations, often towards binding a different factor than their ancestral neighbor sites. These results are based on a statistical analysis of 346 cis-regulatory modules in the Drosophila melanogaster genome, and a comparison set of intergenic regulatory sequence in Saccharomyces cerevisiae. In fly regulatory modules, pairs of binding sites show significantly enhanced sequence similarity up to distances of about 50 bp. We analyze these data in terms of an evolutionary model with two distinct modes of site formation: (i) evolution from independent sequence origin and (ii) divergent evolution following duplication of a common ancestor sequence. Our results suggest that pervasive formation of binding sites by local sequence duplications distinguishes the complex regulatory architecture of higher eukaryotes from the simpler architecture of unicellular organisms

Gamma Ray Pulsars: Multiwavelength Observations

High-energy gamma rays are a valuable tool for studying particle acceleration and radiation in the magnetospheres of energetic pulsars. The seven or more pulsars seen by instruments on the Compton Gamma Ray Observatory (CGRO) show that: the light curves usually have double-peak structures (suggesting a broad cone of emission); gamma rays are frequently the dominant component of the radiated power; and all the spectra show evidence of a high-energy turnover. For all the known gamma-ray pulsars, multiwavelength observations and theoretical models based on such observations offer the prospect of gaining a broad understanding of these rotating neutron stars. The Gamma-ray Large Area Space Telescope (GLAST), now in planning for a launch in 2007, will provide a major advance in sensitivity, energy range, and sky coverage.Comment: To appear in Cosmic Gamma Ray Sources, Kluwer ASSL Series, Edited by K.S. Cheng and G.E. Romer

Virtual Blocks: a serious game for spatial ability improvement on mobile devices

This paper presents a novel spatial instruction system for improving spatial abilities of engineering students. A 3D mobile game application called Virtual Blocks has been designed to provide a 3D virtual environment to build models with cubes that help students to perform visualization tasks to promote the development of their spatial ability during a short remedial course. A validation study with 26 freshman engineering students at La Laguna University (Spain) has concluded that the training had a measurable and positive impact on students spatial ability. In addition, the results obtained using a satisfaction questionnaire show that Virtual Blocks is considered an easy to use and stimulating application.This work has been partially supported by the (Spanish) National Program for Studies and Analysis project "Evaluation and development of competencies associated to the spatial ability in the new engineering undergraduate courses" (Ref. EA2009-0025) and the (Spanish) National Science Project "Enhancing Spatial REasoning and VIsual Cognition with advanced technological tools (ESREVIC)" (Ref TIN2010-21296-C02-02)Martín Dorta, NN.; Sanchez Berriel, I.; Bravo, M.; Hernández, J.; Saorin, JL.; Contero, M. (2014). Virtual Blocks: a serious game for spatial ability improvement on mobile devices. Multimedia Tools and Applications. 73(3):1575-1595. https://doi.org/10.1007/s11042-013-1652-0S15751595733Baartmans BG, Sorby SA (1996) Introduction to 3-D spatial visualization. Prentice Hall, Englewood CliffsClements D, Battista M (1992) Geometry and spatial reasoning. In: Grouws DA (ed) Handbook of research on mathematics teaching and learning. New York, pp 420–464Cohen J (1988) Statistical power analysis for the behavioral sciences, 2nd edn. Erlbaum, HillsdaleDe Lisi R, Cammarano DM (1996) Computer experience and gender differences in undergraduate mental rotation performance. Comput Hum Behav 12:351–361Deno JA (1995) The relationship of previous experiences to spatial visualization ability. Eng Des Graph J 59(3):5–17Feng J, Spence I, Pratt J (2007) Playing an action video game reduces gender differences in spatial cognition. Psychol Sci 18(10):850–855French JW (1951) The description of aptitude and achievement tests in terms of rotated factors. Psychometric monograph 5Guilford JP, Lacy JI (1947) Printed classification tests, A.A.F. Aviation Psychological Progress Research Report, 5. US. Government Printing Office, Washington DCHalpern DF (2000) Sex differences and cognitive abilities. Erlbaum, MahwahHöfele C (2007) Mobile 3D graphics: learning 3D graphics with the Java Micro Edition. Editorial ThomsonKajiya JT, Kay TL (1989) Rendering fur with three dimensional textures. In Proceedings of the 16th Annual Conference on Computer Graphics and interactive Techniques SIGGRAPH ’89. ACM Press, New York pp 271–280Linn MC, Petersen AC (1985) Emergence and characterization of gender differences in spatial abilities: a meta-analysis. Child Dev 56:1479–1498Martin-Dorta N, Sanchez-Berriel I, Bravo M, Hernandez J, Saorin JL, Contero M (2010) A 3D educational mobile game to enhance student’s spatial skills, ICALT, pp.6–10, 2010 10th IEEE International Conference on Advanced Learning TechnologiesMartin-Dorta N, Saorin J, Contero M (2008) Development of a fast remedial course to improve the spatial abilities of engineering students. J Eng Educ 27(4):505–514Martin-Dorta N, Saorin JL, Contero M (2011) Web-based spatial training using handheld touch screen devices. Educ Technol Soc 14(3):163–177McGee MG (1979) Human spatial abilities: psychometric studies and environmental, genetic, hormonal, and neurological influences. Psychol Bull 86:889–918Noguera JM, Segura RJ, Ogayar CJ, Joan-Arinyo R (2011) Navigating large terrains using commodity mobile devices. Comput Geosci 37:1218–1233Okagaki L, Frensch PA (1994) Effects of video game playing on measures of spatial performance: gender effects in late adolescence. J Appl Dev Psychol 15(1):33–58Pulli K, Aarnio T, Miettinen V, Roimela K, Vaarala J (2007) Mobile 3D graphics with OpenGL ES and M3G. Editorial Morgan KaufmannQuaiser-Pohl C, Geiser C, Lehmann W (2005) The relationship between computer-game preference, gender, and mental-rotation ability. Personal Individ Differ 40(3):609–619Smith IM (1964) Spatial ability- its educational and social significance. The University of London Press, LondonSorby S (2007) Developing 3D spatial skills for engineering students. Australas Assoc Eng Educ 13(1):1–11Terlecki MS, Newcombe NS (2005) How important is the digital divide? The relation of computer and videogame usage to gender differences in mental rotation ability. Sex Roles 53(5/6):433–441Terlecki MS, Newcombe NS, Little M (2008) Durable and generalized effects of spatial experience on mental rotation: gender differences in growth patterns. Appl Cogn Psychol 22:996–1013Thurstone LL (1950) Some primary abilities in visual thinking (Tech. Rep. No. 59). IL University of Chicago Psychometric Laboratory, ChicagoThurstone LL, Thurstone TG (1941) Factorial studies of intelligence. Psychometric monographs. Chicago Press, ChicagoVanderberg S, Kuse A (1978) Mental Rotation, a group test of three dimensional spatial visualization. Percept Mot Skills 47:599–604Zimmerman WS (1954) Hypotheses concerning the nature of the spatial factors. Educ Psychol Meas 14:396–40

Detection of the pairwise kinematic Sunyaev-Zel'dovich effect with BOSS DR11 and the Atacama Cosmology Telescope

We present a new measurement of the kinematic Sunyaev-Zeldovich effect using data from the Atacama Cosmology Telescope (ACT) and the Baryon Oscillation Spectroscopic Survey (BOSS). Using 600 square degrees of overlapping sky area, we evaluate the mean pairwise baryon momentum associated with the positions of 50,000 bright galaxies in the BOSS DR11 Large Scale Structure catalog. A non-zero signal arises from the large-scale motions of halos containing the sample galaxies. The data fits an analytical signal model well, with the optical depth to microwave photon scattering as a free parameter determining the overall signal amplitude. We estimate the covariance matrix of the mean pairwise momentum as a function of galaxy separation, using microwave sky simulations, jackknife evaluation, and bootstrap estimates. The most conservative simulation-based errors give signal-to-noise estimates between 3.6 and 4.1 for varying galaxy luminosity cuts. We discuss how the other error determinations can lead to higher signal-to-noise values, and consider the impact of several possible systematic errors. Estimates of the optical depth from the average thermal Sunyaev-Zeldovich signal at the sample galaxy positions are broadly consistent with those obtained from the mean pairwise momentum signal.Comment: 15 pages, 8 figures, 2 table

Using email reminders to engage physicians in an Internet-based CME intervention

BACKGROUND: Engaging practicing physicians in educational strategies that reinforce guideline adoption and improve the quality of healthcare may be difficult. Push technologies such as email offer new opportunities to engage physicians in online educational reinforcing strategies. The objectives are to investigate 1) the effectiveness of email announcements in engaging recruited community-based primary care physicians in an online guideline reinforcement strategy designed to promote Chlamydia screening, 2) the characteristics of physicians who respond to email announcements, as well as 3) how quickly and when they respond to email announcements. METHODS: Over a 45-week period, 445 recruited physicians received up to 33 email contacts announcing and reminding them of an online women's health guideline reinforcing CME activity. Participation was defined as physician log-on at least once to the website. Data were analyzed to determine participation, to compare characteristics of participants with recruited physicians who did not participate, and to determine at what point and when participants logged on. RESULTS: Of 445 recruited physicians with accurate email addresses, 47.2% logged on and completed at least one module. There were no significant differences by age, race, or specialty between participants and non-participants. Female physicians, US medical graduates and MDs had higher participation rates than male physicians, international medical graduates and DOs. Physicians with higher baseline screening rates were significantly more likely to log on to the course. The first 10 emails were the most effective in engaging community-based physicians to complete the intervention. Physicians were more likely to log on in the afternoon and evening and on Monday or Thursday. CONCLUSIONS: Email course reminders may enhance recruitment of physicians to interventions designed to reinforce guideline adoption; physicians' response to email reminders may vary by gender, degree, and country of medical training. Repetition of email communications contributes to physician online participation

Branched Chain Fatty Acids Reduce the Incidence of Necrotizing Enterocolitis and Alter Gastrointestinal Microbial Ecology in a Neonatal Rat Model

Branched chain fatty acids (BCFA) are found in the normal term human newborn's gut, deposited as major components of vernix caseosa ingested during late fetal life. We tested the hypothesis that premature infants' lack of exposure to gastrointestinal (GI) BCFA is associated with their microbiota and risk for necrotizing enterocolitis (NEC) using a neonatal rat model.Pups were collected one day before scheduled birth. The pups were exposed to asphyxia and cold stress to induce NEC. Pups were assigned to one of three experimental treatments. DF (dam-fed); Control, hand-fed rat milk substitute; BCFA, hand-fed rat milk substitute with 20%w/w BCFA. Total fat was equivalent (11%wt) for both the Control and BCFA groups. Cecal microbiota were characterized by 16S rRNA gene pyrosequencing, and intestinal injury, ileal cytokine and mucin gene expression, interleukin-10 (IL-10) peptide immunohistochemistry, and BCFA uptake in ileum phospholipids, serum and liver were assessed.NEC incidence was reduced by over 50% in the BCFA group compared to the Control group as assessed in ileal tissue; microbiota differed among all groups. BCFA-fed pups harbored greater levels of BCFA-associated Bacillus subtilis and Pseudomonas aeruginosa compared to Controls. Bacillus subtilis levels were five-fold greater in healthy pups compared to pups with NEC. BCFA were selectively incorporated into ileal phospholipids, serum and liver tissue. IL-10 expression increased three-fold in the BCFA group versus Controls and no other inflammatory or mucosal mRNA markers changed.At constant dietary fat level, BCFA reduce NEC incidence and alter microbiota composition. BCFA are also incorporated into pup ileum where they are associated with enhanced IL-10 and may exert other specific effects