Evolution of populations expanding on curved surfaces

This is the author accepted manuscript. The final version is available from EPL Association via the DOI in this recordThe expansion of a population into new habitat is a transient process that leaves its footprints in the genetic composition of the expanding population. How the structure of the environment shapes the population front and the evolutionary dynamics during such a range expansion is little understood. Here, we investigate the evolutionary dynamics of populations consisting of many selectively neutral genotypes expanding on curved surfaces. Using a combination of individual-based off-lattice simulations, geometrical arguments, and lattice-based stepping-stone simulations, we characterise the effect of individual bumps on an otherwise flat surface. Compared to the case of a range expansion on a flat surface, we observe a transient relative increase, followed by a decrease, in neutral genetic diversity at the population front. In addition, we find that individuals at the sides of the bump have a dramatically increased expected number of descendants, while their neighbours closer to the bump's centre are far less lucky. Both observations can be explained using an analytical description of straight paths (geodesics) on the curved surface. Complementing previous studies of heterogeneous flat environments, the findings here build our understanding of how complex environments shape the evolutionary dynamics of expanding populations.Nederlandse Organisatie voor Wetenschappelijk Onderzoek I (NWO-I)American Physical SocietySociedade Brasileira de FísicaFAPESPCenter for Computation and Visualization, Brown Universit

Interstellar neutral helium in the heliosphere from IBEX observations. III. Mach number of the flow, velocity vector, and temperature from the first six years of measurements

We analyzed observations of interstellar neutral helium (ISN~He) obtained from the Interstellar Boundary Explorer (IBEX) satellite during its first six years of operation. We used a refined version of the ISN~He simulation model, presented in the companion paper by Sokol_et al. 2015, and a sophisticated data correlation and uncertainty system and parameter fitting method, described in the companion paper by Swaczyna et al 2015. We analyzed the entire data set together and the yearly subsets, and found the temperature and velocity vector of ISN~He in front of the heliosphere. As seen in the previous studies, the allowable parameters are highly correlated and form a four-dimensional tube in the parameter space. The inflow longitudes obtained from the yearly data subsets show a spread of ~6 degree, with the other parameters varying accordingly along the parameter tube, and the minimum chi-square value is larger than expected. We found, however, that the Mach number of the ISN~He flow shows very little scatter and is thus very tightly constrained. It is in excellent agreement with the original analysis of ISN~He observations from IBEX and recent reanalyses of observations from Ulysses. We identify a possible inaccuracy in the Warm Breeze parameters as the likely cause of the scatter in the ISN~He parameters obtained from the yearly subsets, and we suppose that another component may exist in the signal, or a process that is not accounted for in the current physical model of ISN~He in front of the heliosphere. From our analysis, the inflow velocity vector, temperature, and Mach number of the flow are equal to lambda_ISNHe = 255.8 +/- 0.5 degree, beta_ISNHe = 5.16 +/- 0.10 degree, T_ISNHe = 7440 +/- 260 K, v_ISNHe = 25.8 +/- 0.4$ km/s, and M_ISNHe = 5.079 +/- 0.028, with uncertainties strongly correlated along the parameter tube.Comment: Updated reference

Anti-HIV-1 activity of cellulose acetate phthalate: Synergy with soluble CD4 and induction of "dead-end" gp41 six-helix bundles

BACKGROUND: Cellulose acetate phthalate (CAP), a promising candidate microbicide for prevention of sexual transmission of the human immunodeficiency virus type 1 (HIV-1) and other sexually transmitted disease (STD) pathogens, was shown to inactivate HIV-1 and to block the coreceptor binding site on the virus envelope glycoprotein gp120. It did not interfere with virus binding to CD4. Since CD4 is the primary cellular receptor for HIV-1, it was of interest to study CAP binding to HIV-1 complexes with soluble CD4 (sCD4) and its consequences, including changes in the conformation of the envelope glycoprotein gp41 within virus particles. METHODS: Enzyme-linked immunosorbent assays (ELISA) were used to study CAP binding to HIV-1-sCD4 complexes and to detect gp41 six-helix bundles accessible on virus particles using antibodies specific for the α-helical core domain of gp41. RESULTS: 1) Pretreatment of HIV-1 with sCD4 augments subsequent binding of CAP; 2) there is synergism between CAP and sCD4 for inhibition of HIV-1 infection; 3) treatment of HIV-1 with CAP induced the formation of gp41 six-helix bundles. CONCLUSIONS: CAP and sCD4 bind to distinct sites on HIV-1 IIIB and BaL virions and their simultaneous binding has profound effects on virus structure and infectivity. The formation of gp41 six-helical bundles, induced by CAP, is known to render the virus incompetent for fusion with target cells thus preventing infection

The effects of a kappa-distribution in the heliosheath on the global heliosphere and ENA flux at 1 AU

We investigate heliosheath energetic neutral atom (ENA) fluxes at keV energies, by assuming that the heliosheath proton distribution can be approximated by a kappa-distribution. The choice of the kappa parameter derives from observational data of the solar wind (SW). This has direct applications to the upcoming IBEX mission. We will look at all-sky ENA maps within the IBEX energy range (10 eV to 6 keV), as well as ENA energy spectra in several directions. We find that the use of kappa, as opposed to a Maxwellian, gives rise to greatly increased ENA fluxes above 1 keV, while medium energy fluxes are somewhat reduced. We show how IBEX data can be used to estimate the spectral slope in the heliosheath, and that the use of kappa reduces the differences between ENA maps at different energies. We also investigate the effect introducing a kappa-distribution has on the global interaction between the SW and the local interstellar medium (LISM), and find that there is generally an increase in energy transport from the heliosphere into the LISM, due to the modified profile of ENA's energies. This results in a termination shock that moves out by 4 AU, a heliopause that moves in by 9 AU and a bow shock 25 AU farther out, in the nose direction

A randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of neramexane in patients with moderate to severe subjective tinnitus

<p>Abstract</p> <p>Background</p> <p>Neramexane is a new substance that exhibits antagonistic properties at α₉α₁₀cholinergic nicotinic receptors and <it>N</it>-methyl-D-aspartate receptors, suggesting potential efficacy in the treatment of tinnitus.</p> <p>Methods</p> <p>A total of 431 outpatients with moderate to severe subjective tinnitus (onset 3-18 months before screening) were assigned randomly to receive either placebo or neramexane mesylate (25 mg/day, 50 mg/day and 75 mg/day) for 16 weeks, with assessment at 4-week intervals. The primary (intention-to-treat) efficacy analysis was based on the change from baseline in Week 16 in the total score of the adapted German short version of the validated Tinnitus Handicap Inventory questionnaire (THI-12).</p> <p>Results</p> <p>Compared with placebo, the largest improvement was achieved in the 50 mg/d neramexane group, followed by the 75 mg/d neramexane group. This treatment difference did not reach statistical significance at the pre-defined endpoint in Week 16 (<it>p </it>= 0.098 for 50 mg/d; <it>p </it>= 0.289 for 75 mg/d neramexane), but consistent numerical superiority of both neramexane groups compared with placebo was observed. Four weeks after the end of treatment, THI-12 scores in the 50 mg/d group were significantly better than those of the controls. Secondary efficacy variables supported this trend, with <it>p </it>values of < 0.05 for the 50 mg/d neramexane group associated with the functional-communicational subscores of the THI-12 and the assessments of tinnitus annoyance and tinnitus impact on life as measured on an 11-point Likert-like scale. No relevant changes were observed for puretone threshold, for tinnitus pitch and loudness match, or for minimum masking levels. The 25 mg/d neramexane group did not differ from placebo. Neramexane was generally well tolerated and had no relevant influence on laboratory values, electrocardiography and vital signs. Dizziness was the most common adverse event and showed a clear dose-dependence.</p> <p>Conclusions</p> <p>This study demonstrated the safety and tolerability of neramexane treatment in patients with moderate to severe tinnitus. The primary efficacy variable showed a trend towards improvement of tinnitus suffering in the medium- and high-dose neramexane groups. This finding is in line with consistent beneficial effects observed in secondary assessment variables. These results allow appropriate dose selection for further studies.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NCT00405886</p

Role of Defect Interaction in Boundary Mobility and Cation Diffusivity of CeO 2

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65842/1/j.1151-2916.1994.tb04596.x.pd

Restoring tibiofemoral alignment during ACL reconstruction results in better knee biomechanics

"Published online: 24 October 2017"PURPOSE: Anterior cruciate ligament (ACL) reconstruction (ACLR) aims to restore normal knee joint function, stability and biomechanics and in the long term avoid joint degeneration. The purpose of this study is to present the anatomic single bundle (SB) ACLR that emphasizes intraoperative correction of tibiofemoral subluxation that occurs after ACL injury. It was hypothesized that this technique leads to optimal outcomes and better restoration of pathological tibiofemoral joint movement that results from ACL deficiency (ACLD). METHODS: Thirteen men with unilateral ACLD were prospectively evaluated before and at a mean follow-up of 14.9 (SD = 1.8) months after anatomic SB ACLR with bone patellar tendon bone autograft. The anatomic ACLR replicated the native ACL attachment site anatomy and graft orientation. Emphasis was placed on intraoperative correction of tibiofemoral subluxation by reducing anterior tibial translation (ATT) and internal tibial rotation. Function was measured with IKDC, Lysholm and the Tegner activity scale, ATT was measured with the KT-1000 arthrometer and tibial rotation (TR) kinematics were measured with 3Dmotion analysis during a high-demand pivoting task. RESULTS: The results showed significantly higher TR of the ACL-deficient knee when compared to the intact knee prior to surgery (12.2° ± 3.7° and 10.7° ± 2.6° respectively, P = 0.014). Postoperatively, the ACLR knee showed significantly lower TR as compared to the ACL-deficient knee (9.6°±3.1°, P = 0.001) but no difference as compared to the control knee (n.s.). All functional scores were significantly improved and ATT was restored within normal values (P < 0.001). CONCLUSIONS: Intraoperative correction of tibiofemoral subluxation that results after ACL injury is an important step during anatomic SB ACLR. The intraoperative correction of tibiofemoral subluxation along with the replication of native ACL anatomy results in restoration of rotational kinematics of ACLD patients to normal levels that are comparable to the control knee. These results indicate that the reestablishment of tibiofemoral alignment during ACLR may be an important step that facilitates normal knee kinematics postoperatively. LEVEL OF EVIDENCE: Level II, prospective cohort study.The authors gratefully acknowledge the funding support from the Hellenic Association of Orthopaedic Surgery and Traumatology (HAOST-EEXOT)info:eu-repo/semantics/publishedVersio