HIV-1 Infection in Cyprus, the Eastern Mediterranean European Frontier: A Densely Sampled Transmission Dynamics Analysis from 1986 to 2012

Since HIV-1 treatment is increasingly considered an effective preventionstrategy, it is important to study local HIV-1 epidemics to formulate tailored preventionpolicies. The prevalence of HIV-1 in Cyprus was historically low until 2005. To investigatethe shift in epidemiological trends, we studied the transmission dynamics of HIV-1 in Cyprususing a densely sampled Cypriot HIV-1 transmission cohort that included 85 percent ofHIV-1-infected individuals linked to clinical care between 1986 and 2012 based on detailedclinical, epidemiological, behavioral and HIV-1 genetic information. Subtyping andtransmission cluster reconstruction were performed using maximum likelihood and Bayesianmethods, and the transmission chain network was linked to the clinical, epidemiological andbehavioral data. The results reveal that for the main HIV-1 subtype A1 and B sub-epidemics,young and drug-naïve HIV-1-infected individuals in Cyprus are driving the dynamics of thelocal HIV-1 epidemic. The results of this study provide a better understanding of thedynamics of the HIV-1 infection in Cyprus, which may impact the development of preventionstrategies. Furthermore, this methodology for analyzing densely sampled transmissiondynamics is applicable to other geographic regions to implement effective HIV-1 preventionstrategies in local settings

HIV-1 Infection in Cyprus, the Eastern Mediterranean European Frontier: A Densely Sampled Transmission Dynamics Analysis from 1986 to 2012

Since HIV-1 treatment is increasingly considered an effective preventionstrategy, it is important to study local HIV-1 epidemics to formulate tailored preventionpolicies. The prevalence of HIV-1 in Cyprus was historically low until 2005. To investigatethe shift in epidemiological trends, we studied the transmission dynamics of HIV-1 in Cyprususing a densely sampled Cypriot HIV-1 transmission cohort that included 85 percent ofHIV-1-infected individuals linked to clinical care between 1986 and 2012 based on detailedclinical, epidemiological, behavioral and HIV-1 genetic information. Subtyping andtransmission cluster reconstruction were performed using maximum likelihood and Bayesianmethods, and the transmission chain network was linked to the clinical, epidemiological andbehavioral data. The results reveal that for the main HIV-1 subtype A1 and B sub-epidemics,young and drug-naïve HIV-1-infected individuals in Cyprus are driving the dynamics of thelocal HIV-1 epidemic. The results of this study provide a better understanding of thedynamics of the HIV-1 infection in Cyprus, which may impact the development of preventionstrategies. Furthermore, this methodology for analyzing densely sampled transmissiondynamics is applicable to other geographic regions to implement effective HIV-1 preventionstrategies in local settings

Corresponding Functional Dynamics across the Hsp90 Chaperone Family: Insights from a Multiscale Analysis of MD Simulations

Understanding how local protein modifications, such as binding small-molecule ligands, can trigger and regulate large-scale motions of large protein domains is a major open issue in molecular biology. We address various aspects of this problem by analyzing and comparing atomistic simulations of Hsp90 family representatives for which crystal structures of the full length protein are available: mammalian Grp94, yeast Hsp90 and E.coli HtpG. These chaperones are studied in complex with the natural ligands ATP, ADP and in the Apo state. Common key aspects of their functional dynamics are elucidated with a novel multi-scale comparison of their internal dynamics. Starting from the atomic resolution investigation of internal fluctuations and geometric strain patterns, a novel analysis of domain dynamics is developed. The results reveal that the ligand-dependent structural modulations mostly consist of relative rigid-like movements of a limited number of quasi-rigid domains, shared by the three proteins. Two common primary hinges for such movements are identified. The first hinge, whose functional role has been demonstrated by several experimental approaches, is located at the boundary between the N-terminal and Middle-domains. The second hinge is located at the end of a three-helix bundle in the Middle-domain and unfolds/unpacks going from the ATP- to the ADP-state. This latter site could represent a promising novel druggable allosteric site common to all chaperones

Mechanical and Assembly Units of Viral Capsids Identified via Quasi-Rigid Domain Decomposition

Key steps in a viral life-cycle, such as self-assembly of a protective protein container or in some cases also subsequent maturation events, are governed by the interplay of physico-chemical mechanisms involving various spatial and temporal scales. These salient aspects of a viral life cycle are hence well described and rationalised from a mesoscopic perspective. Accordingly, various experimental and computational efforts have been directed towards identifying the fundamental building blocks that are instrumental for the mechanical response, or constitute the assembly units, of a few specific viral shells. Motivated by these earlier studies we introduce and apply a general and efficient computational scheme for identifying the stable domains of a given viral capsid. The method is based on elastic network models and quasi-rigid domain decomposition. It is first applied to a heterogeneous set of well-characterized viruses (CCMV, MS2, STNV, STMV) for which the known mechanical or assembly domains are correctly identified. The validated method is next applied to other viral particles such as L-A, Pariacoto and polyoma viruses, whose fundamental functional domains are still unknown or debated and for which we formulate verifiable predictions. The numerical code implementing the domain decomposition strategy is made freely available

Synthesis of new cyano derivatives on the basis of disubstituted indenones

225-228<span style="font-size:15.0pt;mso-bidi-font-size:8.0pt;font-family:Fd731912-Identity-H; mso-bidi-font-family:Fd731912-Identity-H;color:#131313">2,3-Disubstituted indenones 1<span style="font-size:15.0pt;mso-bidi-font-size: 8.0pt;font-family:Fd748002-Identity-H;mso-bidi-font-family:Fd748002-Identity-H; color:#131313">a-e<span style="font-size:15.0pt;mso-bidi-font-size: 8.0pt;font-family:Fd748002-Identity-H;mso-bidi-font-family:Fd748002-Identity-H; color:#131313">, <span style="font-size:15.0pt;mso-bidi-font-size:8.0pt; font-family:Fd731912-Identity-H;mso-bidi-font-family:Fd731912-Identity-H; color:#131313">possessing substituents of <span style="font-size:15.0pt;mso-bidi-font-size:8.0pt;font-family:Fd731912-Identity-H; mso-fareast-font-family:" times="" new="" roman";mso-bidi-font-family:fd731912-identity-h;="" color:#131313;mso-ansi-language:en-us;mso-fareast-language:en-us;mso-bidi-language:="" ar-sa"=""> electron donor or electron acceptor type localised in p-position of the phenyl group, are converted into the corresponding 3-cyano-1 indanones <span style="font-size:15.0pt;mso-bidi-font-size: 8.0pt;font-family:Fd748002-Identity-H;mso-fareast-font-family:" times="" new="" roman";="" mso-bidi-font-family:fd748002-identity-h;color:#131313;mso-ansi-language:en-us;="" mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">2a-e<span style="font-size:15.0pt;mso-bidi-font-size:8.0pt;font-family:Fd748002-Identity-H; mso-fareast-font-family:" times="" new="" roman";mso-bidi-font-family:fd748002-identity-h;="" color:#131313;mso-ansi-language:en-us;mso-fareast-language:en-us;mso-bidi-language:="" ar-sa"=""> <span style="font-size:15.0pt;mso-bidi-font-size:8.0pt; font-family:Fd731912-Identity-H;mso-fareast-font-family:" times="" new="" roman";="" mso-bidi-font-family:fd731912-identity-h;color:#131313;mso-ansi-language:en-us;="" mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">by the action of KCN and (NH4)2 CO3. The structure of the products <span style="font-size: 15.0pt;mso-bidi-font-size:8.0pt;font-family:Fd748002-Identity-H;mso-fareast-font-family: " times="" new="" roman";mso-bidi-font-family:fd748002-identity-h;color:#131313;="" mso-ansi-language:en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">2a-e<span style="font-size:15.0pt;mso-bidi-font-size:8.0pt;font-family:Fd748002-Identity-H; mso-fareast-font-family:" times="" new="" roman";mso-bidi-font-family:fd748002-identity-h;="" color:#131313;mso-ansi-language:en-us;mso-fareast-language:en-us;mso-bidi-language:="" ar-sa"=""> <span style="font-size:15.0pt;mso-bidi-font-size:8.0pt; font-family:Fd731912-Identity-H;mso-fareast-font-family:" times="" new="" roman";="" mso-bidi-font-family:fd731912-identity-h;color:#131313;mso-ansi-language:en-us;="" mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">have been confirmed by spectral analysis.</span

Use of technology virtual reality for the study of human - Operator in extreme conditions

Astronaut's training includes self-forming a mental model of the upcoming flight. In fact, this model consists of images of the