The prefusion structure of herpes simplex virus glycoprotein B.

Cell entry of enveloped viruses requires specialized viral proteins that mediate fusion with the host membrane by substantial structural rearrangements from a metastable pre- to a stable postfusion conformation. This metastability renders the herpes simplex virus 1 (HSV-1) fusion glycoprotein B (gB) highly unstable such that it readily converts into the postfusion form, thereby precluding structural elucidation of the pharmacologically relevant prefusion conformation. By identification of conserved sequence signatures and molecular dynamics simulations, we devised a mutation that stabilized this form. Functionally locking gB allowed the structural determination of its membrane-embedded prefusion conformation at sub-nanometer resolution and enabled the unambiguous fit of all ectodomains. The resulting pseudo-atomic model reveals a notable conservation of conformational domain rearrangements during fusion between HSV-1 gB and the vesicular stomatitis virus glycoprotein G, despite their very distant phylogeny. In combination with our comparative sequence-structure analysis, these findings suggest common fusogenic domain rearrangements in all class III viral fusion proteins

The pre-fusion structure of Herpes simplex virus glycoprotein B

Cell entry of enveloped viruses requires specialized viral proteins which mediate fusion with the host membrane by substantial structural rearrangements from a metastable pre- to a stable postfusion conformation. This metastability renders the Herpes simplex virus (HSV-1) fusion glycoprotein B (gB) highly unstable such that it readily converts into the post-fusion form, thereby precluding structural elucidation of the pharmacologically relevant pre-fusion conformation. By identification of conserved sequence signatures and molecular dynamics simulations, we devised a mutation that stabilized this form. Functionally locking gB, allowed the structural determination of its membrane-embedded pre-fusion conformation at sub-nanometer resolution and enabled the unambiguous fit of all ectodomains. The resulting pseudo-atomic model reveals a striking conservation of conformational domain rearrangements during fusion between HSV-1 gB and the Vesicular Stomatitis Virus glycoprotein G (VSV-G) despite their very distant phylogeny. In combination with our comparative sequence-structure analysis, these findings suggest common fusogenic domain rearrangements in all class III viral fusion proteins. Rey, M. Topf, K

Modeling, Evaluation, and Scale on Artificial Pedestrians: A Literature Review

Modeling pedestrian dynamics and their implementation in a computer are challenging and important issues in the knowledge areas of transportation and computer simulation. The aim of this article is to provide a bibliographic outlook so that the reader may have quick access to the most relevant works related to this problem. We have used three main axes to organize the article's contents: pedestrian models, validation techniques, and multiscale approaches. The backbone of this work is the classification of existing pedestrian models; we have organized the works in the literature under five categories, according to the techniques used for implementing the operational level in each pedestrian model. Then the main existing validation methods, oriented to evaluate the behavioral quality of the simulation systems, are reviewed. Furthermore, we review the key issues that arise when facing multiscale pedestrian modeling, where we first focus on the behavioral scale (combinations of micro and macro pedestrian models) and second on the scale size (from individuals to crowds). The article begins by introducing the main characteristics of walking dynamics and its analysis tools and concludes with a discussion about the contributions that different knowledge fields can make in the near future to this exciting area

Analýza životního cyklu fosilních motorových paliv a biopaliv pro tvorbu koncepčních dokumentů zavedení daně z CO2 v oblasti mobilních zdrojů znečišťování

V rámci projektu bude řešena analýza hodnocení životního cyklu fosilních motorových paliv a biopaliv, jejichž použití se jeví jako perspektivní v současnosti a v horizontu blízké budoucnosti, ať již ve formě směsného motorového paliva, či v podobě čistého paliva. Hlavními cíli autorů studie bude vyhodnotit bilanci emisí CO2 v celém životním cyklu definovaných motorových paliv a energetickou bilanci výroby jednotlivých motorových paliv. Nad rámec současného stavu řešení LCA analýz bude také během řešení projektu zpracována analýza hodnocení ekonomických nákladů v celém životním cyklu (LCCA – Life-Cycle Cost Assessment), která bude sloužit jako podkladový materiál pro návrh zavedení daně z CO2 v oblasti mobilních zdrojů znečišťování a také pro další aplikace nástrojů, zajišťujících udržitelné využívání motorových paliv