A cascaded laser acceleration scheme for the generation of spectrally controlled proton beams

We present a novel, cascaded acceleration scheme for the generation of spectrally controlled ion beams using a laser-based accelerator in a 'double-stage' setup. An MeV proton beam produced during a relativistic laser–plasma interaction on a thin foil target is spectrally shaped by a secondary laser–plasma interaction on a separate foil, reliably creating well-separated quasi-monoenergetic features in the energy spectrum. The observed modulations are fully explained by a one-dimensional (1D) model supported by numerical simulations. These findings demonstrate that laser acceleration can, in principle, be applied in an additive manner.Deutsche Forschungsgemeinschaft (DFG contract no. TR18)Deutsche Forschungsgemeinschaft (contract no. 03ZIK052)European Union (Laserlab Europe

Characterization and social correlates of fecal testosterone and cortisol excretion in wild male Saguinus mystax

Reproductive success in male primates can be influenced by testosterone (T) and cortisol (C). We examined them in wild Saguinus mystax via fecal hormone analysis. Firstly, we wanted to characterize male hormonal status over the course of the year. Further we tested the influence of the reproductive status of the breeding female, social instability, and intergroup encounter rates on T levels, comparing the results with predictions of the challenge hypothesis (Wingfield et al., 1990). We also tested for interindividual differences in hormonal levels, possibly related to social or breeding status. We collected data during a 12-mo study on 2 groups of moustached tamarins at the Estación Biológica Quebrada Blanco in northeastern Peru. We found fairly similar T and C levels over the course of the year for all males. Yet an elevation of T shortly after the birth of infants, during the phase of ovarian inactivity of the group’s breeding female, was evident. Hormonal levels were not significantly elevated during a phase of social instability, did not correlate with intergroup encounter rates, and did not differ between breeding and nonbreeding males. Our results confirm the challenge hypothesis (Wingfield et al., 1990). The data suggest that reproductive competition inmoustached tamarins is not based on endocrinological, but instead on behavioral mechanisms, possibly combined with sperm competition.Deutsche Forschungsgemeinschaft (HE 1870/10-1,2

Mapping the Complex Morphology of Cell Interactions with Nanowire Substrates Using FIB-SEM

Using high resolution focused ion beam scanning electron microscopy (FIB-SEM) we study the details of cell-nanostructure interactions using serial block face imaging. 3T3 Fibroblast cellular monolayers are cultured on flat glass as a control surface and on two types of nanostructured scaffold substrates made from silicon black (Nanograss) with low- and high nanowire density. After culturing for 72 hours the cells were fixed, heavy metal stained, embedded in resin, and processed with FIB-SEM block face imaging without removing the substrate. The sample preparation procedure, image acquisition and image post-processing were specifically optimised for cellular monolayers cultured on nanostructured substrates. Cells display a wide range of interactions with the nanostructures depending on the surface morphology, but also greatly varying from one cell to another on the same substrate, illustrating a wide phenotypic variability. Depending on the substrate and cell, we observe that cells could for instance: break the nanowires and engulf them, flatten the nanowires or simply reside on top of them. Given the complexity of interactions, we have categorised our observations and created an overview map. The results demonstrate that detailed nanoscale resolution images are required to begin understanding the wide variety of individual cells' interactions with a structured substrate. The map will provide a framework for light microscopy studies of such interactions indicating what modes of interactions must be considered

The structure of HIV-1 Rev filaments suggests a bilateral model for Rev-RRE assembly.

HIV-1 Rev protein mediates the nuclear export of viral RNA genomes. To do so, Rev oligomerizes cooperatively onto an RNA motif, the Rev-response element (RRE), forming a complex that engages with the host nuclear export machinery. To better understand Rev oligomerization, we determined four crystal structures of Rev N-terminal domain dimers, which show that they can pivot about their dyad axis, giving crossing-angles of 90° to 140° . In parallel, we performed cryo-EM of helical Rev filaments. Filaments vary from 11 to 15 nm in width, reflecting variations in dimer crossing-angle. These structures contain additional density, indicating that C-terminal domains become partially ordered in the context of filaments. This conformational variability may be exploited in the assembly of RRE/Rev complexes. Our data also revealed a third interface between Revs which offers an explanation for how the arrangement of Rev subunits adapts to the ‘A’-shaped architecture of the RRE in export-active complexes

FtsZ induces membrane deformations via torsional stress upon GTP hydrolysis

FtsZ is a key component in bacterial cell division, being the primary protein of the presumably contractile Z ring. In vivo and in vitro, it shows two distinctive features that could so far, however, not be mechanistically linked: self-organization into directionally treadmilling vortices on solid supported membranes, and shape deformation of flexible liposomes. In cells, circumferential treadmilling of FtsZ was shown to recruit septum-building enzymes, but an active force production remains elusive. To gain mechanistic understanding of FtsZ dependent membrane deformations and constriction, we design an in vitro assay based on soft lipid tubes pulled from FtsZ decorated giant lipid vesicles (GUVs) by optical tweezers. FtsZ filaments actively transform these tubes into spring-like structures, where GTPase activity promotes spring compression. Operating the optical tweezers in lateral vibration mode and assigning spring constants to FtsZ coated tubes, the directional forces that FtsZ-YFP-mts rings exert upon GTP hydrolysis can be estimated to be in the pN range. They are sufficient to induce membrane budding with constricting necks on both, giant vesicles and E.coli cells devoid of their cell walls. We hypothesize that these forces result from torsional stress in a GTPase activity dependent manner.Projekt DEALFederal Ministry of Education and Research of GermanyDeutsche ForschungsgemeinschaftMax-Planck-Gesellschaf

2017 EACTS/EACTA Guidelines on patient blood management for adult cardiac surgery

Authors/Task Force Members: Christa Boer (EACTA Chairperson)(Netherlands), Michael I. Meesters (Netherlands), Milan Milojevic (Netherlands), Umberto Benedetto (UK), Daniel Bolliger (Switzerland), Christian von Heymann (Germany), Anders Jeppsson (Sweden), Andreas Koster (Germany), Ruben L. Osnabrugge (Netherlands), Marco Ranucci (Italy), Hanne Berg Ravn (Denmark), Alexander B.A. Vonk (Netherlands), Alexander Wahba (Norway), Domenico Pagano (EACTS Chairperson)(UK),. Document Reviewers: Moritz W.V. Wyler von Ballmoos (USA), Mate Petricevic (Croatia), Arie Pieter Kappetein (Netherlands), Miguel Sousa-Uva (Portugal), Georg Trummer (Germany), Peter M. Rosseel (Netherlands), Michael Sander (Germany), Pascal Colson (France), Adrian Bauer (Germany)

Precision 3D‐printed cell scaffolds mimicking native tissue composition and mechanics

Cellular dynamics are modeled by the 3D architecture and mechanics of the extracellular matrix (ECM) and vice versa. These bidirectional cell‐ECM interactions are the basis for all vital tissues, many of which have been investigated in 2D environments over the last decades. Experimental approaches to mimic in vivo cell niches in 3D with the highest biological conformity and resolution can enable new insights into these cell‐ECM interactions including proliferation, differentiation, migration, and invasion assays. Here, two‐photon stereolithography is adopted to print up to mm‐sized high‐precision 3D cell scaffolds at micrometer resolution with defined mechanical properties from protein‐based resins, such as bovine serum albumin or gelatin methacryloyl. By modifying the manufacturing process including two‐pass printing or post‐print crosslinking, high precision scaffolds with varying Young's moduli ranging from 7‐300 kPa are printed and quantified through atomic force microscopy. The impact of varying scaffold topographies on the dynamics of colonizing cells is observed using mouse myoblast cells and a 3D‐lung microtissue replica colonized with primary human lung fibroblast. This approach will allow for a systematic investigation of single‐cell and tissue dynamics in response to defined mechanical and bio‐molecular cues and is ultimately scalable to full organs

Communicable Diseases Prioritized for Surveillance and Epidemiological Research: Results of a Standardized Prioritization Procedure in Germany, 2011

To establish strategic priorities for the German national public health institute (RKI) and guide the institute's mid-term strategic decisions, we prioritized infectious pathogens in accordance with their importance for national surveillance and epidemiological research.We used the Delphi process with internal (RKI) and external experts and a metric-consensus approach to score pathogens according to ten three-tiered criteria. Additional experts were invited to weight each criterion, leading to the calculation of a median weight by which each score was multiplied. We ranked the pathogens according to the total weighted score and divided them into four priority groups.., Respiratory syncytial virus or Hantavirus) indicate a possible under-recognised importance within the current German public health framework. A process to strengthen respective surveillance systems and research has been started. The prioritization methodology has worked well; its modular structure makes it potentially useful for other settings

Rapid sample delivery for megahertz serial crystallography at X-ray FELs

Liquid microjets are a common means of delivering protein crystals to the focus of X-ray free-electron lasers (FELs) for serial femtosecond crystallography measurements. The high X-ray intensity in the focus initiates an explosion of the microjet and sample. With the advent of X-ray FELs with megahertz rates, the typical velocities of these jets must be increased significantly in order to replenish the damaged material in time for the subsequent measurement with the next X-ray pulse. This work reports the results of a megahertz serial diffraction experiment at the FLASH FEL facility using 4.3 nm radiation. The operation of gas-dynamic nozzles that produce liquid microjets with velocities greater than 80 m s-1 was demonstrated. Furthermore, this article provides optical images of X-ray-induced explosions together with Bragg diffraction from protein microcrystals exposed to trains of X-ray pulses repeating at rates of up to 4.5 MHz. The results indicate the feasibility for megahertz serial crystallography measurements with hard X-rays and give guidance for the design of such experiments

Evaluating Temporal Factors in Combined Interventions of Workforce Shift and School Closure for Mitigating the Spread of Influenza

10.1371/journal.pone.0032203PLoS ONE7