362 research outputs found
Dexterous Orbital Servicing System (DOSS)
The Dexterous Orbiter Servicing System (DOSS) is a dexterous robotic spaceflight system that is based on the manipulator designed as part of the Flight Telerobotics Servicer program for the Space Station Freedom and built during a 'technology capture' effort that was commissioned when the FTS was cancelled from the Space Station Freedom program. The FTS technology capture effort yielded one flight manipulator and the 1 g hydraulic simulator that had been designed as an integrated test tool and crew trainer. The DOSS concept was developed to satisfy needs of the telerobotics research community, the space shuttle, and the space station. As a flight testbed, DOSS would serve as a baseline reference for testing the performance of advanced telerobotics and intelligent robotics components. For shuttle, the DOSS, configured as a movable dexterous tool, would be used to provide operational flexibility for payload operations and contingency operations. As a risk mitigation flight demonstration, the DOSS would serve the International Space Station to characterize the end to end system performance of the Special Purpose Dexterous Manipulator performing assembly and maintenance tasks with actual ISSA orbital replacement units. Currently, the most likely entrance of the DOSS into spaceflight is a risk mitigation flight experiment for the International Space Station
Shuttle-launch triangular space station
A triangular space station deployable in orbit is described. The framework is comprized of three trusses, formed of a pair of generally planar faces consistine of foldable struts. The struts expand and lock into rigid structural engagement forming a repetition of equilater triangles and nonfolding diagonal struts interconnecting the two faces. The struts are joined together by node fittings. The framework can be packaged into a size and configuration transportable by a space shuttle. When deployed, the framework provides a large work/construction area and ample planar surface area for solar panels and thermal radiators. A plurity of modules are secured to the framework and then joined by tunnels to make an interconnected modular display. Thruster units for the space station orientation and altitude maintenance are provided
Advanced cryo-tomography workflow developments - correlative microscopy, milling automation and cryo-lift-out
Cryo-electron tomography (cryo-ET) is a groundbreaking technology for 3D visualisation and analysis of biomolecules in the context of cellular structures. It allows structural investigations of single proteins as well as their spatial arrangements within the cell. Cryo-tomograms provide a snapshot of the complex, heterogeneous and transient subcellular environment. Due to the excellent structure preservation in amorphous ice, it is possible to study interactions and spatial relationships of proteins in their native state without interference caused by chemical fixatives or contrasting agents. With the introduction of focused ion beam (FIB) technology, the preparation of cellular samples for electron tomography has become much easier and faster. The latest generation of integrated FIB and scanning electron microscopy (SEM) instruments (dual beam microscopes), specifically designed for cryo-applications, provides advances in automation, imaging and the preparation of high-pressure frozen bulk samples using cryo-lift-out technology. In addition, correlative cryo-fluorescence microscopy provides cellular targeting information through integrated software and hardware interfaces. The rapid advances, based on the combination of correlative cryo-microscopy, cryo-FIB and cryo-ET, have already led to a wealth of new insights into cellular processes and provided new 3D image data of the cell. Here we introduce our recent developments within the cryo-tomography workflow, and we discuss the challenges that lie ahead. Lay Description This article describes our recent developments for the cryo-electron tomography (cryo-ET) workflow. Cryo-ET offers superior structural preservation and provides 3D snapshots of the interior of vitrified cells at molecular resolution. Before a cellular sample can be imaged by cryo-ET, it must be made accessible for transmission electron microscopy. This is achieved by preparing a 200-300 nm thin cryo-lamella from the cellular sample using a cryo-focused ion beam (cryo-FIB) microscope. Cryo-correlative light and electron microscopy (cryo-CLEM) is used within the workflow to guide the cryo-lamella preparation to the cellular areas of interest. We cover a basic introduction of the cryo-ET workflow and show new developments for cryo-CLEM, which facilitate the connection between the cryo-light microscope and the cryo-FIB. Next, we present our progress in cryo-FIB software automation to streamline cryo-lamella preparation. In the final section we demonstrate how the cryo-FIB can be used for 3D imaging and how bulk-frozen cellular samples (obtained by high-pressure freezing) can be processed using the newly developed cryo-lift-out technology
Analysis of Stochastic Strategies in Bacterial Competence: A Master Equation Approach
Competence is a transiently differentiated state that certain bacterial cells reach when faced with a stressful environment. Entrance into competence can be attributed to the excitability of the dynamics governing the genetic circuit that regulates this cellular behavior. Like many biological behaviors, entrance into competence is a stochastic event. In this case cellular noise is responsible for driving the cell from a vegetative state into competence and back. In this work we present a novel numerical method for the analysis of stochastic biochemical events and use it to study the excitable dynamics responsible for competence in Bacillus subtilis. Starting with a Finite State Projection (FSP) solution of the chemical master equation (CME), we develop efficient numerical tools for accurately computing competence probability. Additionally, we propose a new approach for the sensitivity analysis of stochastic events and utilize it to elucidate the robustness properties of the competence regulatory genetic circuit. We also propose and implement a numerical method to calculate the expected time it takes a cell to return from competence. Although this study is focused on an example of cell-differentiation in Bacillus subtilis, our approach can be applied to a wide range of stochastic phenomena in biological systems
Determination of scattering lengths from measurement of atom lifetime
The DIRAC experiment at CERN has achieved a sizeable production of
atoms and has significantly improved the precision on its lifetime
determination. From a sample of 21227 atomic pairs, a 4% measurement of the
S-wave scattering length difference
has been attained, providing an important test of Chiral Perturbation Theory.Comment: 6 pages, 6 figure
Numerical Weather Prediction (NWP) and hybrid ARMA/ANN model to predict global radiation
We propose in this paper an original technique to predict global radiation
using a hybrid ARMA/ANN model and data issued from a numerical weather
prediction model (ALADIN). We particularly look at the Multi-Layer Perceptron.
After optimizing our architecture with ALADIN and endogenous data previously
made stationary and using an innovative pre-input layer selection method, we
combined it to an ARMA model from a rule based on the analysis of hourly data
series. This model has been used to forecast the hourly global radiation for
five places in Mediterranean area. Our technique outperforms classical models
for all the places. The nRMSE for our hybrid model ANN/ARMA is 14.9% compared
to 26.2% for the na\"ive persistence predictor. Note that in the stand alone
ANN case the nRMSE is 18.4%. Finally, in order to discuss the reliability of
the forecaster outputs, a complementary study concerning the confidence
interval of each prediction is proposedComment: Energy (2012)
The Transcriptional Regulator Rok Binds A+T-Rich DNA and Is Involved in Repression of a Mobile Genetic Element in Bacillus subtilis
The rok gene of Bacillus subtilis was identified as a negative regulator of competence development. It also controls expression of several genes not related to competence. We found that Rok binds to extended regions of the B. subtilis genome. These regions are characterized by a high A+T content and are known or believed to have been acquired by horizontal gene transfer. Some of the Rok binding regions are in known mobile genetic elements. A deletion of rok resulted in higher excision of one such element, ICEBs1, a conjugative transposon found integrated in the B. subtilis genome. When expressed in the Gram negative E. coli, Rok also associated with A+T-rich DNA and a conserved C-terminal region of Rok contributed to this association. Together with previous work, our findings indicate that Rok is a nucleoid associated protein that serves to help repress expression of A+T-rich genes, many of which appear to have been acquired by horizontal gene transfer. In these ways, Rok appears to be functionally analogous to H-NS, a nucleoid associated protein found in Gram negative bacteria and Lsr2 of high G+C Mycobacteria
Convergence of Free Energy Profile of Coumarin in Lipid Bilayer
Atomistic molecular dynamics (MD) simulations of druglike
molecules
embedded in lipid bilayers are of considerable interest as models
for drug penetration and positioning in biological membranes. Here
we analyze partitioning of coumarin in dioleoylphosphatidylcholine
(DOPC) bilayer, based on both multiple, unbiased 3 μs MD simulations
(total length) and free energy profiles along the bilayer normal calculated
by biased MD simulations (∼7 μs in total). The convergences
in time of free energy profiles calculated by both umbrella sampling
and z-constraint techniques are thoroughly analyzed. Two sets of starting
structures are also considered, one from unbiased MD simulation and
the other from “pulling” coumarin along the bilayer
normal. The structures obtained by pulling simulation contain water
defects on the lipid bilayer
surface, while those acquired from unbiased simulation have no membrane
defects. The free energy profiles converge more rapidly when starting
frames from unbiased simulations are used. In addition, z-constraint
simulation leads to more rapid convergence than umbrella sampling,
due to quicker relaxation of membrane defects. Furthermore, we show
that the choice of RESP, PRODRG, or Mulliken charges considerably
affects the resulting free energy profile of our model drug along
the bilayer normal. We recommend using z-constraint biased MD simulations
based on starting geometries acquired from unbiased MD simulations
for efficient calculation of convergent free energy profiles of druglike
molecules along bilayer normals. The calculation of free energy profile
should start with an unbiased simulation, though the polar molecules
might need a slow pulling afterward. Results obtained with the recommended
simulation protocol agree well with available experimental data for
two coumarin derivatives
Mural Cell Associated VEGF Is Required for Organotypic Vessel Formation
Background: Blood vessels comprise endothelial cells, mural cells (pericytes/vascular smooth muscle cells) and basement membrane. During angiogenesis, mural cells are recruited to sprouting endothelial cells and define a stabilizing context, comprising cell-cell contacts, secreted growth factors and extracellular matrix components, that drives vessel maturation and resistance to anti-angiogenic therapeutics. Methods and Findings: To better understand the basis for mural cell regulation of angiogenesis, we conducted high content imaging analysis on a microtiter plate format in vitro organotypic blood vessel system comprising primary human endothelial cells co-cultured with primary human mural cells. We show that endothelial cells co-cultured with mural cells undergo an extensive series of phenotypic changes reflective of several facets of blood vessel formation and maturation: Loss of cell proliferation, pathfinding-like cell migration, branching morphogenesis, basement membrane extracellular matrix protein deposition, lumen formation, anastamosis and development of a stabilized capillary-like network. This phenotypic sequence required endothelial-mural cell-cell contact, mural cell-derived VEGF and endothelial VEGFR2 signaling. Inhibiting formation of adherens junctions or basement membrane structures abrogated network formation. Notably, inhibition of mural cell VEGF expression could not be rescued by exogenous VEGF. Conclusions: These results suggest a unique role for mural cell-associated VEGF in driving vessel formation and maturation
Tools and data services registry: a community effort to document bioinformatics resources.
Life sciences are yielding huge data sets that underpin scientific discoveries fundamental to improvement in human health, agriculture and the environment. In support of these discoveries, a plethora of databases and tools are deployed, in technically complex and diverse implementations, across a spectrum of scientific disciplines. The corpus of documentation of these resources is fragmented across the Web, with much redundancy, and has lacked a common standard of information. The outcome is that scientists must often struggle to find, understand, compare and use the best resources for the task at hand.Here we present a community-driven curation effort, supported by ELIXIR-the European infrastructure for biological information-that aspires to a comprehensive and consistent registry of information about bioinformatics resources. The sustainable upkeep of this Tools and Data Services Registry is assured by a curation effort driven by and tailored to local needs, and shared amongst a network of engaged partners.As of November 2015, the registry includes 1785 resources, with depositions from 126 individual registrations including 52 institutional providers and 74 individuals. With community support, the registry can become a standard for dissemination of information about bioinformatics resources: we welcome everyone to join us in this common endeavour. The registry is freely available at https://bio.tools
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