258 research outputs found
An Efficient and Lightweight Illumination model for Planetary Bodies including Direct and Diffuse Radiation
We present a numerical illumination model to calculate direct as well as diffuse
or Hapke scattered radiation scenarios on arbitrary planetary surfaces. This includes
small body surfaces such as main belt asteroids as well as e.g. the lunar surface. The
model is based on the raytracing method. This method is not restricted to spherical
or ellipsiodal shapes but digital terrain data of arbitrary spatial resolution can be fed
into the model. Solar radiation is the source of direct radiation, wavelength-dependent effects (e.g. albedo) can be accounted for. Mutual illumination of individual bodies in implemented (e.g. in binary or multiple systems) as well as self-illumination (e.g. crater floors by crater walls) by diffuse or Hapke radiation. The model is validated by statistical methods. A chi-square test is undertaken to compare simnulated images with DAWN
images acquired during the survey phase at small body 4 Vesta
A Healthy and Ecologically Balanced Environment: An Argument for a Third Generation Right
Chymotrypsin-like serine proteases are found in high abundance in mast cell granules. By site-directed mutatgenesis, we have previously shown that basic amino acids in positions 143 and 192 (Arg and Lys respectively) of the human mast cell chymase are responsible for an acidic amino acid residue preference in the P2' position of substrates. In order to study the influence of these two residues in determining the specificity of chymase inhibitors, we have synthesized five different potent inhibitors of the human chymase. The inhibitory effects of these compounds were tested against the wild-type enzyme, against two single mutants Arg143Gln and Lys192Met and against a double mutant, Arg143Gln+Lys192Met. We observed a markedly reduced activity of all five inhibitors with the double mutant, indicating that these two basic residues are involved in conferring the specificity of these inhibitors. The single mutants showed an intermediate phenotype, with the strongest effect on the inhibitor by the mutation in Lys192. The Lys192 and the double mutations also affected the rate of cleavage of angiotensin I but did not seem to affect the specificity in the cleavage of the Tyr(4)-Ile(5) bond. A more detailed knowledge about which amino acids that confer the specificity of an enzyme can prove to be of major importance for development of highly specific inhibitors for the human chymase and other medically important enzymes
Complete genome sequences of escherichia coli phages vB_EcoM-EP75 and vB_EcoP-EP335
Phages vB_EcoM-EP75 (EP75) and vB_EcoP-EP335 (EP335) specifically infect Shiga toxin (Stx)-producing Escherichia coli (STEC) O157 strains. EP75 has a genome size of 158,143 bp and belongs to the genus Vi1virus The genome size of EP335 is 76,622 bp, and it belongs to the genus Phieco32virus
Spatial coherence control and analysis via micromirror-based mixed-state ptychography
Flexible and fast control of the phase and amplitude of coherent light,
enabled by digital micromirror devices (DMDs) and spatial light modulators
(SLMs), has been a driving force for recent advances in optical tweezers,
nonlinear microscopy, and wavefront shaping. In contrast, engineering spatially
partially coherent light remains widely elusive due to the lack of tools
enabling a joint analysis and control sequence. Here, we report an approach to
coherence engineering that combines a quasi-monochromatic, thermal source and a
DMD together with a ptychographic scanning microscope. The reported method
opens up new routes to low-cost coherence control, with applications in
micromanipulation, nanophotonics, and quantitative phase contrast imaging
Genetic variants of chemokine receptor CCR7 in patients with systemic lupus erythematosus, Sjogren's syndrome and systemic sclerosis
<p>Abstract</p> <p>Background</p> <p>The chemokine receptor CCR7 is a key organizer of the immune system. Gene targeting in mice revealed that Ccr7-deficient animals are severely impaired in the induction of central and peripheral tolerance. Due to these defects, Ccr7-deficient mice spontaneously develop multi-organ autoimmunity showing symptoms similar to those observed in humans suffering from connective tissue autoimmune diseases. However, it is unknown whether mutations of <it>CCR7 </it>are linked to autoimmunity in humans.</p> <p>Results</p> <p>DNA samples were collected from 160 patients suffering from connective tissue autoimmune disease (Sjogren's syndrome, n = 40; systemic lupus erythematosus, SLE, n = 20 and systemic sclerosis, n = 100) and 40 health subjects (n = 40). All participants in this study were of German descent. Samples were screened for single nucleotide polymorphisms (SNP) by sequencing the coding region of the <it>CCR7 </it>gene as well asthe exon flaking intron sites and parts of the regions encoding for the 5'- and 3'-UTR. <it>CCR7 </it>variants were rare. We identified six different sequence variants, which occurred in heterozygosis. The identified SNP were observed at position -60 C/T (observed 1x), +6,476 A/G (7x), +6,555 C/T (15x), +6,560 C/T (6x), +10,440 A/G (3x) and +11,475 C/A (1x). Four of these variants (+6,476 A/G, +6,555 C/T, +6,560 C/T and +10,440 A/G) display allelic frequencies between 1% and 5 % and were present in both patients and control groups. The variants +6,476 A/G, +6,555 C/T, +6,560 C/T are located in the intron 2, while the +10,440 A/G variant corresponds to a silent mutation in exon 3. The variants -60 C/T and +11,475 C/A which are located at the 5'-UTR and 3-UTR respectively, display allelic frequencies below 1%. No correlation between these variants and the autoimmune diseases investigated could be observed. However, reporter gene expression assay demonstrated that the mutation at the -60 C/T position in homozygosis leads to reduced luciferase activity.</p> <p>Conclusion</p> <p>These results suggest that variants of <it>CCR7 </it>gene occur at an extremely low frequency in the German population and that neither Sjogren's syndrome, systemic lupus erythematosus, nor systemic sclerosis are associated with these variants. Nevertheless, the decreased luciferase activity observed in cells transfected with the promoter region bearing the -60 C/T mutation suggests that this <it>CCR7 </it>variant could potentially lead to increased susceptibility to autoimmunity.</p
Late-Time Correlators and Complex Geodesics in de Sitter Space
We study two-point correlation functions of a massive free scalar field in de
Sitter space using the heat kernel formalism. Focusing on two operators in
conjugate static patches we derive a geodesic approximation to the two-point
correlator valid for large mass and at late times. This expression involves a
sum over two complex conjugate geodesics that correctly reproduces the
large-mass, late-time limit of the exact two-point function in the Bunch-Davies
vacuum. The exponential decay of the late-time correlator is associated to the
timelike part of the complex geodesics. We emphasize that the late-time
exponential decay is in tension with the finite maximal entropy of empty de
Sitter space, and we briefly discuss how non-perturbative corrections might
resolve this paradox.Comment: 18 pages, 8 figures. v2: 19 pages + 2 pages appendices, 11 figures.
Matches published versio
DEVELOPMENT OF A DEPLOYABLE DECELERATOR CONCEPT FOR SMALL MARS LANDERS
Small exploration spacecraft and landers have proven to be
scientifically useful and capable with missions such as Philae
or Hayabusa 2. For the exploration of planetary bodies with
atmospheres, novel and efficient entry, descent and landing
(EDL) technologies are being explored. One of these concepts is the rigid deployable decelerator, which would be an
alternative to existing EDL systems if proven to be feasible.
For a Mars micro lander mission with an entry mass of 25 kg
and a ballistic coefficient of 3:5 kg=m2, a concept for a deployable decelerator was developed. First, a flow-field analysis of different possible geometries of the deployed structure
with Ansys Fluent was performed. From this, the pressure
and temperature distribution and qualitatively the heat flux
density along the profile wall of each geometry were determined. Subsequently, for a conical geometry, a design for
a deployment mechanism was developed based on the umbrella concept, where a deployable structure spans a flexible
thermally resistant cloth. The mechanism developed is a combination of folding parallelised struts, similar to an umbrella,
and telescopic rods. Focusing on the strut structure and based
on the results of the flow field analysis, with Ansys it was then
investigated whether the design can in principle withstand the
mechanical loads generated by the maximum dynamic pressure and how the temperature behind the deployed cloth is
distributed under the maximum thermal load
Deployment dynamics analysis of CALLISTO’s approach and landing system
Prior to landing of reusable space transportation systems, the vehicle’s landing legs needs to be fully deployed to enable a safe landing and further re-use of the space vehicle. During that phase the deployment system has to overcome harsh and challenging environmental conditions. In this study, a numerical simulator is developed in order to investigate these influences on the landing leg deployment dynamics. By means of an extensive aerodynamic database and a broad approach flight domain, the influence of aerodynamics, exhaust plume, and vehicle’s attitude on the deployment dynamics is analyzed. This study shows on the example of the first stage demonstrator CALLISTO (Cooperative Action Leading to Launcher Innovation in Stage Toss back Operations), that thrust level, vehicle attitude, and the deployment system parameters affect the deployment performance
Cyclophilin inhibitors restrict Middle East respiratory syndrome coronavirus via interferon-λ in vitro and in mice
While severe coronavirus infections, including Middle East respiratory syndrome coronavirus (MERS-CoV), cause lung injury with high mortality rates, protective treatment strategies are not approved for clinical use.
We elucidated the molecular mechanisms by which the cyclophilin inhibitors cyclosporin A (CsA) and alisporivir (ALV) restrict MERS-CoV to validate their suitability as readily available therapy in MERS-CoV infection.
Calu-3 cells and primary human alveolar epithelial cells (hAECs) were infected with MERS-CoV and treated with CsA or ALV or inhibitors targeting cyclophilin inhibitor-regulated molecules including calcineurin, nuclear factor of activated T-cells (NFATs) or mitogen-activated protein kinases. Novel CsA-induced pathways were identified by RNA sequencing and manipulated by gene knockdown or neutralising antibodies. Viral replication was quantified by quantitative real-time PCR and 50% tissue culture infective dose. Data were validated in a murine MERS-CoV infection model.
Both CsA and ALV reduced MERS-CoV titres and viral RNA replication in Calu-3 cells and hAECs, improving epithelial integrity. While neither calcineurin nor NFAT inhibition reduced MERS-CoV propagation, blockade of c-Jun N-terminal kinase diminished infectious viral particle release but not RNA accumulation. Importantly, CsA induced interferon regulatory factor 1 (IRF1), a pronounced type III interferon (IFNλ) response and expression of antiviral genes. Downregulation of IRF1 or IFNλ increased MERS-CoV propagation in the presence of CsA. Importantly, oral application of CsA reduced MERS-CoV replication in vivo, correlating with elevated lung IFNλ levels and improved outcome.
We provide evidence that cyclophilin inhibitors efficiently decrease MERS-CoV replication in vitro and in vivo via upregulation of inflammatory antiviral cell responses, in particular IFNλ. CsA might therefore represent a promising candidate for treating MERS-CoV infection
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