Active Thermal Architecture for Cryogenic Optical Instrumentation (ATACOI)

The Active Thermal Architecture for Cryogenic Optical Instrumentation (ATACOI) project will demonstrate an advanced thermal control system for CubeSats and enable the use of cryogenic electro-optical instrumentation on small satellite platforms. Specifically, the project focuses on the development of a deployable solar tracking radiator, a rotationally flexible rotary union fluid joint, and a thermal/vibrational isolation system for miniature cryogenic detectors. This technology will represent a significant improvement over the current state of the art for CubeSat thermal control, which generally relies on simple passive and conductive methods

Structure and Mechanism of a Metal-Sensing Regulatory RNA

SummaryOrganisms maintain the correct balance of intracellular metals primarily through metal-sensing proteins that control transport and storage of the target ion(s). Here, we reveal the basis of metal sensing and genetic control by a metalloregulatory RNA. Our data demonstrate that a previously uncharacterized orphan riboswitch, renamed the “M-box,” is a divalent metal-sensing RNA involved in Mg2+ homeostasis. A combination of genetic, biochemical, and biophysical techniques demonstrate that Mg2+ induces a compacted tertiary architecture for M-box RNAs that regulates the accessibility of nucleotides involved in genetic control. Molecular details are provided by crystallographic structure determination of a Mg2+-bound M-box RNA. Given the distribution of this RNA element, it may constitute a common mode for bacterial metal ion regulation, and its discovery suggests the possibility of additional RNA-based metal sensors in modern and primordial organisms

Hydra: software for tailored processing of H/D exchange data from MS or tandem MS analyses

<p>Abstract</p> <p>Background</p> <p>Hydrogen/deuterium exchange mass spectrometry (H/DX-MS) experiments implemented to characterize protein interaction and protein folding generate large quantities of data. Organizing, processing and visualizing data requires an automated solution, particularly when accommodating new tandem mass spectrometry modes for H/DX measurement. We sought to develop software that offers flexibility in defining workflows so as to support exploratory treatments of H/DX-MS data, with a particular focus on the analysis of very large protein systems and the mining of tandem mass spectrometry data.</p> <p>Results</p> <p>We present a software package ("Hydra") that supports both traditional and exploratory treatments of H/DX-MS data. Hydra's software architecture tolerates flexible data analysis procedures by allowing the addition of new algorithms without significant change to the underlying code base. Convenient user interfaces ease the organization of raw data files and input of peptide data. After executing a user-defined workflow, extracted deuterium incorporation values can be visualized in tabular and graphical formats. Hydra also automates the extraction and visualization of deuterium distribution values. Manual validation and assessment of results is aided by an interface that aligns extracted ion chromatograms and mass spectra, while providing a means of rapidly reprocessing the data following manual adjustment. A unique feature of Hydra is the automated processing of tandem mass spectrometry data, demonstrated on a large test data set in which 40,000 deuterium incorporation values were extracted from replicate analysis of approximately 1000 fragment ions in one hour using a typical PC.</p> <p>Conclusion</p> <p>The customizable workflows and user-friendly interfaces of Hydra removes a significant bottleneck in processing and visualizing H/DX-MS data and helps the researcher spend more time executing new experiments and interpreting results. This increased efficiency will encourage the analysis of larger protein systems. The ability to accommodate the tandem MS dimension supports alternative data collection and analysis strategies, as well as higher resolution localization of deuteration where permitted by the fragmentation mechanism.</p

The Continuous Skolem-Pisot Problem: On the Complexity of Reachability for Linear Ordinary Differential Equations

We study decidability and complexity questions related to a continuous analogue of the Skolem-Pisot problem concerning the zeros and nonnegativity of a linear recurrent sequence. In particular, we show that the continuous version of the nonnegativity problem is NP-hard in general and we show that the presence of a zero is decidable for several subcases, including instances of depth two or less, although the decidability in general is left open. The problems may also be stated as reachability problems related to real zeros of exponential polynomials or solutions to initial value problems of linear differential equations, which are interesting problems in their own right.Comment: 14 pages, no figur

Regulation of heparanase expression in coronary artery disease in diabetic, hyperlipidemic swine

Objective Enzymatic degradation of the extracellular matrix is known to be powerful regulator of atherosclerosis. However, little is known about the enzymatic regulation of heparan sulfate proteoglycans (HSPGs) during the formation and progression of atherosclerotic plaques. Methods and results Swine were rendered diabetic through streptozotocin injection and hyperlipidemic through a high fat diet. Arterial remodeling and local endothelial shear stress (ESS) were assessed using intravascular ultrasound, coronary angiography and computational fluid dynamics at weeks 23 and 30. Coronary arteries were harvested and 142 arterial subsegments were analyzed using histomorphologic staining, immunostaining and real time PCR. Heparanase staining and activity was increased in arterial segments with low ESS, in lesions with thin cap fibroatheroma (TCFA) morphology and in lesions with severely degraded internal elastic laminae. In addition, heparanase staining co-localized with staining for CD45 and MMP-2 within atherosclerotic plaques. Dual staining with gelatinase zymography and heparanase immunohistochemical staining demonstrated co-localization of matrix metalloprotease activity with heparanase staining. A heparanase enzymatic activity assay demonstrated increased activity in TCFA lesions, subsegments with low ESS and in macrophages treated with oxidized LDL or angiotensin II. Conclusions Taken together, our results support a critical role for heparanase in the development of vulnerable plaques and suggest a novel therapeutic target for the treatment of atherosclerosis.Novartis (Firm)Boston Scientific CorporationNational Institutes of Health (U.S.) (Grant R01 GM49039