Serum Lipid Studies in Multiple Sclerosis

Peer Reviewe

Vault-1 - A Mission Architecture for Human Exploration of Near-Earth Objects

In 2011, the Keck Institute for Space Studies hosted the Caltech Space Challenge, a week long workshop/competition directed towards the President's initiative of sending astronauts to an asteroid by 2025. Two teams composed of 16 students each, representing 12 different nations, competed to prepare a mission proposal by the end of the week. This report highlights some of the work done by Team Voyager. Not only is this work useful in showing that a manned mission to a Near-Earth Object is feasible by 2025, but it also demonstrates the utility of intense, relatively short student competitions. This study is an outline of Vault-1, a proposed human mission to a Near-Earth Object. In addition to continuing human exploration, Vault-1 aims to make new discoveries about the origins of the Solar System, to develop technologies geared towards deep space exploration and a manned Mars mission, and to gain critical knowledge and experience to better protect Earth from future asteroid impacts. The primary target of this endeavor is 1999AO10, an asteroid that is larger than 30 m that also has an achievable mission duration of less than 200 days. 2000SG344 is a viable secondary target. Vault-1 will nominally carry 3 crew members to 1999AO10; after 14 days at the asteroid, the astronauts will return safely to the Earth with samples from the asteroid

Ignition characteristics of dual-fuel methane-n-hexane-oxygen-diluent mixtures in a rapid compression machine and a shock tube

Ignition delay times of methane-n-hexane-oxygen-dulent mixtures were studied experimentally and numerically in a wide temperature range (640–2335 K) using both a rapid compression machine (RCM) and a shock tube (ST). The RCM results demonstrated a two-stage ignition and negative temperature coefficient (NTC) behavior. Increasing n-hexane concentration, pressure and equivalence ratio shortened the ignition delay time. For the ST experiments, the addition of 10% n-hexane (relative to methane) can reduce the ignition delay time dramatically. However, no further reduction effect can be achieved with increasing addition of n-hexane from 10% to 20%. In addition, increasing equivalence ratio reduces the effect of n-hexane addition on ignition delay time. Three detailed chemical mechanisms, CaltechMech, GalwayMech and LLNLMech, were evaluated based on a quantitative error analysis. LLNLMech and CaltechMech demonstrated the best performance in the RCM and ST temperature ranges, respectively. Chemical kinetic analyses showed that the addition of n-hexane to methane provides some chemical pathways not available for methane oxidation which result in the production of active radicals and eventually accelerate the ignition of the methane-oxygen mixtures. The crucial intermediate species for the ignition process are H_2O_2 and H under RCM and ST conditions, respectively

Comparative proteomic profiling reveals mechanisms for early spinal cord vulnerability in CLN1 disease

CLN1 disease is a fatal inherited neurodegenerative lysosomal storage disease of early childhood, caused by mutations in the CLN1 gene, which encodes the enzyme Palmitoyl protein thioesterase-1 (PPT-1). We recently found significant spinal pathology in Ppt1-deficient (Ppt1−/−) mice and human CLN1 disease that contributes to clinical outcome and precedes the onset of brain pathology. Here, we quantified this spinal pathology at 3 and 7 months of age revealing significant and progressive glial activation and vulnerability of spinal interneurons. Tandem mass tagged proteomic analysis of the spinal cord of Ppt1−/−and control mice at these timepoints revealed a significant neuroimmune response and changes in mitochondrial function, cell-signalling pathways and developmental processes. Comparing proteomic changes in the spinal cord and cortex at 3 months revealed many similarly affected processes, except the inflammatory response. These proteomic and pathological data from this largely unexplored region of the CNS may help explain the limited success of previous brain-directed therapies. These data also fundamentally change our understanding of the progressive, site-specific nature of CLN1 disease pathogenesis, and highlight the importance of the neuroimmune response. This should greatly impact our approach to the timing and targeting of future therapeutic trials for this and similar disorders

Genes Involved in Systemic and Arterial Bed Dependent Atherosclerosis - Tampere Vascular Study

BACKGROUND: Atherosclerosis is a complex disease with hundreds of genes influencing its progression. In addition, the phenotype of the disease varies significantly depending on the arterial bed. METHODOLOGY/PRINCIPAL FINDINGS: We characterized the genes generally involved in human advanced atherosclerotic (AHA type V-VI) plaques in carotid and femoral arteries as well as aortas from 24 subjects of Tampere Vascular study and compared the results to non-atherosclerotic internal thoracic arteries (n=6) using genome-wide expression array and QRT-PCR. In addition we determined genes that were typical for each arterial plaque studied. To gain a comprehensive insight into the pathologic processes in the plaques we also analyzed pathways and gene sets dysregulated in this disease using gene set enrichment analysis (GSEA). According to the selection criteria used (>3.0 fold change and p-value <0.05), 235 genes were up-regulated and 68 genes down-regulated in the carotid plaques, 242 genes up-regulated and 116 down-regulated in the femoral plaques and 256 genes up-regulated and 49 genes down-regulated in the aortic plaques. Nine genes were found to be specifically induced predominantly in aortic plaques, e.g., lactoferrin, and three genes in femoral plaques, e.g., chondroadherin, whereas no gene was found to be specific for carotid plaques. In pathway analysis, a total of 28 pathways or gene sets were found to be significantly dysregulated in atherosclerotic plaques (false discovery rate [FDR] <0.25). CONCLUSIONS: This study describes comprehensively the gene expression changes that generally prevail in human atherosclerotic plaques. In addition, site specific genes induced only in femoral or aortic plaques were found, reflecting that atherosclerotic process has unique features in different vascular beds