1,784 research outputs found
An Overview and Status of NASA's Radioisotope Power Conversion Technology NRA
NASA's Advanced Radioisotope Power Systems (RPS) development program is developing next generation radioisotope power conversion technologies that will enable future missions that have requirements that can not be met by either photovoltaic systems or by current Radioisotope Power System (RPS) technology. The Advanced Power Conversion Research and Technology project of the Advanced RPS development program is funding research and technology activities through the NASA Research Announcement (NRA) 02-OSS-01, "Research Opportunities in Space Science 2002" entitled "Radioisotope Power Conversion Technology" (RPCT), August 13, 2002. The objective of the RPCT NRA is to advance the development of radioisotope power conversion technologies to provide significant improvements over the state-of-practice General Purpose Heat Source/Radioisotope Thermoelectric Generator by providing significantly higher efficiency to reduce the number of radioisotope fuel modules, and increase specific power (watts/kilogram). Other Advanced RPS goals include safety, long-life, reliability, scalability, multi-mission capability, resistance to radiation, and minimal interference with the scientific payload. Ten RPCT NRA contracts were awarded in 2003 in the areas of Brayton, Stirling, thermoelectric (TE), and thermophotovoltaic (TPV) power conversion technologies. This paper will provide an overview of the RPCT NRA, and a brief summary of accomplishments over the first 18 months but focusing on advancements made over the last 6 months
Evolution Of Feeding Shapes Swimming Kinematics Of Barnacle Naupliar Larvae: A Comparison Between Trophic Modes
A central goal in evolutionary biology is connecting morphological features with ecological functions. For marine invertebrate larvae, appendage movement determines locomotion, feeding, and predator avoidance ability. Barnacle larvae are morphologically diverse, and the morphology of non-feeding lecithotrophic nauplii are distinct from those that are planktotrophic. Lecithotrophic larvae have a more globular body shape and simplified appendages when compared with planktotrophs. However, little is known about whether and how such morphological changes affect kinematics, hydrodynamics, and ecological functions. Here, we compared the nauplii kinematics and hydrodynamics of a lecithotrophic Rhizocephalan species, Polyascus planus, against that of the planktotrophic nauplii of an intertidal barnacle, Tetraclita japonica. High-speed, micro-particle image velocimetry analysis showed that the Polyascus nauplii swam faster and had higher amplitude and more synchronous appendage beating than the Tetraclita nauplii. This fast swimming was accompanied by a faster attenuation of induced flow with distance, suggesting reduced predation risk. Tetraclita nauplii had more efficient per beat cycles with less backward displacement during the recovery stroke. This “anchoring effect” resulted from the anti-phase beating of appendages. This movement, together with a high-drag body form, likely helps direct the suction flow toward the ventral food capturing area. In sum, the tradeoff between swimming speed and predation risks may have been an important factor in the evolution of the observed larval forms
Status of NASA's Advanced Radioisotope Power Conversion Technology Research and Development
NASA s Advanced Radioisotope Power Systems (RPS) development program is funding the advancement of next generation power conversion technologies that will enable future missions that have requirements that can not be met by either the ubiquitous photovoltaic systems or by current Radioisotope Power Systems (RPS). Requirements of advanced radioisotope power systems include high efficiency and high specific power (watts/kilogram) in order to meet mission requirements with less radioisotope fuel and lower mass. Other Advanced RPS development goals include long-life, reliability, and scalability so that these systems can meet requirements for a variety of future space applications including continual operation surface missions, outer-planetary missions, and solar probe. This paper provides an update on the Radioisotope Power Conversion Technology Project which awarded ten Phase I contracts for research and development of a variety of power conversion technologies consisting of Brayton, Stirling, thermoelectrics, and thermophotovoltaics. Three of the contracts continue during the current Phase II in the areas of thermoelectric and Stirling power conversion. The accomplishments to date of the contractors, project plans, and status will be summarized
Three patients with homozygous familial hypercholesterolemia: Genomic sequencing and kindred analysis.
BackgroundHomozygous Familial Hypercholesterolemia (HoFH) is an inherited recessive condition associated with extremely high levels of low-density lipoprotein (LDL) cholesterol in affected individuals. It is usually caused by homozygous or compound heterozygous functional mutations in the LDL receptor (LDLR). A number of mutations causing FH have been reported in literature and such genetic heterogeneity presents great challenges for disease diagnosis.ObjectiveWe aim to determine the likely genetic defects responsible for three cases of pediatric HoFH in two kindreds.MethodsWe applied whole exome sequencing (WES) on the two probands to determine the likely functional variants among candidate FH genes. We additionally applied 10x Genomics (10xG) Linked-Reads whole genome sequencing (WGS) on one of the kindreds to identify potentially deleterious structural variants (SVs) underlying HoFH. A PCR-based screening assay was also established to detect the LDLR structural variant in a cohort of 641 patients with elevated LDL.ResultsIn the Caucasian kindred, the FH homozygosity can be attributed to two compound heterozygous LDLR damaging variants, an exon 12 p.G592E missense mutation and a novel 3kb exon 1 deletion. By analyzing the 10xG phased data, we ascertained that this deletion allele was most likely to have originated from a Russian ancestor. In the Mexican kindred, the strikingly elevated LDL cholesterol level can be attributed to a homozygous frameshift LDLR variant p.E113fs.ConclusionsWhile the application of WES can provide a cost-effective way of identifying the genetic causes of FH, it often lacks sensitivity for detecting structural variants. Our finding of the LDLR exon 1 deletion highlights the broader utility of Linked-Read WGS in detecting SVs in the clinical setting, especially when HoFH patients remain undiagnosed after WES
A Tail’s Tale: Biomechanical Roles Of Dorsal Thoracic Spine Of Barnacle Nauplii
Many marine invertebrates have complex life histories that begin with a planktonic larval stage. Similar to other plankton, these larval invertebrates often possess protruding body extensions, but their function beyond predator deterrence is not well-documented. For example, the planktonic nauplii of crustaceans have spines. Using the epibiotic pedunculate barnacle Octolasmis spp., we investigated how the dorsal thoracic spine affects swimming and fluid disturbance by comparing nauplii with their spines partially removed against those with intact spines. Our motion analysis showed that amputated Octolasmis spp. swam slower, in jerkier trajectories, and were less efficient per stroke cycle than those with intact spines. Amputees showed alterations in limb beat pattern: larger beat amplitude, increased phase lag, and reduced contralateral symmetry. These changes might partially help increase propulsive force generation and streamline the flow, but were insufficient to restore full function. Particle image velocimetry further showed that amputees had a larger relative area of influence, implying elevated risk by rheotactic predator. Body extensions and their interactions with limb motion play important biomechanical roles in shaping larval performance, which likely influences the evolution of form
The pathogenesis of cingulate atrophy in behavioral variant frontotemporal dementia and Alzheimer’s disease
BACKGROUND: Early atrophy of the cingulate cortex is a feature of both behavioral variant frontotemporal dementia (bvFTD) and Alzheimer’s disease (AD), with degeneration of the anterior cingulate region increasingly recognized as a strong predictor of bvFTD. The total number of neurons in this region, rather than the density of neurons, is associated with mood disturbance in other dementias, although there are no data on the extent and magnitude of neuronal loss in patients with bvFTD. While the density of small populations of neurons in this region has been assessed, it is unlikely that the degree of atrophy of the cingulate cortex seen in bvFTD can be explained by the loss of these subpopulations. This suggests that there is more generalized degeneration of neurons in this region in bvFTD. The present study assesses total neuronal number, as well as characteristic pathologies, in the anterior and posterior cingulate cortices of pathologically confirmed bvFTD (N = 11) and AD (N = 9) patients compared with age-matched controls (N = 14). The bvFTD cohort comprised 5 cases with tau pathology (Pick’s disease), and 6 with TDP-43 pathology. RESULTS: At postmortem, atrophy was detected in the anterior and posterior cingulate cortices of bvFTD cases, but only in the posterior cingulate cortex of AD cases. As predicted, there was a significant reduction in both the density and total number of neurons in the anterior but not the posterior cingulate cortex of bvFTD cases with the opposite observed for the AD cases. Importantly, neuronal loss in the anterior cingulate cortex was only observed in cases with tau pathology. CONCLUSIONS: This study confirms significant neuronal loss in the posterior but not anterior cingulate cortex in AD, and demonstrates that significant neuron loss in bvFTD occurs only in the anterior cingulate cortex but only in cases with tau pathology compared with cases with TDP pathology. We propose that significant neurodegeneration in the anterior cingulate cortex may be useful in differentiating the pathological subtypes in vivo
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Increased Epithelial Gaps in the Small Intestine Are Predictive of Hospitalization and Surgery in Patients With Inflammatory Bowel Disease
Objectives: Epithelial gaps resulting from intestinal cell extrusions can be visualized with confocal laser endomicroscopy (CLE) during colonoscopy and increased in normal-appearing terminal ileum of inflammatory bowel disease (IBD) patients. Cell-shedding events on CLE were found to be predictive of disease relapse. The aim of this study was to assess the prognostic value of epithelial gap densities for major clinical events (hospitalization or surgery) in follow-up. Methods: We prospectively followed IBD patients undergoing colonoscopy with probe-based CLE (pCLE) for clinical events including symptom flares, medication changes, hospitalization, or surgery. Survival analysis methods were used to compare event times for the composite outcome of hospitalization or surgery using log-rank tests and Cox proportional hazards models. We also examined the relationship of gap density with IBD flares, need for anti-tumor necrosis factor therapy, disease duration, gender and endoscopic disease severity, and location. Results: A total of 21 Crohn's disease and 20 ulcerative colitis patients with a median follow-up of 14 (11–31) months were studied. Patients with elevated gap density were at significantly higher risk for hospitalization or surgery (log-rank test P=0.02). Gap density was a significant predictor for risk of major events, with a hazard ratio of 1.10 (95% confidence interval=1.01, 1.20) associated with each increase of 1% in gap density. Gap density was also correlated with IBD disease duration (Spearman's correlation coefficient rho=0.44, P=0.004), and was higher in male patients (9.0 vs. 3.6 gaps per 100 cells, P=0.038). Conclusions: Increased epithelial gaps in the small intestine as determined by pCLE are a predictor for future hospitalization or surgery in IBD patients
Loss of murine Paneth cell function alters the immature intestinal microbiome and mimics changes seen in neonatal necrotizing enterocolitis
Necrotizing enterocolitis (NEC) remains the leading cause of gastrointestinal morbidity and mortality in premature infants. Human and animal studies suggest a role for Paneth cells in NEC pathogenesis. Paneth cells play critical roles in host-microbial interactions and epithelial homeostasis. The ramifications of eliminating Paneth cell function on the immature host-microbial axis remains incomplete. Paneth cell function was depleted in the immature murine intestine using chemical and genetic models, which resulted in intestinal injury consistent with NEC. Paneth cell depletion was confirmed using histology, electron microscopy, flow cytometry, and real time RT-PCR. Cecal samples were analyzed at various time points to determine the effects of Paneth cell depletion with and without Klebsiella gavage on the microbiome. Deficient Paneth cell function induced significant compositional changes in the cecal microbiome with a significant increase in Enterobacteriacae species. Further, the bloom of Enterobacteriaceae species that occurs is phenotypically similar to what is seen in human NEC. This further strengthens our understanding of the importance of Paneth cells to intestinal homeostasis in the immature intestine
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