NASTRAN used in a production environment

A finite element analysis procedure built around the NASTRAN system is assessed. A number of support programs that were either written or modified to interface with NASTRAN and some improvements that were made to NASTRAN itself are noted. Some typical models are analyzed and an actual schedule is followed for constructing and analyzing the models to support a large design program

Bone morphogenetic protein 4 (BMP4) loss-of-function variant associated with autosomal dominant Stickler syndrome and renal dysplasia.

Stickler syndrome is a genetic disorder that can lead to joint problems, hearing difficulties and retinal detachment. Genes encoding collagen types II, IX and XI are usually responsible, but some families have no causal variant identified. We investigate a variant in the gene encoding growth factor BMP4 in a family with Stickler syndrome with associated renal dysplasia. Next generation sequencing of the coding region of COL2A1, COL11A1 and a panel of genes associated with congenital anomalies of the kidney and urinary tract (CAKUT) was performed. A novel heterozygous BMP4 variant causing a premature stop codon, c. 130G>T, p.(Gly44Ter), which segregated with clinical features of Stickler syndrome in multiple family members, was identified. No variant affecting gene function was detected in COL2A1 or COL11A1. Skin fibroblasts were cultured with and without emetine, and the mRNA extracted and analysed by Sanger sequencing to assess whether the change was causing nonsense-mediated decay. Nonsense-mediated decay was not observed from the extracted BMP4 mRNA. BMP4 is a growth factor known to contribute to eye development in animals, and gene variants in humans have been linked to microphthalmia/anophthalmia as well as CAKUT. The variant identified here further demonstrates the importance of BMP4 in eye development. This is the first report of a BMP4 DNA variant causing Stickler syndrome, and we suggest BMP4 be added to standard diagnostic gene panels for this condition

Results of a nine month home-based physical activity intervention for people living with HIV.

Background: The purpose of this investigation was to test the feasibility of a home-based moderate-intensity physical activity (MPA) program for people living with HIV/AIDS (PLWHA) currently taking antiretroviral therapy (ART). Methods: 68 participants recruited for a 9-month home-based PA intervention aimed to reduce risk factors of cardiovascular disease for PLWHA taking ART. All participants received an educational weight loss workbook and a pedometer for self-monitoring of physical activity. The intervention group received elastic Therabands® for strength training in addition to telephone based behavioral coaching. Clinical assessments were conducted at baseline and each follow-up which also included psychometric questionnaires and PA levels via the SenseWear® armband accelerometer. Results: Of the 57 completing the study, 29 of those were in the intervention group and 28 were in the standard care group. Results show that the home-based PA intervention was not successful in increasing the total amount of MPA for PLWHA. However there was a trend (p=0.08) of decreasing sedentary time. In a secondary analysis those who increased PA by \u3e10% observed decreases in waist circumference and improved functioning at 18 weeks. None of the changes observed were significant after controlling for all potential confounders. Conclusions: A home-based exercise approach with telephone-based coaching may not be a feasible method for increasing MPA among PLWHA. Slight decreases in sedentary time indicate some positive changes in activity habits. A possible strategy to improve studies similar to this is to incorporate a group based social interaction each week similar to that of a support group

Shell MIddens of the Coast of Balochistan

Summary paper on the prehistoric shell middens of the coast of Las bela in Balochistan and southern Sindh (Pakistan

Overview of the results of the organics PET Study of the cometary samples returned from comet Wild 2 by the Stardust mission

This presenation will provide an overview of the efforts and results produced by the Organics Preliminary Examination Team during their studies of the samples returned from comet Wild 2 by the Stardust spacecraft

Development of advanced blanket performance under irradiation and system integration through JUPITER-II project

a b s t r a c t The Japan-USA collaborative program, JUPITER-II, has made significant progress in a research program titled "The irradiation performance and system integration of advanced blanket" through a six-year plan for [2001][2002][2003][2004][2005][2006]. The scientific concept of this program is to study the elemental technology in macroscopic system integration for advanced fusion blankets based on an understanding of the relevant mechanics at the microscopic level. The program has four main research emphases: (1) Flibe molten salt system: Flibe handling, reduction-oxidation control by Be and Flibe tritium chemistry; thermofluid flow simulation experiment and numerical analysis. (2) Vanadium /Li system: MHD ceramics coating of vanadium alloys and compatibility with Li; neutron irradiation experiment in Li capsule and radiation creep. (3) SiC/He system: Fabrication of advanced composites and property evaluation; thermomechanics of SiC system with solid breeding materials; neutron irradiation experiment in He capsule at high temperatures. (4) Blanket system modeling: Design-based integration modeling of Flibe system and V/Li system; multiscale materials system modeling including He effects. This paper describes the perspective of the program including the historical background, the organization and facilities, and the task objectives. Important recent results are reviewed

Structural and Functional Evolution of the Trace Amine-Associated Receptors TAAR3, TAAR4 and TAAR5 in Primates

The family of trace amine-associated receptors (TAAR) comprises 9 mammalian TAAR subtypes, with intact gene and pseudogene numbers differing considerably even between closely related species. To date the best characterized subtype is TAAR1, which activates the Gs protein/adenylyl cyclase pathway upon stimulation by trace amines and psychoactive substances like MDMA or LSD. Recently, chemosensory function involving recognition of volatile amines was proposed for murine TAAR3, TAAR4 and TAAR5. Humans can smell volatile amines despite carrying open reading frame (ORF) disruptions in TAAR3 and TAAR4. Therefore, we set out to study the functional and structural evolution of these genes with a special focus on primates. Functional analyses showed that ligands activating the murine TAAR3, TAAR4 and TAAR5 do not activate intact primate and mammalian orthologs, although they evolve under purifying selection and hence must be functional. We also find little evidence for positive selection that could explain the functional differences between mouse and other mammals. Our findings rather suggest that the previously identified volatile amine TAAR3–5 agonists reflect the high agonist promiscuity of TAAR, and that the ligands driving purifying selection of these TAAR in mouse and other mammals still await discovery. More generally, our study points out how analyses in an evolutionary context can help to interpret functional data generated in single species

STARDUST Curation and Science at JSC

Dust particles released from comet 81P/Wild-2 were captured in silica aerogel on-board the STARDUST spacecraft and returned to Earth on January 15, 2006. STARDUST recovered thousands of particles ranging in size from 1 to 100 micrometers. During the six month Preliminary Examination period an international consortium of 180 scientists investigated their mineralogy/petrology, organic/inorganic chemistry, optical properties and isotopic compositions. Stardust samples are now available for research by the entire research community

Overview of the Proton-coupled MCT (SLC16A) Family of Transporters: Characterization, Function and Role in the Transport of the Drug of Abuse γ-Hydroxybutyric Acid

The transport of monocarboxylates, such as lactate and pyruvate, is mediated by the SLC16A family of proton-linked membrane transport proteins known as monocarboxylate transporters (MCTs). Fourteen MCT-related genes have been identified in mammals and of these seven MCTs have been functionally characterized. Despite their sequence homology, only MCT1–4 have been demonstrated to be proton-dependent transporters of monocarboxylic acids. MCT6, MCT8 and MCT10 have been demonstrated to transport diuretics, thyroid hormones and aromatic amino acids, respectively. MCT1–4 vary in their regulation, tissue distribution and substrate/inhibitor specificity with MCT1 being the most extensively characterized isoform. Emerging evidence suggests that in addition to endogenous substrates, MCTs are involved in the transport of pharmaceutical agents, including γ-hydroxybuytrate (GHB), 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (statins), salicylic acid, and bumetanide. MCTs are expressed in a wide range of tissues including the liver, intestine, kidney and brain, and as such they have the potential to impact a number of processes contributing to the disposition of xenobiotic substrates. GHB has been extensively studied as a pharmaceutical substrate of MCTs; the renal clearance of GHB is dose-dependent with saturation of MCT-mediated reabsorption at high doses. Concomitant administration of GHB and l-lactate to rats results in an approximately two-fold increase in GHB renal clearance suggesting that inhibition of MCT1-mediated reabsorption of GHB may be an effective strategy for increasing renal and total GHB elimination in overdose situations. Further studies are required to more clearly define the role of MCTs on drug disposition and the potential for MCT-mediated detoxification strategies in GHB overdose

Efficacy of Anti-Inflammatory Therapy in a Model of Acute Seizures and in a Population of Pediatric Drug Resistant Epileptics

Targeting pro-inflammatory events to reduce seizures is gaining momentum. Experimentally, antagonism of inflammatory processes and of blood-brain barrier (BBB) damage has been demonstrated to be beneficial in reducing status epilepticus (SE). Clinically, a role of inflammation in the pathophysiology of drug resistant epilepsies is suspected. However, the use anti-inflammatory drug such as glucocorticosteroids (GCs) is limited to selected pediatric epileptic syndromes and spasms. Lack of animal data may be one of the reasons for the limited use of GCs in epilepsy. We evaluated the effect of the CG dexamethasone in reducing the onset and the severity of pilocarpine SE in rats. We assessed BBB integrity by measuring serum S100β and Evans Blue brain extravasation. Electrophysiological monitoring and hematologic measurements (WBCs and IL-1β) were performed. We reviewed the effect of add on dexamethasone treatment on a population of pediatric patients affected by drug resistant epilepsy. We excluded subjects affected by West, Landau-Kleffner or Lennox-Gastaut syndromes and Rasmussen encephalitis, known to respond to GCs or adrenocorticotropic hormone (ACTH). The effect of two additional GCs, methylprednisolone and hydrocortisone, was also reviewed in this population. When dexamethasone treatment preceded exposure to the convulsive agent pilocarpine, the number of rats developing status epilepticus (SE) was reduced. When SE developed, the time-to-onset was significantly delayed compared to pilocarpine alone and mortality associated with pilocarpine-SE was abolished. Dexamethasone significantly protected the BBB from damage. The clinical study included pediatric drug resistant epileptic subjects receiving add on GC treatments. Decreased seizure frequency (≥50%) or interruption of status epilepticus was observed in the majority of the subjects, regardless of the underlying pathology. Our experimental results point to a seizure-reducing effect of dexamethasone. The mechanism encompasses improvement of BBB integrity. Our results also suggest that add on GCs could be of efficacy in controlling pediatric drug resistant seizures