Three-dimensional computational fluid dynamics for the Spallation Neutron Source liquid mercury target

The Spallation Neutron Source (SNS) is a high-power accelerator-based pulsed spallation source being designed by a multilaboratory team led by Oak Ridge National Laboratory (ORNL) to achieve high fluxes of neutrons for scientific experiments. Computational fluid dynamics (CFD) is being used to analyze the SNS design. The liquid-mercury target is subjected to the neutronic (internal) heat generation that results from the proton collisions with the mercury nuclei. The liquid mercury simultaneously serves as the neutronic target medium, transports away the heat generated within itself, and cools the metallic target structure. Recirculation and stagnation zones within the target are of particular concern because of the likelihood that they will result in local hot spots. These zones exist because the most feasible target designs include a complete U-turn flow redirection. Although the primary concern is that the target is adequately cooled, the pressure drop from inlet to outlet must also be considered because pressure drop directly affects structural loading and required pumping power. Based on the current design, a three-dimensional CFD model has been developed that includes the stainless steel target structure, the liquid-mercury target flow, and the liquid-mercury cooling jacket that wraps around the nose of the target

Thermal-hydraulic analysis of the liquid mercury target for the national spallation neutron source

The National Spallation Neutron Source (NSNS) is a high-energy, accelerator-based spallation neutron source being designed by a multi-laboratory team led by Oak Ridge National Laboratory (ORNL) to achieve very high fluxes of neutrons for scientific experiments. The NSNS is proposed to have a 1 MW beam of high-energy ({approximately}1 GeV) protons upgradable to 5 MW and operating at 60 Hz with a pulse duration of 0.5 {mu}s. Peak steady-state power density in the target is about 640 MW/m{sup 3} for 1 MW, whereas the pulse instantaneous peak power density is as high as 22,000 GW/m{sup 3}. The local peak temperature rise for a single pulse over it`s time-averaged value is only 6{degrees}C, but the rate of this temperature rise during the pulse is extremely fast ({approximately}12 million {degrees}C/s). In addition to the resulting thermal shock and materials compatibility concerns, key feasibility issues for the target are related to its thermal-hydraulic performance. These include proper flow distribution, flow reversals and stagnation zones, possible {open_quotes}hot spots{close_quotes}, cooling of the beam {open_quotes}window{close_quotes}, and the challenge of mitigating the effects of thermal shock through possible injection of helium bubbles. An analytic approach was used on the PC spreadsheet EXCEL to evaluate target design options and to determine the global T/H parameters in the current concept. The general computational fluid dynamics (CFD) code CFX was used to simulate the detailed time-averaged two-dimensional thermal and flow distributions in the liquid mercury. In this paper, an overview of the project and the results of this preliminary work are presented. Heat transfer characteristics of liquid mercury under wetting and non-wetting conditions are discussed, and future directions of the program in T/H analysis and R&D are outlined

Calpain mediates proteolysis of the voltage-gated sodium channel alpha-subunit

Alterations in the expression, molecular composition, and localization of voltage-gated sodium channels play major roles in a broad range of neurological disorders. Recent evidence identifies sodium channel proteolysis as a key early event after ischemia and traumatic brain injury, further expanding the role of the sodium channel in neurological diseases. In this study, we investigate the protease responsible for proteolytic cleavage of voltage-gated sodium channels (NaChs). NaCh proteolysis occurs after protease activation in rat brain homogenates, pharmacological disruption of ionic homeostasis in cortical cultures, and mechanical injury using an in vitro model of traumatic brain injury. Proteolysis requires Ca2+ and calpain activation but is not influenced by caspase-3 or cathepsin inhibition. Proteolysis results in loss of the full-length {alpha}-subunits, and the creation of fragments comprising all domains of the channel that retain interaction even after proteolysis. Cell surface biotinylation after mechanical injury indicates that proteolyzed NaChs remain in the membrane before noticeable evidence of neuronal death, providing a mechanism for altered action potential initiation, propagation, and downstream signaling events after Ca2+ elevation

Proteomics: in pursuit of effective traumatic brain injury therapeutics

Effective traumatic brain injury (TBI) therapeutics remain stubbornly elusive. Efforts in the field have been challenged by the heterogeneity of clinical TBI, with greater complexity among underlying molecular phenotypes than initially conceived. Future research must confront the multitude of factors comprising this heterogeneity, representing a big data challenge befitting the coming informatics age. Proteomics is poised to serve a central role in prescriptive therapeutic development, as it offers an efficient endpoint within which to assess post-TBI biochemistry. We examine rationale for multifactor TBI proteomic studies and the particular importance of temporal profiling in defining biochemical sequences and guiding therapeutic development. Lastly, we offer perspective on repurposing biofluid proteomics to develop theragnostic assays with which to prescribe, monitor and assess pharmaceutics for improved translation and outcome for TBI patients

Modulation of Secreted β-Amyloid Precursor Protein and Amyloid β-Peptide in Brain by Cholesterol

The effects of dietary cholesterol on brain amyloid precursor protein (APP) processing were examined using an APP gene-targeted mouse, genetically humanized in the amyloid beta-peptide (Abeta) domain and expressing the Swedish familial Alzheimer's disease mutations. These mice express endogenous levels of APP holoprotein and abundant human Abeta. Increased dietary cholesterol led to significant reductions in brain levels of secreted APP derivatives, including sAPPalpha, sAPPbeta, Abeta1-40, and Abeta1-42, while having little to no effect on cell-associated species, including full-length APP and the COOH-terminal APP processing derivatives. The changes in levels of sAPP and Abeta in brain all were negatively correlated with serum cholesterol levels and levels of serum and brain apoE. These results demonstrate that secreted APP processing derivatives and Abeta can be modulated in the brain of an animal by diet and provide evidence that cholesterol plays a role in the modulation of APP processing in vivo. APP gene-targeted mice lacking apoE, also have high serum cholesterol levels but do not show alterations in APP processing, suggesting that effects of cholesterol on APP processing require the presence of apoE

Delayed neuronal cell death in brainstem after transient brainstem ischemia in gerbils

<p>Abstract</p> <p>Background</p> <p>Because of the lack of reproducible brainstem ischemia models in rodents, the temporal profile of ischemic lesions in the brainstem after transient brainstem ischemia has not been evaluated intensively. Previously, we produced a reproducible brainstem ischemia model of Mongolian gerbils. Here, we showed the temporal profile of ischemic lesions after transient brainstem ischemia.</p> <p>Results</p> <p>Brainstem ischemia was produced by occlusion of the bilateral vertebral arteries just before their entry into the transverse foramina of the cervical vertebrae of Mongolian gerbils. Animals were subjected to brainstem ischemia for 15 min, and then reperfused for 0 d (just after ischemia), 1 d, 3 d and 7 d (n = 4 in each group). Sham-operated animals (n = 4) were used as control. After deep anesthesia, the gerbils were perfused with fixative for immunohistochemical investigation. Ischemic lesions were detected by immunostaining for microtubule-associated protein 2 (MAP2). Just after 15-min brainstem ischemia, ischemic lesions were detected in the lateral vestibular nucleus and the ventral part of the spinal trigeminal nucleus, and these ischemic lesions disappeared one day after reperfusion in all animals examined. However, 3 days and 7 days after reperfusion, ischemic lesions appeared again and clusters of ionized calcium-binding adapter molecule-1(IBA-1)-positive cells were detected in the same areas in all animals.</p> <p>Conclusion</p> <p>These results suggest that delayed neuronal cell death took place in the brainstem after transient brainstem ischemia in gerbils.</p

Familial risk for gastric carcinoma: an updated study from Sweden

Reliable data on familial risks are important for clinical counselling and cancer genetics. However, the estimates of familial risk of gastric cancer vary widely. We examined the risk of familial gastric cancer using the updated Swedish Family-Cancer Database with 5358 patients among offspring and 36 486 patients among parents. There were 133 families with one parent and one offspring diagnosed with gastric cancer, and 20 families with two affected offspring. Familial standardised incidence ratios (SIRs) were 1.63 and 2.93 when parents and siblings presented with gastric cancer, respectively. The high sibling risk was owing to cancer in the corpus (SIR 7.28). The SIR for cardia cancer was 1.54 when parents were diagnosed with any gastric cancer. Cardia cancer associated with oesophageal cancer, particularly with oesophageal adenocarcinoma. Among specific histologies, signet ring cancer showed an increase. A few associations were noted for discordant sites, including the urinary bladder and the endometrium. H. pylori infection, although not measured in the present study, is probably an important risk factor for the high sibling risk of corpus cancer. Familial clustering of cardia cancer is independent of H. pylori infection, and may have a genetic basis. The familial association of cardia cancer with oesophageal adenocarcinoma may provide aetiological clues