Missense mutations in the perforin (PRF1) gene as a cause of hereditary cancer predisposition

Perforin, a pore-forming toxin released from secretory granules of NK cells and CTLs, is essential for their cytotoxic activity against infected or cancerous target cells. Bi-allelic loss-of-function mutations in the perforin gene are invariably associated with a fatal immunoregulatory disorder, familial haemophagocytic lymphohistiocytosis type 2 (FHL2), in infants. More recently, it has also been recognized that partial loss of perforin function can cause disease in later life, including delayed onset FHL2 and haematological malignancies. Herein we report a family in which a wide range of systemic inflammatory and neoplastic manifestations have occurred across three generations. We found that disease was linked to two missense perforin gene mutations (encoding A91V, R410W) that cause protein misfolding and partial loss of activity. These cases link the partial loss of perforin function with some solid tumours that are known to be controlled by the immune system, as well as haematological cancers. Our findings also demonstrate that perforin gene mutations can contribute to hereditary cancer predisposition

Degradation Issues in Solid Oxide Cells During High Temperature Electrolysis

Idaho National Laboratory (INL) is performing high-temperature electrolysis (HTE) research to generate hydrogen using solid oxide electrolysis cells (SOECs). The project goals are to address the technical and degradation issues associated with the SOECs. This paper provides a summary of ongoing INL and INL-sponsored activities aimed at addressing SOEC degradation. These activities include stack testing, post-test examination, degradation modeling, and issues that need to be addressed in the future. Major degradation issues relating to solid oxide fuel cells (SOFC) are relatively better understood than those for SOECs. Some of the degradation mechanisms in SOFCs include contact problems between adjacent cell components, microstructural deterioration (coarsening) of the porous electrodes, and blocking of the reaction sites within the electrodes. Contact problems include delamination of an electrode from the electrolyte, growth of a poorly (electronically) conducting oxide layer between the metallic interconnect plates and the electrodes, and lack of contact between the interconnect and the electrode. INL's test results on HTE using solid oxide cells do not provide clear evidence as to whether different events lead to similar or drastically different electrochemical degradation mechanisms. Post-test examination of the SOECs showed that the hydrogen electrode and interconnect get partially oxidized and become nonconductive. This is most likely caused by the hydrogen stream composition and flow rate during cooldown. The oxygen electrode side of the stacks seemed to be responsible for the observed degradation because of large areas of electrode delamination. Based on the oxygen electrode appearance, the degradation of these stacks was largely controlled by the oxygen electrode delamination rate. Virkar et al. [19-22] have developed a SOEC model based on concepts in local thermodynamic equilibrium in systems otherwise in global thermodynamic nonequilibrium. This model is under continued development. It shows that electronic conduction through the electrolyte, however small, must be taken into account for determining local oxygen chemical potential within the electrolyte. The chemical potential within the electrolyte may lie out of bounds in relation to values at the electrodes in the electrolyzer mode. Under certain conditions, high pressures can develop in the electrolyte just under the oxygen electrode (anode)/electrolyte interface, leading to electrode delamination. This theory is being further refined and tested by introducing some electronic conduction in the electrolyte.United States. Department of Energy. Office of Energy Efficiency and Renewable EnergyUnited States. Office of the Assistant Secretary for Nuclear Energ

Remanufactured circular mapping catheters: safety, effectiveness and cost.

BACKGROUND: The use of remanufactured single-use devices (SUDs), including cardiac electrophysiology catheters, has become established in the USA and other health care systems but without much published scientific evaluation on the relative safety or efficacy of these devices. In the United Kingdom (UK), the use of remanufactured SUDs has not been routine. We performed a structured evaluation of the safety and efficacy of a remanufactured circular mapping catheter (Stryker® remanufactured Lasso NAV 2515) during its introduction in our centre. METHODS: We prospectively evaluated the performance of a remanufactured circular mapping catheter in 100 consecutive patients undergoing an AF ablation. Operator feedback was obtained, assessing the device appearance, ease of use and function. As an indirect measurement of efficacy, acute procedure metrics were compared to those in 100 propensity-matched cases performed by the same operators using a new device. Cost savings were calculated. RESULTS: No complication occurred in association with the remanufactured device. There was one reported failure of device malfunction-the flexion-extension mechanism of a remanufactured catheter and none in the matched-control group. There was satisfactory communication with the electro-anatomic mapping system. Ease of use of the remanufactured catheter was reported to be similar to a newly manufactured device. Procedural duration was similar with remanufactured devices and matched controls. With 100 cases using the remanufactured device, cost savings amounted to £30,444. CONCLUSIONS: The use of remanufactured circular mapping catheters is safe, efficient and reliable. Widespread use of remanufactured SUDs offers the possibility of significant economic benefit

The Concept and Analytical Investigation of CO2 and Steam Co-Electrolysis for Resource Utilization in Space Exploration

CO2 acquisition and utilization technologies will have a vital role in designing sustainable and affordable life support and in situ fuel production architectures for human and robotic exploration of Moon and Mars. For long-term human exploration to be practical, reliable technologies have to be implemented to capture the metabolic CO2 from the cabin air and chemically reduce it to recover oxygen. Technologies that enable the in situ capture and conversion of atmospheric CO2 to fuel are essential for a viable human mission to Mars. This paper describes the concept and mathematical analysis of a closed-loop life support system based on combined electrolysis of CO2 and steam (co-electrolysis). Products of the coelectrolysis process include oxygen and syngas (CO and H2) that are suitable for life support and synthetic fuel production, respectively. The model was developed based on the performance of a co-electrolysis system developed at Idaho National Laboratory (INL). Individual and combined process models of the co-electrolysis and Sabatier, Bosch, Boudouard, and hydrogenation reactions are discussed and their performance analyses in terms of oxygen production and CO2 utilization are presented

Correlation between vitamin A, E, coenzyme Q10 and degree of insulin resistance in obese and non-obese subjects

The aim of the present study was to investigate correlation between plasma vitamin A, vitamin E, serum coenzyme Q10 levels and degree of insulin resistance in obese and normal weight people. The study was performed on 98 (21 Male, 77 Female) obese people and 78 (20 Male, 58 Female) control subjects. Vitamin A, E and coenzyme Q10 levels were adjusted to the lipid levels. Adjusted vitamin A and E and coenzyme Q10 levels of the obese female group were significantly lower than those of the control female group. Adjusted vitamin A and coenzyme Q10 levels of the obese male group were significantly lower than those of the control male group. Insulin resistance level of the obese female and male groups were significantly higher than that of the control female and male groups. There were no significant correlations between serum coenzyme Q10, plasma vitamin A and E levels and insulin resistance in obese and control subjects. Our findings show that it is essential to use the lipid adjusted levels of lipid soluble nutrients in obesity. Also, we have found no association between insulin resistance and vitamin A, vitamin E and coenzyme Q10 levels in obese subjects

Therapeutic Effects of a New “Indigenous Vaccine” Developed Using Novel Native “Indian Bison Type” Genotype of Mycobacterium avium Subspecies paratuberculosis for the Control of Clinical Johne's Disease in Naturally Infected Goatherds in India

Therapeutic efficacy of an “Indigenous vaccine” has been evaluated with respect to a commercial vaccine (Gudair, Spain), for the control of clinical Johne's disease (JD) in naturally infected goatherds. Seventy-one goats (JD positive) were randomly divided into 3 groups (“Bison”, “Gudair” and “Sham-immunized”). After vaccination, goats were monitored for physical condition, morbidity, mortality, body weights, shedding of M. paratuberculosis (MAP) in feces, internal condition and lesions, as well as humoral and cell-mediated immune responses for 210 days. Study showed marked overall improvement in physical condition of vaccinated goats and average body weight gain was significantly higher (P < .05) in “Bison” group as compared to “Sham-immunized” goats. Mortality due to JD was significantly (P < .05) lower in vaccinated groups than in “sham-immunized”. Morbidity rates (due to diarrhea and weakness) were lower in “Bison” group as compared to other groups. Died goats from vaccinated groups showed regression of gross JD lesions and regeneration of fat layer around visceral organs while “Sham-immunized” goats exhibited frank lesions. Vaccinated goats had higher protective CMI response and also higher antibody titer for the trial period as compared to “Sham immunized”. Both vaccines also reduced shedding of MAP in feces significantly (P < .05). Though the two vaccines effectively restricted the severity of clinical symptoms of JD, however “Indigenous vaccine” was superior in many respects

A Model for Molten Fuel-Coolant Interaction during Melt Slumping in a Nuclear Reactor

This paper describes a simple fuel melt slumping model to replace the current parametric model in SCDAP/RELAP5. Specifically, a fuel-coolant interaction (FCI) model is developed to analyze the slumping molten fuel, molten fuel breakup, heat transfer to coolant, relocation of the molten droplets, size of the partially solidified particles that settle to the bottom of the lower plenum, and melt-plenum interaction, if any. Considering our objectives, the molten fuel jet breakup model, and fuel droplets Lagrangian model as included in a code TEXAS-V with Eulerian thermal hydraulics for water and steam from SCDAP/RELAP5 were used. The model was assessed with experimental data from MAGICO-2000 tests performed at University of California at Santa Barbara, and FARO Test L-08 performed at Joint Research Center, Ispra, Italy. The comparison was found satisfactory

CHALLENGES IN GENERATING HYDROGEN BY HIGH TEMPERATURE ELECTROLYSIS USING SOLID OXIDE CELLS

Idaho National Laboratory’s (INL) high temperature electrolysis research to generate hydrogen using solid oxide electrolysis cells is presented in this paper. The research results reported here have been obtained in a laboratory-scale apparatus. These results and common scale-up issues also indicate that for the technology to be successful in a large industrial setting, several technical, economical, and manufacturing issues have to be resolved. Some of the issues related to solid oxide cells are stack design and performance optimization, identification and evaluation of cell performance degradation parameters and processes, integrity and reliability of the solid oxide electrolysis (SOEC) stacks, life-time prediction and extension of the SOEC stack, and cost reduction and economic manufacturing of the SOEC stacks. Besides the solid oxide cells, balance of the hydrogen generating plant also needs significant development. These issues are process and ohmic heat source needed for maintaining the reaction temperature (~830°C), high temperature heat exchangers and recuperators, equal distribution of the reactants into each cell, system analysis of hydrogen and associated energy generating plant, and cost optimization. An economic analysis of this plant was performed using the standardized H2A Analysis Methodology developed by the Department of Energy (DOE) Hydrogen Program, and using realistic financial and cost estimating assumptions. The results of the economic analysis demonstrated that the HTE hydrogen production plant driven by a high-temperature helium-cooled nuclear power plant can deliver hydrogen at a cost of $3.23/kg of hydrogen assuming an internal rate of return of 10%. These issues need interdisciplinary research effort of federal laboratories, solid oxide cell manufacturers, hydrogen consumers, and other such stakeholders. This paper discusses research and development accomplished by INL on such issues and highlights associated challenges that need to be addressed for hydrogen to become an economical and viable option

Investigating the association between early years foundation stage profile scores and subsequent diagnosis of an autism spectrum disorder: a retrospective study of linked healthcare and education data

Objective: We set out to test whether the early years foundation stage profile (EYFSP) score derived from 17 items assessed by teachers at the end of reception school year had any association with autism spectrum disorder (ASD) diagnosis in subsequent years. This study tested the feasibility of successfully linking education and health data. Design: A retrospective data linkage study. Setting and participants: The Born in Bradford longitudinal cohort of 13, 857 children. Outcome measures: We linked the EYFSP score at the end of reception year with subsequent diagnosis of an ASD, using all ASD general practitioner Read codes. We used the total EYFSP score and a subscore consisting of five key items in the EYFSP, prospectively identified using a panel of early years autism experts. Results: This study demonstrated the feasibility of linking education and health data using ASDs as an exemplar. A total of 8,935 children had linked primary care and education data with 20.7% scoring <25 on the total EYFSP and 15.2% scoring <10 on a EYFSP subscore proposed by an expert panel prospectively. The rate of diagnosis of ASDs at follow-up was just under 1% (84 children), children scoring <25 on the total EYFSP had a 4.1% chance of ASD compared with 0.15% of the remaining children. Using the prospectively designed subscore, this difference was greater (6.4% and 0.12%, respectively). Conclusions: We demonstrate the feasibility of linking education and health data. Performance on teacher ratings taken universally in school reception class can flag children at risk of ASDs. Further research is warranted to explore the utility of EYFSP as an initial screening tool for ASD in early school years