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The emergence of microreactor technology has helped to drive supporting nuclear materials qualification and acceptance processes. One essential component in these small reactors is a solid moderator, which typically consists of metal hydride and cladding. While the behavior and performance of metal-hydride moderators go back to early advanced reactor development for nuclear-powered aviation and space propulsion, there remains a knowledge gap in the understanding of hydrogen transport--related phenomena and irradiation performance for hydride moderators. This impacts the acceptance/qualification of hydride moderators for microreactors. The goal of this technical note is to lay out a potential path forward for advanced moderator qualification and acceptance for designers and developers of microreactors. The proposed approach has benefited from a model microreactor core with the design parameters of a hydride moderator. Based on the model core and design parameters, a simple chart was developed for the major challenges of hydride moderators where potential incidents, causes, effects, and resolutions are described. The relation between the offered resolutions and the maturity of the metal-hydride moderator technology was emphasized using technological readiness. Technological readiness levels (TRLs) were clustered to three sets: physical phenomena related, reactor irradiations, and system demonstration. Some essential needs to fill the knowledge gaps are discussed for physical phenomena--related TRLs. For reactor irradiations, the importance of identifying goals and priorities is stressed to reach certain TRLs. For system demonstration, it is noted that metal-hydride moderator qualification must comply with the overall microreactor design. [ABSTRACT FROM AUTHOR]

As microreactors evolve to become a more affordable and efficient worldwide energy source, the development of moderator material within the system to decrease the required mass of low-enriched uranium fuel is important. The use of low- instead of high-enriched uranium in small nuclear reactors stems from recent national policies associated with nonproliferation. New designs are being developed for a range of applications and nuclear space systems in particular. Using system geometries such as those described in this paper, the next step is to advance the technology readiness level of moderator material such as delta-yttrium hydride (YHx,x = 1.6--2.0) so that it can be qualified for use in a microreactor system. Although characterization of unirradiated material has been documented previously, to fully understand the performance of this material, behavior in relevant irradiation environments must occur. This paper describes the fabrication of yttrium hydride samples through innovative techniques and how these samples were tested in two relevant neutron environments. These two experiments include (1) a critical experiment performed at the National Criticality Experiments Research Center (NCERC) to evaluate reactivity changes in a neutron-critical environment and (2) irradiation in the Advanced Test Reactor (ATR) to assess structural integrity/material form, thermophysical data, hydrogen permeability, and other features post irradiation. For this purpose, hundreds of samples were fabricated for the NCERC and ATR experiments and are described within this paper. [ABSTRACT FROM AUTHOR]

A forced convection PbLi loop has been designed and constructed to test tritium extraction from molten PbLi. This Tritium Extraction eXperiment (TEX) is designed to operate at temperatures and tritium concentrations relevant to the helium cooled lead lithium, water cooled lead lithium, and dual coolant lead lithium breeding blankets. The major systems consist of a moving magnet pump, source permeator, supply tank, test section, and plenum. Additional subsystems, including flowmeters, pressure gauges, valves, and heaters are described. The versatile design of TEX will enable code validation using simple tubular membranes, as well as determining tritium extraction efficiencies for alternative test sections. [ABSTRACT FROM AUTHOR]

R3669 --> 760.5 --> Breathing is essential to life and can be easily disrupted by many adverse events. Disorders such as high cervical spinal cord injury (SCI) and sleep apnea can decrease quality of life and enhance the ill effects of comorbidities like Alzheimer's disease (AD). Previous studies have shown an increase in cognitive impairments in subjects with both sleep apnea and AD. Apolipoprotein E (ApoE) is a protein found throughout the body and central nervous system (CNS) that is involved in the regulation and transport of cholesterol and lipids. Out of the three APOE human alleles (E2, E3, and E4), the E4 allele has been implicated in the early onset and higher risk of AD when compared to E2 or E3. Previous research in our lab has shown that the interaction between APOE genotype and sex has different effects on breathing motor plasticity following a cervical SCI in mice. However, it is unknown how baseline respiratory pattern and capability differs between uninjured individuals expressing either ApoE4 or E3, specifically under hypoxic conditions. Unpublished data from our lab has examined these differences in male mice, showing that E4 male mice have high variation in respiratory pattern, as well as a less robust response to hypoxia. Using ApoE as our independent variable, we measured respiratory parameters of female C57/BL6 ApoE3 and ApoE4 humanized mice using whole body plethysmography (WBP), hypothesizing that ApoE3 animals would display a greater baseline respiratory rate and have a more adaptive, heightened response to hypoxic exposure than those expressing ApoE4. Preliminary data comparing E3 female animals (n=8) and E4 female animals (n=8) showed differences across several key measurements. Interestingly, ApoE4 humanized female mice had a more robust response to hypoxic exposure that failed to persist following cessation of hypoxia. However, at baseline, E4 female animals showed no differences in respiratory pattern in contrast to our previously collected male ApoE4 data. These results indicate a critical role of the APOE genotype in the regulation of breathing and response to hypoxic conditions which differs between males and females. To further understand this distinction, future experiments will examine differences in levels of brainstem and spinal cord serotonin expression between ApoE3 and E4 males and females, as well as plasticity following injury in areas high in ApoE expression. [ABSTRACT FROM AUTHOR]

R4661 --> 760.7 --> Breathing is vital for life and is both uniquely complex and vulnerable to disruption. Disorders of breathing such as those that occur in sleep apnea and even high cervical spinal cord injury (SCI) can impair quality of life and potentiate the ill effects of comorbidities like Alzheimer's disease (AD). Indeed, studies have shown greater cognitive and cardiovascular impairments in subjects with sleep apnea and AD. Apolipoprotein E (ApoE) is a ubiquitous protein found throughout the body and CNS which aids in the regulation and transport of cholesterol and lipids. Moreover, the E4 allele confers a higher risk of early onset AD than either the E2 or E3 alleles. Previous research in our lab has shown the interaction between ApoE genotype and sex differentially affects breathing motor plasticity following SCI in mice. However, it is unknown how baseline respiratory pattern and capability during hypoxic challenge may differ between uninjured individuals expressing APOE4 and E3 alleles. Thus, with APOE genotype as our independent variable, we measured the respiratory parameters of male E3 and E4 targeted replacement mice using whole body plethysmography (WBP), hypothesizing that E3 animals would display a more adaptive, heightened response to hypoxic exposure than those expressing E4. Preliminary data comparing E3 animals (n=9) and E4 animals (n=8) demonstrated differences across several key measurements. At baseline, E4 animals were shown to breathe in an energy inefficient manner as exemplified high measures in tidal volume and frequency. During sustained hypoxia, frequency, tidal volume, and minute volume initially increased across all animals, but APOE3 animals mounted a much more robust and sustained response with APOE4 values falling well below baseline measures prior to termination of hypoxia. These preliminary results suggest a critical role of the APOE genotype in regulation of baseline breathing and in response to hypoxic conditions and that possessing the APOE4 allele may confer vulnerabilities in respiratory function and during environmental challenges leading to cognitive decline. Future directions include examining anatomically critical CNS respiratory regions and neural cell function. [ABSTRACT FROM AUTHOR]

The TGFβ signaling pathway is essential to epithelial homeostasis and is often inhibited during progression of esophageal squamous cell carcinoma. Recently, an important role for TGFβ signaling has been described in the crosstalk between epithelial and stromal cells regulating squamous tumor cell invasion in mouse models of head-and-neck squamous cell carcinoma (HNSCC). Loss of TGFβ signaling, in either compartment, leads to HNSCC however, the mechanisms involved are not well understood. Using organotypic reconstruct cultures (OTC) to model the interaction between epithelial and stromal cells that occur in dysplastic lesions, we show that loss of TGFβ signaling promotes an invasive phenotype in both fibroblast and epithelial compartments. Employing immortalized esophageal keratinocytes established to reproduce common mutations of esophageal squamous cell carcinoma, we show that treatment of OTC with inhibitors of TGFβ signaling (A83-01 or SB431542) enhances invasion of epithelial cells into a fibroblast-embedded Matrigel/collagen I matrix. Invasion induced by A83-01 is independent of proliferation but relies on protease activity and expression of ADAMTS-1 and can be altered by matrix density. This invasion was associated with increased expression of pro-inflammatory cytokines, IL1 and EGFR ligands HB-EGF and TGFα. Altering EGF signaling prevented or induced epithelial cell invasion in this model. Loss of expression of the TGFβ target gene ROBO1 suggested that chemorepulsion may regulate keratinocyte invasion. Taken together, our data show increased invasion through inhibition of TGFβ signaling altered epithelial-fibroblasts interactions, repressing markers of activated fibroblasts, and altering integrin-fibronectin interactions. These results suggest that inhibition of TGFβ signaling modulates an array of pathways that combined promote multiple aspects of tumor invasion. [ABSTRACT FROM AUTHOR]

Fusion and fission reactions are profoundly dependent on hydrogen for sustained reactions. Fusion is fueled by the isotopes of hydrogen, and predominantly hydrogen-based moderators slow fission neutrons to propagate chain reactions. Intentional tritium production in fusion and concomitant tritium production in fission reactors introduce challenges. The technology to efficiently extract, harvest, and quantify tritium in and from advanced fission molten salt coolants and fusion molten tritium breeder materials will require more pronounced research and development. Measuring and quantifying hydrogen is necessary in all areas of nuclear materials. Although many characterization techniques cannot directly detect hydrogen, numerous techniques provide the necessary information to understand the behavior of hydrogen in nuclear materials. [ABSTRACT FROM AUTHOR]

The plasma-material interface and its impact on the performance of magnetically confined thermonuclear fusion plasmas are considered to be one of the key scientific gaps in the realization of nuclear fusion power. At this interface, high particle and heat flux from the fusion plasma can limit the material's lifetime and reliability and therefore hinder operation of the fusion device. Lithium-based surfaces are now being used in major magnetic confinement fusion devices and have observed profound effects on plasma performance including enhanced confinement, suppression and control of edge localized modes (ELM), lower hydrogen recycling and impurity suppression. The critical spatial scale length of deuterium and helium particle interactions in lithium ranges between 5-100 nm depending on the incident particle energies at the edge and magnetic configuration. Lithium-based surfaces also range from liquid state to solid lithium coatings on a variety of substrates (e.g., graphite, stainless steel, refractory metal W/Mo/etc., or porous metal structures). Temperature-dependent effects from lithium-based surfaces as plasma facing components (PFC) include magnetohydrodynamic (MHD) instability issues related to liquid lithium, surface impurity, and deuterium retention issues, and anomalous physical sputtering increase at temperatures above lithium's melting point. The paper discusses the viability of lithium-based surfaces in future burning-plasma environments such as those found in ITER and DEMO-like fusion reactor devices. [ABSTRACT FROM AUTHOR]

Background: Obstructive sleep apnea (OSA) increases risk for cognitive decline and Alzheimer's disease (AD). While the underlying mechanisms remain unclear, hypoxemia during OSA has been implicated in cognitive impairment. OSA during rapid eye movement (REM) sleep is usually more severe than in non-rapid eye movement (NREM) sleep, but the relative effect of oxyhemoglobin desaturation during REM versus NREM sleep on memory is not completely characterized. Here, we examined the impact of OSA, as well as the moderating effects of AD risk factors, on verbal memory in a sample of middle-aged and older adults with heightened AD risk. Methods: Eighty-one adults (mean age:61.7 ± 6.0 years, 62% females, 32% apolipoprotein E ε4 allele (APOE4) carriers, and 70% with parental history of AD) underwent clinical polysomnography including assessment of OSA. OSA features were derived in total, NREM, and REM sleep. REM-NREM ratios of OSA features were also calculated. Verbal memory was assessed with the Rey Auditory Verbal Learning Test (RAVLT). Multiple regression models evaluated the relationships between OSA features and RAVLT scores while adjusting for sex, age, time between assessments, education years, body mass index (BMI), and APOE4 status or parental history of AD. The significant main effects of OSA features on RAVLT performance and the moderating effects of AD risk factors (i.e., sex, age, APOE4 status, and parental history of AD) were examined. Results: Apnea–hypopnea index (AHI), respiratory disturbance index (RDI), and oxyhemoglobin desaturation index (ODI) during REM sleep were negatively associated with RAVLT total learning and long-delay recall. Further, greater REM-NREM ratios of AHI, RDI, and ODI (i.e., more events in REM than NREM) were related to worse total learning and recall. We found specifically that the negative association between REM ODI and total learning was driven by adults 60 + years old. In addition, the negative relationships between REM-NREM ODI ratio and total learning, and REM-NREM RDI ratio and long-delay recall were driven by APOE4 carriers. Conclusion: Greater OSA severity, particularly during REM sleep, negatively affects verbal memory, especially for people with greater AD risk. These findings underscore the potential importance of proactive screening and treatment of REM OSA even if overall AHI appears low. [ABSTRACT FROM AUTHOR]

Tungsten (W) samples were damaged by neutron and 6.4 MeV Fe-ion irradiation above 1000 K simulating the divertor operation temperature. Deuterium (D) retention properties were examined by decorating the damaged W with D and subsequent thermal desorption spectroscopy (TDS) measurements. Vacancy clusters were the major D trapping site in the W irradiated with Fe-ion at 873 K, although D retention by vacancy clusters decreased in the W irradiated with Fe-ion at 1173 K due to dynamic annealing. The D de-trapping activation energy from vacancy clusters was found to be 1.85 eV. D retention in neutron damage W was larger than that damaged by Fe-ion due to the uniform distribution of irradiation defects. The D desorption behaviors from neutron damaged W was simulated well by assuming the D de-trapping activation energy to be 1.52 eV. [ABSTRACT FROM AUTHOR]

The southwestern United States has experienced expansion of conifer species ( Juniperus spp. and Pinus ponderosa ) into areas of semi-arid grassland over the past century. The expansion of conifers can limit palatable forage and reduce grass and forb communities. Conifer species are sometimes thinned through hydraulic mulching or selective cutting. We assessed the effects of these treatments on mule deer ( Odocoileus hemionus ) habitat in northeastern New Mexico to determine if conifer thinning improved cover of preferred forage species for mule deer in areas with and without ungulates. We measured plant cover and occurrence of preferred forage species in the summers of 2011 and 2012. An ongoing regional drought probably reduced vegetation response, with preferred forage species and herbaceous cover responding to conifer thinning or ungulate exclusion immediately following treatment, but not the following year. In 2011, areas that received thinning treatments had a higher abundance of preferred forage when compared to sites with no treatment. Grass coverage exhibited an immediate response in 2011, with ungulate exclosures containing 8% more coverage than areas without exclosures. The results suggest that conifer thinning and ungulate exclusion may elicit a positive response, however in the presence of drought; the positive effects are only short-term. [ABSTRACT FROM AUTHOR]

Lung organogenesis requires precise timing and coordination to effect spatial organization and function of the parenchymal cells. To provide a systematic broad-based view of the mechanisms governing the dynamic alterations in parenchymal cells over crucial periods of development, we performed a single-cell RNA-sequencing timeseries yielding 102,571 epithelial, endothelial and mesenchymal cells across nine time points from embryonic day 12 to postnatal day 14 in mice. Combining computational fate-likelihood prediction with RNA in situ hybridization and immunofluorescence, we explore lineage relationships during the saccular to alveolar stage transition. The utility of this publicly searchable atlas resource (www.sucrelab.org/lungcells) is exemplified by discoveries of the complexity of type 1 pneumocyte function and characterization of mesenchymal Wnt expression patterns during the saccular and alveolar stages - wherein major expansion of the gas-exchange surface occurs. We provide an integrated view of cellular dynamics in epithelial, endothelial and mesenchymal cell populations during lung organogenesis. [ABSTRACT FROM AUTHOR]

• Two-hour oral glucose tolerance test, FDG PET, and cognition were assessed. • Indices of insulin secretion (IS) and resistance were derived from the oral glucose tolerance test. • Lower IS predicted higher cerebral glucose metabolism in middle-aged adults. • IS was not related to cerebral glucose metabolism in older adults. • Lower IS was related to better immediate recall. Insulin resistance (IR) has been related to reduced cerebral glucose metabolism in regions identified as hypometabolic in Alzheimer's clinical syndrome. Insulin secretion (IS) has been less studied than IR despite findings that decreased IS is an early indicator of future type 2 diabetes and a potential predictor of Alzheimer's clinical syndrome. We investigated whether higher IR and lower IS would be associated with greater age-related reductions in regional cerebral glucose metabolism and worse cognitive performance. Two-hour oral glucose tolerance testing and 18F-fluorodeoxyglucose positron emission tomography were performed on 1–2 occasions on a sample of healthy middle-aged and older adults from the Wisconsin Alzheimer's Disease Research Center. Neuropsychological tests were completed during Alzheimer's Disease Research Center Clinical Core visits. Pattern of findings suggested that lower (not higher) IS was related to higher regional cerebral glucose metabolism in middle aged but not older adults, and lower (not higher) IS was also related to better immediate recall. In the context of healthy insulin sensitivity, lower IS may be beneficial to brain health. [Display omitted] [ABSTRACT FROM AUTHOR]

Deuterium retention behavior in tungsten damaged by fast neutrons at high temperatures (0.43 dpa at 918 K and 0.74 dpa at 1079 K) and 6.4 MeV Fe2+ (0.3 dpa at R.T.) were investigated to evaluate the tritium retention property of fusion reactor divertors. A deuterium gas absorption method was carried out to avoid additional damage that may be induced by plasma exposure, then, deuterium retention and desorption behaviors were investigated quantitatively by means of thermal desorption spectroscopy and the following simulation code. The deuterium desorption spectra for tungsten samples were analyzed by the numerical code which includes the elementary steps of hydrogen isotope migration processes including diffusion, trapping, detrapping, and surface recombination. The evaluated deuterium detrapping energy from the irradiation defects in neutron irradiated tungsten sample was larger than that in 6.4 MeV Fe2+ irradiated tungsten. It was suggested that the dominant deuterium trapping site in the neutron irradiated tungsten would be voids which was formed by the accumulation of vacancies during neutron irradiation under high temperature and long duration. [ABSTRACT FROM AUTHOR]

Dense vanadium-based membranes offer high permeability and perfect selectivity to hydrogen isotopes, maintain favorable neutronic properties, and are compatible with liquid metals such as PbLi. These properties make vanadium membranes a promising fusion fuel cycle technology for processes such as tritium extraction from PbLi and exhaust processing. Surface contamination has a deleterious effect on the gas-phase hydrogen permeation through vanadium, and the reported permeabilities range from 10-14 to 10-7 mol m-1 s-1 Pa-0.5. Thin dense films of palladium applied to clean vanadium surfaces enable a consistently high hydrogen permeability. In this study, uncoated vanadium resulted in deuterium permeabilities ranging from 2.8 × 10-11 to 6.4 × 10-9 mol m-1 s-1 Pa-0.5 at 300 °C–700 °C, respectively. Post-test analysis revealed a VO x surface layer and VC x subsurface layer formed on the feed side, while the as-received surface oxide dissolved leaving a submonolayer oxide on the permeate surface. The Pd-coated V resulted in a maximum deuterium permeability of 2.1 × 10-7 mol m-1 s-1 Pa-0.5 at 375 °C upon activation of the Pd surface by oxidation and reduction. The deuterium permeation declined upon heating to 500 °C due to intermetallic diffusion between the Pd and V. The Mo 2 C-coated V resulted in deuterium permeabilities ranging from 2.7 × 10-10 to 1.8 × 10-9 at 500 °C–700 °C, respectively, and a post-test analysis found the carbon in the Mo 2 C layer had dissolved into the V near the interface. Image 1 • D 2 permeation through uncoated V is controlled by surface oxide and carbide layers. • D 2 permeation through Pd coated V has high permeability in activated surface state. • Mo 2 C coated V resulted in carbon transfer from Mo to V forming Mo/VC x. • Hydrogen isotope permeation through V membranes is reviewed. [ABSTRACT FROM AUTHOR]

• The retention of deuterium (D) for 1 dpa Fe ion damaged W-10%Re with dynamic-annealing or post-annealing was investigated by TDS. • The irradiation defects in W-10%Re by room temperature irradiation made a large D retention. • At higher temperature irradiation, D retention for W-10%Re was reduced less than half for both dynamic-annealing and post-annealing cases. • For post-annealing, higher temperature is required to reduce D retention at 800–1000 K compared to that for dynamic-annealing. The deuterium (D) retention for 1 dpa Fe ion damaged W-10%Re with dynamic-annealing or post-annealing was investigated by TDS. Major D 2 desorption was observed at temperatures of 400, 650 and 850 K for 1 dpa damaged W-10%Re without annealing (room temperature). By dynamic-annealing above 573 K, the D 2 desorption stage at 850 K was clearly eliminated. On the other hand, it was found that post-annealing at a higher temperature of 1173 K was required to annihilate this desorption stage. This indicates that the D desorption from the irradiation defects introduced at room temperature (post-annealing) needs higher annealing temperature compared to the dynamic-annealing. The D retention for dynamic-annealed sample was reduced by the recovery of D trapping sites by annealing. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) novel coronavirus 2019 (COVID-19) global pandemic has led to millions of cases and hundreds of thousands of deaths. While older adults appear at high risk for severe disease, hospitalizations and deaths due to SARS-CoV-2 among children have been relatively rare. Integrating single-cell RNA sequencing (scRNA-seq) of developing mouse lung with temporally resolved immunofluorescence in mouse and human lung tissue, we found that expression of SARS-CoV-2 Spike protein primer TMPRSS2 was highest in ciliated cells and type I alveolar epithelial cells (AT1), and TMPRSS2 expression increased with aging in mice and humans. Analysis of autopsy tissue from fatal COVID-19 cases detected SARS-CoV-2 RNA most frequently in ciliated and secretory cells in airway epithelium and AT1 cells in peripheral lung. SARS-CoV-2 RNA was highly colocalized in cells expressing TMPRSS2. Together, these data demonstrate the cellular spectrum infected by SARS-CoV-2 in lung epithelium and suggest that developmental regulation of TMPRSS2 may underlie the relative protection of infants and children from severe respiratory illness. [ABSTRACT FROM AUTHOR]

• Hydrogen (H) and deuterium (D) permeation fluxes for tungsten (W) by H-D mixed plasma were studied to clarify the hydrogen isotope effect on permeation by newly designed plasma driven permeation (PDP) device. • When single species of h or d was irradiated, the h permeation rate showed approximately 1.6 times as high as that of d. • H and d permeation fluxes were clearly reduced by seeding he in H-D mixed plasma. At lower temperature (∼723 K), the ratio of steady permeation fluxes of h and d was about 75 : 25, confirming the high permeation flux of h. • H and d permeation fluxes were reached almost unity at 923 K. Hydrogen (H) and deuterium (D) permeation fluxes for tungsten (W) by H-D mixed plasma were studied to clarify the hydrogen isotope effect on permeation by a newly designed plasma driven permeation (PDP) device at Shizuoka University. A mixed H-D plasma was produced by introducing H and D gasses with various ratios. The atomic ratio and permeation flux in the plasma were measured during the experiments. It was found that the H:D atomic ratio in the plasma was almost proportional to the introduced H:D gas ratio. When single species of H or D was irradiated, the H permeation rate showed approximately 1.6 times as high as that of D. Under H-D mixed plasma irradiation, the highest HD permeation rate was observed when the atomic ratio of H:D in the plasma was 50:50. In addition, the effect of He seeding on H-D mixed plasma driven permeation behavior was also evaluated. The recycling of hydrogen isotopes on the upstream side was enhanced due to the formation of He bubbles near the surface, which would prevent the dissolution of hydrogen isotopes into bulk W and enhance the reflection process during plasma exposure. H and D permeation fluxes were clearly reduced by seeding He in H-D mixed plasma. At lower temperature (∼723 K), the ratio of steady permeation fluxes of H and D was about 75 : 25, confirming the high permeation flux of H. These results have demonstrated a significant hydrogen isotope effect, even if He was seeded or not. As the temperature increased, H and D permeation fluxes approached unity at 923 K. This indicates that the hydrogen isotope effect was determined by the combination of recycling / reflection at or beneath the surface, which will be controlled by the temperature during plasma exposure. [ABSTRACT FROM AUTHOR]

Abstract Deuterium (D) retention behaviors for the 3 keV Helium (He+) implanted damaged-Tungsten (W) and 10 keV Carbon (C+) - 3 keV He+ simultaneous implanted damaged-W were evaluated by thermal desorption spectroscopy (TDS) to understand the synergetic effect of defect formation and C/He existence on D retention behavior for W with various damage level. For the He+ implantation, the retention of D trapped by dislocation loops was controlled by 3 keV He+ fluence. The D retention in the deeper region was reduced by He+ implantation with higher He+ fluence due to the formation of He bubbles and dense defects at the surface region which would reduce the effective D diffusion coefficient. In addition, in the case of the simultaneous C+ - He+ implantation, the reduction of D retention trapped in the deeper region was also found by the higher C+ - He+ fluence. It can be said that D retention behavior was controlled by the formation of He induced defects and accumulation of He near the surface even if the damages were introduced in the deeper region. [ABSTRACT FROM AUTHOR]

Abstract The Idaho National Laboratory (INL) Fusion Safety Program (FSP) is the Office of Fusion Energy Sciences' (FES) lead laboratory for Magnetic Fusion Energy (MFE) Safety. Our mission is to assist the US and international fusion communities in developing the inherent safety and environmental potential of fusion power by: 1) Developing fusion licensing data and analysis tools, 2) Participating in national and international collaborations and design studies, and 3) Assisting the US and international fusion community in licensing activities and guidance in operational safety. To achieve our mission, the FSP maintains core competencies in the several areas, two of which are: fusion safety code development and tritium retention and permeation in fusion plasma facing component (PFC) and blanket materials. This article details recent accomplishments of our program in these areas and future directions for fusion safety research and development at INL. [ABSTRACT FROM AUTHOR]

R4911 --> 783.14 --> Nearly 60% of all spinal cord injuries (SCI) occur at the cervical level. These high‐level injuries can lead to quadriplegia, autonomic dysregulation, and interruption of the descending respiratory pathways required for breathing. As respiratory motor function is required for life, it is critical to restore breathing as soon as possible after cervical SCI. Indeed, therapeutic techniques in animal studies have been successful at restoring breathing function after SCI; however, these interventions appear to be more effective at chronic than acute timepoints post‐injury. One potential cause for this observation is the impact the injury has on the gastrointestinal (GI) tract and gut microbiome, which have previously been shown to have detrimental effects on recovery outcomes, including lower limb motor function and emotional affect as indicated by increased anxiety‐like behavior. However, the impact the gut microbiome has on the recovering spinal cord at different timepoints, levels, and injury severities still needs to be fully realized. We aimed to build upon these previous findings and investigate the impact of cervical SCI on the gut microbiome over time and up to chronic timepoints. We hypothesized that cervical SCI leads to transient changes in the gut microbiome, which are most severe acutely after injury impeding functional recovery of breathing, but resolve over time and thus eventually allow for more profound recovery. To test our hypotheses, we performed left C2 hemisections on adult female rats, collected fecal samples from injured, sham, and naïve animals, and assessed microbiome composition at various timepoints pre‐ and post‐injury. Preliminary results suggest that following cervical SCI (up to 12 weeks post injury), robust differences in gut microbiome are apparent compared to non‐injured animals. Future studies will classify bacterial identities and assess the impact of the post‐injury gut microbiome on respiratory motor function and plasticity, as well as inter‐institutional differences. [ABSTRACT FROM AUTHOR]

Background: Tumor metastasis is responsible for 90% of cancer-related deaths. Recently, a strong link between microRNA dysregulation and human cancers has been established. However, the molecular mechanisms through which microRNAs regulate metastasis and cancer progression remain unclear. Methods: We analyzed the reciprocal expression regulation of miR-31 and SOX4 in esophageal squamous and adenocarcinoma cell lines by qRT-PCR and Western blotting using overexpression and shRNA knock-down approaches. Furthermore, methylation studies were used to assess epigenetic regulation of expression. Functionally, we determined the cellular consequences using migration and invasion assays, as well as proliferation assays. Immunoprecipitation and ChIP were used to identify complex formation of SOX4 and co-repressor components. Results: Here, we report that SOX4 promotes esophageal tumor cell proliferation and invasion by silencing miR-31 via activation and stabilization of a co-repressor complex with EZH2 and HDAC3. We demonstrate that miR-31 is significantly decreased in invasive esophageal cancer cells, while upregulation of miR-31 inhibits growth, migration and invasion of esophageal adenocarcinoma (EAC) and squamous cell carcinoma (ESCC) cell lines. miR-31, in turn, targets SOX4 for degradation by directly binding to its 3'-UTR. Additionally, miR-31 regulates EZH2 and HDAC3 indirectly. SOX4, EZH2 and HDAC3 levels inversely correlate with miR-31 expression in ESCC cell lines. Ectopic expression of miR-31 in ESCC and EAC cell lines leads to down regulation of SOX4, EZH2 and HDAC3. Conversely, pharmacologic and genetic inhibition of SOX4 and EZH2 restore miR-31 expression. We show that SOX4, EZH2 and HDAC3 form a co-repressor complex that binds to the miR-31 promoter, repressing miR-31 through an epigenetic mark by H3K27me3 and by histone acetylation. Clinically, when compared to normal adjacent tissues, esophageal tumor samples show upregulation of SOX4, EZH2, and HDAC3, and EZH2 expression is significantly increased in metastatic ESCC tissues. Conclusions: Thus, we identified a novel molecular mechanism by which the SOX4, EZH2 and miR-31 circuit promotes tumor progression and potential therapeutic targets for invasive esophageal carcinomas. [ABSTRACT FROM AUTHOR]

Targeted loss of E-cadherin and TGFβ receptor II leads to spontaneous squamous cell carcinoma in constitutive and inducible knock-out mouse models. Tumors develop in the oral cavity and forestomach with a long latency and have the potential for regional and distant metastasis.Although the etiology of squamous cell carcinomas of the oral mucosa is well understood, the cellular origin and the exact molecular mechanisms leading to their formation are not. Previously, we observed the coordinated loss of E-cadherin (CDH1) and transforming growth factor beta receptor II (TGFBR2) in esophageal squamous tumors. To investigate if the coordinated loss of Cdh1 and Tgfbr2 is sufficient to induce tumorigenesis in vivo, we developed two mouse models targeting ablation of both genes constitutively or inducibly in the oral–esophageal epithelium. We show that the loss of both Cdh1 and Tgfbr2 in both models is sufficient to induce squamous cell carcinomas with animals succumbing to the invasive disease by 18 months of age. Advanced tumors have the ability to invade regional lymph nodes and to establish distant pulmonary metastasis. The mouse tumors showed molecular characteristics of human tumors such as overexpression of Cyclin D1. We addressed the question whether TGFβ signaling may target known stem cell markers and thereby influence tumorigenesis. From our mouse and human models, we conclude that TGFβ signaling regulates key aspects of stemness and quiescence in vitro and in vivo. This provides a new explanation for the importance of TGFβ in mucosal homeostasis. [ABSTRACT FROM AUTHOR]

Activation of PI3K/AKT pathway correlates with poor prognosis in patients with neuroblastoma. Our previous studies have demonstrated that PI3K/AKT signaling is critical for the oncogenic transformations induced by gastrin-releasing peptide (GRP) and its receptor, GRP-R, in neuroblastoma. Moreover, PI3K/AKT-dependent oncogenic transformations require N-myc, an extensively studied oncogene in neuroblastoma. Whether AKT directly regulates the expression of N-myc oncogene is yet to be determined. Here, we report a novel finding that of the three AKT isoforms, AKT2 specifically regulated N-myc expression in neuroblastoma cells. We also confirmed that GRP-R is upstream of AKT2 and in turn, regulated N-myc expression via AKT2 in neuroblastoma cells. Functional assays demonstrated that attenuation of AKT2 impaired cell proliferation and anchorage-independent cell growth, and decreased the secretion of angiogenic factor VEGF in vitro. Furthermore, silencing AKT2 inhibited migration and invasion of neuroblastoma cells in vitro. Xenografts established by injecting AKT2 silenced human neuroblastoma cells into murine spleen expressed decreased levels of AKT2 and resulted in fewer liver metastases compared to controls in vivo. Hence, our study highlights the potential molecular mechanism(s) mediating the oncogenic role of GRP/GRP-R and demonstrates a novel role for AKT2 in neuroblastoma tumorigenesis, indicating that targeting the GRP/GRP-R/AKT2 axis may be important for developing novel therapeutics in the treatment of clinically aggressive neuroblastoma. [ABSTRACT FROM AUTHOR]

Abstract: Chemistry as well as sputtering and reflection dynamics of lithiated carbon material, bombarded by slow hydrogen atoms are studied. We present a realistic method for computational simulation of the dynamics of the polar Li–C–O–H material dynamics. It is based on an approximate, semi-empirical quantum mechanics of electrons and classical mechanics of nuclei. Results are validated qualitatively by comparison with experiments and with a first principle DFT computations. In particular, we explain observed details of the hydrogen bonding chemistry in lithiated carbon, showing that incoming hydrogen interacts preferably with Li-C rather than C structures. [Copyright &y& Elsevier]

Background: Wilms tumor (WT) is thought to arise in children of Black African ancestry with greater frequency than in Whites. To clarify the biological basis for race disparities in WT, we first verified that Black children residing in Tennessee have an increased incidence of WT, and second, established molecular profiles in WT that are specific to race. Materials and Methods: To assess race disparities in WT epidemiology, the Tennessee Cancer Registry (TCR) was queried for all in-state patients less than 20 y of age and registered between 1999 and 2008. To explore race disparities in WT biology, six Black and four White WT specimens acquired in Tennessee were analyzed using imaging mass spectrometry (IMS). Results: TCR data show that Black children are over-represented among WT patients (29%) relative to all other childhood cancers (18.5%; P = 0.01). WT ranked the fifth most common cancer diagnosis among Blacks, but ninth among Whites. The diagnosis of WT occurred 79% more frequently among Blacks (n = 28) than Whites (n = 69; P = 0.01), and proportionally more Blacks tended to present with distant disease. Although overall survival from WT was not statistically different between Blacks (92.9%) and Whites (94.0%), Black males showed the lowest survival (85%; P = 0.21). IMS analysis identified peptide spectra from both WT blastema and stroma that independently classify specimens according to race with greater than 80% accuracy. Conclusions: In Tennessee, Black children appear more susceptible than Whites to develop WT. Race-specific molecular profiles can be determined that may help to clarify pathways of Wilms tumorigenesis and the biological basis for race disparities in WT incidence and biology. [Copyright &y& Elsevier]

The ε4 allele of Apolipoprotein (APOE4) is the strongest genetic risk factor for Alzheimer's disease (AD), the most common form of dementia. Cognitively normal APOE4 carriers have developed amyloid beta (Aβ) plaques and cerebrovascular, metabolic and structural deficits decades before showing the cognitive impairment. Interventions that can inhibit Aβ retention and restore the brain functions to normal would be critical to prevent AD for the asymptomatic APOE4 carriers. A major goal of the study was to identify the potential usefulness of rapamycin (Rapa), a pharmacological intervention for extending longevity, for preventing AD in the mice that express human APOE4 gene and overexpress Aβ (the E4FAD mice). Another goal of the study was to identify the potential pharmacogenetic differences in response to rapamycin between the E4FAD and E3FAD mice, the mice with human APOE ε3 allele. We used multi-modal MRI to measure in vivo cerebral blood flow (CBF), neurotransmitter levels, white matter integrity, water content, cerebrovascular reactivity (CVR) and somatosensory response; used behavioral assessments to determine cognitive function; used biochemistry assays to determine Aβ retention and blood-brain barrier (BBB) functions; and used metabolomics to identify brain metabolic changes. We found that in the E4FAD mice, rapamycin normalized bodyweight, restored CBF (especially in female), BBB activity for Aβ transport, neurotransmitter levels, neuronal integrity and free fatty acid level, and reduced Aβ retention, which were not observe in the E3FAD-Rapa mice. In contrast, E3FAD-Rapa mice had lower CVR responses, lower anxiety and reduced glycolysis in the brain, which were not seen in the E4FAD-Rapa mice. Further, rapamycin appeared to normalize lipid-associated metabolism in the E4FAD mice, while slowed overall glucose-associated metabolism in the E3FAD mice. Finally, rapamycin enhanced overall water content, water diffusion in white matter, and spatial memory in both E3FAD and E4FAD mice, but did not impact the somatosensory responses under hindpaw stimulation. Our findings indicated that rapamycin was able to restore brain functions and reduce AD risk for young, asymptomatic E4FAD mice, and there were pharmacogenetic differences between the E3FAD and E4FAD mice. As the multi-modal MRI methods used in the study are readily to be used in humans and rapamycin is FDA-approved, our results may pave a way for future clinical testing of the pharmacogenetic responses in humans with different APOE alleles, and potentially using rapamycin to prevent AD for asymptomatic APOE4 carriers. [ABSTRACT FROM AUTHOR]