Elevated temperature nanoindentation and in-situ SEM mechanical testing of uranium fuels

Due to the Fukushima nuclear accident there has been a large effort by several countries to develop accident tolerant fuel forms for commercial light water reactors. A challenge with the current UO2 fuel is its low thermal conductivity which leads to higher center line temperatures in the fuel. New nuclear fuel forms are looking to increase the thermal conductivity and other thermophysical proprieties while also maintaining adequate mechanical properties and uranium loading. The elastic modulus, fracture toughness, and creep properties of the fuel are important for modeling the pellet clad mechanical interactions during operation of a nuclear reactor. During the operation of a nuclear reactor the cladding material creeps down and fuel pellet swells which leads to physical contact between the two. The pellet clad mechanical interactions can lead to potential cladding failures and release of radioactive material. The advanced fuel forms that are under consideration for replacing UO2 in commercial light water reactors is UN, U3Si2, composite UO2 and UO2 with additives. The composite UO2 is looking to increase the thermal conductivity with different additions and the UO2 with additives are intended to increase the grain size of the UO2. The increase in grain size can reduce the release of fission gas products into the plenum of the cladding rod improving the operational lifetime of the fuel. While there is a large amount of work on the thermal properties of these accident tolerant fuel forms the literature is quite sparse on the mechanical properties necessary for modeling such interactions as the pellet clad mechanical interactions. Please click Additional Files below to see the full abstract

Improving Roadside Design to Forgive Human Errors

AbstractAccidents involving roadsides are typically extremely “unforgiving”. Even though the roadside design can affect only marginally the actual number of accidents occurring on a road, the severity of crashes can be considerably reduced if roadsides are designed to be more “forgiving”.Within the IRDES project a practical and uniform guideline that allows the road designer to improve the forgivingness of the roadside and a practical tool for assessing the effectiveness of applying a given roadside treatment have been produced for the following set of roadside features: barrier terminals; shoulder rumble strips; forgiving support structures for road equipment; shoulder width

Distributed Variance Reduction with Optimal Communication

We consider the problem of distributed variance reduction: $n$ machines each receive probabilistic estimates of an unknown true vector $\Delta$, and must cooperate to find a common estimate of $\Delta$ with lower variance, while minimizing communication. Variance reduction is closely related to the well-studied problem of distributed mean estimation, and is a key procedure in instances of distributed optimization, such as data-parallel stochastic gradient descent. Previous work typically assumes an upper bound on the norm of the input vectors, and achieves an output variance bound in terms of this norm. However, in real applications, the input vectors can be concentrated around the true vector $\Delta$, but $\Delta$ itself may have large norm. In this case, output variance bounds in terms of input norm perform poorly, and may even increase variance. In this paper, we show that output variance need not depend on input norm. We provide a method of quantization which allows variance reduction to be performed with solution quality dependent only on input variance, not on input norm, and show an analogous result for mean estimation. This method is effective over a wide range of communication regimes, from sublinear to superlinear in the dimension. We also provide lower bounds showing that in many cases the communication to output variance trade-off is asymptotically optimal. Further, we show experimentally that our method yields improvements for common optimization tasks, when compared to prior approaches to distributed mean estimation.Comment: 28 pages, 14 figure

Long term results of postoperative Intensity-Modulated Radiation Therapy (IMRT) in the treatment of Squamous Cell Carcinoma (SCC) located in the oropharynx or oral cavity

Background: To report our long-term results with postoperative intensity-modulated radiation therapy (IMRT) in patients suffering from squamous-cell carcinoma (SCC) of the oral cavity or oropharynx. Methods: Seventy five patients were retrospectively analyzed. Median age was 58 years and 84 % were male. 76 % of the primaries were located in the oropharynx. Surgery resulted in negative margins (R0) in 64 % of the patients while 36 % suffered from positive margins (R1). Postoperative stages were as follows: stage1:4 %, stage2:9 %, stage3:17 %, stage4a:69 % with positive nodes in 84 %. Perineural invasion (Pn+) and extracapsular extension (ECE) were present in 7 % and 29 %, respectively. All patients received IMRT using the step-and-shoot approach with a simultaneously integrated boost (SIB) in 84 %. Concurrent systemic therapy was applied to 53 patients, mainly cisplatin weekly. Results: Median follow-up was 55 months (5–150). 13 patients showed locoregional failures (4 isolated local, 4 isolated neck, 5 combined) transferring into 5-year-LRC rates of 85 %. Number of positive lymph nodes (n > 2) and presence of ECE were significantly associated with decreased LRC in univariate analysis, but only the number of nodes remained significant in multivariate analysis. Overall treatment failures occurred in 20 patients (9 locoregional only, 7 distant only, 4 combined), transferring into 3-and 5-year-FFTF rates of 77 % and 75 %, respectively. The 3-and 5-year-OS rates were 80 % and 72 %, respectively. High clinical stage, high N stage, number of positive nodes (n > 2), ECE and Pn1 were significantly associated with worse FFTF and OS in univariate analysis, but only number of nodes remained significant for FFTF in multivariate analysis. Maximum acute toxicity was grade 3 in 64 % and grade 4 in 1 %, mainly hematological or mucositis/dysphagia. Maximum late toxicity was grade 3 in 23 % of the patients, mainly long-term tube feeding dependency. Conclusion: Postoperative IMRT achieved excellent LRC and good OS with acceptable acute and low late toxicity rates. The number of positive nodes (n > 2) was a strong prognostic factor for all endpoints in univariate and the only significant factor for LRC and FFTF in multivariate analysis. Patients with feeding tubes due to postoperative complications had an increased risk for long-term feeding tube dependency

Binding, thermodynamics, and selectivity of a non-peptide antagonist to the melanocortin-4 receptor

The melanocortin-4 receptor (MC4R) is a potential drug target for treatment of obesity, anxiety, depression, and sexual dysfunction. Crystal structures for MC4R are not yet available, which has hindered successful structure-based drug design. Using microsecond-scale molecular-dynamics simulations, we have investigated selective binding of the non-peptide antagonist MCL0129 to a homology model of human MC4R (hMC4R). This approach revealed that, at the end of a multi-step binding process, MCL0129 spontaneously adopts a binding mode in which it blocks the agonistic-binding site. This binding mode was confirmed in subsequent metadynamics simulations, which gave an affinity for human hMC4R that matches the experimentally determined value. Extending our simulations of MCL0129 binding to hMC1R and hMC3R, we find that receptor subtype selectivity for hMC4R depends on few amino acids located in various structural elements of the receptor. These insights may support rational drug design targeting the melanocortin systems

Differential gene expression in pristane-induced arthritis susceptible DA versus resistant E3 rats

Arthritis susceptibility genes were sought by analysis of differential gene expression between pristane-induced arthritis (PIA)-susceptible DA rats and PIA-resistant E3 rats. Inguinal lymph nodes of naïve animals and animals 8 days after pristane injection were analyzed for differential gene expression. mRNA expression was investigated by microarray and real-time PCR, and protein expression was analyzed by flow cytometry or ELISA. Twelve genes were significantly differentially expressed when analyzed by at least two independent methods, and an additional five genes showed a strong a tendency toward differential expression. In naïve DA rats IgE, the bone marrow stromal cell antigen 1 (Bst1) and the MHC class II β-chain (MhcII) were expressed at a higher level, and the immunoglobulin kappa chain (Igκ) was expressed at a lower level. In pristane-treated DA rats the MHC class II β-chain, gelatinase B (Mmp9) and the protein tyrosine phosphatase CL100 (Ptpn16) were expressed at a higher level, whereas immunoglobulins, the CD28 molecule (Cd28), the mast cell specific protease 1 (Mcpt1), the carboxylesterase precursor (Ces2), K-cadherin (Cdh6), cyclin G1 (Ccng1), DNA polymerase IV (Primase) and the tumour associated glycoprotein E4 (Tage) were expressed at a lower level. Finally, the differentially expressed mRNA was confirmed with protein expression for some of the genes. In conclusion, the results show that animal models are well suited for reproducible microarray analysis of candidate genes for arthritis. All genes have functions that are potentially important for arthritis, and nine of the genes are located within genomic regions previously associated with autoimmune disease