SINGLE-SHELL TANK INTEGRITY PROJECT ANALYSIS OF RECORD-PRELIMINARY MODELING PLAN FOR THERMAL AND OPERATING LOADS

This document is a Phase I deliverable for the Single-Shell Tank Analysis of Record effort. This document is not the Analysis of Record. The intent of this document is to guide the Phase II detailed modeling effort. Preliminary finite element models for each of the tank types were developed and different case studies were performed on one or more of these tank types. Case studies evaluated include thermal loading, waste level variation, the sensitivity of boundary effects (soil radial extent), excavation slope or run to rise ratio, soil stratigraphic (property and layer thickness) variation at different farm locations, and concrete material property variation and their degradation under thermal loads. The preliminary analysis document reviews and preliminary modeling analysis results are reported herein. In addition, this report provides recommendations for the next phase of the SST AOR project, SST detailed modeling. Efforts and results discussed in this report do not include seismic modeling as seismic modeling is covered by a separate report. The combined results of both static and seismic models are required to complete this effort. The SST AOR project supports the US Department of Energy's (DOE) Office of River Protection (ORP) mission for obtaining a better understanding of the structural integrity of Hanford's SSTs. The 149 SSTs, with six different geometries, have experienced a range of operating histories which would require a large number of unique analyses to fully characterize their individual structural integrity. Preliminary modeling evaluations were conducted to determine the number of analyses required for adequate bounding of each of the SST tank types in the Detailed Modeling Phase of the SST AOR Project. The preliminary modeling was conducted in conjunction with the Evaluation Criteria report, Johnson et al. (2010). Reviews of existing documents were conducted at the initial stage of preliminary modeling. These reviews guided the topics that were explored in the SST preliminary modeling. The reviews determined the level of detail necessary to perform the analyses of the SSTs. To guide the Phase II detailed modeling effort, preliminary finite element models for each of the tank types were developed and different case studies were performed on one or more of these tank types. Case studies evaluated include thermal loading, waste level variation, the sensitivity of boundary effects (soil radial extent), excavation slope or run to rise ratio, soil stratigraphic (property and layer thickness) variation at different farm locations, and concrete material property variation and their degradation under thermal loads. Conclusions were derived from case studies on one of the tank types when no additional runs of similar cases on other types of tanks were found necessary to derive those conclusions. The document reviews provided relatively complete temperature histories for Type IV tanks. The temperature history data for Type I, II, and III tanks was almost nonexistent for years prior to 1975. Document reviews indicate that there might be additional useful data in the US Department of Energy, Richland Operations Office (DOE-RL) records in Seattle, WA, and these records need to be reviewed to extract data that might have been disregarded during previous reviews. Thermal stress analyses were conducted using different temperature distribution scenarios on Type IV tanks. Such studies could not be carried out for other tank types due to lack of temperature history data. The results from Type IV tank analyses indicate that factors such as temperature distribution in the tank waste and rate of rise in waste temperature have a significant impact on the thermal stresses in the tank structures. Overall, the conclusion that can drawn from the thermal stress analyses is that these studies should be carried out for all tank types during the detailed analysis phase with temperature values that are reasonably close to the typical temperature histories of the respective tank types. If and/or when additional waste temperature data is acquired for tank Type I, II, and III tanks, additional cases need to be considered as tank structural integrity is sensitive to thermal loads. A few case studies were also performed using Type IV-b models to comprehend the effects of excavation boundaries, change in soil stratigraphy (layer thickness and properties), and radial extent of soil in the finite element models. The result from the case studies indicates that the slight variation in soil stratigraphy has little effects on the tank sections force and moment demands under mechanical loads. The case study for excavation slope or backfill transition boundary indicated that inclusion of such boundary yields conservative demands in the wall region while demands at other locations remain unaffected. Hence this excavation slope will be modeled in the detailed analysis of SSTs

Early immune pressure initiated by tissue-resident memory T cells sculpts tumor evolution in non-small cell lung cancer

Tissue-resident memory T (TRM) cells provide immune defense against local infection and can inhibit cancer progression. However, it is unclear to what extent chronic inflammation impacts TRM activation and whether TRM cells existing in tissues before tumor onset influence cancer evolution in humans. We performed deep profiling of healthy lungs and lung cancers in never-smokers (NSs) and ever-smokers (ESs), finding evidence of enhanced immunosurveillance by cells with a TRM-like phenotype in ES lungs. In preclinical models, tumor-specific or bystander TRM-like cells present prior to tumor onset boosted immune cell recruitment, causing tumor immune evasion through loss of MHC class I protein expression and resistance to immune checkpoint inhibitors. In humans, only tumors arising in ES patients underwent clonal immune evasion, unrelated to tobacco-associated mutagenic signatures or oncogenic drivers. These data demonstrate that enhanced TRM-like activity prior to tumor development shapes the evolution of tumor immunogenicity and can impact immunotherapy outcomes

Weather effects on the patterns of people's everyday activities: a study using GPS traces of mobile phone users

This study explores the effects that the weather has on people's everyday activity patterns. Temperature, rainfall, and wind speed were used as weather parameters. People's daily activity patterns were inferred, such as place visited, the time this took place, the duration of the visit, based on the GPS location traces of their mobile phones overlaid upon Yellow Pages information. Our analysis of 31,855 mobile phone users allowed us to infer that people were more likely to stay longer at eateries or food outlets, and (to a lesser degree) at retail or shopping areas when the weather is very cold or when conditions are calm (non-windy). When compared to people's regular activity patterns, certain weather conditions affected people's movements and activities noticeably at different times of the day. On cold days, people's activities were found to be more diverse especially after 10AM, showing greatest variations between 2PM and 6PM. A similar trend is observed between 10AM and midnight on rainy days, with people's activities found to be most diverse on days with heaviest rainfalls or on days when the wind speed was stronger than 4 km/h, especially between 10AM–1AM. Finally, we observed that different geographical areas of a large metropolis were impacted differently by the weather. Using data of urban infrastructure to characterize areas, we found strong correlations between weather conditions upon people's accessibility to trains. This study sheds new light on the influence of weather conditions on human behavior, in particular the choice of daily activities and how mobile phone data can be used to investigate the influence of environmental factors on urban dynamics

Contribution of discourse and morphosyntax skills to reading comprehension in Chinese dyslexic and typically developing children

This study aimed at identifying important skills for reading comprehension in Chinese dyslexic children and their typically developing counterparts matched on age (CA controls) or reading level (RL controls). The children were assessed on Chinese reading comprehension, cognitive, and reading-related skills. Results showed that the dyslexic children performed significantly less well than the CA controls but similarly to RL controls in most measures. Results of multiple regression analyses showed that word-level reading-related skills like oral vocabulary and word semantics were found to be strong predictors of reading comprehension among typically developing junior graders and dyslexic readers of senior grades, whereas morphosyntax, a text-level skill, was most predictive for typically developing senior graders. It was concluded that discourse and morphosyntax skills are particularly important for reading comprehension in the non-inflectional and topic-prominent Chinese system

Noise correlation in PET, CT, SPECT and PET/CT data evaluated using autocorrelation function: a phantom study on data, reconstructed using FBP and OSEM

BACKGROUND: Positron Emission Tomography (PET), Computed Tomography (CT), PET/CT and Single Photon Emission Tomography (SPECT) are non-invasive imaging tools used for creating two dimensional (2D) cross section images of three dimensional (3D) objects. PET and SPECT have the potential of providing functional or biochemical information by measuring distribution and kinetics of radiolabelled molecules, whereas CT visualizes X-ray density in tissues in the body. PET/CT provides fused images representing both functional and anatomical information with better precision in localization than PET alone. Images generated by these types of techniques are generally noisy, thereby impairing the imaging potential and affecting the precision in quantitative values derived from the images. It is crucial to explore and understand the properties of noise in these imaging techniques. Here we used autocorrelation function (ACF) specifically to describe noise correlation and its non-isotropic behaviour in experimentally generated images of PET, CT, PET/CT and SPECT. METHODS: Experiments were performed using phantoms with different shapes. In PET and PET/CT studies, data were acquired in 2D acquisition mode and reconstructed by both analytical filter back projection (FBP) and iterative, ordered subsets expectation maximisation (OSEM) methods. In the PET/CT studies, different magnitudes of X-ray dose in the transmission were employed by using different mA settings for the X-ray tube. In the CT studies, data were acquired using different slice thickness with and without applied dose reduction function and the images were reconstructed by FBP. SPECT studies were performed in 2D, reconstructed using FBP and OSEM, using post 3D filtering. ACF images were generated from the primary images, and profiles across the ACF images were used to describe the noise correlation in different directions. The variance of noise across the images was visualised as images and with profiles across these images. RESULTS: The most important finding was that the pattern of noise correlation is rotation symmetric or isotropic, independent of object shape in PET and PET/CT images reconstructed using the iterative method. This is, however, not the case in FBP images when the shape of phantom is not circular. Also CT images reconstructed using FBP show the same non-isotropic pattern independent of slice thickness and utilization of care dose function. SPECT images show an isotropic correlation of the noise independent of object shape or applied reconstruction algorithm. Noise in PET/CT images was identical independent of the applied X-ray dose in the transmission part (CT), indicating that the noise from transmission with the applied doses does not propagate into the PET images showing that the noise from the emission part is dominant. The results indicate that in human studies it is possible to utilize a low dose in transmission part while maintaining the noise behaviour and the quality of the images. CONCLUSION: The combined effect of noise correlation for asymmetric objects and a varying noise variance across the image field significantly complicates the interpretation of the images when statistical methods are used, such as with statistical estimates of precision in average values, use of statistical parametric mapping methods and principal component analysis. Hence it is recommended that iterative reconstruction methods are used for such applications. However, it is possible to calculate the noise analytically in images reconstructed by FBP, while it is not possible to do the same calculation in images reconstructed by iterative methods. Therefore for performing statistical methods of analysis which depend on knowing the noise, FBP would be preferred

Abrogation of IL-6-mediated JAK signalling by the cyclopentenone prostaglandin 15d-PGJ2 in oral squamous carcinoma cells

Cyclopentenone 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) exerts antineoplastic effects on various types of human cancer. We recently showed that treatment with 15d-PGJ2 induces apoptosis accompanied by downregulation of the oncogenic signal transducer and activator of transcription 3 (Stat3) signalling in human oral squamous cell carcinoma (SCC) cells. The current study examines the effects of 15d-PGJ2 on the epidermal growth factor receptor (EGFR) and Janus Kinase (JAK)-mediated signalling pathways. Inhibition of Stat3 by 15d-PGJ2 was abolished by exogenous stimulation with transforming growth factor alpha (TGF-α), but not interleukin 6 (IL-6), supporting a selective effect of 15d-PGJ2 on IL-6-mediated signalling. Importantly, 15d-PGJ2 selectively abrogated constitutive and IL-6-mediated JAK phosphorylation without affecting EGFR-activated levels. Moreover, the inhibitory effect of 15d-PGJ2 on JAK signalling required the reactive α,β-unsaturated carbon within the cyclopentenone ring. Targeting of JAK signalling using a specific JAK inhibitor also abolished Stat3 phosphorylation and resulted in apoptosis in oral SCC cells. Our findings provide the first evidence for 15d-PGJ2–mediated downregulation of constitutive and IL-6-induced JAK signalling in cancer and support that JAK inhibition and suppression of EGFR-independent Stat3 activation by 15d-PGJ2 represent a promising approach for induction of apoptosis in oral SCC cells

The N-Terminal residues 43 to 60 form the interface for dopamine mediated α-synuclein dimerisation

α-synuclein (α-syn) is a major component of the intracellular inclusions called Lewy bodies, which are a key pathological feature in the brains of Parkinson's disease patients. The neurotransmitter dopamine (DA) inhibits the fibrillisation of α-syn into amyloid, and promotes α-syn aggregation into SDS-stable soluble oligomers. While this inhibition of amyloid formation requires the oxidation of both DA and the methionines in α-syn, the molecular basis for these processes is still unclear. This study sought to define the protein sequences required for the generation of oligomers. We tested N- (α-syn residues 43-140) and C-terminally (1-95) truncated α-syn, and found that similar to full-length protein both truncated species formed soluble DA: α-syn oligomers, albeit 1-95 had a different profile. Using nuclear magnetic resonance (NMR), and the N-terminally truncated α-syn 43-140 protein, we analysed the structural characteristics of the DA:α-syn 43-140 dimer and α-syn 43-140 monomer and found the dimerisation interface encompassed residues 43 to 60. Narrowing the interface to this small region will help define the mechanism by which DA mediates the formation of SDS-stable soluble DA:α-syn oligomers

Do Gene Variants Influencing Adult Adiposity Affect Birth Weight? A Population-Based Study of 24 Loci in 4,744 Danish Individuals

Several obesity risk alleles affecting adult adiposity have been identified by the recent wave of genome wide association studies. We aimed to examine the potential effect of these variants on fetal body composition by investigating the variants in relation to birth weight and ponderal index of the newborn.Midwife records from the Danish State Archives provided information on mother's age, parity, as well as birth weight, birth length and prematurity of the newborn in 4,744 individuals of the population-based Inter99 study. Twenty-four risk alleles showing genome-wide associations with adult BMI and/or waist circumference were genotyped. None of the 24 risk variants tested showed an association with birth weight or ponderal index after correction for multiple testing. Birth weight was divided into three categories low (≤10(th) percentile), normal (10(th)-90(th) percentile) and high birth weight (≥90th percentile) to allow for non-linear associations. There was no difference in the number of risk alleles between the groups (p = 0.57). No interactions between each risk allele and birth weight in the prediction of adult BMI were observed. An obesity risk score was created by summing up risk alleles. The risk score did not associate with fetal body composition. Moreover there was no interaction between the risk score and birth weight/ponderal index in the prediction of adult BMI.24 common variants associated with adult adiposity did not affect or interact with birth weight among Danes suggesting that the effects of these variants predominantly arise in the post-natal life

Sentinel node lymphocytes: tumour reactive lymphocytes identified intraoperatively for the use in immunotherapy of colon cancer

The sentinel node is the first lymph node to receive lymphatic drainage from a tumour and is usually the first site of metastases. Today, the sentinel node is used for tumour staging. Here, we focus on its immunological role and investigate lymphocytic function in sentinel nodes, identified intraoperatively by peritumoural dye injection, from 15 patients with colon cancer. Tumour infiltrating lymphocytes, sentinel and nonsentinel lymph node cells and peripheral blood leukocytes were studied by flow cytometry, proliferation assays and interferon-γ secretion after activation with autologous tumour homogenate. Whereas tumour-infiltrating lymphocytes were nonresponsive in the proliferation assays, lymphocytes from sentinel nodes proliferated dose dependently and secreted interferon-γ upon stimulation with tumour homogenate. The responses were of varying magnitude and tended to be weaker in metastatic sentinel nodes. Sentinel node lymphocytes represents an enriched source of tumour reactive lymphocytes, and may be useful in future trials of adoptive immunotherapy

Late weaning and maternal closeness, associated with advanced motor and visual maturation, reinforce autonomy in healthy, 2-year-old children.

We studied neurodevelopmental outcomes and behaviours in healthy 2-year old children (N = 1306) from Brazil, India, Italy, Kenya and the UK participating in the INTERGROWTH-21st Project. There was a positive independent relationship of duration of exclusive breastfeeding (EBF) and age at weaning with gross motor development, vision and autonomic physical activities, most evident if children were exclusively breastfed for ≥7 months or weaned at ≥7 months. There was no association with cognition, language or behaviour. Children exclusively breastfed from birth to 6 months had, in a dose-effect pattern, adjusting for confounding factors, higher scores for "emotional reactivity". The positive effect of EBF and age at weaning on gross motor, running and climbing scores was strongest among children with the highest scores in maternal closeness proxy indicators. EBF, late weaning and maternal closeness, associated with advanced motor and vision maturation, independently influence autonomous behaviours in healthy children