Task 4 supporting technology. Part 2: Detailed test plan for thermal seals. Thermal seals evaluation, improvement and test. CAN8-1, Reusable Launch Vehicle (RLV), advanced technology demonstrator: X-33. Leading edge and seals thermal protection system technology demonstration

The objective is to develop the advanced thermal seals to a technology readiness level (TRL) of 6 to support the rapid turnaround time and low maintenance requirements of the X-33 and the future reusable launch vehicle (RLV). This program is divided into three subtasks: (1) orbiter thermal seals operation history review; (2) material, process, and design improvement; and (3) fabrication and evaluation of the advanced thermal seals

Disparities in Healthcare Coverage and Utilization after Expanded Dependent Coverage

Background. A goal of expanding insurance coverage is reducing racial disparities in healthcare utilization, however the effects of such expansions under the affordable care act (ACA) on disparities remain unclear. The 2010 dependent coverage expansion provided an opportunity to evaluate disparities following a major coverage expansion. Objectives. We sought to understand changes in emergency department (ED)utilization following a major insurance expansion, the 2010 dependent coverage expansion. Research Design. We present changes in coverage and utilization among young adults (19-25 years old) before and after the dependent coverage expansion, compared to a control group (26-31 years old) unaffected by the provision using administrative records from four states (California, Florida, Massachusetts and New York) using a difference in difference methodology. ResultsWe identified 9,089,116 adults aged 19-31 with at least one ED visit between 2008 and 2013. While rates of ED utilization continue to increase, we found dependent coverage expansion was associated with a reduced increase in adjusted ED utilization among Whites, Blacks, and Asians (p Conclusions. Expansion of dependent insurance coverage was associated with significantly different ED healthcare utilization patterns among Hispanics than among other young adults. This suggests that eligibility or accessibility of dependent coverage remains a barrier to care for young Hispanics

Epstein-Barr Virus Nuclear Antigen 3C Stabilizes Gemin3 to Block p53-mediated Apoptosis

The Epstein-Barr nuclear antigen 3C (EBNA3C), one of the essential latent antigens for Epstein-Barr virus (EBV)-induced immortalization of primary human B lymphocytes in vitro, has been implicated in regulating cell proliferation and anti-apoptosis via interaction with several cellular and viral factors. Gemin3 (also named DDX20 or DP103) is a member of DEAD RNA helicase family which exhibits diverse cellular functions including DNA transcription, recombination and repair, and RNA metabolism. Gemin3 was initially identified as a binding partner to EBNA2 and EBNA3C. However, the mechanism by which EBNA3C regulates Gemin3 function remains unclear. Here, we report that EBNA3C directly interacts with Gemin3 through its C-terminal domains. This interaction results in increased stability of Gemin3 and its accumulation in both B lymphoma cells and EBV transformed lymphoblastoid cell lines (LCLs). Moreover, EBNA3C promotes formation of a complex with p53 and Gemin3 which blocks the DNA-binding affinity of p53. Small hairpin RNA based knockdown of Gemin3 in B lymphoma or LCL cells remarkably attenuates the ability of EBNA3C to inhibit the transcription activity of p53 on its downstream genes p21 and Bax, as well as apoptosis. These findings provide the first evidence that Gemin3 may be a common target of oncogenic viruses for driving cell proliferation and anti-apoptotic activities

PEARL: Personalizing Large Language Model Writing Assistants with Generation-Calibrated Retrievers

Powerful large language models have facilitated the development of writing assistants that promise to significantly improve the quality and efficiency of composition and communication. However, a barrier to effective assistance is the lack of personalization in LLM outputs to the author's communication style and specialized knowledge. In this paper, we address this challenge by proposing PEARL, a retrieval-augmented LLM writing assistant personalized with a generation-calibrated retriever. Our retriever is trained to select historic user-authored documents for prompt augmentation, such that they are likely to best personalize LLM generations for a user request. We propose two key novelties for training our retriever: 1) A training data selection method that identifies user requests likely to benefit from personalization and documents that provide that benefit; and 2) A scale-calibrating KL-divergence objective that ensures that our retriever closely tracks the benefit of a document for personalized generation. We demonstrate the effectiveness of PEARL in generating personalized workplace social media posts and Reddit comments. Finally, we showcase the potential of a generation-calibrated retriever to double as a performance predictor and further improve low-quality generations via LLM chaining.Comment: Pre-print, work in progres

Discovery of tissue-specific exons using comprehensive human exon microarrays

Comprehensive exon microarrays with a simple intra-gene normalization algorithm were used to detect human tissue-specific alternative splicing events, suggesting significant expression outside of known exons and well annotated genes and a high frequency of alternative splicing events

Investigation of Type 2 Diabetes Risk Alleles Support CDKN2A/B, CDKAL1, and TCF7L2 As Susceptibility Genes in a Han Chinese Cohort

Background: Recent genome-wide association studies (GWASs) have reported several genetic variants to be reproducibly associated with type 2 diabetes. Additional variants have also been detected from a metaanalysis of three GWASs, performed in populations of European ancestry. In the present study, we evaluated the influence of 17 genetic variants from 15 candidate loci, identified in type 2 diabetes GWASs and the metaanalysis, in a Han Chinese cohort. Methodology/Principal Findings: Selected type 2 diabetes-associated genetic variants were genotyped in 1,165 type 2 diabetic patients and 1,136 normoglycemic control individuals of Southern Han Chinese ancestry. The OR for risk of developing type 2 diabetes was calculated using a logistic regression model adjusted for age, sex, and BMI. Genotype-phenotype associations were tested using a multivariate linear regression model. Genetic variants in CDKN2A/B, CDKAL1, TCF7L2, TCF2, MC4R, and PPARG showed a nominal association with type 2 diabetes (P <= 0.05), of whom the three first would stand correction for multiple testing: CDKN2A/B rs10811661, OR: 1.26 (1.12-1.43) P = 1.8* 10(-4); CDKAL1 rs10946398, OR: 1.23 (1.09-1.39); P = 7.1* 10(-4), and TCF7L2 rs7903146, OR: 1.61 (1.19-2.18) P = 2.3* 10(-3). Only nominal phenotype associations were observed, notably for rs8050136 in FTO and fasting plasma glucose (P = 0.002), postprandial plasma glucose (P = 0.002), and fasting C-peptide levels (P = 0.006) in the diabetic patients, and with BMI in controls (P = 0.033). Conclusions/Significance: We have identified significant association between variants in CDKN2A/B, CDKAL1 and TCF7L2, and type 2 diabetes in a Han Chinese cohort, indicating these genes as strong candidates conferring susceptibility to type 2 diabetes across different ethnicities

Rapid Assessment of Breast Tumor Margins Using Deep Ultraviolet Fluorescence Scanning Microscopy

Significance: Re-excision rates for women with invasive breast cancer undergoing breast conserving surgery (or lumpectomy) have decreased in the past decade but remain substantial. This is mainly due to the inability to assess the entire surface of an excised lumpectomy specimen efficiently and accurately during surgery. Aim: The goal of this study was to develop a deep-ultraviolet scanning fluorescence microscope (DUV-FSM) that can be used to accurately and rapidly detect cancer cells on the surface of excised breast tissue. Approach: A DUV-FSM was used to image the surfaces of 47 (31 malignant and 16 normal/benign) fresh breast tissue samples stained in propidium iodide and eosin Y solutions. A set of fluorescence images were obtained from each sample using low magnification (4  ×  ) and fully automated scanning. The images were stitched to form a color image. Three nonmedical evaluators were trained to interpret and assess the fluorescence images. Nuclear–cytoplasm ratio (N/C) was calculated and used for tissue classification. Results: DUV-FSM images a breast sample with subcellular resolution at a speed of 1.0  min  /  cm2. Fluorescence images show excellent visual contrast in color, tissue texture, cell density, and shape between invasive carcinomas and their normal counterparts. Visual interpretation of fluorescence images by nonmedical evaluators was able to distinguish invasive carcinoma from normal samples with high sensitivity (97.62%) and specificity (92.86%). Using N/C alone was able to differentiate patch-level invasive carcinoma from normal breast tissues with reasonable sensitivity (81.5%) and specificity (78.5%). Conclusions: DUV-FSM achieved a good balance between imaging speed and spatial resolution with excellent contrast, which allows either visual or quantitative detection of invasive cancer cells on the surfaces of a breast surgical specimen

The Moderating Effect of Different Types of Internet Use on the Relationship between Transitional Aging Changes and Self-esteem of Older Adults

This study investigates the moderating effect of different types of Internet use regarding the relationship between three transitional aging changes and self-esteem of older adults. The current paper is still in progress; this is a research-in-progress paper. An aging population increases government expenditures and family responsibilities, thus drawing more attention from the academic community. Recent research posits that self-esteem tends to decline in individuals from the ages around 50-65 due to role loss, social loss, and dissatisfaction resulting from unaccomplished life goals. To address this issue, previous studies considered that the general use of the Internet may help to enhance self-esteem among older adults. To fill this research gap, the present study proposes that the cultural use of the Internet could moderate role loss of older adults, while social use of the Internet could mitigate social loss. Furthermore, economic use could moderate the dissatisfaction of unfulfilled life goals. Regarding various theoretical contributions, this is the first study to apply different types of Internet use, so as to investigate its moderating effect concerning the relationship between transitional aging changes and self-esteem. Findings of the present study can also help shed light on interventions for the caregiver in both community centers and the domestic environment to moderate the decline of self-esteem among older adults. The data will be collected through surveys distributed to District Elderly Community Centers (DECCs) in Hong Kong. Multiple regression analysis will then be utilized to test the moderating effect of each type of Internet use