Model B4 : multi-decade creep and shrinkage prediction of traditional and modern concretes

To improve the sustainability of concrete infrastructure, engineers face the challenge of incorporating new concrete materials while pushing the expected design life beyond 100 years. The time-dependent creep and shrinkage response of concrete governs the serviceability and durability in this multi-decade time frame. It has been shown that current prediction equations for creep and shrinkage underestimate material deformations observed in structures outside of a laboratory environment. A new prediction model for creep and shrinkage is presented that can overcome some of the shortcomings of the current equations. The model represents an extension and systematic recalibration of model B3, a 1995 RILEM Recommendation, which derives its functional form from the phenomena of diffusion, chemical hydration, moisture sorption, and the evolution of micro-stresses in the cement structure. The model is calibrated through a joint optimization of a new enlarged laboratory test database and a new database of bridge deflection records to overcome the bias towards short-term behavior. A framework for considering effects of aggregates, admixtures, additives, and higher temperatures is also incorporated

Instrumentation and Measurement Strategy for the NOAA SENEX Aircraft Campaign as Part of the Southeast Atmosphere Study 2013

Natural emissions of ozone-and-aerosol-precursor gases such as isoprene and monoterpenes are high in the southeastern US. In addition, anthropogenic emissions are significant in the southeastern US and summertime photochemistry is rapid. The NOAA-led SENEX (Southeast Nexus) aircraft campaign was one of the major components of the Southeast Atmosphere Study (SAS) and was focused on studying the interactions between biogenic and anthropogenic emissions to form secondary pollutants. During SENEX, the NOAA WP-3D aircraft conducted 20 research flights between 27 May and 10 July 2013 based out of Smyrna, TN. Here we describe the experimental approach, the science goals and early results of the NOAA SENEX campaign. The aircraft, its capabilities and standard measurements are described. The instrument payload is summarized including detection limits, accuracy, precision and time resolutions for all gas-and-aerosol phase instruments. The inter-comparisons of compounds measured with multiple instruments on the NOAA WP-3D are presented and were all within the stated uncertainties, except two of the three NO 2 measurements. The SENEX flights included day- and nighttime flights in the southeastern US as well as flights over areas with intense shale gas extraction (Marcellus, Fayetteville and Haynesville shale). We present one example flight on 16 June 2013, which was a daytime flight over the Atlanta region, where several crosswind transects of plumes from the city and nearby point sources, such as power plants, paper mills and landfills, were flown. The area around Atlanta has large biogenic isoprene emissions, which provided an excellent case for studying the interactions between biogenic and anthropogenic emissions. In this example flight, chemistry in and outside the Atlanta plumes was observed for several hours after emission. The analysis of this flight showcases the strategies implemented to answer some of the main SENEX science questions

Differential Impact of Tetratricopeptide Repeat Proteins on the Steroid Hormone Receptors

Tetratricopeptide repeat (TPR) motif containing co-chaperones of the chaperone Hsp90 are considered control modules that govern activity and specificity of this central folding platform. Steroid receptors are paradigm clients of Hsp90. The influence of some TPR proteins on selected receptors has been described, but a comprehensive analysis of the effects of TPR proteins on all steroid receptors has not been accomplished yet.We compared the influence of the TPR proteins FK506 binding proteins 51 and 52, protein phosphatase-5, C-terminus of Hsp70 interacting protein, cyclophillin 40, hepatitis-virus-B X-associated protein-2, and tetratricopeptide repeat protein-2 on all six steroid hormone receptors in a homogeneous mammalian cell system. To be able to assess each cofactor's effect on the transcriptional activity of on each steroid receptor we employed transient transfection in a reporter gene assay. In addition, we evaluated the interactions of the TPR proteins with the receptors and components of the Hsp90 chaperone heterocomplex by coimmunoprecipitation. In the functional assays, corticosteroid and progesterone receptors displayed the most sensitive and distinct reaction to the TPR proteins. Androgen receptor's activity was moderately impaired by most cofactors, whereas the Estrogen receptors' activity was impaired by most cofactors only to a minor degree. Second, interaction studies revealed that the strongly receptor-interacting co-chaperones were all among the inhibitory proteins. Intriguingly, the TPR-proteins also differentially co-precipitated the heterochaperone complex components Hsp90, Hsp70, and p23, pointing to differences in their modes of action.The results of this comprehensive study provide important insight into chaperoning of diverse client proteins via the combinatorial action of (co)-chaperones. The differential effects of the TPR proteins on steroid receptors bear on all physiological processes related to steroid hormone activity

Genome-Wide Progesterone Receptor Binding: Cell Type-Specific and Shared Mechanisms in T47D Breast Cancer Cells and Primary Leiomyoma Cells

Progesterone, via its nuclear receptor (PR), exerts an overall tumorigenic effect on both uterine fibroid (leiomyoma) and breast cancer tissues, whereas the antiprogestin RU486 inhibits growth of these tissues through an unknown mechanism. Here, we determined the interaction between common or cell-specific genome-wide binding sites of PR and mRNA expression in RU486-treated uterine leiomyoma and breast cancer cells.ChIP-sequencing revealed 31,457 and 7,034 PR-binding sites in breast cancer and uterine leiomyoma cells, respectively; 1,035 sites overlapped in both cell types. Based on the chromatin-PR interaction in both cell types, we statistically refined the consensus progesterone response element to G•ACA• • •TGT•C. We identified two striking differences between uterine leiomyoma and breast cancer cells. First, the cis-regulatory elements for HSF, TEF-1, and C/EBPα and β were statistically enriched at genomic RU486/PR-targets in uterine leiomyoma, whereas E2F, FOXO1, FOXA1, and FOXF sites were preferentially enriched in breast cancer cells. Second, 51.5% of RU486-regulated genes in breast cancer cells but only 6.6% of RU486-regulated genes in uterine leiomyoma cells contained a PR-binding site within 5 kb from their transcription start sites (TSSs), whereas 75.4% of RU486-regulated genes contained a PR-binding site farther than 50 kb from their TSSs in uterine leiomyoma cells. RU486 regulated only seven mRNAs in both cell types. Among these, adipophilin (PLIN2), a pro-differentiation gene, was induced via RU486 and PR via the same regulatory region in both cell types.Our studies have identified molecular components in a RU486/PR-controlled gene network involved in the regulation of cell growth, cell migration, and extracellular matrix function. Tissue-specific and common patterns of genome-wide PR binding and gene regulation may determine the therapeutic effects of antiprogestins in uterine fibroids and breast cancer

Impact of medical student participation in student-run clinics on education, residency selection, and patient care: a review of selected articles

Student-run clinics (SRCs) are becoming increasingly popular at medical schools in the United States. These clinics have provided a variety of benefits, including serving disadvantaged populations and providing early clinical exposure for students. There has been no consensus on the impact of SRCs on medical education, specialty selection, and patient care. This review provides a thorough overview of student and patient outcomes as a function of medical students volunteering at SRCs. We queried PubMed for original literature published in English between the years 2000 and 2020. Inclusion criteria included primary research articles evaluating the impact of medical student participation in SRCs on education, specialty selection, and patient care. All articles included in the final review were agreed upon by three reviewers, and the pertinent data were extracted. Of 10,200 initial search results, seven papers were included in this review. These included two studies evaluating medical education, five studies evaluating residency selection, and three studies analyzing patient care. Three studies were included in multiple evaluations. The relationship between volunteering at SRCs and academic performance is unclear. Clinic volunteers had increased retention of empathy compared to non-volunteers. Additionally, clinic volunteers provided satisfactory care as determined by patient-reported outcomes, and were not more likely to pursue primary care specialties. As SRCs are increasing in number, research into the impact on medical students and patients is necessary to understand how these clinics may affect the field of health care. It is important to further evaluate how medical student involvement in SRCs can further improve patient care and outcomes