The Evolving Philosophy of Climate Control for Historic House Museums in Subtropical Climates: Recommendations for the Aiken-Rhett House, Charleston, South Carolina

This study was designed to determine the most appropriate type of climate control system for the Aiken-Rhett House (1820-22), a historic house museum located in Charleston, South Carolina. The Aiken-Rhett property is unique in that it has never been restored and the current stewards of the museum have taken a conservation philosophy to the interpretation of the house. This house museum is rare because it is one of the few remaining unrestored antebellum structures in the South. Although grand mansions were never intended to exist in a state of decline, as the Aiken-Rhett does now, the preserved layers of time provide visitors with a sense of place and connect them to the past. Therefore, preserving this house museum and its original nineteenth-century finishes is of great importance to its interpretive value. Because a majority of the house is not climate-controlled, the building and its finishes are subjected to the high heat and humidity of Charleston, accelerating the deterioration of the historic building fabric. The owners of the property, Historic Charleston Foundation, are seeking new ideas for a climate control system to better protect the building and the collections that are exhibited inside. The type of environment that is beneficial for museum collections is not always best for historic buildings. This study aims to find the most appropriate interior climate control system for the building and its finishes, while collections and visitor comfort are treated as secondary priorities. The final recommendations will respect the historic fabric of the Aiken-Rhett House, while also providing economical and sustainable solutions for its continued care

Clotrimazole Preferentially Inhibits Human Breast Cancer Cell Proliferation, Viability and Glycolysis

BACKGROUND: Clotrimazole is an azole derivative with promising anti-cancer effects. This drug interferes with the activity of glycolytic enzymes altering their cellular distribution and inhibiting their activities. The aim of the present study was to analyze the effects of clotrimazole on the growth pattern of breast cancer cells correlating with their metabolic profiles. METHODOLOGY/PRINCIPAL FINDINGS: Three cell lines derived from human breast tissue (MCF10A, MCF-7 and MDA-MB-231) that present increasingly aggressive profiles were used. Clotrimazole induces a dose-dependent decrease in glucose uptake in all three cell lines, with K(i) values of 114.3±11.7, 77.1±7.8 and 37.8±4.2 µM for MCF10A, MCF-7 and MDA-MB-231, respectively. Furthermore, the drug also decreases intracellular ATP content and inhibits the major glycolytic enzymes, hexokinase, phosphofructokinase-1 and pyruvate kinase, especially in the highly metastatic cell line, MDA-MB-231. In this last cell lineage, clotrimazole attenuates the robust migratory response, an effect that is progressively attenuated in MCF-7 and MCF10A, respectively. Moreover, clotrimazole reduces the viability of breast cancer cells, which is more pronounced on MDA-MB-231. CONCLUSIONS/SIGNIFICANCE: Clotrimazole presents deleterious effects on two human breast cancer cell lines metabolism, growth and migration, where the most aggressive cell line is more affected by the drug. Moreover, clotrimazole presents little or no effect on a non-tumor human breast cell line. These results suggest, at least for these three cell lines studied, that the more aggressive the cell is the more effective clotrimazole is

Patterns of change and stability in the gender division of household labour in Australia, 1986-1997

Recent research in Australia and overseas has suggested that we are witnessing a convergence of men's and women's time on domestic labour activities. But there is disagreement about whether this is due to women reducing their time on housework or men increasing their time on housework. This article addresses these issues using national survey data collected in Australia in 1986, 1993 and 1997. The results show some changes in the proportional responsibilities of men and women in the home with men reporting a greater share of traditional indoor activities. But overall both men and women are spending less time on housework. In particular, women's time on housework has declined by six hours per week since 1986. Hence, while the gender gap between men's and women's involvement in the home is getting smaller, it is not the result of men increasing their share of the load, but is due to the large decline in women's time spent on domestic labour. There is also evidence of change in the relationship. between paid and unpaid work for women. Women's hours of,paid labour had a greater impact on their involvement in domestic labour in 1997 compared to a decade earlier. The article concludes that women's increased labour force involvement in combination with changing patterns and styles, of consumption is leading to some changes in the gender-division:of household labour, but not in the direction anticipated by earlier commentators on the domestic division of labour

Drug antagonism and single-agent dominance result from differences in death kinetics

Cancer treatment generally involves drugs used in combinations. Most previous work has focused on identifying and understanding synergistic drug-drug interactions; however, understanding antagonistic interactions remains an important and understudied issue. To enrich for antagonism and reveal common features of these combinations, we screened all pairwise combinations of drugs characterized as activators of regulated cell death. This network is strongly enriched for antagonism, particularly a form of antagonism that we call \u27single-agent dominance\u27. Single-agent dominance refers to antagonisms in which a two-drug combination phenocopies one of the two agents. Dominance results from differences in cell death onset time, with dominant drugs acting earlier than their suppressed counterparts. We explored mechanisms by which parthanatotic agents dominate apoptotic agents, finding that dominance in this scenario is caused by mutually exclusive and conflicting use of Poly(ADP-ribose) polymerase 1 (PARP1). Taken together, our study reveals death kinetics as a predictive feature of antagonism, due to inhibitory crosstalk between cell death pathways

InGaAs/AlInAsSb avalanche photodiodes with low noise and strong temperature stability

High-sensitivity avalanche photodiodes (APDs) are used to amplify weak optical signals in a wide range of applications, including telecommunications, data centers, spectroscopy, imaging, light detection and ranging, medical diagnostics, and quantum applications. This paper reports antimony-based separate absorption, charge, and multiplication structure APDs on InP substrates. Al0.7In0.3As0.79Sb0.21 is used for the multiplier region, and InGaAs is used as the absorber. The excess noise is comparable to that of silicon APDs; the k-value is more than one order of magnitude lower than that of APDs that use InP or InAlAs for the gain region. The external quantum efficiency without an anti-reflection coating at 1550 nm is 57%. The gradient of the temperature coefficient of avalanche breakdown voltage is 6.7 mV/K/μm, which is less than one-sixth that of InP APDs, presenting the potential to reduce the cost and complexity of receiver circuits. Semi-insulating InP substrates make high-speed operation practical for widely reported AlxIn1−xAsySb1−y-based APDs

Transcriptomic analysis reveals optimal cytokine combinations for SARS-CoV-2-specific T cell therapy products

Adoptive T cell immunotherapy has been used to restore immunity against multiple viral targets in immunocompromised patients after bone-marrow transplantation and has been proposed as a strategy for preventing coronavirus 2019 (COVID-19) in this population. Ideally, expanded severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-virus-specific T cells (CSTs) should demonstrate marked cell expansion, T cell specificity, and CD8+ T cell skewing prior to adoptive transfer. However, current methodologies using IL-4 + IL-7 result in suboptimal specificity, especially in CD8 cells. Using a microexpansion platform, we screened various cytokine cocktails (IL-4 + IL-7, IL-15, IL-15 + IL-4, IL-15 + IL-6, and IL-15 + IL-7) for the most favorable culture conditions. IL-15 + IL-7 optimally balanced T cell expansion, polyfunctionality, and CD8+ T cell skewing of a final therapeutic T cell product. Additionally, the transcriptomes of CD4 and CD8 T cells cultured with IL-15 + IL-7 displayed the strongest induction of antiviral type I interferon (IFN) response genes. Subsequently, microexpansion results were successfully translated to a Good Manufacturing Practice (GMP)-applicable format where IL-15 + IL-7 outperformed IL-4 + IL-7 in specificity and expansion, especially in the desirable CD8 T cell compartment. These results demonstrate the functional implications of IL-15-, IL-4-, and IL-7-containing cocktails for therapeutic T cell expansion, which could have broad implication for cellular therapy, and pioneer the use of RNA sequencing (RNA-seq) to guide viral-specific T cell (VST) product manufacturing