Instituting equity and inclusion in market-based approaches: reaching the poor and disabled in sanitation

This paper describes iDE’s approach to mainstreaming equity and inclusion within its market-based approach from the beginning of a program and not as an afterthought. The paper focuses on two separate strategies aimed at increasing access and equity among different groups. The first is the use of financial tools to increase access for very poor consumers in Bangladesh and Cambodia. The second part of the paper focuses on iDE’s user-centered design approach and experimentation with new construction technologies in constructing a latrine shelter for disabled users

Joint single-cell DNA accessibility and protein epitope profiling reveals environmental regulation of epigenomic heterogeneity.

Here we introduce Protein-indexed Assay of Transposase Accessible Chromatin with sequencing (Pi-ATAC) that combines single-cell chromatin and proteomic profiling. In conjunction with DNA transposition, the levels of multiple cell surface or intracellular protein epitopes are recorded by index flow cytometry and positions in arrayed microwells, and then subject to molecular barcoding for subsequent pooled analysis. Pi-ATAC simultaneously identifies the epigenomic and proteomic heterogeneity in individual cells. Pi-ATAC reveals a casual link between transcription factor abundance and DNA motif access, and deconvolute cell types and states in the tumor microenvironment in vivo. We identify a dominant role for hypoxia, marked by HIF1α protein, in the tumor microvenvironment for shaping the regulome in a subset of epithelial tumor cells

Ets-2 and Components of Mammalian SWI/SNF Form a Repressor Complex That Negatively Regulates the BRCA1Promoter

Ets-2 is a transcriptional activator that can be modulated by ras-dependent phosphorylation. Evidence is presented indicating that ets-2 can also act as a transcriptional repressor. In the breast cancer cell line MCF-7, exogenous ets-2 repressed the activity of a BRCA1promoter-luciferase reporter dependent on a conserved ets-2-binding site in this promoter. Conditional overproduction of ets-2 in MCF-7 cells resulted in repression of endogenousBRCA1 mRNA expression. To address the mechanism by which ets-2 could act as a repressor, a biochemical approach was used to identify proteins that interacted with the ets-2 pointed domain. From this analysis, components of the mammalian SWI/SNF chromatin remodeling complex were found to interact with ets-2. Brg-1, the ATP-hydrolyzing component of the SWI/SNF complex, along with the BAF57/p50 and Ini1 subunits could be co-immunoprecipitated from cells with ets-2. The pointed domain of ets-2 directly interacted in vitro with the C-terminal region of Brg-1 in a phosphorylation-dependent manner. The combination ofBrg-1 and ets-2 could repress theBRCA1 promoter reporter in transfection assays. These results support a role for ets-2 as a repressor and indicate that components of the mammalian SNF/SWI complex are required as co-repressors

CONTROL OF THE CA2+ - NFAT-IL-2 PATHWAY BY LRRK2 IN ASPERGILLUS-STIMULATED DENDRITIC CELLS

Ph.DDOCTOR OF PHILOSOPH

Rescue of a genotype 4 human hepatitis E virus from cloned cDNA and characterization of intergenotypic chimeric viruses in cultured human liver cells and in pigs

Hepatitis E virus (HEV) is an important but extremely understudied human pathogen. Genotypes 1 and 2 are restricted to humans, whereas genotypes 3 and 4 are zoonotic, infecting both humans and pigs. This report describes, for the first time, the successful rescue of infectious HEV in vitro and in vivo from cloned cDNA of a genotype 4 human HEV (strain TW6196E). The complete genomic sequence of the TW6196E virus was determined and a full-length cDNA clone (pHEV-4TW) was assembled. Capped RNA transcripts from the pHEV-4TW clone were replication competent in Huh7 cells and infectious in HepG2/C3A cells. Pigs inoculated intrahepatically with capped RNA transcripts from pHEV-4TW developed an active infection, as evidenced by faecal virus shedding and seroconversion, indicating the successful rescue of infectious genotype 4 HEV and cross-species infection of pigs by a genotype 4 human HEV. To demonstrate the utility of the genotype 4 HEV infectious clone and to evaluate the potential viral determinant(s) for species tropism, four intergenotypic chimeric clones were constructed by swapping various genomic regions between genotypes 1 and 4, and genotypes 1 and 3. All four chimeric clones were replication competent in Huh7 cells, but only the two chimeras with sequences swapped between genotypes 1 and 4 human HEVs produced viruses capable of infecting HepG2/C3A cells. None of the four chimeras was able to establish a robust infection in pigs. The availability of a genotype 4 HEV infectious clone affords an opportunity to delineate the molecular mechanisms of HEV cross-species infection in the future

Experimental Study on the Flexural Behavior of Reinforced Polystyrene Blocks in Concrete Beams

A new type of lightweight beam system was recently proposed by embedding polystyrene in beams to improve structural efficiency. This removes the non-performing concrete in the neutral axis and tension region to provide a comparable strength as a solid beam. There are, however, limited studies conducted to investigate the structural behavior of such beams. Therefore, this research presents an experimental investigation to assess the effect of polystyrene shapes in the beams. This involved testing a solid beam and five lightweight beams under flexural load using a four-point load test. The inclusion of polystyrene was estimated to have reduced the self-weight of beams by 8.6% to 11.8% when compared with the solid beam. The results also showed the ellipse polystyrene with a width of 70 mm and height of 50 mm produced the highest effective strength to weight ratio (sw) of 1.12 and performed 12% better than the solid beam. Moreover, the lightweight beams have more weight reduced than the strength, and those with ellipse polystyrene were found to have performed better than circular ones based on first crack load, ultimate load, and effective strength to weight ratio (sw). The beams with ellipse polystyrene allowed better stress distribution and this gave them a higher strength than sphere shape. For industry application, the polystyrene content is recommended to be greater than 10% while the effective strength to weight ratio (sw) of the beam is greater than 1. The successful reduction of the weight without affecting the structural performance has the ability to help in reducing construction costs

Identification and Functional Evaluation of Anti-Cancer Ilmmunomodulators from Physalis peruviana (Poha)

Our Creative Inquiry team is researching the anti-tumor potential of compounds isolated from Physalis peruviana (poha) fruit. CellTiter 96 Aqueous Non-radiative Cell Proliferation Assays (Promega, 2012) were performed to screen the inhibitory activity of the compounds on human lung carcinoma A549 cells and breast cancer MDA-MB- 231 cells with the corresponding non-tumorigenic epithelial cell line NL20 and MCF-10A as controls. The cells were treated with compounds at concentrations of 0μg/ml, 2μg/ml, 5μg/ml, and 20μg/ml and incubated for 24, 48, and 72 hours

BLiMP: The Benchmark of Linguistic Minimal Pairs for English

We introduce The Benchmark of Linguistic Minimal Pairs (shortened to BLiMP), a challenge set for evaluating what language models (LMs) know about major grammatical phenomena in English. BLiMP consists of 67 sub-datasets, each containing 1000 minimal pairs isolating specific contrasts in syntax, morphology, or semantics. The data is automatically generated according to expert-crafted grammars, and aggregate human agreement with the labels is 96.4%. We use it to evaluate n-gram, LSTM, and Transformer (GPT-2 and Transformer-XL) LMs. We find that state-of-the-art models identify morphological contrasts reliably, but they struggle with semantic restrictions on the distribution of quantifiers and negative polarity items and subtle syntactic phenomena such as extraction islands.Comment: To appear in TAC

BLiMP: A Benchmark of Linguistic Minimal Pairs for English

We introduce BLiMP (The Benchmark of Linguistic Minimal Pairs), a human-solvable challenge set for evaluating language models (LMs) that covers a broad range of major grammatical phenomena in English. BLiMP consists of over 30 datasets, each containing 1000 minimal pairs isolating specific contrasts in syntax, morphology, or semantics. Like GLUE (Wang et al., 2018), BLiMP makes it easy to directly compare models. Evaluating n-gram, LSTM, and Transformer LMs (GPT-2 and TransformerXL), we find that transformers are strongest overall, achieving (near) human performance on agreement and binding. However, phenomena like wh-islands and NPI licensing remain challenging even for state-of-the-art LMs

Energy-Related Indicators and Breast Cancer Risk among White and Black Women

Energy-related indicators, including physical activity, energy intake, body mass index (BMI) and adult weight change, have been linked to breast cancer risk. Very few studies of these associations have been conducted among black women, therefore we used the Nashville Breast Health Study (NBHS) to determine whether similar effects were seen in black and white women. The NBHS is a population-based case-control study of breast cancer among women age 25 to 75 years conducted between 2001 and 2010 in and around the Nashville Metropolitan area. Telephone interviews and self-administered food frequency questionnaires were completed with 2,614 incident breast cancer cases ascertained through hospitals and the statewide cancer registry, and 2,306 controls selected using random digit dialing. Among premenopausal white and black women, there was little effect of adult exercise or other energy-related indicators on breast cancer risk, regardless of tumor estrogen receptor (ER) status. The beneficial effect of adult exercise on postmenopausal breast cancer appeared to be comparable between white and black women (highest tertile relative to none - white odds ratio [OR] 0.8, 95% confidence interval [CI] 0.6-1.0, p for trend=0.05; black OR 0.7, 95% CI 0.4-1.1, p for trend=0.07); however, among black women the reduction was limited to those with ER-positive disease. White and black women should be encouraged to engage in more physical activity to reduce their risk of postmenopausal breast cancer