AdS4 backgrounds with N>16 supersymmetries in 10 and 11 dimensions

We explore all warped $AdS_4\times_w M^{D-4}$ backgrounds with the most general allowed fluxes that preserve more than 16 supersymmetries in $D=10$- and $11$-dimensional supergravities. After imposing the assumption that either the internal space $M^{D-4}$ is compact without boundary or the isometry algebra of the background decomposes into that of AdS$_4$ and that of $M^{D-4}$, we find that there are no such backgrounds in IIB supergravity. Similarly in IIA supergravity, there is a unique such background with 24 supersymmetries locally isometric to $AdS_4\times \mathbb{CP}^3$, and in $D=11$ supergravity all such backgrounds are locally isometric to the maximally supersymmetric $AdS_4\times S^7$ solution.Comment: 53 pages. v2: minor changes and references added. v3: typos corrected and minor footnote added, published versio

Elevated Hydrostatic Pressure Selectively Enhances Matricellular Gene Expression in Human Trabecular Meshwork Cells

Primary open-angle glaucoma (POAG) is a progressive optic neuropathy characterized by loss of peripheral vision secondarily associated with elevated intraocular pressure (IOP). Transforming growth factor (TGF)-β2 is markedly elevated in the aqueous humor (AH) of patients with POAG. It has been previously shown that TGF-β2 increases IOP, in part, by inducing expression and release of endothelin-1 (ET-1) and connective tissue growth factor (CTGF) within the trabecular meshwork (TM). ET-1 and CTGF may ultimately lead to increases in IOP by enhancing TM cell contractility and extracellular matrix (ECM) deposition. Here we confirm that TGF-β2 enhances mRNA content of ET-1, CTGF, and various ECM components in cultured human TM cells. In addition, we demonstrate a dose- and time-dependent decrease in the bradykinin B2 receptor expression in response to exogenous TGF-β2. This finding represents a novel mechanism by which TGF-β2 may elevate IOP through perturbation of the kallikrein- kinin system. Despite these advancements, the direct effect of elevated IOP on TM cell responsiveness remains unknown. To accurately model and characterize the effect of elevated IOP on the TM in vitro, we designed and built a custom hydrostatic pressure chamber. Cultured human TM cells exposed to elevated hydrostatic pressure exhibit decreased viability, accumulation of F-actin, and selective changes in the expression of matricellular and structural ECM genes associated with the pathogenesis of POAG including TGF-β2, ET-1, and CTGF. Furthermore, secreted ET-1, in response to elevated hydrostatic pressure, acts in an autocrine manner through the ETB receptor to enhance TGF-β2 and ppET-1 mRNA, but not CTGF content. The mechanism(s) by which TM cells sense and respond to elevated hydrostatic pressure remain unknown, but findings presented here suggest that neither activation of mechanosensitive TRPV channels nor oxidative stress is involved. Finally, we demonstrate that a second form of mechanical stimuli, fluid sheer stress as a result of increased perfusion flow rate in the anterior segment perfusion assay, can also influence both CTGF and ppET-1 mRNA content in the TM in situ. Taken together, these results support the hypothesis that pressure-dependent changes in TM cell gene expression represent a feed-forward mechanism that exacerbates TGF-β2 associated increases in TM cell contractility and altered ECM synthesis and deposition in affected POAG patients

The Significance of CRISPR/Cas9-Directed CUL3 Knockout on Human Colorectal Cancer Cells

Cancer, the second leading cause of death in the US, is caused by mutations in select genes that alter cellular function leading to uncontrolled proliferation. Understanding the specific genes that drive cancer can lead to the generation of novel cancer therapies. To identify novel genes that drive cancer in the colon (CRC), lungs, and ovaries in mice, Starr et al. employed a transposon-based insertional mutagenesis system. One of the genes identified, APC, is mutated in 70-80% of human CRCs. CUL3, suspected to be a general driver gene, was discovered in the lung cancer screen. CUL3 was analyzed for its role in a human CRC cell line in this study. CUL3 gene knockout was performed using the CRISPR/Cas9 system, which targets mutations to specific genes, thereby knocking out that gene’s function. Three different sites in the CUL3 gene were targeted for mutation and resulted in the creation of 41 separate cell lines with potential CUL3 knockout. Of those 41 cell lines, 25 exhibited qualitatively abnormal phenotypes 10 days after transfection. These phenotypes include slowed growth (25 of 25 cell lines), increased cell size (16 of 25 cell lines), and variation of cell adherence to culture flask surface (11 of 25 cell lines). Knockout was confirmed in 6 cell lines by using PCR in the region of the gene targeted for mutation and sequencing the PCR product. Each cell line was quantitatively evaluated for metabolic activity (or cell growth rate) using an MTS assay. If CUL3 knockout is shown to reduce overall cell growth and increase susceptibility to chemotherapy, this would support the development of new therapies for CRCs that target CUL3 function

Fair trade and development goals in the coffee sector

Although fair trade is a step in the right direction, this thesis argues that some of its claims and approaches may be problematic with respect to development goals. As one of the world’s most highly traded commodities and an income source for tens of millions of people worldwide, coffee has become one of the star products championed by fair trade efforts aimed at sustainable development. The discourse surrounding both fair trade and development has been affected by various theories and criticisms, which is considered in the literature review, influencing the overall trajectory of the discussion. This paper looks at some of the claims made by fair trade organizations, as well as claims made in response by direct trade organizations, identifying where claims overlap or there are gaps in the discourse. By identifying overlaps and gaps, this thesis seeks to reconcile the large discussion surrounding development and the claims made by fair trade companies. In doing so, these issues may provide a starting point for future researchers to delve further into the significance and impact of these approaches for the family farmer as well as provide suggestions for best practices for new or developing social justice and trade-oriented organizations

A non-existence theorem for N>16 supersymmetric AdS3 backgrounds

We show that there are no smooth warped AdS$_3$ solutions in 10- and 11-dimensional supergravities which preserve strictly more than 16 supersymmetries and have internal space a compact without boundary manifold.Comment: 50 page

Die Bedeutung der Quantentheorie für die theoretische Elektrotechnik

Am Beispiel des elektrischen Durchschlages, des Tunneleffektes und der Supraleitung wird aufgezeigt, daß eine quantitative Erfassung elektrischer Leitungsvorgänge nur im Rahmen der Quantentheorie möglich ist.a complete theoretical interpretation of the electrical phenomena in solids requires the quantum theory. This claim is exhibited by the discussion of the electrical breakdown, the tunnel effect and the superconductivity

Is the dream still alive? Tracking homeownership amid changing economic and demographic conditions

The United States (U.S.) is undergoing three major trends, which are converging and changing the housing market. The first trend is housing inventory is constrained in much of the U.S. As a result, home prices have increased to an inflation‐adjusted 49 percent from 2012 to 2017 (National Association of Realtors 2018b) and has become out of reach for many Americans as incomes have risen 14 percent in the same timeframe (U.S. Census Bureau 2018a). The second trend is the homeownership rate for those under the age of 35, Black/African American, and Hispanic/Latino adults has not rebounded since the Great Recession in the United States (U.S.). The third trend is the amount of student loan debt in the U.S. has increased about 70 percent from 2007 to 2017 (Chakrabarti et al. 2017) and is concentrated among those under the age of 35, Black/African Americans, and Hispanic/Latinos. This thesis explores the intersection of these trends through the application of quantitative and qualitative analysis. Through a Two‐Stage Least Squares econometric approach, those with student debt, Black/African American, and Hispanic/Latino buyers purchase a lower priced home, even while controlling household income and home size purchased. These three populations are most at risk to be impacted by the reduction in housing inventory, increased home prices, and the increase in student loan debt. As these three populations face limited affordable housing inventory and student debt increases, the homeownership rate has declined. To understand how local economic and demographic factors play a role, the days on market, unemployment rate, the share of those over the age of 65, and share of those with Bachelor’s degrees within the Metropolitan Statistical Area (MSA) are added into the model. Results from the econometrics are triangulated through focus groups conducted in cities across the U.S. Focus groups explored themes that were not able to be understood through econometrics, such as the idea that individuals may prefer to rent. The thesis contains policy recommendations based on the findings from the econometrics and focus groups