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Sustainable Investment in Retirement Plans: Introduction
Get PDFSince its green shoots first emerged around fifty years ago, acceptance of environmental, social, and governance (ESG) considerations in institutional investing—especially at pension funds—has evolved with distinct shifts in investor preferences. This Pension Research Council volume traces these shifts and their implications, leading up to the present day. Our volume notes that investors have diverse reasons for devoting attention to ESG criteria when deciding where to invest their money. Some have had religious motives, such as Quakers who focus on values; this approach can offer some risk mitigation. Yet models that look at whether divestment actually changes behaviors of companies show that rarely occurs. So it is not always that screening and divestment bring about the changes that investors seek. Accordingly, this book offers a variety of distinct viewpoints from a variety of countries, on whether, how, and when ESG criteria should, and should not, drive pension fund investments
Interactions Of Highly Pathogenic Human Coronaviruses With Dsrna-Induced Innate Immune Pathways
Get PDFIn the last decade, two novel coronaviruses have emerged from zoonotic sources to humans. Middle East Respiratory Syndrome Coronavirus (MERS-CoV) emerged in 2012 causing several outbreaks of severe respiratory illness with a high case fatality ratio of 35%. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) emerged in late 2019 causing a devastating pandemic that has caused over 2.7 million deaths in over 124 million cases as of March 2021. Coronaviruses are positive sense single-stranded RNA viruses and are adept at delaying or suppressing activation of innate immune responses in their hosts, despite detectable double-stranded (ds)RNA production during infection. Our goal was to understand how the highly pathogenic human coronaviruses, MERS-CoV and SARS-CoV-2, interact with and evade the dsRNA-induced innate immune pathways: type I and III interferon (IFN) production and signaling, protein kinase R (PKR), and oligo adenylate synthetase ribonuclease L (OAS/RNase L). We found that MERS-CoV evades activation of IFN, PKR and OAS/RNase L due to the activities of three different proteins. We show during authentic MERS-CoV infection that dsRNA-binding accessory protein NS4a blocks PKR activation and IFN mRNA expression, and that accessory protein NS4b blocks IFN induction through its phosphodiesterase (PDE) activity and nuclear localization. Furthermore, we examined the role of conserved coronavirus protein nsp15 endoribonuclease (EndoU) catalytic activity during MERS-CoV infection. We found that inactivation of EndoU during MERS-CoV infection had mild effects on the dsRNA-induced innate immune pathways. However, inactivation of EndoU in combination with loss of expression of accessory protein NS4a or inactivation of PDE activity of NS4b caused defects in infectious virus production and robust activation of the innate immune pathways in MERS-CoV infected A549DPP4 cells. This highlighted redundant functions of EndoU, NS4a, and NS4b that together lead to strong suppression and evasion of dsRNA induced innate immunity during MERS-CoV infection. We also investigated the interactions of SARS-CoV-2 with the dsRNA-induced pathways. We found that SARS-CoV-2, unlike MERS-CoV, induced mild IFN expression and moderately activated PKR and OAS/RNase L in lung derived cell lines. Our findings fill some of the gaps in knowledge of how highly pathogenic human coronaviruses interact with the innate immune system
Life On The Border: Constructing The México/u.s. Borderlands, 1961-1971.
No full textIn 1961, Mexican President Adolfo López Mateos launched a program that at- tempted to reinvigorate and develop the northern borderland region of México. The Programa Nacional Fronterizo (National Border Program, PRONAF) sought, among its established goals, to: “improve the general environment of the border cities… Promote the constant raising of the cultural standards of the population…and stress the values of our history, folklore, language, culture and arts.” Through projects of urban beautifica- tion, it would build the entrance gates of the country, and civic, cultural and commercial centers that would attract and maintain a certain type of tourism.
I argue that Mario Pani’s master plans not only sought to exalt Mexico’s national identity through an architecture, at once both modern and yet appearing to be linked to an indigenous past; but that the few actual built projects were an architecture of hybrid- ity, that of resistance to, and assimilation of, the post-war American way of life in the midst of Cold War politics. While the Mexican centralist government wanted to prevent the Americanization of the borderlands by building the last cultural frontline that would remind fronterizos of their mexicanidad, it also wanted to build “the biggest storefront” that, by leveraging on the purchasing power of its northern neighbor, would allow Méxi- co to be seen as an equal participant in the new world economy
Differential Essential Dimension
Get PDFRoughly speaking, the essential dimension of an algebraic object is the minimum number of parameters needed to specify the object. It was first introduced by J. Buhler and Z. Reichstein where it was used to bound the number of parameters that one may eliminate from a general polynomial by means of Tschirnhaus transformations.
In this thesis we define an analogue of essential dimension in differential algebra. As application, we show that the number of parameters in a general homogeneous linear differential equation over a field cannot be reduced via gauge transformations over the given field. We also bound the number of parameters needed to describe certain generic Picard-Vessiot extensions
Elucidating The Role Of The African-Centric P47s Variant Of Tp53 In Metabolism And Ferroptosis
Get PDFThe tumor suppressor gene TP53 is the most frequently mutated gene in cancer and plays a key role in mediating several processes that are critical for preventing tumor formation and progression. Known as the guardian of the genome, p53 regulates hundreds of genes involved in various pathways such as apoptosis, cell cycle arrest and senescence. In recent years, the role of p53 in metabolism, redox state and ferroptosis has begun to emerge. Our lab has identified an African-specific polymorphic variant of p53 that encodes a serine residue instead of a proline at amino acid 47 (hereafter S47) and predisposes carriers to cancer. The S47 variant is impaired for tumor suppression and ferroptosis, and S47 cells have an altered redox state. We sought to use the tumor prone S47 model as a tool to better understand the role of p53 in tumor suppression. Our results demonstrate that mice carrying the S47 variant have greater metabolic efficiency compared to those with WT p53, along with increased mTOR activity. This difference in mTOR stems from an impaired protein-protein interaction that occurs in S47, ultimately due to a difference in cellular redox state. We next identified PLTP as a p53 target gene that shows decreased transactivation in the S47 variant and mediates ferroptosis resistance by enhancing lipid storage in HepG2 cells. Taken together, this work sheds light on the emerging roles p53 plays in tumor suppression, metabolism and ferroptosis. It also provides a better understanding of an ethnic genetic variant of p53. We expect this work will enable better personalized medicine approaches and therapeutic options for people who carry this variant
Reactive Planning With Legged Robots In Unknown Environments
Get PDFUnlike the problem of safe task and motion planning in a completely known environment, the setting where the obstacles in a robot\u27s workspace are not initially known and are incrementally revealed online has so far received little theoretical interest, with existing algorithms usually demanding constant deliberative replanning in the presence of unanticipated conditions. Moreover, even though recent advances show that legged platforms are becoming better at traversing rough terrains and environments, legged robots are still mostly used as locomotion research platforms, with applications restricted to domains where interaction with the environment is usually not needed and actively avoided.
In order to accomplish challenging tasks with such highly dynamic robots in unexplored environments, this research suggests with formal arguments and empirical demonstration the effectiveness of a hierarchical control structure, that we believe is the first provably correct deliberative/reactive planner to engage an unmodified general purpose mobile manipulator in physical rearrangements of its environment. To this end, we develop the mobile manipulation maneuvers to accomplish each task at hand, successfully anchor the useful kinematic unicycle template to control our legged platforms, and integrate perceptual feedback with low-level control to coordinate each robot\u27s movement.
At the same time, this research builds toward a useful abstraction for task planning in unknown environments, and provides an avenue for incorporating partial prior knowledge within a deterministic framework well suited to existing vector field planning methods, by exploiting recent developments in semantic SLAM and object pose and triangular mesh extraction using convolutional neural net architectures. Under specific sufficient conditions, formal results guarantee collision avoidance and convergence to designated (fixed or slowly moving) targets, for both a single robot and a robot gripping and manipulating objects, in previously unexplored workspaces cluttered with non-convex obstacles. We encourage the application of our methods by providing accompanying software with open-source implementations of our algorithms
Investigation Of High-Surface-Area Titanate (atio3) Thin Films Prepared By Atomic Layer Deposition
Get PDFHeterogeneous catalysis is critically important in the chemical-processing and energy-related industries. Ideally, reaction sites on heterogeneous catalysts can be regenerated, and the catalysts should be active throughout the catalytic process. However, harsh reaction conditions and parallel side reactions can be harmful to the metal catalysts, making deactivation a common phenomenon. Finding a catalyst that is stable can be a challenging yet significant task. Metal-doped perovskite materials have been referred to as “intelligent catalysts” because of the ability to insert and remove metal cations from the support lattice under cyclic redox conditions. The concept of “intelligent catalysts” became interesting because the stability of the doped metals was found to be significantly improved. However, the concept was not entirely successful due to the low specific surface areas of these materials, the slow kinetics for ingress and egress from the lattice, and poor metal utilization. Reducing the length scale of the perovskite materials could potentially overcome these problems, and it can be achieved by coating a thin perovskite film with a thickness of around 1nm on a high-surface-area onto an inert support. Work in this thesis used Atomic Layer Deposition (ALD) to deposit titanates (ATiO3, A=Ca, Sr or Ba) that were roughly 1-nm thick onto high-surface-area substrates. When using these thin-film materials as supports for catalytically active metals, the thin-film samples showed properties similar to their bulk counterparts. Improved stabilities were found on the systems where strong interactions occur. However, the interactions between metals and the thin-film perovskite materials were found to be different from bulk “intelligent catalysts” in some ways. The differences between bulk and thin-film systems can lead to very different particle geometries and catalytic properties. Systematic comparisons of metal-perovskite interactions were performed for the titanate thin films with different A-site cations. Changing A-site cations can lead to changes in metal properties, including but not limited to the metal geometries, reducibilities, and the resulting catalytic performances. The role of A-site cations in determining the forms and degrees of metal-perovskite interactions were also discussed
Unfolding Musicking Archives At The Northwest Amazon
Get PDFThis dissertation proposes a decolonial revision of the archive consolidated by scholars, travelers and missionaries who previously sound recorded the Northwestern Amazon region, and introduces alternative ways of producing archival artifacts open to non-Indigenous and Indigenous perspectives and epistemologies alike. It studies the formation of sonic archives and points of listening that represented worlds of Indigenous expressivity in sound during the twentieth century in the Vaupés region, southern Colombia. This study focuses on Tukanoan musicking and specifically with the Cubeo Emi-Hehenewa clan, an Amazonian indigenous community living in a village called Camutí located at the Vaupés River Basin. This dissertation aims to reposition ethnomusicological practice in the Northwest Amazon as a collaborative and ethical research endeavor that can contribute new theoretical and methodological knowledge about and from the Vaupés region
Insights Into Functional Noncoding Rna Elements Through The Analysis Of Human Genetic Variation
Get PDFMost of the human genome is noncoding but knowing how and when genetic variation in noncoding regions of the genome can impact biology and disease susceptibility remains challenging. Here, we apply an integrated genomics approach towards understanding and elucidating new patterns of functional genetic variation in untranslated regions of protein-coding messenger RNAs.
G-quadruplex (G4) sequences are abundant in untranslated regions (UTRs) of human messenger RNAs, but their functional importance remains unclear. In Part 1 of this dissertation, we integrate multiple sources of genetic and genomic data to show that putative G-quadruplex forming sequences (pG4) in 5’ and 3’ UTRs are selectively constrained and enriched for cis-eQTLs and RNA-binding protein (RBP) interactions. Using over 15,000 whole genome sequences, we find evidence of strong negative selection acting on central guanines of UTR pG4s. At multiple GWAS-implicated SNPs within pG4 UTR sequences, we find robust allelic imbalance in gene expression across diverse tissue contexts in GTEx, suggesting that variants affecting G4 formation in UTRs may also contribute to phenotypic variation. Our results establish UTR G4s as important cis-regulatory elements and point to a link between disruption of UTR pG4 and disease.
In Part 2 of this dissertation, we examine patterns of selective pressure in non-canonical open reading frames (ncORFs) mapped throughout the human genome. Ribosome-profiling has uncovered pervasive translation in ncORFs, however the biological significance of this phenomenon remains unclear. Using genetic variation from 71,702 human genomes, we assess patterns of selection in translated upstream open reading frames (uORFs) in 5’UTRs. We show that uORF variants introducing new stop codons, or strengthening existing stop codons, are under strong negative selection comparable to protein-coding missense variants. Using these variants, we map and validate new gene-disease associations in two independent biobanks containing exome sequencing from 10,900 and 32,268 individuals, respectively, and elucidate their impact of protein expression in human cells. Our results suggest new mechanisms relating uORF variation to reduced protein expression and demonstrate that translation at uORFs is genetically constrained in 50% of human genes.
Together, these studies help emphasize the importance of noncoding RNA regulatory elements in mediating post-transcriptional regulation of gene expression and illuminate new patterns of functional variation in UTRs with human disease relevance