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Additional file 1: Supplementary Material 1. Stata and R code used for analysis. This text file includes the Stata and R code used to produced the results in the paper.

Additional file 2.

World Bank Group President David Malpass spoke about the broad, rapid, and affordable access to Coronavirus (COVID-19) vaccines which will be at the core of a resilient economic recovery that lifts everyone. He mentioned that the World Bank Group’s forty-year engagement with China has been mutually beneficial and continues to evolve. He thanked China for its large contribution to IDA19, which is particularly noteworthy given China’s stage of development. He highlighted on the lending relationship with China which is also evolving steadily, with a strong focus on analytical and advisory services and strong engagement from the International Finance Corporation. He expressed that China’s economy needs further reform to get the most benefit as it returns to sustained growth. China’s Coronavirus (COVID-19) economic policy response has been weighted towards supporting firms and banks and encouraging public investment, in relative terms, while direct transfers to households have been limited. Greening of China’s growth going forward should form a core objective of the fourteenth five-year plan. Regarding progress on debt relief and transparency, he mentioned that private creditors have not been participating, leaving official bilateral creditors shouldering much of the burden.

In response to the rapidly evolving COVID-19 pandemic, the U.S. Food and Drug Administration (FDA) has rapidly issued 49 emergency use authorizations (EUAs) for SARS-CoV-2 in vitro diagnostic test-kits. A critical metric in the performance evaluation for a diagnostic test kit is the analytical sensitivity, which is measured by the limit of detection (LOD). Commercial RNA stocks with known titers are used to determine LOD. We identified a problem with the titer reported for the commercial stocks when examining the analytical sensitivity of the reverse transcription quantitative PCR (RT-qPCR) protocol that is recommended by the Centers for Disease Control and Prevention (CDC) using plasmid DNA from Integrated DNA Technologies (IDT), synthetic RNA from BEI Resources (BEI), and extracted genomic RNA from BEI. We detected 3/3 positives for reactions containing synthetic RNA at a concentration of 0.1 copies/reaction (based on the supplier's label concentration). The apparent better-than-single-molecule performance is a statistically highly unlikely event, indicating a potential inaccuracy in the supplier's quantification of the stock material. Using an ultrasensitive and precise assay, reverse transcription digital PCR (RT-dPCR), we independently quantified concentrations of commercial SARS-CoV-2 plasmid DNA and SARS-CoV-2 RNA stocks. For plasmid DNA, the actual concentration measured by RT-dPCR was 11% of the nominal label concentration. For synthetic RNA, the actual concentration measured by RT-dPCR for one lot was 770% of the label concentration and for a different lot was 57% of the label concentration. For genomic RNA, the concentration measured by RT-dPCR for one lot was 240% of the label concentration and for a different lot it was 300% of the label concentration. This SARS-CoV-2 genomic RNA from BEI Resources has been used in at least 11 approved FDA Emergency Use Authorizations as of April 27, 2020. Such deviations of reported RNA or DNA stock concentrations from true concentrations can result in inaccurate quantification and calculation of LOD. Precise and accurate reporting of DNA and RNA stock concentrations by commercial suppliers will enable accurate quantification of assay performance, which is urgently needed to improve evaluation of different assays by diagnostic developers and regulatory bodies.

This is the second of a new series of Debt Reports for 2020 to be published online, at regular intervals, over the course of the year. Debt Report 2020 Edition II is published at a time when many countries are struggling to cope with the deadly impact of COVID-19 and a large part of the global economy is shut down, generating both demand and supply side shocks. It is too soon to assess what the economic and financial costs will be, much less predict the impact on capital flows. However, learning from past global crises, low- and middle-income countries face serious risks. Pre-COVID-19 debt inflows from private creditors were forecast as subdued on account of the downturn in the global economy in 2019 and pre-crisis projections are for only a moderate recovery in 2020. This crisis is putting even more pressure on global economic growth and capital flows. As always in times of crisis, the World Bank and the IMF have stepped up to the plate, pledging a total of $62 billion of fast-disbursing funds to support low- and middle-income countries to mitigate the impact of the virus. They have issued a joint communique calling on official bilateral creditors in G20 countries to suspend debt payments from any of the world’s poores t countries that request forbearance, to allow time for an assessment of the impact of the crisis and the possible debt relief needs of each country. The aim of these Debt Reports is to provide users with analyses of evolving trends and developments related to external debt and public debt in individual countries and regional groups, with primary emphasis on low- and middle-income countries, and to keep users abreast of debt-related issues and initiatives.

The dissertation is composed of two sections. The first section is composed of chapters one, two, and three and describes the study of macrocyclic β-hairpin peptides derived from β-sheet peptides. The second section is composed of chapters four and five and discusses the curricular innovations made to support the remote instruction of an organic chemistry lecture course, a general chemistry laboratory course, and an organic chemistry laboratory course at the onset of the COVID-19 pandemic. Chapter 1 describes the use of acetylation as a means to modulate and study the effect of charge on the oligomeric assembly and toxicity of familial Alzheimer’s disease (FAD) mutants of Aβ. FAD is an inherited form of Alzheimer’s disease that has an earlier onset due to point mutations within the sequence of Aβ that alter the rate of aggregation and toxicity of the peptide. The most common site of these mutations is position 22 in which the native glutamic acid may be replaced with a glycine (E22G), glutamine (E22Q), or lysine (E22K). Previous work in our lab using a macrocyclic chemical model system of the Aβ peptide that incorporates residues 16-22 and 30-36 established that there was a correlation between the net charges of these mutant peptides and their oligomeric assemblies and toxicities as measured by SDS-PAGE, LDH-release assays, and dye leakage assays. In this chapter I further probe the effect of charge on the oligomeric assembly and toxicity of the FAD mutant peptides using our lab’s chemical model system of Aβ. To control for the hydrophobicity and size of the residues that vary between the mutants, I used acetylation as a tool to manipulate the net charge of the peptides. This work demonstrates that the toxicities of the peptides strongly correlate with their net charges based on LDH-release assays and dye leakage assays. The oligomeric assemblies of the peptides assessed by SDS-PAGE suggest that charge is a factor that impacts their assembly, but that the position of acetylation also influences the assembly. Chapter 2 discusses the synthesis and X-ray crystallographic structure of a macrocyclic peptide derived from an amyloidogenic peptide called medin. Amyloidogenic peptides and proteins are rich sources of supramolecular assemblies. Sequences derived from well-known amyloids, including Aβ, human islet amyloid polypeptide, and tau have been found to assemble as fibrils, nanosheets, ribbons, and nanotubes. The supramolecular assembly of medin, a 50-amino acid peptide that forms fibrillary deposits in aging human vasculature, has not been heavily investigated. In this chapter, I present an X-ray crystallographic structure of a cyclic β-sheet peptide derived from the 19−36 region of medin that assembles to form interpenetrating cubes. The edge of each cube is composed of a single peptide, and each vertex is occupied by a divalent metal ion. This structure may be considered a metal−organic framework (MOF) containing a large peptide ligand. This work demonstrates that peptides containing Glu or Asp that are preorganized to adopt β-hairpin structures can serve as ligands and assemble with metal ions to form MOFs. Chapter 3 presents the development of an IQGAP1 WW domain-derived peptide with the ability to bind p110α. IQGAP1 is a scaffold protein that mediates the PI(3)K-Akt pathway that is upregulated in many cancers. The WW domain within the scaffold directly binds to p110α, one of the subunits of PI(3)K. Disrupting the interaction between p110α and the WW domain using a competitive inhibitor has been proposed as a promising approach to selectively negatively affecting cancer cells dependent on the PI(3)K-Akt pathway. In this chapter, I share the design and synthesis of a β-hairpin mimic peptide derived from the WW domain of IQGAP1, and I demonstrate that the peptide can compete for binding to p110α against the native IQGAP1 WW domain. This study is ongoing and future work will focus on elucidating the secondary structure of the peptide inhibitor by NMR and X-ray crystallography and determining if the secondary structure the peptide adopts is essential for its binding capability. Chapters 4 and 5 describe the conversion of in-person chemistry courses to online versions in response to the COVID-19 pandemic. As the SARS-CoV-2 pandemic spread throughout the world, universities were faced with extraordinary challenges. Shelter-in-place orders were given, in-person classes were cancelled, and at the University of California Irvine, instructors had less than two weeks to convert spring quarter classes from a face-to-face to an online format. A team-based approach was essential to making this transition. In chapter 4 I share the insights gained during the design and implementation of the final quarter of a large-enrollment online organic chemistry course, as well as student perspectives on the efficacy of key components of the course. In chapter 5, I describe how the curricular, administrative, and logistical challenges of high enrollment general and organic chemistry laboratories were addressed in the transition to remote teaching. I discuss the reasoning behind the approach, how the existing web-based course content was leveraged, the additions and alterations to the curriculum, the replacement of experimental work with videos, the results of both student and TA surveys, and the lessons learned for iterations of these courses in the near future.

In May 2020, the National Statistical Office (NSO), with support from the World Bank, launched the High-Frequency Phone Survey on COVID-19, which tracks the socio-economic impacts of the pandemic on a monthly basis for a period of 12 months. The survey aimed to recontact the entire sample of households that had been interviewed during the Integrated Household Panel Survey (IHPS) 2019 round and that had a phone number for at least one household member or a reference individual. This report presents the findings from the Sixth round of the survey that was conducted during the period of December 10 - December 24, 2020.

C-terminus of Heat-shock protein-70 interacting protein (CHIP) is an E3 ubiquitin ligase canonically known to mark misfolded Heat shock protein (Hsp) clients for degredation. A recent publication from the Craik lab demonstrated CHIP can directly interact with numerous proteins outside of Hsps. While the authors demonstrate the occurrence of Hsp-independent CHIP interactions in cells and that CHIP can ubiquitinate substrates without chaperones in biochemical assays, they were unable to show Hsp-independent substrate ubiquitination in cells. Successful demonstration of CHIP’s Hsp-independent enzymatic activity in cellular contexts could elucidate molecular underpinnings of multiple disease states, including neurodegeneration, cancer, and viral infections, as well as provide insights into the feasibility using Hsp-independent CHIP interactions for targeted degradation of proteins. Chapter 1 describes recombinant antibodies that function as CHIP inhibitors. These were shown to have distinct epitopes and were able to inhibit both CHIP substrate binding and ubiquitination. When reformatted into scFvs for intracellular expression, some antibodies can still bind to CHIP. The recombinant antibodies can be used to examine molecular mechanisms of CHIP interactions in disease states and enable structural studies. In chapter 2, a predicted, Hsp-independent, CHIP interaction with the viral protein ORF28 was examined. Data indicates this interaction occurs in cells, and preliminary results show this interaction may be a mechanism of host protein regulation. Further studies will allow for non-biased identification of interactors and determination of the impacts of these interactions on viral replication. Chapter 3 is a distinct effort from the rest of this thesis, driven by the continued need for the novel of COVID-19 antivirals. Stable, BSL2 models of SARS-CoV-2 replication (replicons) are needed to facilitate the screening and development of small molecule inhibitors, as well as probe the biology of SARS-CoV-2 replication in a non-BSL-3 lab. While multiple designs were attempted and gave some success in generating lines, none had enough assay window to successfully screen for compounds.

This brief presents the main findings from a rapid phone survey conducted by the World Bank across eight South Asian countries. The primary aim of the survey was to understand changes in the labor market among different groups. Additional questions were included on households’ ability to meet basic needs, safety nets, and coping mechanisms. In Sri Lanka, the survey was implemented between September and December 2020, and therefore helps assess the short-term impact of the COVID-19 crisis.

The university's flagship publication, Virginia Tech Magazine, forges stronger relationships among alumni, donors, and friends of Virginia Tech. Featured in this issue: Water Matters As the population around the globe continues to grow and the effects of climate change become more far-reaching, water stress is a growing concern. Across Virginia Tech's campuses, leaders and scientists are developing strategies to protect and preserve this valuable resource. Out of Office The COVID-19 pandemic triggered changes to the workplace. Employers and employees are adapting to a new normal that includes increased opportunities for remote and hybrid work as well as changes in job recruitment methods and team interactions. Virginia Tech Foundation