Alliance One Tobacco (Malawi)
Academic Research Repository at the Institute of Developing EconomiesNot a member yet
52305 research outputs found
Sort by
The 15-Minute City Quantified Using Mobility Data
No full textAmericans travel 7 to 9 miles on average for shopping and recreational activities, which is far longer than the 15-minute (walking) city advocated by ecologically-oriented urban planners. This paper provides a comprehensive analysis of local trip behavior in US cities using GPS data on individual trips from 40 million mobile devices. We define local usage as the share of trips made within 15-minutes walking distance from home, and find that the median US city resident makes only 12% of their daily trips within such a short distance. We find that differences in access to local services can explain eighty percent of the variation in 15-minute usage across metropolitan areas and 74 percent of the variation in usage within metropolitan areas. Differences in historic zoning permissiveness within New York suggest a causal link between access and usage, and that less restrictive zoning rules, such as permitting more mixed-use development, would lead to shorter travel times. Finally, we document a strong correlation between local usage and experienced segregation for poorer, but not richer, urbanites, which suggests that 15-minute cities may also exacerbate the social isolation of marginalized communities.Accepted Manuscrip
Darkness, My Teacher: A Journey into Yangti Yoga
No full textSpiritual practice is vital to the cultivation of our capacity for spiritual caregiving and embodied spiritual understanding. This paper is an experiential account of a journey into the Buddhist practice of yangti yoga, or dark retreat practice, rooted in the Dzogchen tradition of the Nyingma school of Tibetan Buddhism. It documents my early relationship to death, how this led me to the Buddhist path, and my decision to forgo my law career to attend Harvard Divinity School and pursue a career in hospital chaplaincy. The paper traces my experiences during 100 hours of dark retreat and the surprisingly relational dimensions of yangti yoga. As a process of individual and interpersonal reflection, this paper highlights the critical role of spiritual friendship and integration in spiritual life and practice
Essays on Employer Learning in the Labor Market
No full textThe efficient allocation of labor relies on the identification of talent. This dissertation consists of three essays that study information frictions about talent and quantify their impacts on individual career outcomes and aggregate productivity.
The first chapter investigates how employer learning affects individual career mobility and overall productivity in the labor market for computer scientists. The large volume of computer science conference proceedings provide public information on the research ability of authors. I find evidence of public learning by showing that workers with a new paper have higher inter-firm mobility rates than do coworkers without a paper. I test for asymmetric employer learning by exploiting the delayed disclosure of patent applications that accompany some high-quality research papers. Removing the delayed disclosure is estimated to accelerate the positive assortative matching between firms and workers and increase innovation outputs.
Are firms equally likely to identify high-ability workers? The second chapter, co-authored with Sabrina Di Addario, provides an answer in Italy’s labor market for potential inventors. We find a substantial gap between lower-wage and higher-wage firms in the discovery of new inventors who apply for a patent for the first time. We also study how wages are set given imperfect information about talent. Lower-wage firms set a higher wage return to the first patent application of an inventor. We interpret the findings through a model where heterogeneous firms invest in talent discovery and use wage incentives to elicit effort from workers.
The third chapter examines if the learning about an individual’s ability is contaminated by stereotype and in-group bias. I study how women and men are portrayed differently on an anonymous online forum for economists. Discussions about women are more likely to highlight their personal characteristics rather than professional accomplishments. Posts that mention a female economist also have also a higher chance to deviate from professional topics than posts that mention a male. The findings are interpreted via an identity model where male posters are incentivized to boost their own professional identities relative to the out-group in the profession
A new antibiotic traps lipopolysaccharide in its intermembrane transporter
No full textGram-negative bacteria are extraordinarily difficult to kill because their cytoplasmic membrane is surrounded by an outer membrane that blocks the entry of most antibiotics. The impenetrable nature of the outer membrane is due to the presence of a large, amphipathic glycolipid called lipopolysaccharide (LPS) in its outer leaflet1. Assembly of the outer membrane requires transport of LPS across a protein bridge that spans from the cytoplasmic membrane to the cell surface. Maintaining outer membrane integrity is essential for bacterial cell viability, and its disruption can increase susceptibility to other antibiotics2–6. Thus, inhibitors of the seven lipopolysaccharide transport (Lpt) proteins that form this transenvelope transporter have long been sought. A new class of antibiotics that targets the LPS transport machine in Acinetobacter was recently identified. Here, using structural, biochemical and genetic approaches, we show that these antibiotics trap a substrate-bound conformation of the LPS transporter that stalls this machine. The inhibitors accomplish this by recognizing a composite binding site made up of both the Lpt transporter and its LPS substrate. Collectively, our findings identify an unusual mechanism of lipid transport inhibition, reveal a druggable conformation of the Lpt transporter and provide the foundation for extending this class of antibiotics to other Gram-negative pathogens.Version of Recor
PROPHETS OF PLENTY: HOW SCIENTISTS IGNORED NATURAL COMPLEXITY AND OVERPROMISED SUSTAINABLE FISHERIES, 1863-PRESENT
No full textIn this dissertation I argue that fisheries science overpromised and under-delivered large sustainable catches. Fisheries scientists’ presumption of plenitude encouraged them to ignore important aspects of fish ecology like population fluctuations and species interactions. Along with challenges acquiring reliable population data, these ecological factors generated inherent uncertainty and posed barriers to large sustainable catches. By ignoring these ecological factors and assuming abundance when confronted with uncertainty, scientists systematically set catches high enough to incur substantial risk of fishery and ecosystem collapse. This presumption of plenitude emerged from the field’s purpose as a technoscientific method of maximizing sustained catch for benefit of the fishing industry and fish consumers, and despite advances in science and policy, has remained an anchoring concept for fisheries science in ways that put marine ecosystems at continued risk of collapse
The Ruler's Realization: State Protection Buddhism and Shingon Ritual
No full textThis thesis examines the Japanese Buddhist state protection ritual, the Goshichinichi no mishuhō (Mishuhō), introduced by the ninth century Buddhist monk Kūkai. Specifically, I propose that Kūkai nested within the ritual a practice based on the Ninnōkyō sutra, as a means of transforming the emperor in conformity with Buddhist philosophical aims as the proper means of protecting the state. My analysis focuses on Shingon Buddhist school’s ritual theory to explain why Kūkai suggested an additional ritual from those in use in Japan at the time. As part of that analysis, I draw from Kūkai’s work, Himitsu Mandara jūjūshinron (Jūjūshinron), to explain how Kūkai perceived the various texts utilized for state protection practices. Utilizing Kūkai’s own writings I explore Shingon ritual practice and theory relevant to the Mishuhō. Through these sources I consider the intended purpose of ritual meditation, its mechanism, and enunciated ideals relevant to the concept of conferring the benefits of ritual practice experientially upon another, in this case the emperor.
An aspect of Kūkai’s theory holds that the efficacy of the ritual results not only in divine protection, but also a transformation of the ruler, in conformity with the goals of the underlying sutra. The later portion of this thesis considers the degree to which modern clinical studies demonstrate the efficacy of Buddhist practice and whether they parallel the goals of state protection texts. My analysis considers how Buddhist studies can benefit from considering the intended experience for, and benefit to, individual practitioners and society for the practice under consideration
Toxic Rules: Chemical Regulation, International Trade, and the Epistemic Consequences of Standardized Practices
No full textThis dissertation is a study of regulatory epistemology: the practices of managing knowledge, expertise, and evidence in regulatory decision-making. Using chemical regulation as a case study, it examines science at the intersection of commodity trade, regulation, and safety. I demonstrate how the desiderata of bureaucratic efficiency and free-flowing trade have shaped how the U.S. and the Organisation for Economic Co-operation and Development (OECD) developed norms and practices to know and regulate risk.
Since 1900, over 10 million new chemicals have been synthesized; 150,000 have been used in plastics, drugs, foods, and pesticides. Many are known to be harmful. Yet regulatory action has generally been weak and slow, despite robust evidence demonstrating the environmental and health consequences of chemicals in everyday products. This dissertation investigates why many governments have failed to regulate chemicals widely considered toxic: because regulatory agencies including the U.S. Food and Drug Administration (FDA) and Environmental Protection Agency (EPA) have relied on partial knowledge. They have done so to make chemicals governable and to facilitate international trade, reflecting the fact that the epistemic demands of governance and market capitalism are different from those of public health and environmental protection.
In the 1970s, fraudulent studies submitted to regulatory agencies cast doubt on the integrity of chemical safety data—and hence the safety of approved drugs, pesticides, and other chemical products. U.S. regulators formulated quality assurance and reporting standards called Good Laboratory Practices (GLPs). The rules were ostensibly adopted to assure the integrity of toxicology data. This dissertation shows that, at least in the U.S., government officials knew they would never achieve this goal. The aim was not to make laboratory practices and the resultant knowledge good, but rather to make them governable.
As part of the goal of governance, a question that was previously understood as the domain of science—“how do we determine if this chemical is safe?”—became reframed as a matter of economic policy and international governance. In 1981, the twenty-four industrialized nations of the OECD adopted GLPs and Test Guideline protocols as part of their Mutual Acceptance of Data framework. The OECD hoped to protect public safety by ensuring data quality, but their primary aim was to facilitate international trade by creating uniform standards. Namely, the OECD hoped to avoid trade barriers due to conflicting national rules, which would otherwise require companies to test substances multiple times, impeding economic growth. The standards achieved those narrow aims. But over time, reliance on them has restricted the evidence for regulatory action to a subset of studies: standardized studies, generally performed and funded by industry. Most academic studies have been excluded. In many cases, this has meant ignoring evidence from precisely those studies that suggest a need for stronger regulation.
This dissertation highlights a problem with science in regulation writ large: a weakness in how the state knows. Regulatory bodies have invoked procedural fairness and rational management as defenses against charges of public interference in private affairs. Those rationales, in turn, informed how regulators know. The way that they do so—based on standard protocols and credentialed experts—benefits business and government. But does it make scientific sense, and does it protect people or the environment? I argue that the answers are “no.” These frameworks constrain the evidence and expertise used to govern by impeding the uptake of knowledge about and urgently needed action on toxics
Genetic determinants of antibiotic susceptibility reveal novel mechanisms of action and resistance in mycobacteria
No full textThe Mycobacterium genus contains several pathogenic species that cause significant human morbidity and mortality. This includes Mycobacterium tuberculosis (Mtb), the causative pathogen of one of the deadliest infectious diseases in the world, tuberculosis (TB), as well as several nontuberculous mycobacteria (NTM) species, such as Mycobacterium abscessus, that can cause opportunistic lung infections. Pathogenic mycobacteria generally exhibit high levels of antibiotic resistance to multiple classes of antibiotics. However, the current understanding of the genetic determinants of antibiotic resistance in mycobacteria remains poor, and this is further complicated by an incomplete understanding of the mechanisms of action for many antibiotics that are currently used to treat mycobacterial infections. This dissertation aims to identify and characterize the molecular determinants of antibiotic susceptibility in mycobacteria. Overall, we seek to better understand the mechanisms of resistance and drug action of two important anti-mycobacterial antibiotics, linezolid and pretomanid.
In Chapter 1, we discuss our current understanding and outstanding questions regarding intrinsic and acquired antibiotic resistance in mycobacteria. We examine approaches to discover novel genetic determinants, and we discuss how elucidating the mechanisms of action can also help uncover potentiation strategies. In Chapter 2, we perform a genetic screen to uncover the genetic determinants of intrinsic linezolid resistance in M. abscessus. We discover multiple transmembrane proteins that likely play a role in maintaining cell wall integrity, which prevents permeability to linezolid. Furthermore, we also find a novel M. abscessus-specific efflux pump, MAB_2303, that has a direct role linezolid efflux. Together these findings suggest that targeting these transmembrane proteins or MAB_2303 could be promising avenues for potentiating linezolid activity in M. abscessus. In Chapter 3, we characterize an ABC-F family protein, MAB_2736c, in M. abscessus that confers resistance to linezolid, chloramphenicol, and macrolides. We find that MAB_2736c likely confers resistance through a ribosomal protection mechanism that disrupts linezolid’s ability to interact with the ribosome. Our results highlight that ARE-ABC-F proteins are important determinants of intrinsic resistance in mycobacteria. In Chapter 4, we perform a genetic screen in mice to determine differentially required Mtb genes for survival upon pretomanid treatment. We find that the nucleotide excision repair (NER) pathway is essential for Mtb survival upon pretomanid only in physiologically relevant conditions that mimic the infection environment. Additionally, we discover that in these conditions pretomanid causes an increased mutational burden that is heightened in NER pathway mutants. Together, this reveals that DNA damage is a novel in vivo mechanism of action for pretomanid. Lastly, in Chapter 5, we close with a summary of the implications of this body of work, discuss future directions, and define ways in which our findings can be used to develop new strategies to better mycobacterial therapeutics. Ultimately, this work enriches our understanding of the molecular determinants of antibiotic susceptibility in mycobacteria, which is critical for developing alternative therapeutic strategies to combat mycobacterial infections
Development of a Novel ELISA to Detect anti-DENV NS1 IgG in sera from DENV Preimmune Mice Models
No full textDengue is a single-stranded positive-sense RNA virus and has become one of the most critical public health concerns in tropical and subtropical regions. Severe dengue cases can result in dysfunction in the endothelium integrity and increased vascular permeability, leading to severe shock syndrome. The efforts to develop a safe and effective vaccine to prevent dengue virus (DENV) have faced many challenges, particularly in creating one to offer protection against all four antigenically different serotypes. The non-structural glycoprotein 1 (NS1) of the dengue viral genome is found to be mainly associated with intracellular membranes and organelles in infected cells and is highly conserved. It has been proven helpful for diagnosing acute dengue infections and is a likely target for developing a vaccine candidate. DENV research and development is restricted by the need for more available animal models that can fully mimic the pathogenesis of human disease. Mice and other rodents have shown resistance to DENV infection and do not sustain signs of the disease. One approach to utilizing mice models to study the pathology of DENV is to use immunocompetent mice with deficiencies in their host defense response. AG129 mice, direct descendants of the 129S6/SvEv mouse, have null alpha, beta, and gamma receptor interferon (Type II) and are vulnerable to DENV infection. Since NS1 is detectable in the sera of DENV-infected mice as early as one-day post-onset of symptoms, we developed a novel ELISA to measure NS1 IgG antibodies in 129S6, and AG129 immunized mice models. This thesis aimed to investigate the immunogenicity of a tetravalent vaccine candidate against DENV. In order to ensure serotype specificity and broad coverage, mice were vaccinated with a tetravalent test article under different stress conditions. Notably, both mice models exhibit significant responses, with observations suggesting a potential for a specific NS1 capture assay. Our findings suggest that the 129S6 mice model did not exhibit sensitivity to the type of immunogens, as intact interferon interferes with any live virus in the test articles. Alternatively, in the AG129 mice model, two stressed test articles (pH and freeze-thawed) provided different NS1 responses. These data will help build the foundation of a particular NS1 capture assays for all four DENV serotypes. However, despite promising outcomes, further optimization and validation of the ELISA is necessary to quantify antibody response and immunogenicity assessment