8,563 Works

THE ROLE OF ACYL-COA SYNTHETASE-MEDIATED FATTY ACID METABOLISM IN METABOLIC MYOPATHY AND ATHEROSCLEROSIS

Long chain acyl-CoA synthetases (ACSLs), and very long chain acyl-CoA synthetases (ACSVLs) which are also known as fatty acid transporters (FATPs), initiate long chain fatty acid (LCFA) oxidation through activation of LCFA by thiol-esterification. Impaired fatty acid oxidation (FAO) can cause metabolic myopathy; however, the underlying mechanisms by which FAO impairment contributes to the pathogenesis of myopathy remain obscure. Compared to control mice (Acsl1flox/flox), Acsl1M-/- mice had 3.4- and 1.5-fold higher plasma creatine kinase (CK)...

STRUCTURE AND FUNCTION STUDIES OF GUT MICROBIAL BETA-GLUCURONIDASES AND THE RIPP ENZYME PAAA

Bacterial β-glucuronidase (GUS) enzymes cause drug toxicity by reversing Phase II glucuronidation in the gastrointestinal tract. While many human gut microbial GUS enzymes have been examined with model glucuronide substrates like p-nitrophenol-β-D-glucuronide (pNPG), the GUS orthologs that are most efficient at processing drug-glucuronides remain unclear. Here we present the crystal structures of GUS enzymes from human gut commensals Lactobacillus rhamnosus, Ruminococcus gnavus, and Faecalibacterium prausnitzii that possess an active site loop (Loop 1; L1) analogous...

Reasons for Increases in Complications of Diabetes

To the Editor Dr Gregg and colleagues identified a resurgence in diabetes complications in the United States beginning in 2010 and analyzed potential underlying contributors and policy implications. However, there may be another underlying mediator of the effect that the authors did not consider.

INTIMATE PARTNER VIOLENCE AND INCIDENT HIV AMONG ADOLESCENT GIRLS AND YOUNG WOMEN IN AGINCOURT AREA, SOUTH AFRICA

HIV continues to be an epidemic globally, with approximately 2.1 million incident cases reported in 2015. South Africa contributes a substantial number of these cases, with South African adolescent girls and young women (AGYW) contributing up to an estimated 100,000 a year. Given their high risk, more information is needed about potential risk factors for HIV such as intimate partner violence (IPV), based on mixed conclusions in the literature on the IPV - Incident HIV...

Partial least squares methods for functional regression models

An important class of prediction problems in modern biomedical studies is to use medical images as well as genetic and clinical biomarkers at an earlier time point to predict important clinical outcomes, including continuous, discrete, survival and longitudinal outcomes, at a later time point. Functional regression is one of the statistical models to handle this problem by treating medical images as smooth functions. An appealing way is the functional partial least squares method (FPLS). Delaigle...

THE EMERGENCE AND CONSEQUENCES OF SELF-FOCUSED VS. WORLD-FOCUSED EXPERIENCES OF AFFECT

The perception of eeriness in old house is part of the experience of fear. I draw from prior work in philosophy and affective science to argue that affect can be experienced as a property of one’s internal state (self-focused) or as a perceived property in the external world (world-focused). As of yet, there has been no published empirical work examining self-focused vs. world-focused affect, nor is there any empirical work examining the mechanisms through which...

Sanctioned terror: economic sanctions and more efective terrorism

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The literature on unintended consequences of economic sanctions is well developed, but few studies have addressed terrorism in target states, and none have assessed whether that terrorism becomes more effective when sanctions are in place. In this study, we test whether economic sanctions lead to an increase in the lethality of terrorism. Using data from multiple sources, we find that while sanctions are unrelated to the rate of success of terrorist attacks, they are positively...

When Should Asymptomatic Persons Be Tested for COVID-19?

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On August 24, 2020, the Centers for Disease Control and Prevention (CDC) updated its website to highlight that asymptomatic individuals, even those with exposure to a COVID-19 positive contact, do not necessarily need to be tested unless they have medical conditions associated with increased risk of severe illness from COVID-19. The CDC subsequently updated its guidance on September 19, 2020 to support testing of asymptomatic persons, including close contacts of persons with documented SARS-CoV-2 infection....

The Connection Between British Exceptionalism and Brexit

This paper aims to ascertain the direct role of historical British exceptionalism in enabling and galvanizing Brexit. In aiming to answer the question - why did Brexit occur? - it becomes vital to undertake a historical perspective to grasp insight into the mentality underlying the distinctly British claim that Britain is better off without the EU. The answer is unique to the accustomed historical excellence of Great Britain throughout the late 19th and 20th centuries....

Observations from the Eichmann Trial: The Democratic Necessity of Deliberation and Cognitive Diversity

Hannah Arendt’s characterization of Adolf Eichmann in her book Eichmann in Jerusalem: A Report on the Banality of Evil has significant ramifications for contemporary democratic theory, namely that articulated by Sayla Benhabib who advocates for inclusive deliberative processes and Hélène Landemore who emphasizes the necessity of cognitive diversity. This paper applies Benhabib’s and Landemore’s democratic theories to Arendt’s characterization and diagnosis of Adolf Eichmann as an individual who was fundamentally incapable of thinking from the...

Disaster Colonialism: The United Nations Mission in Kosovo (UNMIK)

The international involvement in Kosovo since 1999 serves as a unique, contemporary case of what I refer to as “disaster colonialism.” Disaster colonialism in Kosovo, I argue, was a project, one which needed the fabrication of a “disaster,” (based on the historical event of the 1999 War of Independence) in order for a series of international organizations to establish missions that would proliferate following the end of the war. The conflict between Kosovo and Serbia...

Combating an Ethnopopulist Takeover: Can Poland Return to a Liberal Democracy?

I argue that liberal democracy is still achievable in Poland for three reasons. First, the success of President Duda and PiS was a product of specific conditions existing in 2015. By utilizing their nationalist, populist platform and the lack of EU action to prevent the PiS government’s replacement of independent judges with party loyalists, PiS took advantage of the existing political environment in a way that will not be as easily replicated in the future....

Front Matter

Beginning content for journal issue including: General information about the journal; Director's Note from John D. Stephens, Director of the Center for European Studies; list of members of the Editorial Team and Advisory Board; Managing Editor and author biographies; Table of Contents

An improved inhaled mucolytic to treat airway muco-obstructive diseases

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Rationale: Airways obstruction with thick, adherent mucus is a pathophysiologic and clinical feature of muco-obstructive respiratory diseases, including chronic obstructive pulmonary disease, asthma, and cystic fibrosis (CF). Mucins, the dominant biopolymer in mucus, organize into complex polymeric networks via the formation of covalent disulfide bonds, which govern the viscoelastic properties of the mucus gel. For decades, inhaled N-acetylcysteine (NAC) has been used as a mucolytic to reduce mucin disulfide bonds with little, if any, therapeutic...

Localization of secretory mucins MUC5AC and MUC5B in normal/healthy human airways

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Rationale: MUC5AC and MUC5B are the predominant gel-forming mucins in the mucus layer of human airways. Each mucin has distinct functions and site-specific expression. However, the regional distribution of expression and cell types that secrete each mucin in normal/healthy human airways are not fully understood. Objectives: To characterize the regional distribution of MUC5B and MUC5AC in normal/healthy human airways and assess which cell types produce these mucins, referenced to the club cell secretory protein (CCSP)....

Development and Characterization of Ambient Ionization/Separation Techniques Combined with Mass Spectrometry for Improved Analyte Detection

Mass spectrometry (MS) allows for the rapid detection of a wide variety of analytes from complex mixtures, but the sensitivity and selectivity of analysis are often contingent upon the effectiveness of sample preparation and separation techniques. Ambient ionization is a class of ionization techniques that require minimal to no sample preparation and allow for samples to be analyzed under open-air conditions. The majority of ambient ionization techniques utilize electrospray ionization (ESI) to transfer analytes from...

HOW SCHOOL COMMUNITY MEMBERS DISCUSS POWER DURING A COMMUNITY SCHOOL IMPLEMENTATION: A CASE STUDY

School communities have been shut out of many of the more critical decision-making processes impacting local public schools. Decisions are mostly made as top-down actions from federal mandates, general assemblies, state departments, districts, and school level administration teams, isolating the school communities they are tasked to serve. Foucault proposed that power generally reflects the wants and needs of those in relationship with power (Foucault, 1990; Foucault, 1995). Having relationships with one’s power allows not just...

Clustering individuals based on similarity in idiographic factor loading patterns

Idiographic measurement models such as p-technique and dynamic factor analysis (DFA) are models that explain variability across an individual using time series data. These methods provide more accurate models than models obtained from aggregated data and are preferred for personalized psychotherapy and medicine. However, there is no consensus on how to arrive at nomothetic general- izations from replications of individual-level measurement models, largely due to a lack of principled methods for deciding when latent constructs...

EXAMINING HIV-1 PROVIRAL DNA IN THE LIVER TISSUE OF UNTREATED PEOPLE WITH HIV-ASSOCIATED DEMENTIA

Human immunodeficiency virus type 1 (HIV-1) typically uses CCR5 as a coreceptor and requires a high surface density of its CD4 receptor to target replication in CD4+ T cells. HIV-1 can evolve to enter cells with low surface density CD4. This phenotype is frequently observed in the central nervous system (CNS) of people with HIV-associated dementia (HAD). The putative CNS target cells are macrophage and microglia, both with low CD4. The liver also contains abundant...

INTERSTATE TENSION

The underlying tension between states has a significant impact on international relations, but how can we capture and quantify interstate tension? Taking advantage of the market volatility induced by leaders' threats, I use investors' fear and financial maneuvering to quantify interstate tension. In this thesis, I disentangle interstate conflict from interstate tension and propose a general formula for interstate tension derived from the equation for longitudinal strain in continuum mechanics. As a test case, I...

FIND, INFORM, AND TEST (FIT): A SPATIAL MODELING FRAMEWORK TO ESTIMATE CONTRIBUTIONS OF SPATIALLY DISTRIBUTED SOURCES TO MICROBIAL CONTAMINANTS IN THE ENVIRONMENT

The dissemination of fecal contamination and antibiotic-resistant bacteria from Concentrated Animal Feeding Operations (CAFOs) is a major public health concern. There is a need for modeling the dissemination of microbial contamination from sources to be able to link public health risks to sources such as CAFOs, especially in aquatic environments, such as rivers and streams. Host-associated microbial source tracking markers are a major advancement to quantifying risks associated with water use but fall short of...

Immigration, Social Media, and the Far-Right: A Twitter Study of the Political Communication of Alternative für Deutschland Following Terrorist Events

With the global events of technological advancement and mass migration, the prominence of terrorist incidents and subsequent media coverage is garnering more and more attention. The existing literature on populist communication and population responses to terrorist events indicate a potential correlation between characteristic changes in online political communication by right-wing parties and the occurrence of terrorist events. Terror Management Theory (TMT) and sense-making suggest that a population would be more susceptible to political messaging and...

FEMORAL CARTILAGE RESILIENCY IN INDIVIDUALS WITH ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION AND HEALTHY CONTROLS

Differences in cartilage composition and function have been reported following anterior cruciate ligament reconstruction (ACLR), compared to healthy individuals, likely due to changes in the physiological makeup of the cartilage, which can lead to post-traumatic osteoarthritis (PTOA). Brightness mode ultrasound (US) has recently been used to evaluate the deformation of femoral articular cartilage. The purpose of this study is to utilize US to compare the rate of recovery of femoral cartilage (resilience) cross-sectional area (CSA)...

Precision medicine methodology development with application to survival and genomics data

Precision medicine and genomics data provide chances for better decision making in the public health domain. In this dissertation, we develop some important elements of precision medicine and address some aspects of genomics data. The first element is developing a nonparametric regression method for interval censored data. We develop a method called Interval Censored Recursive Forests (ICRF), an iterative random forest survival estimator for interval censored data. This method solves the splitting bias problem in...

The Underwater Sound: Timbre and Beatmaking Process in Hip Hop Production, 1997-2018

The underwater sound is a term used within hip hop for the composition of instrumental tracks that accompany vocals, typically referred to as beats. In order to produce the underwater sound, beatmakers use a conglomeration of multiple audio effects including but not limited to low pass filtering, lowering the sample rate, and channel shifting, that, when combined, make the listener feel as if they are hearing the song while under water. I argue that the...

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  • University of North Carolina at Chapel Hill
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