1983 research outputs found
Sort by
Dollar Rivals
No full textWritten for a PIIE conference on the 50th anniversary of floating exchange rates, this paper deals with possible alternatives to a unipolar dollar-based system. It considers (1) measures of international currency use; (2) potential challengers to the dollar; (3) network externalities; and (4) the plausibility of gold and digital currencies, as alternatives to regular currencies. On the one hand, network externalities operate in favor of the status quo: the dollar as the single leading international currency. On the other hand, abuse of exorbitant privilege – which now includes not just debasing the currency but also excessive use of sanctions – operates in favor of challengers. A good guess is that the dollar will continue to lose market share slowly to others, but will remain in the lead.Version of Recor
Approaches to improve the diagnosis and treatment of traumatic neuropathic pain
No full text"The most terrible of all tortures which a nerve wound may inflict.” Silas W. Mitchell, a neurologist during the American Civil War, stated in his book Injuries of Nerves and their Consequence. (1) One hundred and fifty years later, patients with a nerve injury describe their pain as "touching a cut power cord connected to the outlet." Neuropathic pain, originating from “a lesion or disease of the somatosensory nervous system”, continues to be one of the most significant challenges for the scientific community. (2) In 2017, the U.S. prevalence of neuropathic pain was 15%, and the number of people affected by this condition continues to grow. (3,4) Traumatic neuropathic pain, one condition that conforms to neuropathic pain, represents a significant cause of disability in adults, with upwards of 30% developing chronic pain with neuropathic characteristics after a peripheral nerve injury. (5,6) The physical and emotional impact is enormous, and the lost productivity value due to chronic pain is estimated to be around 300 billion dollars annually. (7–10) Traumatic neuropathic pain contributes to this economic burden by being more prevalent in middle-aged adults. (5,6) That adds up to the fact that neuropathic pain is a culture medium for opioid dependence and the public health emergency announced by the U.S. Department of Health and Human Services. In 2019, 10.1 million people misused opioid prescriptions, and 64% of the population experiencing neuropathic pain for at least three months reported opioids use, from which 20.9% correspond to potent opioids (i.e., morphine, oxycodone). (3,11)
Despite the efforts to improve the understanding of traumatic neuropathic pain conditions and the literature that reports 70-80% of pain improvement after an accurate diagnosis and surgical treatment, the results do not always translate into functional and painless recovery. (12–17) The approach to neuropathic pain has deficiencies at all stages, from its interpretation and diagnosis to its treatment. The psychosocial component of pain and the lack of tools to guide diagnosis add to pain's complexity and unclear biological bases.
We present a clinical and basic science approach to improve the accuracy of a diagnosis of traumatic neuropathic pain and explore a potential mechanism of neuropathic hypersensitivity after an injury. The first approach describes the implementation of pain sketches for assessing and interpreting pain in patients who underwent a major limb amputation and Targeted Muscle Reinnervation (TMR), a procedure to manage nerve stumps resulting from the amputation. (12–14) The second approach exposes a potential mechanism for the sensitivity that characterized the neuroma, a mass of axons, cells and fibrosis resulting from the aberrant regeneration of an injured nerve. (15)
This thesis aims to further our understanding of this problem and generate additional solutions, which could impact the medical field in a manner that will benefit patients and physicians
A multi-scale map of cell structure fusing protein images and interactions
No full textThe eukaryotic cell is a multi-scale structure with modular organization across at least four orders of magnitude1,2. Two central approaches for mapping this structure – protein fluorescent imaging and protein biophysical association – each generate extensive datasets but of distinct qualities and resolutions that are typically treated separately3,4. Here, we integrate immunofluorescent images in the Human Protein Atlas5 with ongoing affinity purification experiments from the BioPlex resource6 to create a unified hierarchical map of eukaryotic cell architecture. Integration involves configuring each approach to produce a general measure of protein distance, then calibrating the two measures using machine learning. The evolving map, called the Multi-Scale Integrated Cell (MuSIC 1.0), currently resolves 69 subcellular systems of which approximately half are undocumented. Based on these findings we perform 134 additional affinity purifications, validating close subunit associations for the majority of systems. The map elucidates roles for poorly characterized proteins, such as the appearance of FAM120C in chromatin; identifies new protein assemblies in ribosomal biogenesis, RNA splicing, nuclear speckles, and ion transport; and reveals crosstalk between cytoplasmic and mitochondrial ribosomal proteins. By integration across scales, MuSIC substantially increases the mapping resolution obtained from imaging while giving protein interactions a spatial dimension, paving the way to incorporate many molecular data types in proteome-wide maps of cells.Accepted Manuscrip
Iron Metabolism, Incident Heart Failure Phenotypes and Cardiac Dysfunction in Late Life
No full textIron contributes to a variety of biological processes, such as oxygen transport, mitochondrial respiration, and free radical protection with particular importance in cells with high energy requirements, such as cardiomyocytes. People with iron deficiency suffer from a range of symptoms, including fatigue, dizziness, pallor, restless leg syndrome, and even pica, among many others. Iron deficiency is the most common nutritional disorder worldwide and affects many children and young women in low and middle-income countries. Iron deficiency also affects many older adults, in whom gastrointestinal blood loss, and decreased iron absorption account for most cases. In late life, reduced iron stores are associated with a higher risk of impaired physical and cognitive capacity and mortality. Iron deficiency can be diagnosed using readily available blood biomarkers and can be treated using oral supplements and intravenous iron products. Given the widespread prevalence of iron deficiency and the ability to identify and manage iron deficiency cases, studying the effects of iron deficiency may have important public health implications.
Iron metabolism plays an important role in cardiomyocyte function given the high energy requirements of this cell type. In patients with chronic heart failure, iron deficiency is associated with impaired functional capacity and higher risks of heart failure hospitalization and death independent of anemia. Like heart failure, the prevalence of iron deficiency increases with older age. Nevertheless, the role of iron deficiency in the development of subclinical cardiac dysfunction and its progression to incident heart failure in late life remains unknown.
While the gold standard method for iron deficiency diagnosis is the assessment of iron in bone marrow biopsy, blood biomarkers are routinely used in clinical practice. Circulating ferritin levels are used to diagnose total body iron stores. Hepcidin regulates plasma and tissue iron levels by degrading and blocking iron binding to the iron exporter ferroportin. Ferritin may provide insight into absolute iron deficiency, whereas hepcidin may allow assessment of functional iron deficiency.
I sought to assess the relationships between plasma ferritin and hepcidin with incident heart failure (manuscript 1) and subclinical cardiac dysfunction (manuscript 2) and among older adults in the Atherosclerosis Risk in Communities (ARIC) study, an ongoing, longitudinal, observational cohort study of adults in four communities across the United States.
In Study 1, we evaluated the association of lower ferritin and hepcidin levels with incident heart failure. We detected an association of lower levels of ferritin and hepcidin with higher risks of incident heart failure overall and incident heart failure with preserved ejection fraction, but not heart failure with reduced ejection fraction.
In Study 2, we observed cross-sectional associations of lower ferritin and hepcidin levels with measures of LV diastolic dysfunction and higher LV filling pressure. The associations were consistent across gender categories and independent of several potential confounders. The results highlight the potential contributions of iron deficiency to cardiac dysfunction independent of concomitant anemia. The results of the two studies build up and show that lower iron stores were not only associated with the intermediate phenotype of cardiac dysfunction but also with the clinical outcome of incident HF
A neural network trained for prediction mimics diverse features of biological neurons and perception
No full textVersion of Recor
State-of-the-art energetic and morphological modelling of the launching site of the M87 jet
No full textAccepted Manuscrip
The Evolution of Alternative Genetic Codes
No full textThe genetic code is so critical to the production of all proteins in the cell that it was once thought to be a “frozen accident”, incapable of evolving further. However, the discovery of alternative genetic codes in dozens of clades of bacteria, eukaryotes, archaea, organelles, and viruses has shown that it is flexible to some degree. In Chapter 1, I review major concepts in alternative genetic code evolution: the evolutionary trajectories by which alternative genetic codes can evolve, how changes to the translational machinery allow for codon reassignment, and potential selective pressures that could drive reassignment. In Chapters 2 and 3, I describe Codetta, a computational tool for predicting the genetic code from a nucleotide sequence. In Chapter 2, I use Codetta to screen over 250,000 bacterial and archaeal genomes and identify five bacterial clades using new genetic codes. All of the new reassignments affect arginine codons, highlighting a potential sensitivity of arginine codons to reassignment. In a clade of uncultivated Enterosoma bacteria, AGG has been reassigned from arginine to become the dominant methionine codon and appears to have evolved by a change in the aminoacylation of the original arginine tRNA. The other reassignments all affect the arginine codons CGA and/or CGG. These clades all have very low genomic GC content, an evolutionary force which likely drove GC-rich codons to rarity and allowed for their reassignment. The CGA and CGG reassignments are explored in more detail in Chapter 4, including close outgroup species with unusual tRNA features that may shed light on intermediate stages of reassignment
Measured Music: Diagrammatics of Musical Time from Baghdad to Paris, 850-1350
No full textThis dissertation examines the ways in which individuals in the medieval greater Mediterranean—the Afro-Eurasian region that interweaves the Christianate and Islamicate worlds—measured musical time. I begin from the assumption that time can only be known and made sense of through cultural techniques of time measurement. After laying out my methodological approach in Chapter 1, the following chapters investigate the music-theoretical practices by which time was measured. In Chapter 2, I consider the polymath Abū Naṣr al-Fārābī’s (d. 950) theory of īqāʿāt (rhythmic patterns) and introduce what I call his music-theoretical “tools of the trade”: the physical surrogates that theorists relied on to make sense of musical time, and orient their readers in the cognition of its measurement. The multiple affordances of these tools—which included the plectrum, warp and weft, weights, and prosodic notations—allowed al-Fārābī to organize his system around the principles of speed and duration. Chapter 3 focuses on how Latin grammarians, Islamicate physicians, and music theorists treated the voice and the pulse as “airy” matters, governed by musical motion, which could be “geometricized” in three dimensions: length, width, and depth. I show how each dimension corresponded to different, discrete, and measurable aspects of music—what today we might call “parameters.” The theorists examined in this chapter include the anonymous authors of the Musica Enchiriadis and the so-called Paleofrankish notations, the polymath Ibn Sīnā (980–1037), and the physician Solomon ben Abraham Ibn Yaʿīsh (d.1345, Seville). In Chapter 4, I stage a dialogue between al-Fārābī and the thirteenth-century theorists Johannes of Garlandia and Franco of Cologne. I argue that their different approaches to measuring musical time were premised upon a shared cognitive practice: the treatment of their temporal systems of modes as diagrammatic forms, that is, inscriptions (be they acoustically sounded or simply implied) of the cognitive operations involved in time measurement. In the Introduction and the first part of Chapter 4, I also offer critical reflections on the notion of the “medieval Mediterranean,” and investigate how it relates to past and present “chronotropic frameworks”: i.e. historiographical frameworks that temporalize and spatialize the relation between a culture and its Others
Streptococcal Pyrogenic Exotoxin B Cleaves GSDMA and Triggers Pyroptosis
No full textAccepted Manuscrip
Abigail Adams’ 1776 Smallpox Inoculation As Demonstration of Women’s Increased Independence in the American Revolution
No full textThis thesis analyzes Abigail Adams’ efforts to inoculate herself and her children against smallpox in July 1776. She pursued the procedure independently, only informing her husband John Adams after the fact. Some scholarship maintains the lack of notice to John Adams was due to anger at his lack of response to her “Remember the ladies” letter of March 1776, but this thesis concludes that other contextual factors affected her decision. Adams’ early life grounded her in scientific inquiry as well as a religious outlook that allowed her to pursue medical procedures while still believing in providence to make them succeed. Adams participated in a network of New England women left without male heads of household early in the American Revolution, exchanging domestic information and mutual support. Men’s absence from home resulted in a larger sphere of action for women who developed confidence in the running of their households. Because George Washington inoculated the Continental Army, more colonial men than women received inoculation, but Adams’ unique circumstances of literacy, wealth, exposure to medical doctors, and trust in science all led to her July 1776 decision. Adams’ actions are a case study indicative of the larger trend of women gaining confidence, competence, and forms of independence during the American Revolution