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Biophysical Characterization Of Somatosensory Responses In Drosophila Class Iv Dendritic Arborization Neurons, Rajshekhar Basak

Yale Graduate School of Arts and Sciences Dissertations

Drosophila Class IV neurons are polymodal nociceptors that detect noxious mechanical, thermal, optical, and chemical stimuli. Escape behaviors in response to attacks by parasitoid wasps are dependent on Class IV cells, whose highly branched dendritic arbors form a fine meshwork that is thought to enable detection of the wasp’s needle-like ovipositor barb. To study how mechanical stimuli trigger cellular responses, we developed a novel, tunable, focused 405-nm laser to create highly localized lesions to probe the conditions needed to evoke responses in Class IV neurons. Chapter 2 describes the development of the assay, physical properties of the stimulus, and its …

A Comparative Approach To Studying Rna Biochemistry Using Timelapse Chemistry And Labeling In Cell Culture (Tilac), Meaghan Christina Sullivan

Yale Graduate School of Arts and Sciences Dissertations

RNA sequencing is a sensitive, transcriptome-wide analysis of RNA levels, valuable for assessing changes in gene expression, or measuring RNA enrichment after immunoprecipitation or cellular fractionation. However, accurate quantification of reads in RNA sequencing datasets is challenging due to variance from variable handling during RNA purification, and biases introduced in downstream processing, like shearing and amplification. To address these challenges, I developed TimeLapse Chemistry Labeling in Cell Culture (TILAC), an internally controlled and normalized approach to compare RNA content between samples using RNA metabolic labeling that is analogous to the SILAC method from protein biochemistry. TILAC utilizes the metabolic labels …

Mechanisms And Implications For Evolution Via Sexual Conflict Over Mate Choice, Samuel Spencer Snow

Yale Graduate School of Arts and Sciences Dissertations

In this dissertation, drawing inspiration from natural systems, I 1) establish the plausibility of the evolution of female resistance via sexual conflict over indirect benefits (wherein females evolve resistance in order to retain the genetic benefits of mating with males they prefer), 2) elucidate the complex mechanisms by which this may occur, and 3) reveal and explore new possibilities and outcomes for systems with conflict between males and females over mate choice. In Chapter 1, I present a new quantitative theoretical model that integrates concepts from both sexual selection and sexual conflict traditions, and demonstrate that any trait that hinders …

Insights Into The Regulation And Mechanism Of 26s Proteasome Base Assembly In Saccharomyces Cerevisiae, Chin Leng Cheng

Yale Graduate School of Arts and Sciences Dissertations

In eukaryotes, the 19S proteasome base contains a heterohexameric ring that is made up of six distinct AAA+ ATPase proteins called Rpt1-Rpt6. In contrast, the archaeal proteasome base is composed of only a single type AAA+ ATPase protein called the proteasome-activating nucleotidase (PAN) that forms a homohexameric ring. A crystal structure of the N-terminal part of PAN in Methanocaldococcus jannaschii a trimer-of-dimers arrangement that is dependent on the alternating cis-trans configuration of the peptide bond preceding a conserved proline residue (P91) located between the coiled coil (CC) and oligonucleotide/oligosaccharide-binding (OB) domains. This proline is also found in Rpt1(P96), Rpt2(P103), Rpt3(P93), …

Regulation Of Bone Marrow Hematopoietic Stem Cell Niches, Runfeng Miao

Yale Graduate School of Arts and Sciences Dissertations

In adult mammals, Hematopoietic stem cells (HSCs) depend on specialized bone marrow (BM) HSC niches for quiescence, proliferation, self-renewal, and differentiation. HSC niches are predominantly composed of non-hematopoietic cells, including perivascular mesenchymal stem and progenitor cells (MSPCs) and endothelial cells (ECs). Although historically defined as HSC niches, more recent studies demonstrated that these niches are also critical for the development and maintenance of hematopoietic progenitors and differentiated hematopoietic cells. Importantly, some terminally differentiated hematopoietic cells such as macrophages, megakaryocytes, and regulatory T cells can in turn relay signals back to the HSC or alter the HSC niche, and control the …

Structural And Functional Characterization Of Lipid-Derived Molecules From The Human Microbiome, Woo Young Cho

Yale Graduate School of Arts and Sciences Dissertations

Scientific evidence for the contribution of the human microbiome to the promotion of human health and disease has been rapidly accumulating. With advances in sequencing technologies and bioinformatics, more specific correlations can be made between certain bacterial strains and/or their genes to specific disease phenotypes. However, the molecular mechanisms by which bacteria are able to influence human health remains largely elusive. Bacteria are known to interact with their environment by production and modulation of small molecules. Bacterially-produced lipid-derived molecules play important signaling roles and modulate eukaryotic cellular responses through the activation of various receptors.

The Role Of Microvascular Signaling In The Neurogenic Niche, Rita Matta

Yale Graduate School of Arts and Sciences Dissertations

Stroke is among the leading causes of death and disability worldwide, partly due to the lack of effective therapies to facilitate the recovery of damaged brain tissue. Stem cell therapies used to treat neurological diseases are promising, owing to their innate ability to enhance endogenous repair mechanisms and promote functional recovery. However, the maintenance of stem cells in a quiescent state throughout delivery remains a significant challenge. This challenge only exacerbates the difficulty of therapeutic strategies attributed to the low survival rate of engrafted cells within the inflamed, cytotoxic brain. Tissue engineering provides the opportunity to develop cell delivery strategies …

Development Of A Bioartificial Vascular Pancreas For Type 1 Diabetes Treatment, Edward Xu Han

Yale Graduate School of Arts and Sciences Dissertations

Type 1 diabetes (T1D) results from the autoimmune destruction of pancreatic islets and is a growing and chronic health problem. Although exogenous insulin injections can help T1D patients manage their blood glucose levels, constant patient vigilance and compliance is required. Less than 40% of diabetic patients can maintain their therapeutic targets. As a result, around 30% of patients older than 40 years of age have diabetes related complications. Transplantation of pancreatic islets has been shown to be effective, in some patients, for the long-term treatment of type I diabetes. However, transplantation of islets into either the portal vein or the …

Genomic Analysis Of Rare Human Diseases, Weilai Dong

Yale Graduate School of Arts and Sciences Dissertations

Many rare human diseases have a strong genetic basis. Rare germline and somatic mutations exert risks to Mendelian diseases and cancer, respectively. The development of next-generation sequencing and genomic analysis approaches facilitate the characterization of rare causal variants to human diseases. This thesis describes the genomic approaches to identify underlying genetic factors in three rare human diseases focusing on analysis of three distinct genetic mechanisms: congenital heart disease caused by recessive genotypes, congenital hydrocephalus caused by dominant genotypes, and uterus leiomyosarcoma, caused by somatic mutations. Congenital heart disease (CHD) is a structural malformation of the heart and great vessels present …

Clinical And Translational Cancer Research By Genomics And Transcriptomics Data Analysis, Xiaotong Li

Yale Graduate School of Arts and Sciences Dissertations

As the second most-frequent cause of death worldwide, cancer comprises a collection of diseases characterized by uncontrollable cell division and spread into surrounding tissues. Diagnosis and treatment of cancer are very challenging due to its huge heterogeneity and rapid progression. Leveraging remarkable achievements in biomedical experimental procedures and techniques, more comprehensive knowledge and deeper understanding of cancer biology have been discovered and applied to interpret the molecular intricacy and variations of cancer at multiple levels, spanning genome, epigenome, transcriptome, proteome and metabolome. With the advancement of high-throughput sequencing technologies, enormous amount of data from each level (i.e. omics data) has …

Sustainability Reporting - Need For Greater Standardisation And Transparency, Maria Ferlin, Johan Blixt, Emma Brattstr¶M

Documents

No abstract provided.

Slippery Fish: Enforcing Regulation When Agents Learn And Adapt, Andres Gonzalez Lira, Ahmed Mushfiq Mobarak

Discussion Papers

Attempts to curb undesired behavior through regulation gets complicated when agents can adapt to circumvent enforcement. We test a model of enforcement with learning and adaptation, by auditing vendors selling illegal fish in Chile in a randomized controlled trial, and tracking them daily using mystery shoppers. Conducting audits on a predictable schedule and (counter-intuitively) at high frequency is less effective, as agents learn to take advantage of loopholes. A consumer information campaign proves to be almost as cost-effective and curbing illegal sales, and obviates the need for complex monitoring and policing. The Chilean government subsequently chooses to scale up this …

Archives Of Human Rights And Historical Memory: An Analysis Of Archival Practices ‘From Below’ In Four Ngos In Colombia, Claire L. Taylor, Lucia Brandi, Cecilia A. Acosta Sánchez, Marcelo Díaz Vallejo

Journal of Contemporary Archival Studies

This article centres on four Colombian NGOs who focus on victims of conflict, paying particular attention to the substantial body of material which they collect and curate related to their work, their activities, and the victims that they represent, and which thus comprise a form of unofficial, grassroots archives of the Colombian conflict. The article details the process undertaken by the research team in engaging with the NGOs to examine the current state of their archives, and the problems and issues they have encountered. Firstly, we provide an overview of the context in which the four selected NGOs are working, …

Classic Article: Gravitational Circulation In Straits And Estuaries, Donald V. Hansen, Maurice Rattray Jr.

Journal of Marine Research

A coupled set of partial differential equations and associated boundary conditions is written to describe circulation and salt-flux processes for estuaries in which turbulent mixing results primarily from tidal currents. Similarity solutions, motivated by characteristic salinity distributions observed in estuaries, are obtained for this set of equations and are compared with observational data. The circulation is separated into modes analogous to the barotropic, baroclinic, and Ekman modes of oceanic circulation. The salinity distribution, although coupled to the velocity distribution, is found to vary independently of it as well. The theoretical results are discussed in regard to: (i) correlation between the …

Editor's Commentary: On Properties Of Seawater Defined By Temperature, Salinity, And Pressure, Kenneth H. Brink

Journal of Marine Research

A classical, and highly productive, approach to studying hydrographic data in the ocean is to use T–S (Temperature–Salinity) analysis. This is a convenient methodology that allows definition of water mass types and quantification of mixing. Information about temperature, salinity and pressure (depth) can further be used to calculate the water’s density...

Classic Article: A Bathythermograph, Athelstan F. Spilhaus

Journal of Marine Research

In the study of the homogeneous layer in the ocean, Rossby and Montgomery (1935) found it desirable to have an instrument which would provide a continuous record of temperature against pressure in the surface layers of the ocean. A preliminary instrument named an “oceanograph” was constructed and used during the summer of 1934. The manifold uses to which such an instrument could be put presaged a widespread employment of the apparatus. This, however, did not come about because of certain inherent difficulties in Rossby’s design. The record was made on a large smoked foil, and thus entailed the attachment of …

Editor's Commentary: On The Process Of Upwelling, Kenneth H. Brink

Journal of Marine Research

Although Harald Sverdrup is now probably best known for his work on basin-scale ocean circulation, his interests were remarkably diverse, and included continental shelf processes. As a coastal oceanographer, I can’t resist highlighting this contribution to the coastal upwelling literature. A relatively simple data set is exploited here, consisting of cross-shelf sections taken near Point Conception, California...

Observations Of Nonlinear Momentum Fluxes Over The Inner Continental Shelf, Thomas P. Connolly, Steven J. Lentz

Journal of Marine Research

Nonlinear momentum fluxes over the inner continental shelf are examined using moored observations from multiple years at two different locations in the Middle Atlantic Bight. Inner shelf dynamics are often described in terms of a linear alongshore momentum balance, dominated by frictional stresses generated at the surface and bottom. In this study, observations over the North Carolina inner shelf show that the divergence of the cross-shelf flux of alongshore momentum is often substantial relative to the wind stress during periods of strong stratification. During upwelling at this location, offshore fluxes of alongshore momentum in the surface layer partially balance the …

Editor's Commentary: Control Of Salinity In An Estuary By A Transition, Kenneth H. Brink, Harlow G. Farmer

Journal of Marine Research

In 1900, Martin Knudson (Knudson 1900; Burchard et al. 2018) considered the salt and volume fluxes for a steady-state estuary. He arrived at very useful relationships between the flux of fresh water coming in from upstream compared to the output salinity and volume flux. While these relations are fundamental and extremely useful, they do not close the problem. Rather, there is always one more piece of information needed; for example, to know the flux of brackish water onto the shelf, you still have to know the outflow salinity...

Classic Article: On Properties Of Seawater Defined By Temperature, Salinity, And Pressure, George Veronis

Journal of Marine Research

Hydrographic station data, consisting principally of temperature and salinity determinations, have been used by physical oceanographers to develop a climatological picture of the distribution of these quantities in the oceans of the world. Density as determined by Knudsen's formula, taken together with hydrostatic and geostrophic dynamics, also provides a crude picture of oceanic flow. However, the data probably contain substantially more information than has been derived from them in the past.The quantity that is orthogonal to potential-density curves in the θS plane is suggested as a useful variable to complement the information contained in potential density. The derivation of …

Nitrogen Cycling In Muddy Sediments Of Great Peconic Bay, Usa: Seasonal N Reaction Balances And Multi-Year Flux Patterns, Stuart Waugh, Robert C. Aller

Journal of Marine Research

To better understand the capacity of sediments to serve as both source and sink of nitrogen (N) and to identify any evidence of evolving changes in sedimentary N cycling, N₂ production, N remineralization, and N₂ fixation were studied over a multi-year period (2010–2015) in bioturbated mud of Great Peconic Bay, a temperate northeastern U. S. estuary. Benthic fluxes and rates of organic matter remineralization were measured using in situ and ex situ incubations. Net annual NH⁺ ₄, NO–₃/NO–₂, and N₂–N fluxes (μ = 1.1, 0.03, and 1.2 mmol m ^{–2 …}

Density And Size-Dependent Bioturbation Effects Of The Infaunal Polychaete Nephtys Incisa On Sediment Biogeochemistry And Solute Exchange, Emma Michaud, Robert C. Aller, Qingzhi Zhu, Christina Heilbrun, Georges Stora

Journal of Marine Research

The impact of bioturbation on the geochemistry of aquatic sediments is known to depend on the benthic infauna species that are present. However, burrowing and activity patterns of each species may also change during the different stages of a life cycle. In this study, we examined the effects of four size classes of the polychaete Nephtys incisa on burrow networks and sediment biogeochemistry. In our experimental aquaria, the total biovolume (~ biomass) of Nephtys was kept constant, but different age classes were introduced, so the size and abundance varied between treatments. Despite differences in the geometry of burrow networks (due …

Complement-Induced Post-Translational Regulation Of Tgf-Ss Signaling On Endothelial Cells, Kevin Liu

Yale Medicine Thesis Digital Library

Cardiac allograft vasculopathy (CAV) is a complex vaso-occlusive complication of heart transplantation currently identified as a major limiting factor to long-term survival in those who receive a cardiac transplant. In CAV, neointimal lesions form in graft vessels leading to ischemic complications and ultimately allograft loss. CAV is medically untreatable and affects ~50% of heart transplant patients. Endothelial cells (ECs) are a critical site where CAV lesions form, and antibodies produced by the recipient that bind to donor HLA molecules on graft endothelium (donor specific antibodies) have been identified as a key mediator in this process. Recent studies have further identified …

A Comprehensive Study Of Comorbidities And Treatments Including Tnf-⍺ Inhibitors In Patients With Acute Scleritis, Ahmad Abdel-Aty

Yale Medicine Thesis Digital Library

Scleritis is a highly symptomatic inflammatory disease of the sclera. We conducted a retrospective study to identify demographic factors and comorbidities associated with resolution of scleritis, to compare patient outcomes on different treatments for scleritis, and to compare treatment utilization by the different medical specialties that manage scleritis. The medical records of all patients with a CPT code for scleritis seen at a tertiary care center from January 1, 2013 to January 1, 2020 were reviewed. Data was collected on demographic factors, comorbidities, and treatment. The primary outcome measures were time until resolution of disease, defined as quiescence of inflammation …

Characteristics, Motivations, And Experiences Of Women Using Nitrous Oxide During Childbirth, Gwendolyn Towers

Yale Medicine Thesis Digital Library

CHARACTERISTICS, MOTIVATIONS, AND EXPERIENCES OF WOMEN USING NITROUS OXIDE IN CHILDBIRTH

Gwendolyn Towers, Michelle Telfer, Jessica L. Illuzzi. Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT

Nitrous oxide labor analgesia is growing in popularity in the United States, with little known regarding the factors driving this trend or about women’s experiences with the method. This study, which includes both a quantitative and a qualitative component, contributes to our understanding of the use of nitrous oxide labor analgesia in the US by exploring the following: (1) who uses the method and how these women …

The Future Of Global Interventional Radiology, Austin-Marley Windham-Herman

Yale Medicine Thesis Digital Library

Interventional Radiology (IR) has become an integral component of modern, developed healthcare systems. The minimally invasive, image-guided procedures that the field offers are highly effective and often lead to significantly less morbidity than alternative surgical options. The growth of IR globally is in an early phase; however, patients and healthcare systems stand to benefit from its rapid expansion and integration around the world.

Globally, billions of people are without access to safe surgery and diagnostic imaging. However, the democratization of radiology resources such as portable ultrasound and low-cost medical devices is making IR more accessible than ever before. Global healthcare …

Upwelling Velocity And Ventilation In The Western South China Sea Deduced From Cfc-12 And Sf6 Observations, Weimin Wang, Peng Huang, Hengxiang Deng, Mian Chen, Minggang Cai, Zhiyou Jing, Shihao Luo, Xuehong Zheng, Chunhui Wang, Hongwei Ke

Journal of Marine Research

This study presents observations of the transient tracers CFC-12 and SF₆ in the western South China Sea during the fall of 2015. A CFC-12 maximum was discovered in the western South China Sea at the subsurface layer (150–200 m), which could be traced back to the North Pacific Tropical Water. The transit time distribution approach was used to estimate the ventilation time in this area. The constrained Δ /Γ ratio of 0.5 was obtained using CFC-12/SF₆ tracer pair. This ratio is lower than the empirical unit ratio of one as used for previous estimates. Waters in the northern …

Editor's Commentary: A Bathythermograph, Kenneth H. Brink

Journal of Marine Research

In this classic, Athelstan Spilhaus reports on his progress on a prototype of the mechanical bathythermograph, a project that C.-G. Rossby encouraged him to pursue. Although now most often seen in museums or on movie sets (they look a bit like rockets), bathythermographs were extremely influential from the later 1930s into the 1950s. These remarkable, durable instruments allowed continuous traces of temperature versus depth (previously measured as bottle temperatures at typically 50-m separations), and so opened up an entirely new vision of what ocean thermal structure actually looks like. Spilhaus further provides some actual data...

Classic Article: On The Process Of Upwelling, H. U. Sverdrup

Journal of Marine Research

The phenomenon of upwelling which is present along many coasts has been discussed from various points of view. A general explanation of the phenomenon has been given by application of Ekman’s theory of wind driven currents (Thorade 1909; McEwen 1912), and emphasis has been put on the velocity of the vertical motion (McEwen 1934) or on the depth from which water is brought to the surface (Sverdrup 1930; Gunther 1936). Defant (1936) has discussed the horizontal and vertical motion and the distribution of density within the region of upwelling off the coast of southwest Africa, but his analysis is based …

Regulated Apoptosis In C. Elegans Development, Nathan Lifton

Yale Medicine Thesis Digital Library

REGULATED APOPTOSIS IN CAENORHABDITIS ELEGANS DEVELOPMENT.Nathan Lifton, Alison Kochersberger, and Marc Hammarlund, Department of Genetics, Yale University School of Medicine, New Haven, CT. We have used chromosome engineering in C. elegans to develop a model animal in which cells normally undergoing developmental programmed cell death (DPCD) survive and are visibly marked. This system uses three elements: The first is a mutation in the apoptosis activator, ced-3, that drives developmental programmed cell death, such that cells normally killed by DPCD survive. The second is a cassette in which the gene encoding the bacterial enzyme Cre recombinase is expressed under transcriptional control …