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Specifying And Targeting Cognitive-Affective Dysfunctions In Antisocial Individuals, Allison Mary Stuppy-Sullivan

Yale Graduate School of Arts and Sciences Dissertations

Antisocial behavior includes a wide range of behaviors that violate social norms, from criminal acts to substance misuse. The adverse consequences of antisocial behavior produce a great physical and emotional burden on perpetrators, victims, and family members. This burden is not addressed adequately, with incarceration being the most common intervention for antisocial behavior. When individuals who chronically engage in antisocial behavior are offered therapeutic treatments, the majority neither complete nor benefit from them. One reason existing treatments do not fully address antisocial behavior is because they do not consider or target cognitive-affective dysfunctions driving such behavior, and mechanistic research, to …

Proteome-Wide Screening For Mitogen-Activated Protein Kinase Docking Motifs And Interactors, Guangda Shi

Yale Graduate School of Arts and Sciences Dissertations

AbstractProteome-wide screening for mitogen-activated protein kinase docking motifs and interactors Guangda Shi 2021 Kinases catalyze the transfer of phosphate to substrates, a reaction critical for many cellular events. Mitogen-activated protein kinases (MAPKs), including ERK, p38, and JNK, phosphorylate hundreds of substrates, and each plays a pivotal role in distinct processes such as cell growth, survival, differentiation, and apoptosis. To correctly respond to external stimuli, MAPKs use several mechanisms to achieve a high degree of selectivity for their target substrates. A critical aspect of MAPK specificity comes from docking interactions occurring between sites distal from the site of catalysis and short …

On The Role Of Stability In Animal Morphology And Neural Control, Neelima Sharma

Yale Graduate School of Arts and Sciences Dissertations

Mechanical stability is vital for the fitness and survival of animals and is a crucial aspect of robot design and control. Stability depends on multiple factors, including the body's intrinsic mechanical response and feedback control. But feedback control is more fragile than the body's innate mechanical response or open-loop control strategies because of sensory noise and time-delays in feedback. This thesis examines the overarching hypothesis that stability demands have played a crucial role in how animal form and function arise through natural selection and motor learning. In two examples, finger contact and overall body stability, we investigated the relationship between …

Characterizing Photophysics Of Photoconvertible-Fluorescent Protein Meos3.2 For Quantitative Fluorescence Microscopy, Mengyuan Sun

Yale Graduate School of Arts and Sciences Dissertations

Photoconvertible fluorescent proteins (PCFPs) are widely used in super-resolution microscopy, and studies of cellular dynamics. Their photoconversion properties have enabled single-molecule localization microscopy (SMLM) by temporally separating closely-spaced molecules. However, our understanding of their photophysics is still limited, hampering their quantitative application. For example, counting fluorescently-tagged fusion proteins from the discrete localizations of individual molecules is still difficult. The red-to-green photoconvertible fluorescent protein mEos3.2 is favored by many due to its monomeric property, high brightness, photostability, compatibility with live cells, and 1:1 labeling stoichiometry. The fluorescent protein mEos3.2 is fused to the coding sequence of a protein of interest in …

Immune Activation By Novel Allobaculum Species Reveals Reciprocal Epistasis Among Human Gut Commensals, Tyler A. Rice

Yale Graduate School of Arts and Sciences Dissertations

Gut commensal microbes that elicit human immune responses are noteworthy for their ability to influence both local mucosal inflammation and, more rarely, systemic antibody responses. Here we isolated and characterized novel strains belonging to genus Allobaculum from inflammatory bowel disease (IBD) stool samples. In defined gnotobiotic mouse models we recapitulated the inflammatory effects of Allobaculum sps. and their notable induction of systemic immune responses at baseline. A microbial ecology screen revealed that this taxon is inversely correlated with Akkermansia muciniphila, and co-colonization experiments uncovered microbe-dependent redirection of immune phenotypes, which we term reciprocal epistasis. These immunostimulatory gut commensal strains exemplify …

Regulation Of Tim-3 By Phosphatidylserine, Courtney Mccaul Smith

Yale Graduate School of Arts and Sciences Dissertations

TIM-3, or T cell, immunoglobulin, and mucin domain-containing protein-3, is a transmembrane glycoprotein expressed by several types of immune cells, including T cells, making it an important regulator of the immune response. However, the biology of TIM-3 is complicated, as it has been shown to variously promote and inhibit the function of T cells and other immune cells. Understanding the contexts in which TIM-3 serves these dual roles has remained difficult, as the ligands that regulate the activity of this receptor are still unclear. Several molecules have been proposed to regulate TIM-3, including phosphatidylserine (PS), galectin-9, carcinoembryonic antigen-related cell adhesion …

Structural Studies On Mechanisms Of Samhd1 Function And Dysfunction, Joshua Temple

Yale Graduate School of Arts and Sciences Dissertations

Sterile α-motif and HD domain-containing protein 1 (SAMHD1) is a pivotal enzyme that maintains cellular nucleotide homeostasis. SAMHD1 forms a tetramer upon binding GTP and a dNTP at allosteric sites, activating its triphosphohydrolase activity against substrate deoxynucleoside triphosphates (dNTPs). This dNTPase activity, in combination with other functions in DNA repair, cell cycle regulation, and nucleic acid binding, is important to other facets of SAMHD1 biology as a critical mediator of antiviral defense, cancer suppression, and autoimmune regulation. An array of post-translational modifications on SAMHD1 present an additional layer of functional regulation – most notably phosphorylation at residue T592, a master …

Development Of Diverse Bifunctional Molecules For Interrogating Dcps, Her3, Brachyury, And Phosphorylation-Driven Diseases Towards Therapeutic Applications, Jake Charles Swartzel

Yale Graduate School of Arts and Sciences Dissertations

Technologies that hijack cellular pathways using bifunctional small molecules have recently risen to the forefront of the drug discovery world. The first targeted protein degradation (TPD) technology to be developed, PROteolysis Targeting Chimeras (PROTACs), were disclosed two decades ago. The recent successes of AR and ER-degrading PROTACs in pioneering clinical trials has propelled interest in developing novel platforms to further expand the druggable proteome and the arsenal of strategies that are available for therapeutic intervention. This thesis is focused on the development of novel bifunctional molecules that enable interrogation of diseases driven by traditionally challenging protein targets. The first chapter …

Elucidating The Molecular Mechanism Of Cis-Regulation By The Long Noncoding Rna Lincrna-P21, Lauren Nicole Winkler

Yale Graduate School of Arts and Sciences Dissertations

Pervasive transcription is a hallmark of mammalian genomes. Although protein-coding genes span only a small fraction of the genome, more than two-thirds is transcribed, yielding thousands of noncoding transcripts whose expression exhibits a tight correlation with cell type, disease state, and other biological phenomena. A subset of these transcripts, termed long noncoding RNAs (lncRNAs) on account of their length (>200 nucleotides) and lack of apparent coding potential, have been shown to play functional roles in processes ranging from immune signaling to organogenesis. In contrast to trans-acting lncRNAs, which may operate in either the nucleus or cytoplasm, cis-acting lncRNAs remain …

Graph Priors, Optimal Transport, And Deep Learning In Biomedical Discovery, Alexander Tong

Yale Graduate School of Arts and Sciences Dissertations

Recent advances in biomedical data collection allows the collection of massive datasets measuring thousands of features in thousands to millions of individual cells. This data has the potential to advance our understanding of biological mechanisms at a previously impossible resolution. However, there are few methods to understand data of this scale and type. While neural networks have made tremendous progress on supervised learning problems, there is still much work to be done in making them useful for discovery in data with more difficult to represent supervision. The flexibility and expressiveness of neural networks is sometimes a hindrance in these less …

Learning, Optimization And Data Translation With Deep Neural Networks, Ganlin Song

Yale Graduate School of Arts and Sciences Dissertations

Neural networks have been intensively studied as machine learning models and widely applied in various areas. This thesis investigates three problems related to the theory and application of neural networks. First, we analyze a learning scheme for neural networks that uses random weights in the backpropagation training algorithm, which is considered to be more biologically plausible than the standard training procedure. We establish theory that shows the convergence of the loss and the alignment between the forward weights of the network and the random weights used in the backward pass. Second, we study a family of optimization problems where the …

Development Of Enantioselective Synthetic Routes To (–)-Myrocin G And (–)-Euonyminol., Martin Tomanik

Yale Graduate School of Arts and Sciences Dissertations

In the first chapter, I describe the development of a synthetic strategy towards (–)-myrocin G (8), the putative active form of the antiproliferative fungal metabolite (+)-myrocin C (4). Myrocin C (4) has been proposed to cross-link DNA by two-fold nucleotide addition; however, this proposed bioalkylation hypothesis has not been tested with native DNA. Our synthetic efforts provided a highly convergent total synthesis of myrocin G (8) in 15 steps from simple starting materials. A key steps in the sequence involved a carefully designed fragment coupling–cyclization cascade (see 85 + 89 → 90). This transformation effectively unites the iodocyclopropane 85 with …

Electrochemical Hydrogen Peroxide Generation With Anthraquinone Chemistry For Advanced Oxidation Process, Qianhong Zhu

Yale Graduate School of Arts and Sciences Dissertations

Hydrogen peroxide plays a critical role in many industrial applications, including chemical synthesis and environmental remediation. For example, in advanced oxidation process of water treatment, hydrogen peroxide is activated to hydroxyl radical by catalysts or UV light for non-selective and rapid degradation of non-biodegradable, toxic, recalcitrant organic micropollutants. Industrial anthraquinone process, which synthesizes hydrogen peroxide from hydrogen and oxygen gas in organic phase, requires intensive capital investment, expensive reactants, high energy inputs, and raises many environmental concerns. Electrochemical production of hydrogen peroxide with air, water and electricity as inputs has emerged as a promising alternative method because it is low-cost, …

Fitting Women To Their Work: The Vocational Vision Of Helen M. Bennett, Lisa R. Lindell

Hilton M. Briggs Library Faculty Publications

"A WOMAN CAN DO ANYTHING IF SHE PUTS HER MIND ON IT."' This conviction propelled the career choices of Helen Marie Bennett in the late nineteenth and early twentieth centuries and the vocational message she communicated. Bennett commenced her wide-ranging life's pursuits in western South Dakota, where she was raised, and brought them to culmination in Chicago, where she became a leader in the emerging field of vocational guidance. She firmly believed that all paths should be open to women and that women had a responsibility to find and follow their own vocation. Bennett's life experiences and interests sparked and …

Mid-Atlantic Ethics Committee Newsletter, Fall 2021

Mid-Atlantic Ethics Committee Newsletter

No abstract provided.

Honors Oracle, October 2021, Marshall University Honors College

Honors Oracle

Marshall University’s Honors College newsletter.

Engineering At San Jose State University, Fall 2021, San Jose State University, Charles W. Davidson College Of Engineering

Engineering at San Jose State University

No abstract provided.

Santa Clara Magazine, Volume 62 Number 2, Fall 2021, Santa Clara University

Santa Clara Magazine

18 - WE ARE THE CHAMPIONS The pandemic stole an entire year of games from them. But this team still won it all. Written by Harold Gutmann. Illustrated by Liam Eisenberg.

26 - INFORMED BY STRUGGLE. How hardship forged a sense of gratitude in SCU finance professor Meir Statman and his wife, Navah. Written by Deborah Lohse.

30 - TWEETING GOOD There’s a Bronco who finds hope, God, and cat pictures online. We talk with @padreSJ. Interviewed by Leslie Griffy. Illustrated by Kyle Hilton.

34 - SIGNALS FROM A CHANGING PLANET. The imprints of humans on the environment spell a …

Dipl 6005 Public International Law, On-Line Course, Catherine Tinker Phd

Diplomacy Syllabi

This course explores the history and nature of international law and how international law and courts address selected issues currently challenging the global community. The course will focus on the creation and implementation of international law; global governance; relations between and among states; and relations between states and non-state actors, including individuals and international organizations.

The course introduces and examines the traditional sources of international law and the actors of international law through history and today. Students will be encouraged to examine issues where new international law and policy is being made in response to global challenges — sustainable development, …

Heterogeneity Of Magnitude, Allergen Immunodominance, And Cytokine Polarization Of Cockroach Allergen-Specific T Cell Responses In Allergic Sensitized Children., Ricardo Da Silva Antunes, Aaron Sutherland, April Frazier, Veronique Schulten, Anna Pomés, Jill Glesner, Agustin Calatroni, Matthew C Altman, Robert A Wood, George T O'Connor, Jacqueline A Pongracic, Gurjit K Khurana Hershey, Carolyn M Kercsmar, Rebecca S Gruchalla, Michelle Gill, Andrew H Liu, Edward Zoratti, Meyer Kattan, Paula J Busse, Leonard B Bacharier, Stephen J. Teach, Lisa M Wheatley, Alkis Togias, William W Busse, Daniel J Jackson, Alessandro Sette

Pediatrics Faculty Publications

Background: Characterization of allergic responses to cockroach (CR), a common aeroallergen associated with asthma, has focused mainly on IgE reactivity, but little is known about T cell responses, particularly in children. We conducted a functional evaluation of CR allergen-specific T cell reactivity in a cohort of CR allergic children with asthma.

Methods: Peripheral blood mononuclear cells (PBMCs) were obtained from 71 children, with mild-to-moderate asthma who were enrolled in a CR immunotherapy (IT) clinical trial, prior to treatment initiation. PBMC were stimulated with peptide pools derived from 11 CR allergens, and CD4+ T cell responses assessed by intracellular cytokine staining. …

Grants Development Office Newsletter: Issue 5, Grants Development Office

Grants Development Office Newsletter

No abstract provided.

Profile: A Model For Living And Learning, Communications And Marketing

Profile (1996-)

In this issue: Campaign Results; Janet Schrunk Ericksen Named Acting Chancellor; UMN Morris Legacy Spans Four Generations; Giving News; Campus News Briefs; The Big Picture; Alumni News; Class Notes; Cougar News

Incident Light And Morphology Determine Coral Productivity Along A Shallow To Mesophotic Depth Gradient, Michael P. Lesser, Marc Slattery, Curtis D. Mobley

Faculty and Student Publications

While the effects of irradiance on coral productivity are well known, corals along a shallow to mesophotic depth gradient (10–100 m) experience incident irradiances determined by the optical properties of the water column, coral morphology, and reef topography. Modeling of productivity (i.e., carbon fixation) using empirical data shows that hemispherical colonies photosynthetically fix significantly greater amounts of carbon across all depths, and throughout the day, compared with plating and branching morphologies. In addition, topography (i.e., substrate angle) further influences the rate of productivity of corals but does not change the hierarchy of coral morphologies relative to productivity. The differences in …

Sequentialdynamics Of Stearoyl-Coa Desaturase-1(Scd1)/Ligand Binding And Unbinding Mechanism: A Computational Study, Anna B. Petroff, Rebecca L. Weir, Charles R. Yates, Joseph D. Ng

Faculty and Student Publications

Stearoyl-CoA desaturase-1 (SCD1 or delta-9 desaturase, D9D) is a key metabolic protein that modulates cellular inflammation and stress, but overactivity of SCD1 is associated with diseases, including cancer and metabolic syndrome. This transmembrane endoplasmic reticulum protein converts saturated fatty acids into monounsaturated fatty acids, primarily stearoyl-CoA into oleoyl- CoA, which are critical products for energy metabolism and membrane composition. The present computational molecular dynamics study characterizes the molecular dynamics of SCD1 with substrate, product, and as an apoprotein. The modeling of SCD1:fatty acid interactions suggests that: (1) SCD1:CoA moiety interactions open the substrate-binding tunnel, (2) SCD1 stabilizes a substrate conformation …

Annual Report Of Donors 2020-2021, Bridgewater College

Bridgewater Magazine

No abstract provided.

Smokejumper Biographies For 1946 Rookie Class, R - Z, National Smokejumper Association

Smokejumper Biographies by Rookie Year

This document contains short biographies of smokejumpers who rookied in 1946.

Office Of Research & Sponsored Programs Newsletter, Office Of Research & Sponsored Programs

Newsletters

In this Issue:

• New Pre-Award Support Coordinator

• TRiO Talent Search Expands

• 2022 ideaFest

• RSCA Awards Announced

• 2022 Student Research Competition Now Open!

Grant News Highlights: HSU and UC Davis Launch NEW Tech Center with NorCal SBDC pg. 5

P.I. Spotlight: Rafael Cuevas Uribe & Rick Zechman pg. 7

The 4th Annual Undergraduate Fall Symposium Category Winners, West Virginia University

Fall Undergraduate Research Symposium

No abstract provided.

4th Annual Fall Undergraduate Research Symposium, West Virginia University

Fall Undergraduate Research Symposium

No abstract provided.

Friends Of The Philip L. Wright Zoological Museum, No. 38, University Of Montana--Missoula. Philip L. Wright Zoological Museum

Philip L. Wright Zoological Museum (UMZM) Newsletters

From the Curator -- Welcome Back, Soon! -- Specimens in Flight -- 2021 Marmot Madness Report -- Avis Marvelous -- Facility Feature -- Backroom Notes -- Who's in the Museum