Digital Commons Network^™

Structural Basis For Dna Proofreading, Gina Buchel, Ashok Nayak, Karl Herbine, Azadeh Sarfallah, Viktoriia Sokolova, Angelica Zamudio-Ochoa, Dmitry Temiakov

Department of Biochemistry and Molecular Biology Faculty Papers

DNA polymerase (DNAP) can correct errors in DNA during replication by proofreading, a process critical for cell viability. However, the mechanism by which an erroneously incorporated base translocates from the polymerase to the exonuclease site and the corrected DNA terminus returns has remained elusive. Here, we present an ensemble of nine high-resolution structures representing human mitochondrial DNA polymerase Gamma, Polγ, captured during consecutive proofreading steps. The structures reveal key events, including mismatched base recognition, its dissociation from the polymerase site, forward translocation of DNAP, alterations in DNA trajectory, repositioning and refolding of elements for primer separation, DNAP backtracking, and displacement …

Imagining Ai: How The World Sees Intelligent Machines, Amine Oudghiri

Critical Humanities

Imagining AI: How the World Sees Intelligent Machines

Algorithmic Reason: Tobias Blanke Interviewed By Puspa Damai, Tobias Blanke, Puspa Damai

Critical Humanities

Algorithmic Reason: Tobias Blanke

interviewed by Puspa Damai

Effect Of Flecainide And Ibutilide Alone And In Combination To Terminate And Prevent Recurrence Of Atrial Fibrillation, Alexander Burashnikov, José M. Di Diego, Bence Patocskai, Debra S. Echt, Luiz Belardinelli, Charles Antzelevitch

Division of Cardiology Faculty Papers

BACKGROUND: There is a need for improved approaches to rhythm control therapy of atrial fibrillation (AF).

METHODS: The effectiveness of flecainide (1.5 µmol/L) and ibutilide (20 nmol/L), alone and in combination, to cardiovert and prevent AF recurrence was studied in canine-isolated coronary-perfused right atrioventricular preparations. We also examined the safety of the combination of flecainide (1.5 µmol/L) and ibutilide (50 nmol/L) using canine left ventricular wedge preparations.

RESULTS: Sustained AF (>1 hour) was inducible in 100%, 60%, 20%, and 0% of atria in the presence of acetylcholine alone, acetylcholine+ibutilide, acetylcholine+flecainide, and acetylcholine+ibutilide+flecainide, respectively. When used alone, flecainide and ibutilide …

Banks Brace For Auditor Shuffle In New Year As Per Rbi's Three Year Tenure Mandate, Amol Dethe

Documents

No abstract provided.

A Novel Multimodal Postoperative Pain Protocol For 1- To 2-Level Open Lumbar Fusions: A Retrospective Cohort Study, Michael Markowitz, Barrett I. Woods, Gregory D. Schroeder, Christopher K Kepler, David Kaye, Mark Kurd, Joshua Armstrong, Alex R. Vaccaro, Kris Radcliff

Rothman Institute Papers

BACKGROUND: There has been increased interest in exploring methods to reduce postoperative pain without opioid medications. In 2015, a multimodal analgesia protocol was used involving the perioperative use of celecoxib, gabapentin, intravenous acetaminophen, lidocaine, and liposomal bupivacaine. Overall, the goal was to reduce the utilization of scheduled opioids in favor of nonopioid pain management.

METHODS: The results of a consecutive series of 1- to 2-level open primary lumbar fusions were compared to a cohort of patients after the implementation the perioperative multimodal pain management protocol. Primary endpoints included patient-reported pain scores and secondary endpoints included length of stay.

RESULTS: There …

A Distinct Human Cell Type Expressing Mhcii And Rorγt With Dual Characteristics Of Dendritic Cells And Type 3 Innate Lymphoid Cells, Alina Ulezko Antonova, Silvia Lonardi, Matilde Monti, Francesco Missale, Changxu Fan, Matthew L Coates, Mattia Bugatti, Natalia Jaeger, Patrick Fernandes Rodrigues, Simone Brioschi, Tihana Trsan, José L Fachi, Khai M Nguyen, Ryan M Nunley, Daniele Moratto, Stefania Zini, Lingjia Kong, Jacques Deguine, Mark E Peeples, Ramnik J Xavier, Menna R Clatworthy, Ting Wang, Marina Cella, William Vermi, Marco Colonna

The Brown Foundation: Institute of Molecular Medicine

Recent studies have characterized various mouse antigen-presenting cells (APCs) expressing the lymphoid-lineage transcription factor RORγt (Retinoid-related orphan receptor gamma t), which exhibit distinct phenotypic features and are implicated in the induction of peripheral regulatory T cells (Tregs) and immune tolerance to microbiota and self-antigens. These APCs encompass Janus cells and Thetis cell subsets, some of which express the AutoImmune REgulator (AIRE). RORγt+ MHCII+ type 3 innate lymphoid cells (ILC3) have also been implicated in the instruction of microbiota-specific Tregs. While RORγt+ APCs have been actively investigated in mice, the identity and function of these cell subsets in humans remain elusive. …

Managing Protected Areas: People And Places, Niall Finneran, Denise Hewlett, Richard Clarke, Richard Gunton, Debra Gray, Ainara Terradillos, Danny Byrne, Sheela Agarwal

Plymouth Business School

This open access book brings together 16 specially commissioned chapters drawn from a range of different professional-practitioner and academic global perspectives on the importance of the relationship between people and green and blue spaces. It focuses on issues surrounding the importance of natural environments on public health and wellbeing, and the environmental, cultural, and social importance of green and blue spaces that can result through responsible and sustainable adaptive management processes. It explores how the Covid-19 pandemic forced reconsiderations of our relationship with these natural spaces and highlights the important impact of the pace of climate change. While not pretending …

The Associations Of Cardiometabolic And Dietary Variables With Clinical Periodontitis In Adults With And Without Type 2 Diabetes: A Cross-Sectional Study, Arpita Basu, Leigh Ann Richardson, Alicia Carlos, Neamat Hassan Abubakr, Robin L. Weltmann, Jeffrey L. Ebersole

Kinesiology and Nutrition Sciences Faculty Research

Periodontitis is a commonly occurring inflammatory oral disease affecting a large proportion of global and US adults and is characterized by the destruction of the tooth-supporting apparatus. Its etiology is multifactorial, and type 2 diabetes and diet play critical roles in its remission and progression. However, few studies have addressed nutritional and serum vitamin D status in adults with periodontitis in the presence of diabetes. A cross-sectional study (n = 78), and a sub-set of age- and BMI-matched case–control studies (n = 50), were conducted to examine differences in dietary and cardiometabolic variables, and serum vitamin D in adults with …

People Are Less Myopic About Future Than Past Collective Outcomes, Markus Prior, Abdelaziz Alsharawy, Talbot M Andrews

Faculty, Staff and Student Publications

Myopia involves giving disproportionate weight to outcomes that occur close to the present. Myopia in people's evaluations of political outcomes and proposals threatens effective policymaking. It can lead to inefficient spending just before elections, cause inaction on important future policy challenges, and create incentives for government interventions aimed at boosting short-term performance at the expense of long-term welfare. But, are people generally myopic? Existing evidence comes mostly from studies that disregard either the future or collective outcomes. Political science characterizes people as myopic based on how they retrospectively evaluate collective outcomes, such as the state of the economy. Behavioral economics …

"What Is A Wave But 1000 Drops Working Together?": The Role Of Public Libraries In Addressing Lgbtqia+ Health Information Disparities, Vanessa Lynn Kitzie, A. Nick Vera, Valerie Lookingbill, Travis L. Wagner

Faculty Publications

Purpose. This paper presents results from a participatory action research study with 46 LGBTQIA+ community leaders and 60 library workers who participated in four community forums at public libraries across the US. The forums identified barriers to LGBTQIA+ communities addressing their health questions and concerns and explored strategies for public libraries to tackle them.

Design/methodology/approach. Forums followed the World Café format to facilitate collaborative knowledge development and promote participant-led change. Data sources included collaborative notes taken by participants and observational researcher notes. Data analysis consisted of emic/etic qualitative coding.

Findings. Results revealed that barriers experienced by LGBTQIA+ communities are structurally …

Aortic Valve Leaflets Are Asymmetric And Correlated With The Origin Of Coronary Arteries, Taylor S Koerner, Thomas Cunningham, Mayme E Marshall, Lauren S Talley, Megan Childress, Rami M Kharouf, Wen Li, Jorge D Salazar, Antonio F Corno

Faculty, Staff and Student Publications

BACKGROUND: Asymmetry of the aortic valve leaflets has been known since Leonardo Da Vinci, but the relationship between size and shape and origin of the coronary arteries has never been examined. Our aim was to evaluate this anatomy in a population of pediatric patients using a cross-sectional study design.

METHODS: Consecutive pediatric patients with trans-esophageal echocardiography (TEE), with or without trans-thoracic echocardiography (TTE), were included in our study. Exclusion criteria: (I) bicuspid aortic valve; (II) aortic valve stenosis; (III) hypoplasia of aortic valve annulus, or aortic root; (IV) truncal valve; (V) coronary artery atresia; (VI) previous surgery on aortic valve …

Information-Rich 6d Single-Molecule Imaging Design Using Optimization, Tingting Wu

McKelvey School of Engineering Graduate Student Theses & Dissertations

When studying biochemical processes, localizing the targets alone will not paint a complete picture. We also need techniques to probe how biomolecules interact with one another, including how molecules are organized into larger structures, how they are oriented with respect to surrounding molecules, and how local chemical parameters, like pH and hydrophobicity, vary spatially and temporally. My dissertation focuses on single-molecule orientation localization microscopy (SMOLM, Chapter 1). The objective is to develop imaging techniques for measuring how molecules are oriented with respect to their surrounding molecules, namely, 3D orientation. Achieving optimal imaging performance requires careful design of both the forward …

Co-Transmitting Interneurons In The Mouse Olfactory Bulb Regulate Olfactory Detection And Discrimination, Ariel M Lyons-Warren, Evelyne K Tantry, Elizabeth H Moss, Mikhail Y Kochukov, Benjamin D W Belfort, Joshua Ortiz-Guzman, Zachary Freyberg, Benjamin R Arenkiel

Faculty, Staff and Students Publications

Co-transmission of multiple neurotransmitters from a single neuron increases the complexity of signaling information within defined neuronal circuits. Superficial short-axon cells in the olfactory bulb release both dopamine and γ-aminobutyric acid (GABA), yet the specific targets of these neurotransmitters and their respective roles in olfaction have remained unknown. Here, we implement intersectional genetics in mice to selectively block GABA or dopamine release from superficial short-axon cells to identify their distinct cellular targets, impact on circuit function, and behavioral contribution of each neurotransmitter toward olfactory behaviors. We provide functional and anatomical evidence for divergent superficial short-axon cell signaling onto downstream neurons …

Engineered Adoptive T-Cell Therapies For Breast Cancer: Current Progress, Challenges, And Potential, Diego F Chamorro, Lauren K Somes, Valentina Hoyos

Faculty, Staff and Students Publications

Breast cancer remains a significant health challenge, and novel treatment approaches are critically needed. This review presents an in-depth analysis of engineered adoptive T-cell therapies (E-ACTs), an innovative frontier in cancer immunotherapy, focusing on their application in breast cancer. We explore the evolving landscape of chimeric antigen receptor (CAR) and T-cell receptor (TCR) T-cell therapies, highlighting their potential and challenges in targeting breast cancer. The review addresses key obstacles such as target antigen selection, the complex breast cancer tumor microenvironment, and the persistence of engineered T-cells. We discuss the advances in overcoming these barriers, including strategies to enhance T-cell efficacy. …

The 2023 Orthopedic Research Society's International Consensus Meeting On Musculoskeletal Infection: Summary From The In Vitro Section, Noreen J. Hickok, Bingyun Li, Ebru Oral, Sebastian A.J. Zaat, David A. Armbruster, Gerald J. Atkins, Antonia F. Chen, Débora C. Coraça-Huber, Tianhong Dai, Edward M. Greenfield, Rajendra Kasinath, Matthew Libera, Cláudia N.H. Marques, T. Fintan Moriarty, K. Scott Phillips, Kapil Raghuraman, Dacheng Ren, Lia Rimondini, Kordo Saeed, Thomas P. Schaer, Edward M. Schwarz, Christopher Spiegel, Paul Stoodley, Vi Khanh Truong, Shao-Ting Jerry Tsang, Britt Wildemann, Anja R. Zelmer, Annelies S. Zinkernagel

Department of Orthopaedic Surgery Faculty Papers

Antimicrobial strategies for musculoskeletal infections are typically first developed with in vitro models. The In Vitro Section of the 2023 Orthopedic Research Society Musculoskeletal Infection international consensus meeting (ICM) probed our state of knowledge of in vitro systems with respect to bacteria and biofilm phenotype, standards, in vitro activity, and the ability to predict in vivo efficacy. A subset of ICM delegates performed systematic reviews on 15 questions and made recommendations and assessment of the level of evidence that were then voted on by 72 ICM delegates. Here, we report recommendations and rationale from the reviews and the results of …

Advances In Research On Active Faults And Exploration Of Relevant Frontier Scientific Problems, Xu Xiwei, Li Feng, Cheng Jia, Liu Baojin, Chen Guihua, Li Kang, Ren Junjie, Jia Qichao

Coal Geology & Exploration

This study reviewed the approval and initiation processes and major research contents of China's active fault-related projects, such as the urban active fault survey projects, large-scale mapping programs of active faults, and the earthquake hazard assessment of active faults in key earthquake monitoring and prevention areas. By combining the scientific investigation results of the surface rupture zones induced by strong earthquakes over the past 20 years, this study elaborated on significant advances achieved in the following aspects: the survey and positioning techniques for concealed active faults under strong-noise and weak-signal conditions, the quantitative identification techniques for fault activity, theories and …

Enhanced Bmp Signaling In Cathepsin K-Positive Tendon Progenitors Induces Heterotopic Ossification, Hiroyuki Yamaguchi, Margaret Li, Megumi Kitami, Sowmya Swaminathan, Yuji Mishina, Yoshihiro Komatsu

Faculty, Staff and Student Publications

Heterotopic ossification (HO) is abnormal bone growth in soft tissues that results from injury, trauma, and rare genetic disorders. Bone morphogenetic proteins (BMPs) are critical osteogenic regulators which are involved in HO. However, it remains unclear how BMP signaling interacts with other extracellular stimuli to form HO. To address this question, using the Cre-loxP recombination system in mice, we conditionally expressed the constitutively activated BMP type I receptor ALK2 with a Q207D mutation (Ca-ALK2) in Cathepsin K-Cre labeled tendon progenitors (hereafter “Ca-Alk2:Ctsk-Cre”). Ca-Alk2:Ctsk-Cre mice were viable but they formed spontaneous HO in the Achilles tendon. Histological and molecular …

Mechanisms Linking Proteins And Structural Brain Integrity To Biological Markers Of Alzheimer’S Disease, Adam Turnbull, Yejin Kim, Kai Zhang, Tianrui Mao, Xiaoqian Jiang, Victor Henderson, Zihuai He, Feng Vankee Vankee Lin

Faculty, Staff and Student Publications

Background

Medial temporal lobe (MTL) networks, including posterior-medial (PM) and anterior-temporal (AT) subnetworks, are early affected by Alzheimer’s disease (AD) pathologies (tau, neurodegeneration) and are critical for memory, which declines in AD. The biological pathways linking AD pathology, changes in MTL-AT-PM structural connectivity (SC), and cognitive decline, are unknown. Plasma protein levels reflect those in the cerebrospinal fluid, providing a low-invasive potential means of understanding molecular brain changes that occur in AD. These measures may help explain how AD pathology, MTL-AT-PM SC, and cognitive decline are linked at the molecular level. We used predefined aging-related plasma proteins from a meta-analysis …

Vascular Injury Risk Stratification For Lateral Lumbar Interbody Fusion (Llif) At L4-L5: A Morphometric Study Using Magnetic Resonance Imaging, Takashi Hirase, Aaron J Greenberg, Catherine G Ambrose, Derek T Bernstein, Jeffrey J Ratusznik, Rex A W Marco

Faculty, Staff and Student Publications

BACKGROUND: Proper vascular injury risk stratification (VIRS) methods for L4-L5 lateral lumbar interbody fusion (LLIF) surgery have not been well-described. The objective of this study was to propose a novel VIRS method for L4-L5 LLIF surgery via the transpsoas approach.

METHODS: Axial magnetic resonance imaging (MRI) of adult patients were obtained and analyzed. The VIRS scores were assessed using anterior disc line to posterior vessel wall distance, the disc vessel angle (DVA), and the disc edge to vessel distance at the level of L4-L5 disc space.

RESULTS: Ninety-one consecutive adult patients were included in the study. The right common iliac …

Multi-Layer Strip Ionization Chamber For Proton Quality Assurance And Imaging, Shuang Zhou

McKelvey School of Engineering Graduate Student Theses & Dissertations

Proton therapy is the most advanced radiation treatment modality. Proton treatment is delivered via pencil beam scanning (PBS) technique, in which a pencil beam scans the target spot-by-spot and layer-by-layer. An effective quality assurance (QA) device is needed to verify the quality of treatment dose delivery. Current clinical practice employs films or a two-dimensional (2D) detector to measure the dose at one or a few arbitrarily selected depths, which is insensitive to delivery error and time-consuming. A 3D dosimeter that can measure the 3D dose distribution is needed to improve the effectiveness and efficiency of proton QA. Furthermore, preclinical studies …

Citizens Apart? Representing Post-Brexit Youth Politics In The Uk Media, M Holton, J Lee, S Beech, S Mcdowell

School of Geography, Earth and Environmental Sciences

In 2016, the UK voted to leave the European Union (EU). This outcome was not only unexpected but also had clear geographical and age-bound divisions. While people over the age of 65 tended to vote to leave, younger voters were more likely to vote to remain a part of the EU. Reflecting on 7 years of journalism, this paper explores the ways in which young people have been represented by the news media with regards to the issue of Brexit. It analyses a database of 700 news media articles published from 2016 to 2022 across the UK, equating to 100 …

Late-Onset Stiff-Person Syndrome: Challenges In Diagnosis And Management, Marinos Dalakas, Jessica Yi

Department of Neurology Faculty Papers

BACKGROUND: Stiff person syndrome (SPS) is a rare slowly progressive autoimmune neuronal hyperexcitability disease with very-high GAD-65 antibody titers that most commonly presents above the age of 20, with muscle stiffness, painful muscle spasms, slow gait, and falls leading to disability. In other autoimmune disorders, late-onset disease has different symptom-spectrum and outcomes, but there is no information regarding late-onset SPS (LOSPS).

OBJECTIVE: Highlight delayed diagnosis and poor tolerance or incomplete response to therapies of patients with LOSPS and outline how best to increase disease awareness early at onset.

DESIGN A RETROSPECTIVE CHART REVIEWMETHODS: We reviewed GAD-positive SPS patients with symptom …

Is Public Debt Environmentally Friendly? The Role Of Eu Fiscal Rules On Environmental Quality: An Empirical Assessment, Giovanni Carnazza, Thomas Renström, Luca Spataro

Fondazione Eni Enrico Mattei Working Papers

The EU has embarked on multiple initiatives reflecting its commitment to environmental enhancement and sustainable transitions. Notable among these are the European Green Deal and the NextGenerationEU recovery plan, both pivotal in fostering eco-friendly policies and sustainable practices within the region. Conversely, the fiscal rules within the EU, designed to manage budgetary deficits and debt-to-GDP ratios, may pose challenges to the implementation of fiscal measures targeted at achieving environmental quality objectives. These regulatory constraints potentially curtail the fiscal space available for policies aligned with the environmental goals set forth by the EU. To address this issue, using a panel of …

Ypfs Lessons Learned Oral History Project: An Interview With Zoltan Pozsar, Zoltan Pozsar, Sandra Ward

Documents

No abstract provided.

The Effects Of Poly(Ethylene Glycol) Grafting Density On The Extensional Solution Flows Of High Molecular Weight Polyacrylamide, Adam Linscott, Lauren Hong, Svetlana Morozova

Faculty Scholarship

Controlling the extensional rheological properties of solutions is of great interest for a number of applications, such as printing and coatings, as polymeric additives can modify a fluid's droplet size, formation, and breakup. We have measured the extensional flows of polyacrylamide graft poly(ethylene glycol) amine (PAM-g-PEGa) solutions as a function of grafting density. PAM-g-PEGa is synthesized with grafting densities of 2.5%, 5.5%, 8%, and 30% and extensional flow was analyzed with drop-on-substrate rheology. Flow time scales and profiles are then compared to understand the effects of backbone extension from the addition of side chains. At low grafting densities, the viscous …

Effects Of Screen Time On Children's Brain Development: A Scoping Review, Niloofar Jannesar, Todd E. Davenport, Lindsay Gietzen

Pacific Journal of Health

In this scoping review, the effects of screen time on cognitive, linguistic, and social-emotional development in children were studied by examining peer-reviewed articles published between 2018 and 2023. A total of 17 peer-reviewed articles were used in the study. The research reported that screen media provide a learning avenue, though it could be detrimental when children spend their time watching more than appropriate screen media. Furthermore, the study indicated that excessive screen media use may harm children’s executive function, which affects academic performance and language development. Related studies have also shown a correlation between excess screen use and problems like …

Inference Methods For Token-Level Topic Assignments With Fixed Topics, Stephen Cowley

Theses and Dissertations

Topic modeling, an unsupervised technique used to gain high-level understanding of a large collection of documents, often involves two major goals: The discovery of topics used in the corpus (topic-discovery) and the assignment of topics to individual words (token-level topic assignment). While Latent Dirichlet Allocation (LDA) normally performs both of these steps simultaneously, some situations require only the token-level topic assignments, using fixed topics. We evaluate three topic assignment strategies using fixed topics -- Gibbs sampling, iterated conditional modes, and mean field variational inference -- to determine which should be used when only token-level topic assignment is needed. Among these …

Ypfs Lessons Learned Oral History Project: An Interview With John Oros, John Oros, Mary Anne Chute Lynch

Documents

No abstract provided.

Hormone Replacement Therapy Is Associated With Disease Activity Improvement Among Post-Menopausal Women With Inflammatory Bowel Disease, Morgan Freeman, Lauren Lally, Levi Teigen, Elliot Graziano, Raina Shivashankar, Eugenia Shmidt

Division of Gastroenterology and Hepatology Faculty Papers

(1) Background: There are limited data available to guide clinical decision-making regarding the effects of hormone replacement therapy (HRT) in post-menopausal women with inflammatory bowel disease (IBD). In this study, we sought to characterize a population of post-menopausal women with IBD and to determine the effects of HRT on their disease activity. (2) Methods: A multicenter, retrospective, case–control cohort study of post-menopausal women with IBD was conducted. The physician global assessment (PGA) score was used to quantify disease activity. To control for the effects of menopause, IBD patients who had not undergone HRT were used as controls. (3) Results: There …