89,231 results on '"Pollard, A"'
Search Results
2. The Effects of Virtual Tutoring on Young Readers: Results from a Randomized Controlled Trial. EdWorkingPaper No. 24-955
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Annenberg Institute for School Reform at Brown University, Carly D. Robinson, Cynthia Pollard, Sarah Novicoff, Sara White, and Susanna Loeb
- Abstract
In-person tutoring has been shown to improve academic achievement. Though less well-researched, virtual tutoring has also shown a positive effect on achievement but has only been studied in grade five or above. We present findings from the first randomized controlled trial of virtual tutoring for young children (grades K-2). Students were assigned to 1:1 tutoring, 2:1 tutoring, or a control group. Assignment to any virtual tutoring increased early literacy skills by 0.05-0.08 SD with the largest effects for 1:1 tutoring (0.07-0.12 SD). Students initially scoring well below benchmark and first graders experienced the largest gains from 1:1 tutoring (0.15 and 0.20 SD, respectively). Effects are smaller than typically seen from in-person early literacy tutoring programs but still positive and statistically significant, suggesting promise particularly in communities with in-person staffing challenges. [On Your Mark and Uplift Education were partners in this research and additional support was provided by the National Student Support Accelerator Team.]
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- 2024
3. Defect Dynamics in Cholesterics: Beyond the Peach-Koehler Force
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Pollard, Joseph and Morris, Richard G.
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Condensed Matter - Soft Condensed Matter - Abstract
The Peach-Koehler force between disclination lines was originally formulated in the study of crystalline solids, and has since been adopted to provide a notion of interactions between disclination lines in nematic liquid crystals. Here, we argue that the standard formulation of this interaction force seemingly fails for materials where there is a symmetry-broken ground state, and suggest that this is due to the interaction between disclination lines and merons: non-singular yet non-trivial topological solitons. We examine this in the context of chiral nematic (cholesteric) liquid crystals, which provide a natural setting for studying these interactions due to their energetic preference for meron tubes in the form of double-twist cylinders. Through a combination of theory and simulation we demonstrate that, for sufficiently strong chirality, defects of $+1/2$ winding will change their winding through the emission of a meron line, and that interactions between the merons and defects dominate over defect-defect interactions. Instead of Peach-Koehler framework, we employ a method based on contact topology - the Gray stability theorem - to directly calculate the velocity field of the material. We apply our framework to point defects as well as disclination lines. Our results have implications not just for chiral materials, but also for other phases with modulated ground states, such as the twist-bend and splay-bend nematics., Comment: 16 pages, 5 figures
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- 2024
4. Electron Channelling Contrast SEM Imaging of Twist Domains in Transition Metal Dichalcogenide Heterostructures
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Tillotson, Evan, McHugh, James, Howarth, James, Hashimoto, Teruo, Clark, Nick, Weston, Astrid, Enaldiev, Vladimir, Sullivan-Allsop, Samuel, Thornley, William, Wang, Wendong, Lindley, Matthew, Pollard, Andrew, Falko, Vladimir, Gorbachev, Roman, and Haigh, Sarah J.
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Condensed Matter - Materials Science - Abstract
Twisted 2D material heterostructures provide an exciting platform for investigating new fundamental physical phenomena. Many of the most interesting behaviours emerge at small twist angles, where the materials reconstruct to form areas of perfectly stacked crystal separated by partial dislocations. However, understanding the properties of these systems is often impossible without correlative imaging of their local reconstructed domain architecture, which exhibits random variations due to disorder and contamination. Here we demonstrate a simple and widely accessible route to visualise domains in as-produced twisted transition metal dichalcogenide (TMD) heterostructures using electron channelling contrast imaging (ECCI) in the scanning electron microscope (SEM). This non-destructive approach is compatible with conventional substrates and allows domains to be visualised even when sealed beneath an encapsulation layer. Complementary theoretical calculations reveal how a combination of elastic and inelastic scattering leads to contrast inversions at specified detector scattering angles and sample tilts. We demonstrate that optimal domain contrast is therefore achieved by maximising signal collection while avoiding contrast inversion conditions.
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- 2024
5. SCOUT: A Situated and Multi-Modal Human-Robot Dialogue Corpus
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Lukin, Stephanie M., Bonial, Claire, Marge, Matthew, Hudson, Taylor, Hayes, Cory J., Pollard, Kimberly A., Baker, Anthony, Foots, Ashley N., Artstein, Ron, Gervits, Felix, Abrams, Mitchell, Henry, Cassidy, Donatelli, Lucia, Leuski, Anton, Hill, Susan G., Traum, David, and Voss, Clare R.
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Computer Science - Human-Computer Interaction ,Computer Science - Computation and Language ,Computer Science - Robotics ,I.2.7 ,I.2.9 ,I.2.10 ,H.5.2 ,J.7 - Abstract
We introduce the Situated Corpus Of Understanding Transactions (SCOUT), a multi-modal collection of human-robot dialogue in the task domain of collaborative exploration. The corpus was constructed from multiple Wizard-of-Oz experiments where human participants gave verbal instructions to a remotely-located robot to move and gather information about its surroundings. SCOUT contains 89,056 utterances and 310,095 words from 278 dialogues averaging 320 utterances per dialogue. The dialogues are aligned with the multi-modal data streams available during the experiments: 5,785 images and 30 maps. The corpus has been annotated with Abstract Meaning Representation and Dialogue-AMR to identify the speaker's intent and meaning within an utterance, and with Transactional Units and Relations to track relationships between utterances to reveal patterns of the Dialogue Structure. We describe how the corpus and its annotations have been used to develop autonomous human-robot systems and enable research in open questions of how humans speak to robots. We release this corpus to accelerate progress in autonomous, situated, human-robot dialogue, especially in the context of navigation tasks where details about the environment need to be discovered., Comment: 14 pages, 7 figures
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- 2024
6. Human-Robot Dialogue Annotation for Multi-Modal Common Ground
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Bonial, Claire, Lukin, Stephanie M., Abrams, Mitchell, Baker, Anthony, Donatelli, Lucia, Foots, Ashley, Hayes, Cory J., Henry, Cassidy, Hudson, Taylor, Marge, Matthew, Pollard, Kimberly A., Artstein, Ron, Traum, David, and Voss, Clare R.
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Computer Science - Human-Computer Interaction ,Computer Science - Computation and Language ,Computer Science - Robotics ,I.2.7 ,I.2.9 ,I.2.10 ,H.5.2 ,J.7 - Abstract
In this paper, we describe the development of symbolic representations annotated on human-robot dialogue data to make dimensions of meaning accessible to autonomous systems participating in collaborative, natural language dialogue, and to enable common ground with human partners. A particular challenge for establishing common ground arises in remote dialogue (occurring in disaster relief or search-and-rescue tasks), where a human and robot are engaged in a joint navigation and exploration task of an unfamiliar environment, but where the robot cannot immediately share high quality visual information due to limited communication constraints. Engaging in a dialogue provides an effective way to communicate, while on-demand or lower-quality visual information can be supplemented for establishing common ground. Within this paradigm, we capture propositional semantics and the illocutionary force of a single utterance within the dialogue through our Dialogue-AMR annotation, an augmentation of Abstract Meaning Representation. We then capture patterns in how different utterances within and across speaker floors relate to one another in our development of a multi-floor Dialogue Structure annotation schema. Finally, we begin to annotate and analyze the ways in which the visual modalities provide contextual information to the dialogue for overcoming disparities in the collaborators' understanding of the environment. We conclude by discussing the use-cases, architectures, and systems we have implemented from our annotations that enable physical robots to autonomously engage with humans in bi-directional dialogue and navigation., Comment: 52 pages, 14 figures
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- 2024
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7. Where are we at with the water reform programme?
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Pollard, Alan
- Published
- 2023
8. Responding to serious challenges together
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Pollard, Alan
- Published
- 2023
9. Hierarchical annotation of eQTLs by H-eQTL enables identification of genes with cell type-divergent regulation.
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Przytycki, Pawel and Pollard, Katherine
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Quantitative Trait Loci ,Molecular Sequence Annotation ,Humans ,Animals ,Chromatin ,Brain ,Single-Cell Analysis ,Gene Expression Regulation ,Mice - Abstract
While context-type-specific regulation of genes is largely determined by cis-regulatory regions, attempts to identify cell type-specific eQTLs are complicated by the nested nature of cell types. We present hierarchical eQTL (H-eQTL), a network-based model for hierarchical annotation of bulk-derived eQTLs to levels of a cell type tree using single-cell chromatin accessibility data and no clustering of cells into discrete cell types. Using our model, we annotate bulk-derived eQTLs from the developing brain with high specificity to levels of a cell type hierarchy, which allows sensitive detection of genes with multiple distinct non-coding elements regulating their expression in different cell types.
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- 2024
10. Variational inference for pile-up removal at hadron colliders with diffusion models
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Algren, Malte, Pollard, Christopher, Raine, John Andrew, and Golling, Tobias
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High Energy Physics - Phenomenology ,Computer Science - Machine Learning - Abstract
In this paper, we present a novel method for pile-up removal of pp interactions using variational inference with diffusion models, called Vipr. Instead of using classification methods to identify which particles are from the primary collision, a generative model is trained to predict the constituents of the hard-scatter particle jets with pile-up removed. This results in an estimate of the full posterior over hard-scatter jet constituents, which has not yet been explored in the context of pile-up removal. We evaluate the performance of Vipr in a sample of jets from simulated $t\bar{t}$ events overlain with pile-up contamination. Vipr outperforms SoftDrop in predicting the substructure of the hard-scatter jets over a wide range of pile-up scenarios., Comment: 19 pages, 13 figures
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- 2024
11. The Foundational Pose as a Selection Mechanism for the Design of Tool-Wielding Multi-Finger Robotic Hands
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Wang, Sunyu, Oh, Jean H., and Pollard, Nancy S.
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Computer Science - Robotics - Abstract
To wield an object means to hold and move it in a way that exploits its functions. When we wield tools -- such as writing with a pen or cutting with scissors -- our hands would reach very specific poses, often drastically different from how we pick up the same objects just to transport them. In this work, we investigate the design of tool-wielding multi-finger robotic hands based on a hypothesis: the poses that a tool and a hand reach during tool-wielding -- what we call "foundational poses" (FPs) -- can be used as a selection mechanism in the design process. We interpret FPs as snapshots that capture the workings of underlying mechanisms formed by the tool and the hand, and one hand can form multiple mechanisms with the same tool. We tested our hypothesis in a hand design experiment, where we developed a sampling-based design optimization framework that uses FPs to computationally generate many different hand designs and evaluate them in multiple metrics. The results show that more than $99\%$ of the $10,785$ generated hand designs successfully wielded tools in simulation, supporting our hypothesis. Meanwhile, our methods provide insights into the non-convex, multi-objective hand design optimization problem that could be hard to unveil otherwise, such as clustering and the Pareto front. Lastly, we demonstrate our methods' real-world feasibility and potential with a hardware prototype equipped with rigid endoskeleton and soft skin.
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- 2024
12. Closing the reproducibility gap: 2D materials research
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Bøggild, Peter, Booth, Timothy John, Lassaline, Nolan, Jessen, Bjarke Sørensen, Shivayogimath, Abhay, Hofmann, Stephan, Daasbjerg, Kim, Smith, Anders, Nørgaard, Kasper, Zurutuza, Amaia, Asselberghs, Inge, Barkan, Terrance, Taboryski, Rafael, and Pollard, Andrew J.
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Physics - Physics and Society ,Condensed Matter - Materials Science ,Physics - Applied Physics ,Physics - Data Analysis, Statistics and Probability - Abstract
2D materials research has reached significant scientific milestones, accompanied by a rapidly growing industrial sector in the two decades since the field's inception. Such rapid progress requires pushing past the boundary of what is technically and scientifically feasible and carries the risk of disseminating irreproducible research results. This Expert Recommendation addresses the need for enhanced reproducibility in 2D materials science and physics. Through a comprehensive examination of the factors that affect reproducibility the authors present a set of concrete guidelines designed to improve the reliability of research results. The introduction of a Standardised Template for Experimental Procedures (STEP) offers a novel approach to documenting experimental details that are crucial for replication and troubleshooting. We emphasise the importance of involving stakeholders from research, industry, publishing, funding agencies, and policymaking to foster a culture of transparency, reliability, and trust without blind angles and critical oversights. By addressing systemic issues that hinder reproducibility and presenting actionable steps for improvement, we aim to pave the way for more robust research practices in 2D materials science, contributing to the field's scientific maturation and the subsequent development of beneficial technologies., Comment: 24 pages, 3 textboxes, 1 figure, 2 tables
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- 2024
13. Morse Theory and Meron Mediated Interactions Between Disclination Lines in Nematics
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Pollard, Joseph and Morris, Richard G.
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Condensed Matter - Soft Condensed Matter ,Mathematical Physics - Abstract
The topological understanding of nematic liquid crystals is traditionally centered on singularities, or defects, and their classification via homotopy theory. However, this approach has ultimately proved insufficient to properly capture a range of complex behaviours that have been reported in three dimensions. To address this, we argue that a finer understanding of topology is required, in which non-singular but non-trivial topological solitons - so-called merons - play a central role in mediating interactions between disclination lines. We present a comprehensive framework for capturing such behaviour that draws heavily on aspects of Morse theory; the key notion being that merons appear singular under projection onto a two-dimensional surface. This permits the use of singularity theory and dividing curves to characterise nematic textures via tomography, as well as an understanding of topological transitions via surgery theory. We use our ideas to understand and classify complex three-dimensional behaviours, such as the linking, rewiring and crossing of disclination lines, as well as to provide a new perspective on defect charge., Comment: 31 pages, 11 figures
- Published
- 2024
14. The Role of Instructional Designers in the Integration of Generative Artificial Intelligence in Online and Blended Learning in Higher Education
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Swapna Kumar, Ariel Gunn, Robert Rose, Rhiannon Pollard, Margeaux Johnson, and Albert D. Ritzhaupt
- Abstract
The purpose of this exploratory research study was to examine the roles instructional designers (IDs) play in the integration of generative Artificial Intelligence (GenAI) into their higher education institutions, and how they use GenAI technologies in their own professional practices. Data were collected from 15 participants in the United States (U.S.) in an ID role or with similar job titles (e.g., educational technologist). Using a general qualitative approach, semi-structured interviews were conducted in Zoom about IDs' use and integration of GenAI. Our analysis resulted in three primary themes related to IDs' integration of GenAI in online and blended education: (a) the use of GenAI for instructional design; (b) collaborative guidance for faculty integration of GenAI; and (c) training, resources, and guidelines on the integration of GenAI. A common thread through all the themes was IDs' conscientious and cautious approach and ethical concerns about GenAI integration. We unpack these themes and discuss the implications of IDs in higher education integrating GenAI to meet organizational, faculty, and student needs.
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- 2024
15. Repositioning Corrective Feedback to a Meaning-Orientated Approach in the English Language Classroom
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Robert Weekly and Andrew Pollard
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The practice of Corrective Feedback (CF), which is situated within a Second Language Acquisition (SLA) Paradigm, is currently positioned towards an accuracy-orientated delivery based on native speaker norms. This is despite the recognition in different areas of linguistic research that there is considerable variation in the way that English is spoken around the world. This paper argues that the epistemological assumptions and methodological approaches to investigate CF within an SLA paradigm have various underlying weaknesses that undermine research findings. These findings purport to provide support for an accuracy-orientated CF in the English classroom. However, it is suggested in this paper that a meaning-orientated CF would be more reflective and beneficial for students given the transformative changes that have occurred to English over the past 30 years. This perspective is discussed in relation to one teacher's approach to CF who participated in a larger project which examined CF conducted in a British-Sino University.
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- 2024
16. Examining Lessons Learned during the First Year of a Grow Your Own Teacher Preparation Program
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Joy Myers, Virginia Massaro, Meredith Pollard, Katie Shifflett, Lori Killough, and Mark Miller
- Abstract
This paper outlines how four community colleges, and a large public university, collaborated to support over 80 paraprofessionals who sought to finish their bachelor's degree and earn licensure. Funding from a statewide "Grow Your Own" initiative allowed the teacher educators at the community colleges and university to put in place structures to support non-traditional students, and each other, during the first year of this program. Lessons learned and next steps are highlighted.
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- 2024
17. Practice-Based Teacher Education Pedagogies Improve Responsiveness: Evidence from a Lab Experiment. EdWorkingPaper No. 23-873
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Annenberg Institute for School Reform at Brown University, Zid Mancenido, Heather C. Hill, Jeannette Garcia Coppersmith, Hannah Carter, Cynthia Pollard, and Chris Monschauer
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Practice-based teacher education has increasingly been adopted as an alternative to more traditional, conceptually-focused pedagogies, yet the field lacks causal evidence regarding the relative efficacy of these approaches. To address this issue, we randomly assigned 185 college students to one of three experimental conditions reflective of common conceptually-focused and practice-based teacher preparation pedagogies. We find significant and large positive effects of practice-based pedagogies on participants' skills in eliciting and responding to student thinking as demonstrated through a written assessment and a short teaching episode. Our findings contribute to a developing evidence base that can assist policymakers and teacher educators in designing effective teacher preparation at scale.
- Published
- 2023
18. Validation of the Perceptions of Racism in Children and Youth (PRaCY) Scale in Pittsburgh: Associations with Sexual Violence Experiences
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Amber L. Hill, Lynissa R. Stokes, Jordan Pollard, Lan Yu, Maria D. Trent, Elizabeth Miller, and Ashley V. Hill
- Abstract
Background: Racism is a public health crisis impacting the health and wellbeing of adolescents. Finding valid tools to measure race-based discrimination, a form of racism, is necessary to accurately assess the effectiveness of programs aimed to reduce those experiences. Objectives: Our objective was to evaluate measurement invariance of a race-based discrimination scale by gender among a sample of youth (ages 13-19) from historically marginalized groups and to assess associations of race-based discrimination with sexual violence victimization and perpetration. Methods: We used pooled cross-sectional baseline data from two sexual violence prevention programs from 2015 to 2019. Male and female participants were from Manhood 2.0 (a cluster randomized trial) and Sisterhood 2.0 (a quasi-experimental study), respectively. All participants were recruited through community organizations from the same neighborhoods. In this study, we included all non-white youth with completed responses to the 10-item Perceptions of Racism in Children and Youth (PRaCY) Scale. This study was approved by the University of Pittsburgh IRB. Results: We conducted confirmatory factor analysis (N = 749) and measurement invariance among male-identifying (n = 560) and female-identifying (n = 189) participants resulting in a unidimensional factor structure with weak factorial invariance by gender. Lifetime discriminatory experiences were common among all participants. Mean discrimination scores were associated with a significant increase in the odds of lifetime sexual violence victimization in males (OR = 3.03, 95%CI 1.43-6.42) and females (OR = 10.80, 95% CI 2.23-52.33), respectively. Conclusion: We confirmed construct validity of the PRaCY Scale among youth experiencing marginalization and found associations between experiences of discrimination and sexual violence victimization in both boys and girls.
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- 2024
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19. Frontotemporal lobar degeneration targets brain regions linked to expression of recently evolved genes
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Pasquini, Lorenzo, Pereira, Felipe L, Seddighi, Sahba, Zeng, Yi, Wei, Yongbin, Illán-Gala, Ignacio, Vatsavayai, Sarat C, Friedberg, Adit, Lee, Alex J, Brown, Jesse A, Spina, Salvatore, Grinberg, Lea T, Sirkis, Daniel W, Bonham, Luke W, Yokoyama, Jennifer S, Boxer, Adam L, Kramer, Joel H, Rosen, Howard J, Humphrey, Jack, Gitler, Aaron D, Miller, Bruce L, Pollard, Katherine S, Ward, Michael E, and Seeley, William W
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Biological Psychology ,Psychology ,Alzheimer's Disease ,Rare Diseases ,Neurodegenerative ,Aging ,Frontotemporal Dementia (FTD) ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Alzheimer's Disease Related Dementias (ADRD) ,Neurosciences ,Brain Disorders ,Acquired Cognitive Impairment ,Genetics ,Dementia ,2.1 Biological and endogenous factors ,Neurological ,Humans ,Frontotemporal Lobar Degeneration ,Brain ,Male ,Female ,Aged ,DNA-Binding Proteins ,Middle Aged ,tau Proteins ,Atrophy ,Animals ,Evolution ,Molecular ,Gene Expression ,frontotemporal lobar degeneration ,cryptic exon ,human accelerated regions ,TDP-43 ,tau ,gene expression ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Neurology & Neurosurgery ,Biomedical and clinical sciences ,Health sciences - Abstract
In frontotemporal lobar degeneration (FTLD), pathological protein aggregation in specific brain regions is associated with declines in human-specialized social-emotional and language functions. In most patients, disease protein aggregates contain either TDP-43 (FTLD-TDP) or tau (FTLD-tau). Here, we explored whether FTLD-associated regional degeneration patterns relate to regional gene expression of human accelerated regions (HARs), conserved sequences that have undergone positive selection during recent human evolution. To this end, we used structural neuroimaging from patients with FTLD and human brain regional transcriptomic data from controls to identify genes expressed in FTLD-targeted brain regions. We then integrated primate comparative genomic data to test our hypothesis that FTLD targets brain regions linked to expression levels of recently evolved genes. In addition, we asked whether genes whose expression correlates with FTLD atrophy are enriched for genes that undergo cryptic splicing when TDP-43 function is impaired. We found that FTLD-TDP and FTLD-tau subtypes target brain regions with overlapping and distinct gene expression correlates, highlighting many genes linked to neuromodulatory functions. FTLD atrophy-correlated genes were strongly enriched for HARs. Atrophy-correlated genes in FTLD-TDP showed greater overlap with TDP-43 cryptic splicing genes and genes with more numerous TDP-43 binding sites compared with atrophy-correlated genes in FTLD-tau. Cryptic splicing genes were enriched for HAR genes, and vice versa, but this effect was due to the confounding influence of gene length. Analyses performed at the individual-patient level revealed that the expression of HAR genes and cryptically spliced genes within putative regions of disease onset differed across FTLD-TDP subtypes. Overall, our findings suggest that FTLD targets brain regions that have undergone recent evolutionary specialization and provide intriguing potential leads regarding the transcriptomic basis for selective vulnerability in distinct FTLD molecular-anatomical subtypes.
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- 2024
20. Sustained mucosal colonization and fecal metabolic dysfunction by Bacteroides associates with fecal microbial transplant failure in ulcerative colitis patients.
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Zhang, Bing, Magnaye, Kevin, Stryker, Emily, Moltzau-Anderson, Jacqueline, Porsche, Cara, Hertz, Sandra, McCauley, Kathryn, Smith, Byron, Zydek, Martin, Pollard, Katherine, Ma, Averil, El-Nachef, Najwa, and Lynch, Susan
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Humans ,Colitis ,Ulcerative ,Fecal Microbiota Transplantation ,Male ,Female ,Feces ,Bacteroides ,Adult ,Intestinal Mucosa ,Middle Aged ,Gastrointestinal Microbiome ,Treatment Failure ,RNA ,Ribosomal ,16S ,Metabolome - Abstract
Fecal microbial transplantation (FMT) offers promise for treating ulcerative colitis (UC), though the mechanisms underlying treatment failure are unknown. This study harnessed longitudinally collected colonic biopsies (n = 38) and fecal samples (n = 179) from 19 adults with mild-to-moderate UC undergoing serial FMT in which antimicrobial pre-treatment and delivery mode (capsules versus enema) were assessed for clinical response (≥ 3 points decrease from the pre-treatment Mayo score). Colonic biopsies underwent dual RNA-Seq; fecal samples underwent parallel 16S rRNA and shotgun metagenomic sequencing as well as untargeted metabolomic analyses. Pre-FMT, the colonic mucosa of non-responsive (NR) patients harbored an increased burden of bacteria, including Bacteroides, that expressed more antimicrobial resistance genes compared to responsive (R) patients. NR patients also exhibited muted mucosal expression of innate immune antimicrobial response genes. Post-FMT, NR and R fecal microbiomes and metabolomes exhibited significant divergence. NR metabolomes had elevated concentrations of immunostimulatory compounds including sphingomyelins, lysophospholipids and taurine. NR fecal microbiomes were enriched for Bacteroides fragilis and Bacteroides salyersiae strains that encoded genes capable of taurine production. These findings suggest that both effective mucosal microbial clearance and reintroduction of bacteria that reshape luminal metabolism associate with FMT success and that persistent mucosal and fecal colonization by antimicrobial-resistant Bacteroides species may contribute to FMT failure.
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- 2024
21. Taking the pulse of the civil construction industry
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Pollard, Alan
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- 2022
22. What do we do with our water?
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Pollard, Andrew
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- 2022
23. How Kiwis use water at home
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Whittaker, Colin, Pollard, Andrew R., and Smith, Lesley
- Published
- 2022
24. Gauge Freedom and Objective Rates in the Morphodynamics of Fluid Deformable Surfaces: the Jaumann Rate vs. the Material Derivative
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Pollard, Joseph, Al-Izzi, Sami, and Morris, Richard G.
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Physics - Fluid Dynamics ,Condensed Matter - Soft Condensed Matter ,Mathematical Physics - Abstract
Morphodynamic descriptions of fluid deformable surfaces are relevant for a range of biological and soft matter phenomena, spanning materials that can be passive or active, as well as ordered or topological. However, a principled, geometric formulation of the correct hydrodynamic equations has remained opaque, with objective rates proving a central, contentious issue. We argue that this is due to a conflation of several important notions that must be disambiguated when describing fluid deformable surfaces. These are the Eulerian and Lagrangian perspectives on fluid motion, and three different types of gauge freedom: in the ambient space; in the parameterisation of the surface, and; in the choice of frame field on the surface. We clarify these ideas, and show that objective rates in fluid deformable surfaces are time derivatives that are invariant under the first of these gauge freedoms, and which also preserve the structure of the ambient metric. The latter condition reduces a potentially infinite number of possible objective rates to only two: the material derivative and the Jaumann rate. The material derivative is invariant under the Galilean group, and therefore applies to velocities, whose rate captures the conservation of momentum. The Jaumann derivative is invariant under all time-dependent isometries, and therefore applies to local order parameters, or symmetry-broken variables, such as the nematic $Q$-tensor. We provide examples of material and Jaumann rates in two different frame fields that are pertinent to the current applications of the fluid mechanics of deformable surfaces., Comment: 27 pages, 4 figures
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- 2024
25. EHRCon: Dataset for Checking Consistency between Unstructured Notes and Structured Tables in Electronic Health Records
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Kwon, Yeonsu, Kim, Jiho, Lee, Gyubok, Bae, Seongsu, Kyung, Daeun, Cha, Wonchul, Pollard, Tom, Johnson, Alistair, and Choi, Edward
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Computer Science - Computation and Language - Abstract
Electronic Health Records (EHRs) are integral for storing comprehensive patient medical records, combining structured data (e.g., medications) with detailed clinical notes (e.g., physician notes). These elements are essential for straightforward data retrieval and provide deep, contextual insights into patient care. However, they often suffer from discrepancies due to unintuitive EHR system designs and human errors, posing serious risks to patient safety. To address this, we developed EHRCon, a new dataset and task specifically designed to ensure data consistency between structured tables and unstructured notes in EHRs. EHRCon was crafted in collaboration with healthcare professionals using the MIMIC-III EHR dataset, and includes manual annotations of 4,101 entities across 105 clinical notes checked against database entries for consistency. EHRCon has two versions, one using the original MIMIC-III schema, and another using the OMOP CDM schema, in order to increase its applicability and generalizability. Furthermore, leveraging the capabilities of large language models, we introduce CheckEHR, a novel framework for verifying the consistency between clinical notes and database tables. CheckEHR utilizes an eight-stage process and shows promising results in both few-shot and zero-shot settings. The code is available at https://github.com/dustn1259/EHRCon.
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- 2024
26. Efficient Industrial Refrigeration Scheduling with Peak Pricing
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Konda, Rohit, Prescott, Jordan, Chandan, Vikas, Crossno, Jesse, Pollard, Blake, Walsh, Dan, Bohonek, Rick, and Marden, Jason R.
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Electrical Engineering and Systems Science - Systems and Control - Abstract
The widespread use of industrial refrigeration systems across various sectors contribute significantly to global energy consumption, highlighting substantial opportunities for energy conservation through intelligent control design. As such, this work focuses on control algorithm design in industrial refrigeration that minimize operational costs and provide efficient heat extraction. By adopting tools from inventory control, we characterize the structure of these optimal control policies, exploring the impact of different energy cost-rate structures such as time-of-use (TOU) pricing and peak pricing. While classical threshold policies are optimal under TOU costs, introducing peak pricing challenges their optimality, emphasizing the need for carefully designed control strategies in the presence of significant peak costs. We provide theoretical findings and simulation studies on this phenomenon, offering insights for more efficient industrial refrigeration management.
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- 2024
27. Accelerator beam phase space tomography using machine learning to account for variations in beamline components
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Wolski, Andrzej, Botelho, Diego, Dunning, David, and Pollard, Amelia E.
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Physics - Accelerator Physics - Abstract
We describe a technique for reconstruction of the four-dimensional transverse phase space of a beam in an accelerator beamline, taking into account the presence of unknown errors on the strengths of magnets used in the data collection. Use of machine learning allows rapid reconstruction of the phase-space distribution while at the same time providing estimates of the magnet errors. The technique is demonstrated using experimental data from CLARA, an accelerator test facility at Daresbury Laboratory., Comment: 31 pages, 18 figures
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- 2024
28. Efficacy of multimodal treatment involving Baclofen, pelvic floor physiotherapy and polysomnography for sleep related painful erections (SRPE): a single centre observational cohort study
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Alarayedh, Ameer, Gad, Mohamed, Tomita, Kenji, Pook, Celina J., Rexford, Muza, Igualada-Martinez, Paula, Pollard, Colette, Steier, Joerg, and Yap, Tet
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- 2024
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29. Nucleosome fibre topology guides transcription factor binding to enhancers
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O’Dwyer, Michael R., Azagury, Meir, Furlong, Katharine, Alsheikh, Amani, Hall-Ponsele, Elisa, Pinto, Hugo, Fyodorov, Dmitry V., Jaber, Mohammad, Papachristoforou, Eleni, Benchetrit, Hana, Ashmore, James, Makedonski, Kirill, Rahamim, Moran, Hanzevacki, Marta, Yassen, Hazar, Skoda, Samuel, Levy, Adi, Pollard, Steven M., Skoultchi, Arthur I., Buganim, Yosef, and Soufi, Abdenour
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- 2024
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30. Strengthening the Indomitable Spirit of Nurses Through Targeted Resilience Education
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Blaney, Leigh, Abbey, Darin, Pollard, Emmerson, Agyekum, Eric, Slonowsky, Dean, and Macdonald, Anna
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- 2024
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31. Electronic Health Records for Predicting Outcomes to Work-Related Musculoskeletal Disorders: A Scoping Review
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Wassell, M., Vitiello, A., Butler-Henderson, K., Verspoor, K., McCann, P., and Pollard, H.
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- 2024
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32. The test–retest reliability of frontal, sagittal, and transverse spinal measurements during three standing arm positions in adolescents with idiopathic scoliosis measured using ultrasound imaging
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Fehr, Brianna J., Parent, Eric C., Pollard, Janie, Ganci, Aislinn, Du, Linh, Lou, Edmond, and Kawchuk, Greg
- Published
- 2024
- Full Text
- View/download PDF
33. Chromatin remodelling drives immune cell–fibroblast communication in heart failure
- Author
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Alexanian, Michael, Padmanabhan, Arun, Nishino, Tomohiro, Travers, Joshua G., Ye, Lin, Pelonero, Angelo, Lee, Clara Youngna, Sadagopan, Nandhini, Huang, Yu, Auclair, Kirsten, Zhu, Ada, An, Yuqian, Ekstrand, Christina A., Martinez, Cassandra, Teran, Barbara Gonzalez, Flanigan, Will R., Kim, Charis Kee-Seon, Lumbao-Conradson, Koya, Gardner, Zachary, Li, Li, Costa, Mauro W., Jain, Rajan, Charo, Israel, Combes, Alexis J., Haldar, Saptarsi M., Pollard, Katherine S., Vagnozzi, Ronald J., McKinsey, Timothy A., Przytycki, Pawel F., and Srivastava, Deepak
- Published
- 2024
- Full Text
- View/download PDF
34. First reported human use of wireless laparoscopic system: is it ready for prime time?
- Author
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Kim, Hee Kyung Jenny, Abraham, Abel, DeCicco, Jamie, Haas, AJ, Pollard, Robert, and El-Hayek, Kevin
- Published
- 2024
- Full Text
- View/download PDF
35. Nonclinical Sexual Health Support for HIV, Viral Hepatitis, and Other Sexually Transmitted Infections in Gay, Bisexual, and Other Men Who Have Sex With Men: Protocol for a European Community Health Worker Online Survey (ECHOES)
- Author
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Sherriff, Nigel, Huber, Jorg, McGlynn, Nick, Llewellyn, Carrie, Pollard, Alex, Lorente, Nicolas, Folch, Cinta, Cawley, Caoimhe, Panochenko, Oksana, Krone, Michael, Dutarte, Maria, and Casabona, Jordi
- Subjects
Medicine ,Computer applications to medicine. Medical informatics ,R858-859.7 - Abstract
BackgroundThe term “community health worker” (CHW) can apply to a wide range of individuals providing health services and support for diverse populations. Very little is known about the role of CHWs in Europe working in nonclinical settings who promote sexual health and prevent HIV and other sexually transmitted infections (STIs) among gay, bisexual, and other men who have sex with men (MSM). ObjectiveThis paper describes the development and piloting of the first European Community Health Worker Online Survey (ECHOES) as part of the broader European Union-funded ESTICOM (European Surveys and Trainings to Improve MSM Community Health) project. The questionnaire aimed to assess the knowledge, attitudes, and practices of CHWs providing sexual health services to gay, bisexual, and other MSM in European settings. MethodsECHOES comprises three superordinate domains divided into 10 subsections with 175 items (routed) based on a scoping exercise and literature review, online prepiloting, and Europe-wide consultation. Additional piloting and cognitive debriefing interviews with stakeholders were conducted to identify comprehension issues and improve the clarity, intelligibility, accessibility, and acceptability of the survey. Psychometric properties, including internal consistency of the standardized scales used as part of the survey were examined. The final survey was available to 33 countries in 16 languages. ResultsRecruitment closed on January 31, 2018. Data from 1035 CHWs were available for analysis after application of the exclusion criteria. The findings of the ECHOES survey and the wider ESTICOM project, are now available from the ESTICOM website and/or by contacting the first author. ConclusionsThe findings of this survey will help characterize, for the first time, the diverse role of CHWs who provide sexual health services to gay, bisexual, and other MSM in Europe. Importantly, the data will be used to inform the content and design of a dedicated training program for CHWs as part of the larger ESTICOM project and provide recommendations for MSM-specific strategies to improve sexual health in general and to reduce the incidence and prevalence of HIV, viral hepatitis, and other STIs in particular. International Registered Report Identifier (IRRID)RR1-10.2196/15012
- Published
- 2020
- Full Text
- View/download PDF
36. Inflammation in the COVID-19 airway is due to inhibition of CFTR signaling by the SARS-CoV-2 spike protein
- Author
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Caohuy, Hung, Eidelman, Ofer, Chen, Tinghua, Mungunsukh, Ognoon, Yang, Qingfeng, Walton, Nathan I., Pollard, Bette S., Khanal, Sara, Hentschel, Shannon, Florez, Catalina, Herbert, Andrew S., and Pollard, Harvey B.
- Published
- 2024
- Full Text
- View/download PDF
37. The Appalachian Region: A Data Overview from the 2017-2021 American Community Survey. Chartbook
- Author
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Appalachian Regional Commission (ARC), Population Reference Bureau (PRB), Pollard, Kelvin, Srygley, Sara, and Jacobsen, Linda A.
- Abstract
"The Appalachian Region: A Data Overview from the 2017-2021 American Community Survey," also known as "The Chartbook," draws from the most recent American Community Survey and comparable Census Population Estimates. The report contains over 300,000 data points about Appalachia's economy, income, employment, education, and other important indicators--all presented at regional, subregional, state, and county levels. Though that data was collected before, and during the initial ten months of, the COVID-19 pandemic, they provide a critical benchmark for comparison when more pandemic and post-pandemic information becomes available. [For the 2016-2020 Chartbook, see ED625962.]
- Published
- 2023
38. Escape into the Third Dimension in Cholesteric Liquid Crystals
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Pollard, Joseph and Alexander, Gareth P.
- Subjects
Condensed Matter - Soft Condensed Matter - Abstract
Integer winding disclinations are unstable in a nematic and are removed by an `escape into the third dimension', resulting in a non-singular texture. This process is frustrated in a cholesteric material due to the requirement of maintaining a uniform handedness and instead results in the formation of strings of point defects, as well as complex three-dimensional solitons such as heliknotons that consist of linked dislocations. We give a complete description of this frustration using methods of contact topology. Furthermore, we describe how this frustration can be exploited to stabilise regions of the material where the handedness differs from the preferred handedness. These `twist solitons' are stable in numerical simulation and are a new form of topological defect in cholesteric materials that have not previously been studied., Comment: 18 pages, 9 figures
- Published
- 2024
39. Design and Control Co-Optimization for Automated Design Iteration of Dexterous Anthropomorphic Soft Robotic Hands
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Mannam, Pragna, Liu, Xingyu, Zhao, Ding, Oh, Jean, and Pollard, Nancy
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Computer Science - Robotics - Abstract
We automate soft robotic hand design iteration by co-optimizing design and control policy for dexterous manipulation skills in simulation. Our design iteration pipeline combines genetic algorithms and policy transfer to learn control policies for nearly 400 hand designs, testing grasp quality under external force disturbances. We validate the optimized designs in the real world through teleoperation of pickup and reorient manipulation tasks. Our real world evaluation, from over 900 teleoperated tasks, shows that the trend in design performance in simulation resembles that of the real world. Furthermore, we show that optimized hand designs from our approach outperform existing soft robot hands from prior work in the real world. The results highlight the usefulness of simulation in guiding parameter choices for anthropomorphic soft robotic hand systems, and the effectiveness of our automated design iteration approach, despite the sim-to-real gap.
- Published
- 2024
40. Utilizing Load Shifting for Optimal Compressor Sequencing in Industrial Refrigeration
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Konda, Rohit, Chandan, Vikas, Crossno, Jesse, Pollard, Blake, Walsh, Dan, Bohonek, Rick, and Marden, Jason R.
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Electrical Engineering and Systems Science - Systems and Control - Abstract
The ubiquity and energy needs of industrial refrigeration has prompted several research studies investigating various control opportunities for reducing energy demand. This work focuses on one such opportunity, termed compressor sequencing, which entails intelligently selecting the operational state of the compressors to service the required refrigeration load with the least possible work. We first study the static compressor sequencing problem and observe that deriving the optimal compressor operational state is computationally challenging and can vary dramatically based on the refrigeration load. Thus we introduce load shifting in conjunction with compressor sequencing, which entails strategically precooling the facility to allow for more efficient compressor operation. Interestingly, we show that load shifting not only provides benefits in computing the optimal compressor operational state, but also can lead to significant energy savings. Our results are based on and compared to real-world sensor data from an operating industrial refrigeration site of Butterball LLC located in Huntsville, AR, which demonstrated that without load shifting, even optimal compressor operation results in compressors often running at intermediate capacity levels, which can lead to inefficiencies. Through collected data, we demonstrate that a load shifting approach for compressor sequencing has the potential to reduce energy use of the compressors up to 20% compared to optimal sequencing without load shifting.
- Published
- 2024
41. Kinematic Motion Retargeting for Contact-Rich Anthropomorphic Manipulations
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Lakshmipathy, Arjun S., Hodgins, Jessica K., and Pollard, Nancy S.
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Computer Science - Graphics ,Computer Science - Robotics - Abstract
Hand motion capture data is now relatively easy to obtain, even for complicated grasps; however this data is of limited use without the ability to retarget it onto the hands of a specific character or robot. The target hand may differ dramatically in geometry, number of degrees of freedom (DOFs), or number of fingers. We present a simple, but effective framework capable of kinematically retargeting multiple human hand-object manipulations from a publicly available dataset to a wide assortment of kinematically and morphologically diverse target hands through the exploitation of contact areas. We do so by formulating the retarget operation as a non-isometric shape matching problem and use a combination of both surface contact and marker data to progressively estimate, refine, and fit the final target hand trajectory using inverse kinematics (IK). Foundational to our framework is the introduction of a novel shape matching process, which we show enables predictable and robust transfer of contact data over full manipulations while providing an intuitive means for artists to specify correspondences with relatively few inputs. We validate our framework through thirty demonstrations across five different hand shapes and six motions of different objects. We additionally compare our method against existing hand retargeting approaches. Finally, we demonstrate our method enabling novel capabilities such as object substitution and the ability to visualize the impact of design choices over full trajectories.
- Published
- 2024
42. Exploring the roles of RNAs in chromatin architecture using deep learning.
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Kuang, Shuzhen and Pollard, Katherine
- Subjects
Deep Learning ,Chromatin ,Humans ,RNA ,Long Noncoding ,Cell Line ,RNA ,DNA - Abstract
Recent studies have highlighted the impact of both transcription and transcripts on 3D genome organization, particularly its dynamics. Here, we propose a deep learning framework, called AkitaR, that leverages both genome sequences and genome-wide RNA-DNA interactions to investigate the roles of chromatin-associated RNAs (caRNAs) on genome folding in HFFc6 cells. In order to disentangle the cis- and trans-regulatory roles of caRNAs, we have compared models with nascent transcripts, trans-located caRNAs, open chromatin data, or DNA sequence alone. Both nascent transcripts and trans-located caRNAs improve the models predictions, especially at cell-type-specific genomic regions. Analyses of feature importance scores reveal the contribution of caRNAs at TAD boundaries, chromatin loops and nuclear sub-structures such as nuclear speckles and nucleoli to the models predictions. Furthermore, we identify non-coding RNAs (ncRNAs) known to regulate chromatin structures, such as MALAT1 and NEAT1, as well as several new RNAs, RNY5, RPPH1, POLG-DT and THBS1-IT1, that might modulate chromatin architecture through trans-interactions in HFFc6. Our modeling also suggests that transcripts from Alus and other repetitive elements may facilitate chromatin interactions through trans R-loop formation. Our findings provide insights and generate testable hypotheses about the roles of caRNAs in shaping chromatin organization.
- Published
- 2024
43. Systematic decoding of cis gene regulation defines context-dependent control of the multi-gene costimulatory receptor locus in human T cells
- Author
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Mowery, Cody T, Freimer, Jacob W, Chen, Zeyu, Casaní-Galdón, Salvador, Umhoefer, Jennifer M, Arce, Maya M, Gjoni, Ketrin, Daniel, Bence, Sandor, Katalin, Gowen, Benjamin G, Nguyen, Vinh, Simeonov, Dimitre R, Garrido, Christian M, Curie, Gemma L, Schmidt, Ralf, Steinhart, Zachary, Satpathy, Ansuman T, Pollard, Katherine S, Corn, Jacob E, Bernstein, Bradley E, Ye, Chun Jimmie, and Marson, Alexander
- Subjects
Biochemistry and Cell Biology ,Biological Sciences ,Biotechnology ,Human Genome ,Genetics ,1.1 Normal biological development and functioning ,2.1 Biological and endogenous factors ,Humans ,CTLA-4 Antigen ,CD28 Antigens ,Gene Expression Regulation ,Chromatin ,T-Lymphocytes ,Inducible T-Cell Co-Stimulator Protein ,CCCTC-Binding Factor ,CRISPR-Cas Systems ,Medical and Health Sciences ,Developmental Biology ,Agricultural biotechnology ,Bioinformatics and computational biology - Abstract
Cis-regulatory elements (CREs) interact with trans regulators to orchestrate gene expression, but how transcriptional regulation is coordinated in multi-gene loci has not been experimentally defined. We sought to characterize the CREs controlling dynamic expression of the adjacent costimulatory genes CD28, CTLA4 and ICOS, encoding regulators of T cell-mediated immunity. Tiling CRISPR interference (CRISPRi) screens in primary human T cells, both conventional and regulatory subsets, uncovered gene-, cell subset- and stimulation-specific CREs. Integration with CRISPR knockout screens and assay for transposase-accessible chromatin with sequencing (ATAC-seq) profiling identified trans regulators influencing chromatin states at specific CRISPRi-responsive elements to control costimulatory gene expression. We then discovered a critical CCCTC-binding factor (CTCF) boundary that reinforces CRE interaction with CTLA4 while also preventing promiscuous activation of CD28. By systematically mapping CREs and associated trans regulators directly in primary human T cell subsets, this work overcomes longstanding experimental limitations to decode context-dependent gene regulatory programs in a complex, multi-gene locus critical to immune homeostasis.
- Published
- 2024
44. SuPreMo: a computational tool for streamlining in silico perturbation using sequence-based predictive models
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Gjoni, Ketrin and Pollard, Katherine S
- Subjects
Biological Sciences ,Bioinformatics and Computational Biology ,Genetics ,Networking and Information Technology R&D (NITRD) ,Machine Learning and Artificial Intelligence ,Bioengineering ,Humans ,Computational Biology ,Mutagenesis ,Computer Simulation ,Software ,Machine Learning ,Mathematical Sciences ,Information and Computing Sciences ,Bioinformatics ,Biological sciences ,Information and computing sciences ,Mathematical sciences - Abstract
SummaryThe increasing development of sequence-based machine learning models has raised the demand for manipulating sequences for this application. However, existing approaches to edit and evaluate genome sequences using models have limitations, such as incompatibility with structural variants, challenges in identifying responsible sequence perturbations, and the need for vcf file inputs and phased data. To address these bottlenecks, we present Sequence Mutator for Predictive Models (SuPreMo), a scalable and comprehensive tool for performing and supporting in silico mutagenesis experiments. We then demonstrate how pairs of reference and perturbed sequences can be used with machine learning models to prioritize pathogenic variants or discover new functional sequences.Availability and implementationSuPreMo was written in Python, and can be run using only one line of code to generate both sequences and 3D genome disruption scores. The codebase, instructions for installation and use, and tutorials are on the GitHub page: https://github.com/ketringjoni/SuPreMo.
- Published
- 2024
45. Cross-ancestry atlas of gene, isoform, and splicing regulation in the developing human brain
- Author
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Wen, Cindy, Margolis, Michael, Dai, Rujia, Zhang, Pan, Przytycki, Pawel F, Vo, Daniel D, Bhattacharya, Arjun, Matoba, Nana, Tang, Miao, Jiao, Chuan, Kim, Minsoo, Tsai, Ellen, Hoh, Celine, Aygün, Nil, Walker, Rebecca L, Chatzinakos, Christos, Clarke, Declan, Pratt, Henry, Peters, Mette A, Gerstein, Mark, Daskalakis, Nikolaos P, Weng, Zhiping, Jaffe, Andrew E, Kleinman, Joel E, Hyde, Thomas M, Weinberger, Daniel R, Bray, Nicholas J, Sestan, Nenad, Geschwind, Daniel H, Roeder, Kathryn, Gusev, Alexander, Pasaniuc, Bogdan, Stein, Jason L, Love, Michael I, Pollard, Katherine S, Liu, Chunyu, Gandal, Michael J, Akbarian, Schahram, Abyzov, Alexej, Ahituv, Nadav, Arasappan, Dhivya, Almagro Armenteros, Jose Juan, Beliveau, Brian J, Bendl, Jaroslav, Berretta, Sabina, Bharadwaj, Rahul A, Bicks, Lucy, Brennand, Kristen, Capauto, Davide, Champagne, Frances A, Chatterjee, Tanima, Chatzinakos, Chris, Chen, Yuhang, Chen, H Isaac, Cheng, Yuyan, Cheng, Lijun, Chess, Andrew, Chien, Jo-fan, Chu, Zhiyuan, Clement, Ashley, Collado-Torres, Leonardo, Cooper, Gregory M, Crawford, Gregory E, Davila-Velderrain, Jose, Deep-Soboslay, Amy, Deng, Chengyu, DiPietro, Christopher P, Dracheva, Stella, Drusinsky, Shiron, Duan, Ziheng, Duong, Duc, Dursun, Cagatay, Eagles, Nicholas J, Edelstein, Jonathan, Emani, Prashant S, Fullard, John F, Galani, Kiki, Galeev, Timur, Gaynor, Sophia, Girdhar, Kiran, Goes, Fernando S, Greenleaf, William, Grundman, Jennifer, Guo, Hanmin, Guo, Qiuyu, Gupta, Chirag, Hadas, Yoav, Hallmayer, Joachim, Han, Xikun, Haroutunian, Vahram, Hawken, Natalie, He, Chuan, Henry, Ella, Hicks, Stephanie C, Ho, Marcus, Ho, Li-Lun, Hoffman, Gabriel E, Huang, Yiling, Huuki-Myers, Louise A, and Hwang, Ahyeon
- Subjects
Biological Sciences ,Biomedical and Clinical Sciences ,Genetics ,Biological Psychology ,Psychology ,Mental Illness ,Mental Health ,Human Genome ,Neurosciences ,Brain Disorders ,Mental health ,Humans ,Alternative Splicing ,Atlases as Topic ,Autism Spectrum Disorder ,Brain ,Gene Expression Regulation ,Developmental ,Gene Regulatory Networks ,Genome-Wide Association Study ,Protein Isoforms ,Quantitative Trait Loci ,Schizophrenia ,Transcriptome ,Mental Disorders ,PsychENCODE Consortium† ,PsychENCODE Consortium ,General Science & Technology - Abstract
Neuropsychiatric genome-wide association studies (GWASs), including those for autism spectrum disorder and schizophrenia, show strong enrichment for regulatory elements in the developing brain. However, prioritizing risk genes and mechanisms is challenging without a unified regulatory atlas. Across 672 diverse developing human brains, we identified 15,752 genes harboring gene, isoform, and/or splicing quantitative trait loci, mapping 3739 to cellular contexts. Gene expression heritability drops during development, likely reflecting both increasing cellular heterogeneity and the intrinsic properties of neuronal maturation. Isoform-level regulation, particularly in the second trimester, mediated the largest proportion of GWAS heritability. Through colocalization, we prioritized mechanisms for about 60% of GWAS loci across five disorders, exceeding adult brain findings. Finally, we contextualized results within gene and isoform coexpression networks, revealing the comprehensive landscape of transcriptome regulation in development and disease.
- Published
- 2024
46. Massively parallel characterization of regulatory elements in the developing human cortex
- Author
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Deng, Chengyu, Whalen, Sean, Steyert, Marilyn, Ziffra, Ryan, Przytycki, Pawel F, Inoue, Fumitaka, Pereira, Daniela A, Capauto, Davide, Norton, Scott, Vaccarino, Flora M, Pollen, Alex A, Nowakowski, Tomasz J, Ahituv, Nadav, Pollard, Katherine S, Akbarian, Schahram, Abyzov, Alexej, Arasappan, Dhivya, Almagro Armenteros, Jose Juan, Beliveau, Brian J, Bendl, Jaroslav, Berretta, Sabina, Bharadwaj, Rahul A, Bhattacharya, Arjun, Bicks, Lucy, Brennand, Kristen, Champagne, Frances A, Chatterjee, Tanima, Chatzinakos, Chris, Chen, Yuhang, Chen, H Isaac, Cheng, Yuyan, Cheng, Lijun, Chess, Andrew, Chien, Jo-fan, Chu, Zhiyuan, Clarke, Declan, Clement, Ashley, Collado-Torres, Leonardo, Cooper, Gregory M, Crawford, Gregory E, Dai, Rujia, Daskalakis, Nikolaos P, Davila-Velderrain, Jose, Deep-Soboslay, Amy, DiPietro, Christopher P, Dracheva, Stella, Drusinsky, Shiron, Duan, Ziheng, Duong, Duc, Dursun, Cagatay, Eagles, Nicholas J, Edelstein, Jonathan, Emani, Prashant S, Fullard, John F, Galani, Kiki, Galeev, Timur, Gandal, Michael J, Gaynor, Sophia, Gerstein, Mark, Geschwind, Daniel H, Girdhar, Kiran, Goes, Fernando S, Greenleaf, William, Grundman, Jennifer, Guo, Hanmin, Guo, Qiuyu, Gupta, Chirag, Hadas, Yoav, Hallmayer, Joachim, Han, Xikun, Haroutunian, Vahram, Hawken, Natalie, He, Chuan, Henry, Ella, Hicks, Stephanie C, Ho, Marcus, Ho, Li-Lun, Hoffman, Gabriel E, Huang, Yiling, Huuki-Myers, Louise A, Hwang, Ahyeon, Hyde, Thomas M, Iatrou, Artemis, Jajoo, Aarti, Jensen, Matthew, Jiang, Lihua, Jin, Peng, Jin, Ting, Jops, Connor, Jourdon, Alexandre, Kawaguchi, Riki, Kellis, Manolis, Khullar, Saniya, Kleinman, Joel E, Kleopoulos, Steven P, and Kozlenkov, Alex
- Subjects
Biological Sciences ,Bioinformatics and Computational Biology ,Biomedical and Clinical Sciences ,Stem Cell Research - Embryonic - Human ,Stem Cell Research ,Human Genome ,Genetics ,Neurosciences ,Underpinning research ,Aetiology ,1.1 Normal biological development and functioning ,2.1 Biological and endogenous factors ,Neurological ,Humans ,Cerebral Cortex ,Chromatin ,Deep Learning ,Enhancer Elements ,Genetic ,Gene Expression Regulation ,Developmental ,Neurogenesis ,Neurons ,Organoids ,Regulatory Sequences ,Nucleic Acid ,Promoter Regions ,Genetic ,Regulatory Elements ,Transcriptional ,PsychENCODE Consortium‡ ,PsychENCODE Consortium ,General Science & Technology - Abstract
Nucleotide changes in gene regulatory elements are important determinants of neuronal development and diseases. Using massively parallel reporter assays in primary human cells from mid-gestation cortex and cerebral organoids, we interrogated the cis-regulatory activity of 102,767 open chromatin regions, including thousands of sequences with cell type-specific accessibility and variants associated with brain gene regulation. In primary cells, we identified 46,802 active enhancer sequences and 164 variants that alter enhancer activity. Activity was comparable in organoids and primary cells, suggesting that organoids provide an adequate model for the developing cortex. Using deep learning we decoded the sequence basis and upstream regulators of enhancer activity. This work establishes a comprehensive catalog of functional gene regulatory elements and variants in human neuronal development.
- Published
- 2024
47. Metatranscriptomic investigation of single Ixodes pacificus ticks reveals diverse microbes, viruses, and novel mRNA-like endogenous viral elements.
- Author
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Martyn, Calla, Hayes, Beth M, Lauko, Domokos, Midthun, Edward, Castaneda, Gloria, Bosco-Lauth, Angela, Salkeld, Daniel J, Kistler, Amy, Pollard, Katherine S, and Chou, Seemay
- Subjects
Microbiology ,Biological Sciences ,Genetics ,Vector-Borne Diseases ,Emerging Infectious Diseases ,Biotechnology ,Biodefense ,Infectious Diseases ,2.1 Biological and endogenous factors ,Aetiology ,2.2 Factors relating to the physical environment ,Infection ,arthropod vectors ,vector-borne disease ,metagenomics ,endosymbionts ,nonhuman microbiome ,innate immunity ,bioinformatics ,metatranscriptomics - Abstract
Ticks are increasingly important vectors of human and agricultural diseases. While many studies have focused on tick-borne bacteria, far less is known about tick-associated viruses and their roles in public health or tick physiology. To address this, we investigated patterns of bacterial and viral communities across two field populations of western black-legged ticks (Ixodes pacificus). Through metatranscriptomic analysis of 100 individual ticks, we quantified taxon prevalence, abundance, and co-occurrence with other members of the tick microbiome. In addition to commonly found tick-associated microbes, we assembled 11 novel RNA virus genomes from Rhabdoviridae, Chuviridae, Picornaviridae, Phenuiviridae, Reoviridae, Solemovidiae, Narnaviridae and two highly divergent RNA virus genomes lacking sequence similarity to any known viral families. We experimentally verified the presence of these in I. pacificus ticks across several life stages. We also unexpectedly identified numerous virus-like transcripts that are likely encoded by tick genomic DNA, and which are distinct from known endogenous viral element-mediated immunity pathways in invertebrates. Taken together, our work reveals that I. pacificus ticks carry a greater diversity of viruses than previously appreciated, in some cases resulting in evolutionarily acquired virus-like transcripts. Our findings highlight how pervasive and intimate tick-virus interactions are, with major implications for both the fundamental biology and vectorial capacity of I. pacificus ticks.ImportanceTicks are increasingly important vectors of disease, particularly in the United States where expanding tick ranges and intrusion into previously wild areas has resulted in increasing human exposure to ticks. Emerging human pathogens have been identified in ticks at an increasing rate, and yet little is known about the full community of microbes circulating in various tick species, a crucial first step to understanding how they interact with each and their tick host, as well as their ability to cause disease in humans. We investigated the bacterial and viral communities of the Western blacklegged tick in California and found 11 previously uncharacterized viruses circulating in this population.
- Published
- 2024
48. High-resolution African HLA resource uncovers HLA-DRB1 expression effects underlying vaccine response.
- Author
-
Mentzer, Alexander, Dilthey, Alexander, Pollard, Martin, Gurdasani, Deepti, Karakoc, Emre, Carstensen, Tommy, Muhwezi, Allan, Cutland, Clare, Diarra, Amidou, da Silva Antunes, Ricardo, Paul, Sinu, Smits, Gaby, Wareing, Susan, Kim, HwaRan, Pomilla, Cristina, Chong, Amanda, Brandt, Debora, Neaves, Samuel, Timpson, Nicolas, Crinklaw, Austin, Lindestam Arlehamn, Cecilia, Rautanen, Anna, Kizito, Dennison, Parks, Tom, Auckland, Kathryn, Elliott, Kate, Mills, Tara, Ewer, Katie, Edwards, Nick, Fatumo, Segun, Webb, Emily, Peacock, Sarah, Jeffery, Katie, van der Klis, Fiona, Kaleebu, Pontiano, Vijayanand, Pandurangan, Peters, Bjorn, Sette, Alessandro, Cereb, Nezih, Sirima, Sodiomon, Madhi, Shabir, Elliott, Alison, McVean, Gil, Hill, Adrian, Sandhu, Manjinder, and Nielsen, Rasmus
- Subjects
Humans ,HLA-DRB1 Chains ,Infant ,Black People ,Hepatitis B Vaccines ,Quantitative Trait Loci ,Male ,Female ,Uganda ,Antibody Formation ,Pertussis Vaccine ,Vaccination ,Whooping Cough - Abstract
How human genetic variation contributes to vaccine effectiveness in infants is unclear, and data are limited on these relationships in populations with African ancestries. We undertook genetic analyses of vaccine antibody responses in infants from Uganda (n = 1391), Burkina Faso (n = 353) and South Africa (n = 755), identifying associations between human leukocyte antigen (HLA) and antibody response for five of eight tested antigens spanning pertussis, diphtheria and hepatitis B vaccines. In addition, through HLA typing 1,702 individuals from 11 populations of African ancestry derived predominantly from the 1000 Genomes Project, we constructed an imputation resource, fine-mapping class II HLA-DR and DQ associations explaining up to 10% of antibody response variance in our infant cohorts. We observed differences in the genetic architecture of pertussis antibody response between the cohorts with African ancestries and an independent cohort with European ancestry, but found no in silico evidence of differences in HLA peptide binding affinity or breadth. Using immune cell expression quantitative trait loci datasets derived from African-ancestry samples from the 1000 Genomes Project, we found evidence of differential HLA-DRB1 expression correlating with inferred protection from pertussis following vaccination. This work suggests that HLA-DRB1 expression may play a role in vaccine response and should be considered alongside peptide selection to improve vaccine design.
- Published
- 2024
49. Evaluation of self-measure blood pressure monitoring in a southern rural West Virginia health system
- Author
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Durr, Andrya J, Robinson, Craig H, Seabury, Robin A, Calkins, Andrea L, Pollard, Cecil R, Thygeson, N Marcus, Lindberg, Curt C, McColley, Jessica M, and Baus, Adam D
- Published
- 2023
50. Industry in crisis
- Author
-
Pollard, Alan
- Published
- 2021
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