16 research outputs found
Experiencing History: A Roundtable Discussion of Architecture, Theatre, and Culture of England
This presentation features a roundtable discussion among students who traveled to England during Spring Break, March 5-11, 2022. This presentation seeks to share primary and secondary research about England’s architecture and theatre, as well as additional insights about England’s culture and history gained through first-hand experiences of traveling within the city of London and to Stonehenge and Bath
Histone H2AX stabilizes broken DNA strands to suppress chromosome breaks and translocations during V(D)J recombination
The H2AX core histone variant is phosphorylated in chromatin around DNA double strand breaks (DSBs) and functions through unknown mechanisms to suppress antigen receptor locus translocations during V(D)J recombination. Formation of chromosomal coding joins and suppression of translocations involves the ataxia telangiectasia mutated and DNA-dependent protein kinase catalytic subunit serine/threonine kinases, each of which phosphorylates H2AX along cleaved antigen receptor loci. Using Abelson transformed pre–B cell lines, we find that H2AX is not required for coding join formation within chromosomal V(D)J recombination substrates. Yet we show that H2AX is phosphorylated along cleaved Igκ DNA strands and prevents their separation in G1 phase cells and their progression into chromosome breaks and translocations after cellular proliferation. We also show that H2AX prevents chromosome breaks emanating from unrepaired RAG endonuclease-generated TCR-α/δ locus coding ends in primary thymocytes. Our data indicate that histone H2AX suppresses translocations during V(D)J recombination by creating chromatin modifications that stabilize disrupted antigen receptor locus DNA strands to prevent their irreversible dissociation. We propose that such H2AX-dependent mechanisms could function at additional chromosomal locations to facilitate the joining of DNA ends generated by other types of DSBs
PaLM: Scaling Language Modeling with Pathways
Large language models have been shown to achieve remarkable performance
across a variety of natural language tasks using few-shot learning, which
drastically reduces the number of task-specific training examples needed to
adapt the model to a particular application. To further our understanding of
the impact of scale on few-shot learning, we trained a 540-billion parameter,
densely activated, Transformer language model, which we call Pathways Language
Model PaLM. We trained PaLM on 6144 TPU v4 chips using Pathways, a new ML
system which enables highly efficient training across multiple TPU Pods. We
demonstrate continued benefits of scaling by achieving state-of-the-art
few-shot learning results on hundreds of language understanding and generation
benchmarks. On a number of these tasks, PaLM 540B achieves breakthrough
performance, outperforming the finetuned state-of-the-art on a suite of
multi-step reasoning tasks, and outperforming average human performance on the
recently released BIG-bench benchmark. A significant number of BIG-bench tasks
showed discontinuous improvements from model scale, meaning that performance
steeply increased as we scaled to our largest model. PaLM also has strong
capabilities in multilingual tasks and source code generation, which we
demonstrate on a wide array of benchmarks. We additionally provide a
comprehensive analysis on bias and toxicity, and study the extent of training
data memorization with respect to model scale. Finally, we discuss the ethical
considerations related to large language models and discuss potential
mitigation strategies
A global experiment on motivating social distancing during the COVID-19 pandemic
Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges
Loss to Follow-Up in Patients with Proliferative Diabetic Retinopathy after Panretinal Photocoagulation or Intravitreal Anti-VEGF Injections
Child reduction of /s/+C onset clusters:/s/ perceived as an unstressed degenerate syllable
Does Direct Radiologist-Patient Verbal Communication Affect Follow-Up Compliance of Probably Benign Assessments?
Examining gender differentials in the association of low control work with cognitive performance in older workers
Learning from disease registries during a pandemic:Moving toward an international federation of patient registries
High-quality dermatology patient registries often require considerable time to develop and produce meaningful data. Development time is influenced by registry complexity and regulatory hurdles that vary significantly nationally and institutionally. The rapid emergence of the coronavirus disease 2019 (COVID-19) global pandemic has challenged health services in an unprecedented manner. Mobilization of the dermatology community in response has included rapid development and deployment of multiple, partially harmonized, international patient registries, reinventing established patient registry timelines. Partnership with patient organizations has demonstrated the critical nature of inclusive patient involvement. This global effort has demonstrated the value, capacity, and necessity for the dermatology community to adopt a more cohesive approach to patient registry development and data sharing that can lead to myriad benefits. These include improved utilization of limited resources, increased data interoperability, improved ability to rapidly collect meaningful data, and shortened response times to generate real-world evidence. We call on the global dermatology community to support the development of an international federation of patient registries to consolidate and operationalize the lessons learned during this pandemic. This will provide an enduring means of applying this knowledge to the maintenance and development of sustainable, coherent, and impactful patient registries of benefit now and in the future