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High-performance computing (HPC) has become a strategic resource that drives innovation and economic growth. In addition, it is important to educate a workforce with advanced computational skills to maintain economic competitiveness. In this project, we studied 133 domestic and international university HPC centers to understand the status of HPC. Diverse operating models have been identified and analyzed. To explore the need for and challenges associated with HPC within Wisconsin, faculty and students within the University of Wisconsin System and personnel in local industries were surveyed; in addition, we engaged in conversations with university leaders and officials from government agencies. A strong need for HPC resources has been identified, as well as several serious challenges. A state-wide initiative, the Wisconsin Big Data Alliance, which requires legislative support, is recommended as the platform to foster public-private partnerships, drive scientific and technological innovations, and promote workforce development, leading to an efficient usage of computing resources.

For most graduate writers, acclimating to doctoral-level inquiry is fraught with numerous tensions, whether regarding the development of scholarly identity (Gardner et al., 2014), navigating graduate school's newly decentralized sources for support (Simpson, 2012), or mastering the writing and research conventions that govern disciplinary practice. Using a Cultural Historical Activity Theory (CHAT) framework, this case study analyzes the first-term experiences of Miranda, a first-year PhD student from the field of gerontology (who is also a co-author), and the tensions she feels around the drafting and revision of a single paper. Drawing from Engeström (1987), we theorize Miranda's challenges around motive, authority, and expert feedback as comprising three "contradictions" engendered by the contemporary activity system of doctoral-level learning-to-write, contradictions that at once challenge the writer's going presumptions about writing even while they enable new concepts and solutions to emerge. This analysis finally encourages researchers to take a wide, cultural-historical view of the many contexts in which doctoral students write during their first terms, including the instructor-led classroom, the larger culture of the program and institution, and the current high-pressure realities of doctoral-level academic study in the United States.

Bioconjugation of polymers to proteins is a method to impart improved stability and pharmacokinetic properties to biologic systems. However, the precise effects of polymer architecture on the resulting bioconjugates are not well understood. Particularly, cyclic polymers are known to possess unique features such as a decreased hydrodynamic radius when compared to their linear counterparts of the same molecular weight, but have not yet been studied. Here, we report the first bioconjugation of a cyclic polymer, poly(ethylene glycol) (PEG), to a model protein, T4 lysozyme, containing a single engineered cysteine residue (V131C). We compare the stability and activity of this conjugate with those of a linear PEG-T4 lysozyme analogue of similar molecular weight. Furthermore, we used molecular dynamics (MD) simulations to determine the behavior of the polymer-protein conjugates in solution. We introduce cyclic polymer-protein conjugates as potential candidates for the improvement of biologic therapeutics.

Through mechanistic work and rational design, we have developed the fastest organometallic abiotic Cys bioconjugation. As a result, the developed organometallic Au(III) bioconjugation reagents enable selective labeling of Cys moieties down to picomolar concentrations and allow for the rapid construction of complex heterostructures from peptides, proteins, and oligonucleotides. This work showcases how organometallic chemistry can be interfaced with biomolecules and lead to a range of reactivities that are largely unmatched by classical organic chemistry tools.

BACKGROUND: Amyloidosis, a rare multisystem condition, often requires complex, multidisciplinary care. Its low prevalence underscores the importance of efforts to ensure the availability of high-quality patient education materials for better outcomes. ChatGPT (OpenAI) is a large language model powered by artificial intelligence that offers a potential avenue for disseminating accurate, reliable, and accessible educational resources for both patients and providers. Its user-friendly interface, engaging conversational responses, and the capability for users to ask follow-up questions make it a promising future tool in delivering accurate and tailored information to patients. OBJECTIVE: We performed a multidisciplinary assessment of the accuracy, reproducibility, and readability of ChatGPT in answering questions related to amyloidosis. METHODS: In total, 98 amyloidosis questions related to cardiology, gastroenterology, and neurology were curated from medical societies, institutions, and amyloidosis Facebook support groups and inputted into ChatGPT-3.5 and ChatGPT-4. Cardiology- and gastroenterology-related responses were independently graded by a board-certified cardiologist and gastroenterologist, respectively, who specialize in amyloidosis. These 2 reviewers (RG and DCK) also graded general questions for which disagreements were resolved with discussion. Neurology-related responses were graded by a board-certified neurologist (AAH) who specializes in amyloidosis. Reviewers used the following grading scale: (1) comprehensive, (2) correct but inadequate, (3) some correct and some incorrect, and (4) completely incorrect. Questions were stratified by categories for further analysis. Reproducibility was assessed by inputting each question twice into each model. The readability of ChatGPT-4 responses was also evaluated using the Textstat library in Python (Python Software Foundation) and the Textstat readability package in R software (R Foundation for Statistical Computing). RESULTS: ChatGPT-4 (n=98) provided 93 (95%) responses with accurate information, and 82 (84%) were comprehensive. ChatGPT-3.5 (n=83) provided 74 (89%) responses with accurate information, and 66 (79%) were comprehensive. When examined by question category, ChatGTP-4 and ChatGPT-3.5 provided 53 (95%) and 48 (86%) comprehensive responses, respectively, to general questions (n=56). When examined by subject, ChatGPT-4 and ChatGPT-3.5 performed best in response to cardiology questions (n=12) with both models producing 10 (83%) comprehensive responses. For gastroenterology (n=15), ChatGPT-4 received comprehensive grades for 9 (60%) responses, and ChatGPT-3.5 provided 8 (53%) responses. Overall, 96 of 98 (98%) responses for ChatGPT-4 and 73 of 83 (88%) for ChatGPT-3.5 were reproducible. The readability of ChatGPT-4s responses ranged from 10th to beyond graduate US grade levels with an average of 15.5 (SD 1.9). CONCLUSIONS: Large language models are a promising tool for accurate and reliable health information for patients living with amyloidosis. However, ChatGPTs responses exceeded the American Medical Associations recommended fifth- to sixth-grade reading level. Future studies focusing on improving response accuracy and readability are warranted. Prior to widespread implementation, the technologys limitations and ethical implications must be further explored to ensure patient safety and equitable implementation.

Culture is ubiquitous and plays a significant role in student knowledge development and reading comprehension. Therefore, the purpose of this review was to investigate how culture is considered within reading comprehension interventions for students with learning disabilities (LD) from culturally and linguistically diverse backgrounds. Through a search of five prominent academic journals focusing on LD, we identified 41 studies related to reading comprehension interventions. We coded studies for evidence of culturally responsive pedagogy (CRP) as well as discussion of culture within the manuscript. Findings revealed that while many studies featured evidence-based instructional strategies, researchers often did not explicitly reference culture within their interventions or discuss culture when reporting results. An analysis of studies reporting the use of CRP revealed strategies that value students' linguistic backgrounds and lived experiences. Limitations and implications are discussed, and a call to action in future research is presented.

Abstract Background Inflammation and neurohormonal activation play a significant role in the adverse outcome seen in acute myocardial infarction (AMI) and the development of cardiogenic shock (CS), which is associated with a mortality rate up to 50%. Treatment with anti-inflammatory drugs such as tocilizumab, an interleukin-6 receptor antagonist, has been shown to reduce troponin release and reduce the myocardial infarct size in AMI patients and it may therefore have cardioprotective properties. Methods This is a double-blind, placebo-controlled, single-center randomized clinical trial, including adult AMI patients without CS at hospital arrival, undergoing percutaneous coronary intervention (PCI) within 24 h from symptom onset, and at intermediate to high risk of developing CS (ORBI risk score ≥ 10). A total of 100 participants will be randomized to receive a single intravenous dose of tocilizumab (280 mg) or placebo (normal saline). The primary outcome is peak plasma pro-B-type natriuretic peptide (proBNP) within 48 h, assessed using serial measurements at intervals: before infusion, 12, 24, 36, and 48 h after infusion. Secondary endpoints include the following: (1) cardiac magnetic resonance imaging (CMR) during 24–48 h after admission and at follow-up after 3 months with assessment of left ventricular area at risk, final infarct size, and the derived salvage index and (2) biochemical markers of inflammation (C-reactive protein and leukocyte counts) and cardiac injury (troponin T and creatinine kinase MB). Discussion Modulation of interleukin-6-mediated inflammation in patients with AMI, treated with acute PCI, and at intermediate to high risk of in-hospital CS may lead to increased hemodynamic stability and reduced left ventricular infarct size, which will be assessed using blood biomarkers with proBNP as the primary outcome and inflammatory markers, troponin T, and CMR with myocardial salvage index as the secondary endpoints. Trial registration Registered with the Regional Ethics Committee (H-21045751), EudraCT (2021–002028-19), ClinicalTrials.gov (NCT05350592). Study registration date: 2022-03-08, Universal Trial Number U1111-1277–8523.

Abstract Background Cardiogenic shock (CS) occurs in 5–10% of patients with acute myocardial infarction (AMI), and the condition is associated with a 30-day mortality rate of up to 50%. Most of the AMI patients are in SCAI SHOCK stage B upon hospital arrival, but some of these patients will progression through the stages to overt shock (SCAI C-E). Around one third of patients who develop CS are not in shock at the time of hospital admission. Pro-B-type natriuretic peptide (proband) is a biomarker closely related to CS development. The aim of this study is to investigate the potential for preventing progression of hemodynamic instability by early inotropic support with low-dose dobutamine infusion administrated after revascularization in AMI patients with intermediate to high risk of in-hospital CS development. Methods This investigator-initiated, double-blinded, placebo-controlled, randomized, single-center, clinical trial will include 100 AMI patients (≥ 18 years) without CS at hospital admission and at intermediate-high risk of in-hospital CS development (ORBI risk score ≥ 10). Patients will be randomized in a 1:1 ratio to a 24 h intravenous (IV) infusion of dobutamine (5 μg/kg/min) or placebo (NaCl) administrated after acute percutaneous coronary intervention (PCI) (

Abstract Finalization of eukaryotic nuclear DNA replication relies on DNA ligase 1 (LIG1) to seal DNA nicks generated during Okazaki Fragment Maturation (OFM). Using a mutational reporter in Saccharomyces cerevisiae, we previously showed that mutation of the high-fidelity magnesium binding site of LIG1Cdc9 strongly increases the rate of single-base insertions. Here we show that this rate is increased across the nuclear genome, that it is synergistically increased by concomitant loss of DNA mismatch repair (MMR), and that the additions occur in highly specific sequence contexts. These discoveries are all consistent with incorporation of an extra base into the nascent lagging DNA strand that can be corrected by MMR following mutagenic ligation by the Cdc9-EEAA variant. There is a strong preference for insertion of either dGTP or dTTP into 3–5 base pair mononucleotide sequences with stringent flanking nucleotide requirements. The results reveal unique LIG1Cdc9-dependent mutational motifs where high fidelity DNA ligation of a subset of OFs is critical for preventing mutagenesis across the genome.

Assessment of predictive values of clinical symptoms for COVID-19 diagnosis in young adults. Participants: Nonresidential university students (ages 18-25) participating in surveillance testing and mandatory symptom survey between 9/9/2020 and 11/25/2020. Methods: Retrospective study of test results and symptom survey data. Results: Among 6,489 individuals, 288 (4.4%) tested positive for COVID-19, 90 (31.3%) of whom reported symptoms. COVID-19 prevalence among individuals reporting and not reporting symptoms was 17.2% and 3.3%, respectively. The four symptoms with highest positive predictive values (PPVs) were smell/taste loss (PPV = 38.5%), chills (PPV = 31.5%), muscle/joint pain (PPV = 26.0%), and fever (PPV = 25.9%). Conclusions: Institutions should emphasize COVID-19 risk for highly predictive symptoms in public health messaging to inform individuals on when to seek testing or self-isolation. However, low COVID-19 diagnostic accuracy of clinical symptoms and the high pre-symptomatic/asymptomatic rate (69%) highlight the limitations of voluntary testing strategies employed by higher education institutions during the original strain of SARS-CoV-2.

For many professors, testing is primarily a tool for assessing the learning of students. However, research into the "testing effect" has established the value of testing also as a learning tool, not just as an assessment tool. This article provides an overview of this research and also of my own experiences in using a variety of testing approaches. Based on these experiences, the article offers a process for adopting testing as a learning tool, along with a review of design choices. By increasing their use of testing in business law instruction, business law professors will improve learning.

BACKGROUND & AIMS: Anorectal manometry (ARM) is a comprehensive diagnostic tool for evaluating patients with constipation, fecal incontinence, or anorectal pain; however, it is not widely utilized for reasons that remain unclear. The aim of this roundtable discussion was to critically examine the current clinical practices of ARM and biofeedback therapy by physicians and surgeons in both academic and community settings. METHODS: Leaders in medical and surgical gastroenterology and physical therapy with interest in anorectal disorders were surveyed regarding practice patterns and utilization of these technologies. Subsequently, a roundtable was held to discuss survey results, explore current diagnostic and therapeutic challenges with these technologies, review the literature, and generate consensus-based recommendations. RESULTS: ARM identifies key pathophysiological abnormalities such as dyssynergic defecation, anal sphincter weakness, or rectal sensory dysfunction, and is a critical component of biofeedback therapy, an evidence-based treatment for patients with dyssynergic defecation and fecal incontinence. Additionally, ARM has the potential to enhance health-related quality of life and reduce healthcare costs. However, it has significant barriers that include a lack of education and training of healthcare providers regarding the utility and availability of ARM and biofeedback procedures, as well as challenges with condition-specific testing protocols and interpretation. Additional barriers include understanding when to perform, where to refer, and how to use these technologies, and confusion over billing practices. CONCLUSIONS: Overcoming these challenges with appropriate education, training, collaborative research, and evidence-based guidelines for ARM testing and biofeedback therapy could significantly enhance patient care of anorectal disorders.

Start Strong, a 4-week culinary nutrition education and obesity prevention program designed for rural family care providers in low-income areas of Minnesota, was initially an in-person training program and was recently adapted into a virtual version. Using a quasi-experimental design, this study examined within-group and between-group (in-person versus virtual) changes in culinary skill confidence and familiarity with food assistance programs after Start Strong participation. Additionally, we examined post-program participant experiences. The in-person program (n = 12, mean age of 45 years, September 2019) took place at community locations. The virtual program (n = 27, mean age of 41 years, Fall 2021–Winter 2022) used online learning and videoconferencing. Following data collection pre- and post-program, we used t-tests to examine within-group changes after Start Strong participation, repeated measures analysis of variance tests to compare outcomes between the in-person and virtual implementations, and Fisher’s exact test to compare post-survey outcomes. The in-person and virtual programs demonstrated similar improvements in cooking skill confidence and familiarity with food assistance programs. Compared to the virtual program, in-person participants reported significantly greater connection with other providers. This evaluation is relevant to addressing disparities in obesity prevention and provides an initial model for public health and community partnerships with ECE providers.