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Quantum mechanics is counterintuitive, difficult to visualize, mathematically challenging, and abstract. The Physics Education Technology (PhET) Project now includes 18 simulations on quantum mechanics designed to improve the learning of this subject. These simulations include several key features to help students build mental models and intuition about quantum mechanics: visual representations of abstract concepts and microscopic processes that cannot be directly observed, interactive environments that directly couple students' actions to animations, connections to everyday life, and efficient calculations so that students can focus on the concepts rather than the mathematics. Like all PhET simulations, these are developed using the results of research and feedback from educators, and are tested in student interviews and classroom studies. This article provides an overview of the PhET quantum simulations and their development. We also describe research demonstrating their effectiveness and discuss some insights about student thinking. [DOI: 10.1119/1.2885199]

We first present the results of follow-up photometric observations of the He-rich hot B subdwarf LS Tv-14° 116, which confirm the presence of multiperiodic luminosity variations in the light curve of this star. Rather surprisingly, no other follow-up observations of this kind seem to have been published after the initial suggestion in 2005 that LS IV-l4° 116 could be a pulsating star of a new kind. We were able to extract from our data at least six significant periodicities ranging from 1954 s to 5084 s, including the two oscillations uncovered previously. We also present the results of an analysis combining a high signal-to-noise optical spectrum of LS IV- 14° 116 with recently developed non-local thermodynamic equilibrium model atmospheres and synthetic spectra. Our best estimates of the atmospheric parameters of this star are Teff = 34950 ± 250 K, log g = 5.93 ± 0.04, and log N(He)/N(H) = -0.62 ± 0.03 (formal fitting errors only). These place LS tv-14° 116 very near the region of maximum instability in the Teff log g plane for short-period p-mode pulsators of the hot subdwarf type. If the luminosity variations are indeed due to pulsations, then LS IV-14° 116 poses a real challenge to current theory: how can such long observed periods (which would have to be associated with medium- to high-order g-modes) be excited at such a high effective temperature and surface gravity, while the short-period p-modes, more typically excited in this domain, are not observed in this particular star? [ABSTRACT FROM AUTHOR]

The use of symbolic calculators such as MATHEMATICA is becoming more commonplace among upper level physics students. The presence of such powerful calculators can couple strongly to the type of mathematical reasoning students employ. These tools do not merely offer students a convenient way to perform the calculations they would have otherwise done by hand. We present examples from the work of upper level physics majors where MATHEMATICA plays an active role in focusing and sustaining their thoughts around calculation. These students still engage in powerful mathematical reasoning while they calculate, but struggle because of the narrowed breadth of their thinking. We model MATHEMATICA'S influence as an integral part of the constant feedback that occurs in how students frame, and hence focus, their work. [ABSTRACT FROM AUTHOR]

Significance: Spatial frequency domain imaging (SFDI) applies patterned near-infrared illumination to quantify the optical properties of subsurface tissue. The periocular region is unique due to its complex ocular adnexal anatomy. Although SFDI has been successfully applied to relatively flat in vivo tissues, regions that have significant height variations and curvature may result in optical property inaccuracies., Aim: We characterize the geometric impact of the periocular region on SFDI imaging reliability., Approach: SFDI was employed to measure the reduced scattering coefficient ( μ s ' ) and absorption coefficient ( μ a ) of the periocular region in a cast facial tissue-simulating phantom by capturing images along regions of interest (ROIs): inferior temporal quadrant (ITQ), inferior nasal quadrant (INQ), superior temporal quadrant (STQ), central eyelid margin (CEM), rostral lateral nasal bridge (RLNB), and forehead (FH). The phantom was placed on a chin rest and imaged nine times from an "en face" or "side profile" position, and the flat back of the phantom was measured 15 times., Results: The measured μ a and μ s ' of a cast facial phantom are accurate when comparing the ITQ, INQ, STQ, and FH to its flat posterior surface. Paired t tests of ITQ, INQ, STQ, and FH μ a and μ s ' concluded that there is not enough evidence to suggest that imaging orientation impacted the measurement accuracy. Regions of extreme topographical variation, i.e., CEM and RLNB, did exhibit differences in measured optical properties., Conclusions: We are the first to evaluate the geometric implications of wide-field imaging along the periocular region using a solid tissue-simulating facial phantom. Results suggest that the ITQ, INQ, STQ, and FH of a generalized face have minimal impact on the SFDI measurement accuracy. Areas with heightened topographic variation exhibit measurement variability. Device and facial positioning do not appear to bias measurements. These findings confirm the need to carefully select ROIs when measuring optical properties along the periocular region., (© 2024 The Authors.)

Cardiac magnetic resonance imaging (CMR) became over the last 30 years an essential tool in the management of patients with myocarditis. Noninvasive diagnosis of acute myocarditis relies on a clinical picture compatible with myocarditis and fulfilling of the updated 2018 Lake Louise criteria. These criteria include highlights of myocardial edema by conventional T2-weighted sequences or by T2 mapping in one hand and evidence of myocardial injury using late gadolinium enhancement sequences, T1 mapping or extra-cellular volume measurement in the other hand. It is recommended to perform basal examination in the 2 or 3 weeks following acute episode and to repeat CMR during follow-up. The literature reports excellent diagnostic accuracy, between 80% and 90%, making CMR a robust and reliable noninvasive alternative to endomyocardial biopsy. Besides, beyond its diagnostic performance, CMR can also help to identify patients with unfavourable long-term outcome. For instance, medio-ventricular and septal location of late gadolinium enhancement, degree of late gadolinium enhancement extent or high T2 mapping values are independent predictive factors of major cardio-vascular events., Competing Interests: Déclaration de liens d'intérêts Les auteurs déclarent n'avoir aucun lien d'intérêt., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Importance: Age-related macular degeneration (AMD) is a common cause of irreversible vision loss among individuals older than 50 years. Although considerable advances have been made in our understanding of AMD genetics, the differential effects of major associated loci on disease manifestation and progression may not be well characterized., Objective: To elucidate the specific associations of the 2 most common genetic risk loci for AMD, the CFH-CFHR5 locus on chromosome 1q32 (Chr1) and the ARMS2/HTRA1 locus on chromosome 10q26 (Chr10)-independent of one another and in combination-with time to conversion to late-stage disease and to visual acuity loss., Design, Setting, and Participants: This case series study included 502 individuals who were homozygous for risk variants at both Chr1 and Chr10 (termed Chr1&10-risk) or at either Chr1 (Chr1-risk) or Chr10 (Chr10-risk) and who had enrolled in Genetic and Molecular Studies of Eye Diseases at the Sharon Eccles Steele Center for Translational Medicine between September 2009 and March 2020. Multimodal imaging data were reviewed for AMD staging, including grading of incomplete and complete retinal pigment epithelium and outer retinal atrophy., Main Outcomes and Measures: Hazard ratios and survival times for conversion to any late-stage AMD, atrophic or neovascular, and associated vision loss of 2 or more lines., Results: In total, 317 participants in the Chr1-risk group (median [IQR] age at first visit, 75.6 [69.5-81.7] years; 193 women [60.9%]), 93 participants in the Chr10-risk group (median [IQR] age at first visit, 77.5 [72.2-84.2] years; 62 women [66.7%]), and 92 participants in the Chr1&10-risk group (median [IQR] age at first visit, 71.7 [68.0-76.3] years; 62 women [67.4%]) were included in the analyses. After adjusting for age and AMD grade at first visit, compared with 257 participants in the Chr1-risk group, 56 participants in the Chr1&10-risk group (factor of 3.3 [95% CI, 1.6-6.8]; P < .001) and 58 participants in the Chr10-risk group (factor of 2.6 [95% CI, 1.3-5.2]; P = .007) were more likely to convert to a late-stage phenotype during follow-up. This difference was mostly associated with conversion to macular neovascularization, which occurred earlier in participants with Chr1&10-risk and Chr10-risk. Eyes in the Chr1&10-risk group (median [IQR] survival, 5.7 [2.1-11.1] years) were 2.1 (95% CI, 1.1-3.9; P = .03) times as likely and eyes in the Chr10-risk group (median [IQR] survival, 6.3 [2.7-11.3] years) were 1.8 (95% CI, 1.0-3.1; P = .05) times as likely to experience a visual acuity loss of 2 or more lines compared with eyes of the Chr1-risk group (median [IQR] survival, 9.4 [4.1-* (asterisk indicates event rate did not reach 75%)] years)., Conclusions and Relevance: These findings suggest differential associations of the 2 major AMD-related risk loci with structural and functional disease progression and suggest distinct underlying biological mechanisms associated with these 2 loci. These genotype-phenotype associations may warrant consideration when designing and interpreting AMD research studies and clinical trials.

Human pluripotent stem cells (hPSCs), such as induced pluripotent stem cells (iPSCs), hold great promise for drug discovery, toxicology studies, and regenerative medicine. Here, we describe standardized protocols and experimental procedures that combine automated cell culture for scalable production of hPSCs with quantitative high-throughput screening (qHTS) in miniaturized 384-well plates. As a proof of principle, we established dose-response assessments and determined optimal concentrations of 12 small molecule compounds that are commonly used in the stem cell field. Multi-parametric analysis of readouts from diverse assays including cell viability, mitochondrial membrane potential, plasma membrane integrity, and ATP production was used to distinguish normal biological responses from cellular stress induced by small molecule treatment. Collectively, the establishment of integrated workflows for cell manufacturing, qHTS, high-content imaging, and data analysis provides an end-to-end platform for industrial-scale projects and should leverage the drug discovery process using hPSC-derived cell types., (© 2021. Springer Science+Business Media, LLC.)

This chapter was inadvertently published with an error, the ninth point under 'Materials' section must read., (© 2021. Springer Science+Business Media, LLC.)

Efficient translation of human induced pluripotent stem cells (hiPSCs) requires scalable cell manufacturing strategies for optimal self-renewal and functional differentiation. Traditional manual cell culture is variable and labor intensive, posing challenges for high-throughput applications. Here, we established a robotic platform and automated all essential steps of hiPSC culture and differentiation under chemically defined conditions. This approach allowed rapid and standardized manufacturing of billions of hiPSCs that can be produced in parallel from up to 90 different patient- and disease-specific cell lines. Moreover, we established automated multi-lineage differentiation and generated functional neurons, cardiomyocytes, and hepatocytes. To validate our approach, we compared robotic and manual cell culture operations and performed comprehensive molecular and cellular characterizations (e.g., single-cell transcriptomics, mass cytometry, metabolism, electrophysiology) to benchmark industrial-scale cell culture operations toward building an integrated platform for efficient cell manufacturing for disease modeling, drug screening, and cell therapy., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Frailty is common and is associated with increased mortality, lower quality of life, and higher readmission rates in cirrhotic patients. Not only are these outcomes important, but further understanding the impact of frailty on a caregiver's life is crucial to better comprehend caregiver burden in cirrhotic patients and develop strategies to improve care for patients and their caregivers., Methods: A single-center, prospective study was conducted of cirrhotic patients and their caregivers between 4/1/2019 and 11/1/2019. Frailty testing combined aspects from the Fried Frailty Instrument, Short Physical Performance Battery, and activities of daily living. Caregivers completed questionnaires to evaluate caregiver burden using the Zarit Burden Interview (ZBI-12), and perceived social support, using the Interpersonal Support Evaluation List., Results: In total, 94 cirrhotic patients were included, 50% males with a median age of 63.1 years. The most common etiology of cirrhosis was nonalcoholic steatohepatitis. Frailty was prevalent (45.1%). In total, 12.8% of caregivers reported a high burden based on ZBI-12. There was no association between frailty and caregiver burden, hospitalization rates, or death. However, frailty was associated with a higher number of outpatient GI visits (p = 0.002). Lower perceived social support among caregivers was associated with a higher caregiver burden (p < 0.0001)., Conclusion: Frailty is prevalent in cirrhotic patients but is not associated with higher rates of caregiver burden. Low perceived social support among caregivers, however, was associated with higher caregiver burden. It is important to recognize the impact of caregiver burden on caregivers of cirrhotic patients and ensure caregivers have the appropriate support to mitigate burden., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Eczema herpeticum (EH) is a rare complication of atopic dermatitis (AD) caused by disseminated herpes simplex virus (HSV) infection. The role of rare and/or deleterious genetic variants in disease etiology is largely unknown. This study aimed to identify genes that harbor damaging genetic variants associated with HSV infection in AD with a history of recurrent eczema herpeticum (ADEH+)., Methods: Whole genome sequencing (WGS) was performed on 49 recurrent ADEH+ (≥3 EH episodes), 491 AD without a history of eczema herpeticum (ADEH-) and 237 non-atopic control (NA) subjects. Variants were annotated, and a gene-based approach (SKAT-O) was used to identify genes harboring damaging genetic variants associated with ADEH+. Genes identified through WGS were studied for effects on HSV responses and keratinocyte differentiation., Results: Eight genes were identified in the comparison of recurrent ADEH+to ADEH-and NA subjects: SIDT2, CLEC7A, GSTZ1, TPSG1, SP110, RBBP8NL, TRIM15, and FRMD3. Silencing SIDT2 and RBBP8NL in normal human primary keratinocytes (NHPKs) led to significantly increased HSV-1 replication. SIDT2-silenced NHPKs had decreased gene expression of IFNk and IL1b in response to HSV-1 infection. RBBP8NL-silenced NHPKs had decreased gene expression of IFNk, but increased IL1b. Additionally, silencing SIDT2 and RBBP8NL also inhibited gene expression of keratinocyte differentiation markers keratin 10 (KRT10) and loricrin (LOR)., Conclusion: SIDT2 and RBBP8NL participate in keratinocyte's response to HSV-1 infection. SIDT2 and RBBP8NL also regulate expression of keratinocyte differentiation genes of KRT10 and LOR., (© 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Human pluripotent stem cells (hPSCs) are capable of extensive self-renewal yet remain highly sensitive to environmental perturbations in vitro, posing challenges to their therapeutic use. There is an urgent need to advance strategies that ensure safe and robust long-term growth and functional differentiation of these cells. Here, we deployed high-throughput screening strategies to identify a small-molecule cocktail that improves viability of hPSCs and their differentiated progeny. The combination of chroman 1, emricasan, polyamines, and trans-ISRIB (CEPT) enhanced cell survival of genetically stable hPSCs by simultaneously blocking several stress mechanisms that otherwise compromise cell structure and function. CEPT provided strong improvements for several key applications in stem-cell research, including routine cell passaging, cryopreservation of pluripotent and differentiated cells, embryoid body (EB) and organoid formation, single-cell cloning, and genome editing. Thus, CEPT represents a unique poly-pharmacological strategy for comprehensive cytoprotection, providing a rationale for efficient and safe utilization of hPSCs.

Human induced pluripotent stem cell (hiPSC) lines have previously been generated through the NHLBI sponsored NextGen program at nine individual study sites. Here, we examined the structural integrity of 506 hiPSC lines as determined by copy number variations (CNVs). We observed that 149 hiPSC lines acquired 258 CNVs relative to donor DNA. We identified six recurrent regions of CNVs on chromosomes 1, 2, 3, 16 and 20 that overlapped with cancer associated genes. Furthermore, the genes mapping to regions of acquired CNVs show an enrichment in cancer related biological processes (IL6 production) and signaling cascades (JNK cascade & NFκB cascade). The genomic region of instability on chr20 (chr20q11.2) includes transcriptomic signatures for cancer associated genes such as ID1, BCL2L1, TPX2, PDRG1 and HCK. Of these HCK shows statistically significant differential expression between carrier and non-carrier hiPSC lines. Overall, while a low level of genomic instability was observed in the NextGen generated hiPSC lines, the observation of structural instability in regions with known cancer associated genes substantiates the importance of systematic evaluation of genetic variations in hiPSCs before using them as disease/research models., Competing Interests: Declarations of Competing Interest None., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)