Search

Our recent success in exploiting graphical processing units (GPUs) to accelerate quantum chemistry computations led to the development of the ab initio nanoreactor, a computational framework for automatic reaction discovery and kinetic model construction. In this work, we apply the ab initio nanoreactor to methane pyrolysis, from automatic reaction discovery to path refinement and kinetic modeling. Elementary reactions occurring during methane pyrolysis are revealed using GPU-accelerated ab initio molecular dynamics simulations. Subsequently, these reaction paths are refined at a higher level of theory with optimized reactant, product, and transition state geometries. Reaction rate coefficients are calculated by transition state theory based on the optimized reaction paths. The discovered reactions lead to a kinetic model with 53 species and 134 reactions, which is validated against experimental data and simulations using literature kinetic models. We highlight the advantage of leveraging local brute force and Monte Carlo sensitivity analysis approaches for efficient identification of important reactions. Both sensitivity approaches can further improve the accuracy of methane pyrolysis kinetic model. The results in this work demonstrate the power of the ab initio nanoreactor framework for computationally affordable systematic reaction discovery and accurate kinetic modeling.

Summary Objective In knee cartilage from patients with osteoarthritis (OA), both preserved cartilage and damaged cartilage are observed. In this study, we aim to compare preserved with damaged cartilage to identify the molecule(s) that may be responsible for the mechanical loading-induced differences within cartilage degradation. Methods Preserved and damaged cartilage were harvested from the same OA knee joint. RNA Sequencing was performed to examine the transcriptomic differences between preserved and damaged cartilage cells. Estrogen receptor-α (ERα) was identified, and its function of was tested through gene knockin and knockout. The role of ERα in mediating chondrocyte response to mechanical loading was examined via compression of chondrocyte-laded hydrogel in a strain-controlled manner. Findings from the studies on human samples were verified in animal models. Results Level of estrogen receptor α (ERα) was significantly reduced in damaged cartilage compared to preserved cartilage, which were observed in both human and mice samples. Knockdown of ESR1, the gene encoding ERα, resulted in an upregulation of senescence- and OA-relevant markers in chondrocytes. Conversely, knockin of ESR1 partially reversed the osteoarthritic and senescent phenotype of OA chondrocytes. Using a three-dimensional (3D) culture model, we demonstrated that mechanical overload significantly suppressed ERα level in chondrocytes with concomitant upregulation of osteoarthritic phenotype. When ESR1 expression was suppressed, mechanical loading enhanced hypertrophic and osteogenic transition. Conclusion Our study demonstrates a new estrogen-independent role of ERα in mediating chondrocyte phenotype and its response to mechanical loading, and suggests that enhancing ERα level may represent a new method to treat osteoarthritis.

Background: Conflict has deleterious effects on the adjustment of children, adolescence, and emerging adults. The literature is less robust on the adverse effects of conflict avoidance on adjustment as well as the beneficial effect of resolution in these age groups. The literature is markedly sparser on these relationships in adults. Method: We recruited N = 1471 US adults between 18 and 86 years old ( M = 33.94, SD = 11.67). They primarily identified as White with 51% holding at least a bachelor’s degree. Participants responded to the Perceived Family Conflict Subscale, Avoidant Conflict Scale, the Family Conflict Resolution Scale, and the Langner Symptom Survey. Results: A MANOVA modeling the four variables demonstrated a significant difference based on sex for the measure of distress and need for treatment ( Mwomen = 5.31, Mmen = 3.93, p < .001). Separate analyses for men and women yielded the same pattern for each sex. Specifically, low conflict groups, as well as low conflict avoidance groups, scored significantly lower on a measure of distress than the high conflict and conflict avoidance group. For conflict resolution, the high groups scored significantly lower on distress than did the low resolution group. Discussion: The deleterious effect of conflict and conflict avoidance were found in both adult men and women, thereby extending results found in children, teens, and young adults. Similarly, the beneficial effect of conflict resolution manifest in adult men and women, which had been found in young adults. Interventions aimed at reducing conflict avoidance and increasing conflict resolution skills should theoretically reduce stress.

The mental health care system in the United States is fractured and disjointed with temporary and inadequate services for people to receive care. Inequities in care and treatment may be understood by historical policies rooted in structural trauma, herein defined as a functional, organizational tool of violence worsening the impact of traumatic experience on specific vulnerable populations by design, creating the inequities in care and treatment that exist to this day. Those most affected by structural trauma are at a social disadvantage when accessing or attempting to access mental health care services. Although the US mental health care system is universally challenging to navigate as it operates today, it is even more so for the vulnerable and disadvantaged who need access to resources and services. In this article, we describe the current system of how people in the US currently receive mental health care, provide examples of promising new models of care, and propose solutions for addressing the barriers to equitable care. [ Psychiatr Ann . 2021;51(11):516–521.]

Species Sensitivity Distribution (SSD) is a key metric for understanding the potential ecotoxicological impacts of chemicals. However, SSDs have been developed to estimate for only handful of chemicals due to the scarcity of experimental toxicity data. Here we present a novel approach to expand the chemical coverage of SSDs using Artificial Neural Network (ANN). We collected over 2000 experimental toxicity data in Lethal Concentration 50 (LC50) for 8 aquatic species and trained an ANN model for each of the 8 aquatic species based on molecular structure. The R2 values of resulting ANN models range from 0.54 to 0.75 (median R2 = 0.69). We applied the predicted LC50 values to fit SSD curves using bootstrapping method, generating SSDs for 8424 chemicals in the ToX21 database. The dataset is expected to serve as a screening-level reference SSD database for understanding potential ecotoxicological impacts of chemicals.

Significant cellular senescence has been observed in cartilage harvested from patients with osteoarthritis (OA). In this study, we aim to develop a senescence-relevant OA-like cartilage model for developing disease-modifying OA drugs (DMOADs). Specifically, human bone marrow-derived mesenchymal stromal cells (MSCs) were expanded in vitro up to passage 10 (P10-MSCs). Following their senescent phenotype formation, P10-MSCs were subjected to pellet culture in chondrogenic medium. Results from qRT-PCR, histology, and immunostaining indicated that cartilage generated from P10-MSCs displayed both senescent and OA-like phenotypes without using other OA-inducing agents, when compared to that from normal passage 4 (P4)-MSCs. Interestingly, the same gene expression differences observed between P4-MSCs and P10-MSC-derived cartilage tissues were also observed between the preserved and damaged OA cartilage regions taken from human samples, as demonstrated by RNA Sequencing data and other analysis methods. Lastly, the utility of this senescence-initiated OA-like cartilage model in drug development was assessed by testing several potential DMOADs and senolytics. The results suggest that pre-existing cellular senescence can induce the generation of OA-like changes in cartilage. The P4- and P10-MSCs derived cartilage models also represent a novel platform for predicting the efficacy and toxicity of potential DMOADs on both preserved and damaged cartilage in humans.

Genetically modified organisms (GMOs) or genetically modified technology is currently considered an “excluded method” not allowed to be used in, or added to, organic agricultural products under the US Code of Federal Regulations. Despite evidence that GMOs may serve as a safe alternative to conventional crops, they are frequently associated with harmful and unsustainable agricultural practices. We discuss the economic, environmental, nutritional, and food safety concerns of GMOs in organic agriculture, and how GMO technology could benefit it. We propose (1) allowing the use of genetic modification in organic agriculture and (2) an enhanced effort to disseminate science-based information to consumers.

Although the depression and anxiety subscales (DASS-D and DASS-A) of the 21-item Depression, Anxiety, and Stress Scales are commonly used in adolescents, few studies have investigated the convergent validity of/potential cutoff scores for these subscales in U.S. adolescents. To address these gaps, 306 U.S. adolescents completed the DASS-21, Generalized Anxiety Disorder-7 scale (GAD7), and Center for Epidemiological Studies-Depression Scale (CESD). The DASS-D and CESD were strongly correlated, while the DASS-A and GAD7 were strongly correlated in males and more moderately correlated in females. Using the CESD as reference, DASS-D cutoff scores of four for males and five for females provided the best balance of sensitivity and specificity. When using the GAD7 as reference, DASS-A cutoffs of six for females and five for males appeared best. These findings suggest the DASS-A and DASS-D demonstrate good convergent validity and may be suitable for identifying adolescents who are significantly anxious and/or depressed.

While the 21-item version of the Depression, Anxiety, and Stress Scales (DASS-21) is commonly used to measure depression, anxiety, and stress, there is emerging evidence that the DASS-21 total score can be used as a measure of distress in adolescents as well. However, little research has investigated the convergent validity of the DASS-21 as a measure of distress, and no studies have examined potential cutoffs for the DASS-21total score in adolescents. To address these gaps, the present study investigated the convergent validity of the DASS-21’s total score and determined preliminary cutoff scores that could be used to identify adolescents that are clinically distressed. After 306 high school students (mean age = 15.35) from midwestern USA high schools completed the DASS-21 and Langner Symptom Survey (LSS), a MANOVA revealed significant sex differences. In light of these differences, analyses were carried out separately for male and female adolescents. These analyses revealed that the DASS-21 total score was significantly correlated with the LSS for males (r = .80) and females (r = .76). When using adolescents’ classification on the LSS as a reference point, a cutoff score of 14 appeared to be best suited for female adolescents (sensitivity = .78; specificity = .74; AUC = .84), while a cutoff score of 17 appeared best for male adolescents (sensitivity = .72; specificity = .95, AUC = .99). These findings suggest that the DASS-21 total score demonstrates good convergent validity as a measure of distress and may be suitable for identifying adolescents that are clinically distressed. However, further validation of the present preliminary cutoff points is needed.

We present a design to actively simulate gravity for crew members traveling to and from Mars combining tested technology with leading research. The Hyperion mission and spacecraft architecture can be the start of the next generation of spacecraft for deep-space, but to truly be the springboard for future deep space transports, it was designed to require no assistance from resupply depots at destination, prioritize human comfort for long duration transits, and have multiple configurations to adjust for the mission. The design is focused around generating artificial gravity by rotating the fixed-distance habitat and variable-distance counterweight about the propellant system in the center (X axis), while each subsystem is individually developed to support this operation. Through various configurations, the Hyperion spacecraft contains the unique ability to adjust to the mission phase for aerobraking and transport needs, making the concept particularly adept at reducing propellant needs, maintaining artificial gravity with minimal power, and keeping the center of mass in line with the thrust vector. This is accomplished using de-spun solar panels, Ion engines for spin-up and orbital maneuvers, an extendable truss for mass balance, and a phased array communication system. Hyperion was designed to meet NASA 2017–18 Revolutionary Aerospace Systems Concepts - Academic Linkage (RASC-AL) requirements of developing an Artificial Gravity Reusable Crewed Deep Space Transport and is expected to cost no more than $3.0B per year over 11 years. It is expected to be operational by 2032.

The triggers that drive interferon-γ (IFNγ)-producing CD8 T cell (Tc1 cell)-mediated autoimmune hepatitis (AIH) remain obscure. Here, we show that lack of hematopoietic Tet methylcytosine dioxygenase 2 (Tet2), an epigenetic regulator associated with autoimmunity, results in the development of microbiota-dependent AIH-like pathology, accompanied by hepatic enrichment of aryl hydrocarbon receptor (AhR) ligand-producing pathobionts and rampant Tc1 cell immunity. We report that AIH-like disease development is dependent on both IFNγ and AhR signaling, as blocking either reverts ongoing AIH-like pathology. Illustrating the critical role of AhR-ligand-producing pathobionts in this condition, hepatic translocation of the AhR ligand indole-3-aldehyde (I3A)-releasing Lactobacillus reuteri is sufficient to trigger AIH-like pathology. Finally, we demonstrate that I3A is required for L. reuteri-induced Tc1 cell differentiation in vitro and AIH-like pathology in vivo, both of which are restrained by Tet2 within CD8 T cells. This AIH-disease model may contribute to the development of therapeutics to alleviate AIH.

SUMMARY Regulatory T cells (Treg cells) are critical mediators of self-tolerance, but they can also limit effective anti-tumor immunity. Although under homeostasis a small fraction of Treg cells in lymphoid organs express the putative checkpoint molecule Tim-3, this protein is expressed by a much larger proportion of tumor-infiltrating Treg cells. Using a mouse model that drives cell-type-specific inducible Tim-3 expression, we show that expression of Tim-3 by Treg cells is sufficient to drive Treg cells to a more effector-like phenotype, resulting in increases in suppressive activity, effector T cell exhaustion, and tumor growth. We also show that T-reg-cell-specific inducible deletion of Tim-3 enhances anti-tumor immunity. Enhancement of Treg cell function by Tim-3 is strongly correlated with increased expression of interleukin-10 (IL-10) and a shift to a more glycolytic metabolic phenotype. Our data demonstrate that Tim-3+ Treg cells may be a relevant therapeutic target cell type for the treatment of cancer., In brief Regulatory T cells (Treg cells) limit the immune response to tumors, and tumor-infiltrating Treg cells are especially suppressive. However, the mechanisms underlying enhanced Treg cell function are poorly understood. Banerjee et al. show that Tim-3 expression is linked to increased Treg cell suppressive activity, possibly through the cytokine IL-10, in mouse models and people with cancer., Graphical Abstract

Cancer-associated fibroblasts (CAFs) constitute a key component of the tumor microenvironment. Pro-tumoral cancer-associated fibroblasts were presumed absent in glioblastoma given the lack of brain fibroblasts. Using single-cell RNA sequencing we identified CAFs in patient GBMs. CAFs were identified using a negative selection strategy to filter endothelial, epithelial, immune cells and pericytes and for the positive expression of previously defined CAF markers. Copy number variation (CNV) analysis was performed to distinguish CAFs from malignant cells. Single-cell spatial transcriptomics from 16 GBM patients confirmed the proximity of CAFs to mesenchymal GBM stem cells (GSCs), endothelial cells, and M2-macrophages. Serial trypsinization of glioblastoma specimens yielded cells with CAF morphology and transcriptomic profile. CAFs were chemotactically attracted to GSCs and CAFs induced GSC proliferation. To identify CAF and GSC interaction mediators, we created a resource of inferred crosstalk by mapping expression of receptors to their cognate ligands, identifying PDGF and TGFB as mediators of GSC effects on CAFs, and osteopontin and HGF as mediators of CAF-induced GSC enrichment. Furthermore, CAFs were found to induce M2-macrophage polarization by producing the EDA fibronectin variant which binds macrophage toll-like receptor 4 (TLR4) in a targetable manner. Glioblastoma CAFs were enriched in the subventricular zone which houses the neural stem cells that houses GSCs. Including CAFs in GSC-derived xenografts induced in vivo tumor growth and reduced survival in two different xenograft models. These findings are among the first to identify glioblastoma CAFs and their GSC interactions, making them an intriguing target for Glioblastomas.

Background While there are known individual-level risk factors for kidney disease at time of type 2 diabetes diagnosis, little is known regarding the role of community context. We evaluated the association of community socioeconomic deprivation (CSD) and community type with estimated glomerular filtration rate (eGFR) when type 2 diabetes is diagnosed. Methods This was a retrospective cohort study of 13,144 adults with newly diagnosed type 2 diabetes in Pennsylvania. The outcome was the closest eGFR measurement within one year prior to and two weeks after type 2 diabetes diagnosis, calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) equation. We used adjusted multinomial regression models to estimate associations of CSD (quartile 1, least deprivation) and community type (township, borough, city) with eGFR and used adjusted generalized estimating equation models to evaluate whether community features were associated with the absence of diabetes screening in the years prior to type 2 diabetes diagnosis. Results Of the participants, 1279 (9.7%) had hyperfiltration and 1377 (10.5%) had reduced eGFR. Women were less likely to have hyperfiltration and more likely to have reduced eGFR. Black (versus White) race was positively associated with hyperfiltration when the eGFR calculation was corrected for race but inversely associated without the correction. Medical Assistance (ever versus never) was positively associated with reduced eGFR. Higher CSD and living in a city were each positively associated (odds ratio [95% confidence interval]) with reduced eGFR (CSD quartiles 3 and 4 versus quartile 1, 1.23 [1.04, 1.46], 1.32 [1.11, 1.58], respectively; city versus township, 1.38 [1.15, 1.65]). These features were also positively associated with the absence of a type 2 diabetes screening measure. Conclusions In a population-based sample, more than twenty percent had hyperfiltration or reduced eGFR at time of type 2 diabetes diagnosis. Individual- and community-level factors were associated with these outcomes., Highlights • Community factors are associated with kidney health at type 2 diabetes diagnosis. • Community factors are associated with type 2 diabetes screening. • Race and kidney health associations differ based on how kidney health is measured. • Men have greater risk of hyperfiltration at type 2 diabetes diagnosis. • Women have greater risk of reduced kidney function at type 2 diabetes diagnosis.

Methods for predicting the performance of rockets are not new, however they often exist only within private organizations and in order to ensure competitive advantage, organizations tend to not share any details about their inner performance models. This open-source method gives students, design-teams and hobbyists a method to obtain baseline approximations for the performance of both single and multi-stage tandem rockets and provides a method which can easily be modified to meet the end-user’s requirements. The method solves for the mass, flight-path angle, velocity, altitude, and down-range distance using a numerical integrator to solve a set of nonlinear ordinary differential equations.

Highlights • Angiogenesis-related genes are important in the aggressive behavior of dedifferentiated chondrosarcoma. • RNA sequencing shows different gene expression in the two components of dedifferentiated chondrosarcoma. • Differences in heat shock protein expression in dedifferentiated chondrosarcoma suggest relevant treatment targets., Dedifferentiated chondrosarcomas (DDCS) are highly malignant bimorphic mesenchymal tumors with poor outcome and limited treatment options. Genes and proteins involved in angiogenesis play an important role in the development of invasion and metastasis. Immunohistochemical stains targeting HSP70, pERK1/2 and VEGFA were applied to a TMA containing 29 DDCS cases representing both tumor components. Higher expression of HSP70 and pERK1/2 was noted in the dedifferentiated component. RNA sequencing performed in 8 paired cases of DDCS comparing well differentiated and dedifferentiated components, showed higher expression of several HSP70 family members and HSP90 in the dedifferentiated component. Furthermore, high mobility group AT-hook 2 (HMAG2) and SET nuclear proto-oncogene demonstrated higher expression in the dedifferentiated component. Thus, the well differentiated and dedifferentiated components of DDCS are different, histologically and transcriptomically. The dedifferentiated component of DDCS shows higher expression of markers that are associated with malignant behavior. Some of these may represent future treatment targets.

Alloimmune responses driven by donor-specific antibodies (DSAs) can lead to antibody-mediated rejection (ABMR) in organ transplantation. Yet, the cellular states underlying alloreactive B cell responses and the molecular components controlling them remain unclear. Using high-dimensional profiling of B cells in a cohort of 96 kidney transplant recipients, we identified expanded numbers of CD27+CD21– activated memory (AM) B cells that expressed the transcription factor T-bet in patients who developed DSAs and progressed to ABMR. Notably, AM cells were less frequent in DSA+ABMR– patients and at baseline levels in DSA– patients. RNA-Seq analysis of AM cells in patients undergoing ABMR revealed these cells to be poised for plasma cell differentiation and to express restricted IGHV sequences reflective of clonal expansion. In addition to T-bet, AM cells manifested elevated expression of interferon regulatory factor 4 and Blimp1, and upon coculture with autologous T follicular helper cells, differentiated into DSA-producing plasma cells in an IL-21–dependent manner. The frequency of AM cells was correlated with the timing and severity of ABMR manifestations. Importantly, T-bet+ AM cells were detected within kidney allografts along with their restricted IGHV sequences. This study delineates a pivotal role for AM cells in promoting humoral responses and ABMR in organ transplantation and highlights them as important therapeutic targets.

Motivation: The availability of databases identifying allergenic proteins via a transparent and consensus-based scientific approach is of prime importance to support the safety review of genetically-modified foods and feeds, and public safety in general. Over recent years, screening for potential new allergens sequences has become more complex due to the exponential increase of genomic sequence information. To address these challenges, an international collaborative scientific group coordinated by the Health and Environmental Sciences Institute (HESI), was tasked to develop a contemporary, adaptable, high-throughput process to build the COMprehensive Protein Allergen REsource (COMPARE) database, a publicly accessible allergen sequence data resource along with bioinformatics analytical tools following guidelines of FAO/WHO and CODEX Alimentarius Commission. Results: The COMPARE process is novel in that it involves the identification of candidate sequences via automated keyword-based sorting algorithm and manual curation of the annotated sequence entries retrieved from public protein sequence databases on a yearly basis; its process is meant for continuous improvement, with updates being transparently documented with each version; as a complementary approach, a yearly key-word based search of literature databases is added to identify new allergen sequences that were not (yet) submitted to protein databases; in addition, comments from the independent peer-review panel are posted on the website to increase transparency of decision making; finally, sequence comparison capabilities associated with the COMPARE database was developed to evaluate the potential allergenicity of proteins, based on internationally recognized guidelines, FAO/WHO and CODEX Alimentarius Commission Availability and Implementation: COMPARE was first released in January 2017 (COMPARE 2017) and updated annually since then. It is publicly available at: http://www.comparedatabase.org. Bioinformatics analytical tools (COMPASS) associated with the COMPARE allergen database is publicly available directly from the database page, or via: https://comparefasta.foodrisk.org/.

Regulatory T cells (Treg) are critical mediators of self-tolerance but can also limit effective anti-tumor immunity. We and others previously reported that 40-60% percent of Treg-infiltrating head and neck cancer (HNC) and other tumors highly express Tim-3, compared with about 5% in lymphoid organs. Tumor-infiltrating Tim-3+ Treg also have enhanced suppressive function and display a more effector-like phenotype. Using a novel mouse model with cell type-specific Tim-3 expression, we show here that expression of Tim-3 by Treg is sufficient to drive Treg to a more effector-like phenotype, resulting in enhanced suppressive activity and increased tumor growth. These findings may help to reconcile previous reports that some Tim-3 antibodies enhance T cell responses in vivo, while expression of Tim-3 has a cell-intrinsic ability to enhance TCR signaling and T cell activation. Thus, we propose that Tim-3 regulates anti-tumor immunity at least in part through enhancement of Treg function. To our knowledge, this is the first example in which expression of a single co-stimulatory molecule is sufficient to drive differentiation of Treg in this manner.

BACKGROUND: Although antibody-mediated rejection (ABMR) has been long recognized as a leading cause of allograft failure after kidney transplantation, the cellular and molecular processes underlying the induction of deleterious donor-specific antibody (DSA) responses remain poorly understood. METHODS: Using high-dimensional flow cytometry, in vitro assays, and RNA sequencing, we concomitantly investigated the role of T follicular helper (T(FH)) cells and B cells during ABMR in 105 kidney transplant recipients. RESULTS: There were 54 patients without DSAs; of those with DSAs, ABMR emerged in 20 patients, but not in 31 patients. We identified proliferating populations of circulating T(FH) cells and activated B cells emerging in blood of patients undergoing ABMR. Although these circulating T(FH) cells comprised heterogeneous phenotypes, they were dominated by activated (ICOS(+)PD-1(+)) and early memory precursor (CCR7(+)CD127(+)) subsets, and were enriched for the transcription factors IRF4 and c-Maf. These circulating T(FH) cells produced large amounts of IL-21 upon stimulation with donor antigen and induced B cells to differentiate into antibody-secreting cells that produced DSAs. Combined analysis of the matched circulating T(FH) cell and activated B cell RNA-sequencing profiles identified highly coordinated transcriptional programs in circulating T(FH) cells and B cells among patients with ABMR, which markedly differed from those of patients who did not develop DSAs or ABMR. The timing of expansion of the distinctive circulating T(FH) cells and activated B cells paralleled emergence of DSAs in blood, and their magnitude was predictive of IgG3 DSA generation, more severe allograft injury, and higher rate of allograft loss. CONCLUSIONS: Patients undergoing ABMR may benefit from monitoring and therapeutic targeting of T(FH) cell–B cell interactions.

Protein structure determines biological function. Accurately conceptualizing 3D protein/ligand structures is thus vital to scientific research and education. Virtual reality (VR) enables protein visualization in stereoscopic 3D, but many VR molecular-visualization programs are expensive and challenging to use; work only on specific VR headsets; rely on complicated model-preparation software; and/or require the user to install separate programs or plugins. Here we introduce ProteinVR, a web-based application that works on various VR setups and operating systems. ProteinVR displays molecular structures within 3D environments that give useful biological context and allow users to situate themselves in 3D space. Our web-based implementation is ideal for hypothesis generation and education in research and large-classroom settings. We release ProteinVR under the open-source BSD-3-Clause license. A copy of the program is available free of charge from http://durrantlab.com/protein-vr/, and a working version can be accessed at http://durrantlab.com/pvr/., Author summary Proteins are microscopic machines that help maintain, defend, and regulate cells. Properly understanding the three-dimensional structures of these machines–as well as the small molecules that interact with them–can advance scientific fields ranging from basic molecular biology to drug discovery. Virtual reality (VR) is a powerful tool for studying protein structures. But many current systems for viewing molecules in VR, though effective, have challenging usability limitations. We have created a new web application called ProteinVR that overcomes these challenges. ProteinVR enables VR molecular visualization in users’ browsers, without requiring them to install a separate program or plugin. It runs on a broad range of desktop, laptop, and mobile devices. For users without VR headsets, ProteinVR leverages mobile-device orientation sensors or video-game-style keyboard navigation to provide an immersive experience. We release ProteinVR as open-source software and have posted a working version at http://durrantlab.com/pvr/.

The findings of Wilshire Phoenix indicate that CME Bitcoin Futures contribute more to price discovery than its related spot markets. Our analysis was performed using similar methodology previously employed by the SEC’s Division of Economic and Risk Analysis to evaluate price formation. CME Bitcoin Futures have grown to become significant, this is not only demonstrated through trading volume and open interest, but also by influence on spot price formation. A leading futures market suggests the existence of a robust base of traders who may trade on such market for many reasons such as trust in the exchange venue and lower latency. Studies on price formation between the spot and futures markets in other asset classes often find that the futures markets lead.

The Family Climate for Road Safety Scale (FCRSS) was developed to measure parenting behaviors specific to the driving context. The original validation study found a scale structure composed of seven factors. However, this structure has not been consistently replicated. Two- and six-factor structures have also been identified. Further, this measure has not been validated in the U.S. and has not been subjected to measurement invariance testing to determine the factor structure's suitability across sex. Additionally, its ability to predict the driving style of emerging adults with varied driving experience has not been directly examined. The current study utilized exploratory and confirmatory factor analytic procedures to identify the factor structure of the FCRSS in a sample of emerging adults in the U.S. The sample consisted of 4392 students recruited from six universities. The sample was predominantly female (68.8 %), and was 83.5 % White, 6.1 % Black or African American, 5.1 % Asian American, 4.6 % biracial or multiracial, 0.4 % American Indian or Alaskan Native, and 0.2 % Pacific Islander or Hawaiian. Results indicated that a five-factor model of the FCRSS provided the best fit to the data compared to one-, two-, six-, and seven-factor models. The five factors identified for the model were: Noncommitment, Monitoring, Feedback, Communication, and Modeling. Further, invariance testing revealed that the five-factor model fit equally well for males and females. Some factors of the FCRSS predicted driving outcomes and driving styles in the expected directions. These findings have implications for family/parenting-based driving interventions for adolescents and young adults.