A Study of Willingness to Participate in the Development of a Global Human Community

The need for the development of a global human community has been outlined in recent literature. This study examined the willingness of individuals to endorse and act upon values embodied in a global community. A sample of U.S. adults was asked to indicate commitment to values embodied in the United Nations’ Declaration of Human Rights and Franklin D. Roosevelt’s Four Freedoms, through a formulated message. Participants were also asked of actions they can take to support these values, barriers to such action, and related questions. Results were looked at through different demographic and attitudinal factors. Over half of all participants, regardless of demographic group, were interested in making the commitment encapsulated in our message. There is a strong need to better understand and link actions to the development of a global human community. Better ways to connect people with others who can better support their actions are needed

Development of frataxin gene expression measures for the evaluation of experimental treatments in Friedreich\u27s ataxia.

BACKGROUND: Friedreich ataxia is a progressive neurodegenerative disorder caused by GAA triplet repeat expansions or point mutations in the FXN gene and, ultimately, a deficiency in the levels of functional frataxin protein. Heterozygous carriers of the expansion express approximately 50% of normal frataxin levels yet manifest no clinical symptoms, suggesting that therapeutic approaches that increase frataxin may be effective even if frataxin is raised only to carrier levels. Small molecule HDAC inhibitor compounds increase frataxin mRNA and protein levels, and have beneficial effects in animal models of FRDA. METHODOLOGY/PRINCIPAL FINDINGS: To gather data supporting the use of frataxin as a therapeutic biomarker of drug response we characterized the intra-individual stability of frataxin over time, determined the contribution of frataxin from different components of blood, compared frataxin measures in different cell compartments, and demonstrated that frataxin increases are achieved in peripheral blood mononuclear cells. Frataxin mRNA and protein levels were stable with repeated sampling over four and 15 weeks. In the 15-week study, the average CV was 15.6% for protein and 18% for mRNA. Highest levels of frataxin in blood were in erythrocytes. As erythrocytes are not useful for frataxin assessment in many clinical trial situations, we confirmed that PBMCs and buccal swabs have frataxin levels equivalent to those of whole blood. In addition, a dose-dependent increase in frataxin was observed when PBMCs isolated from patient blood were treated with HDACi. Finally, higher frataxin levels predicted less severe neurological dysfunction and were associated with slower rates of neurological change. CONCLUSIONS/SIGNIFICANCE: Our data support the use of frataxin as a biomarker of drug effect. Frataxin levels are stable over time and as such a 1.5 to 2-fold change would be detectable over normal biological fluctuations. Additionally, our data support buccal cells or PBMCs as sources for measuring frataxin protein in therapeutic trials

The European Organisation for Research and Treatment of Cancer, State of Science in radiation oncology and priorities for clinical trials meeting report

Background: New technologies and techniques in radiation oncology and imaging offer opportunities to enhance the benefit of loco-regional treatments, expand treatment to new patient populations such as those with oligometastatic disease and decrease normal tissue toxicity. Furthermore, novel agents have become available which may be combined with radiation therapy, and identification of radiation-related biomarkers can be studied to refine treatment prescriptions. Finally, the use of artificial intelligence (AI) capabilities may also improve treatment quality assurance or the ease with which radiation dosing is prescribed. All of these potential advances present both opportunities and challenges for academic clinical researchers. Methods: Recently, the European Organisation for Research and Treatment of Cancer addressed these topics in a meeting of multiple stakeholders from Europe and North America. The following five themes radiobiology-based biomarkers, new technologies - particularly proton beam therapy, combination systemic and radiation therapy, management of oligometastatic disease and AI opportunities in radiation oncology were discussed in a State of Science format to define key controversies, unanswered questions and propose clinical trial priorities for development. Conclusions: Priorities for clinical trials implementing new science and technologies have been defined. Solutions to integrate the multidimensional complexity of data have been explored. New types of platforms and partnerships can support innovative approaches for clinical research in radiation oncology. (C) 2020 The Authors. Published by Elsevier Ltd

Reproducible big data science: A case study in continuous FAIRness.

Big biomedical data create exciting opportunities for discovery, but make it difficult to capture analyses and outputs in forms that are findable, accessible, interoperable, and reusable (FAIR). In response, we describe tools that make it easy to capture, and assign identifiers to, data and code throughout the data lifecycle. We illustrate the use of these tools via a case study involving a multi-step analysis that creates an atlas of putative transcription factor binding sites from terabytes of ENCODE DNase I hypersensitive sites sequencing data. We show how the tools automate routine but complex tasks, capture analysis algorithms in understandable and reusable forms, and harness fast networks and powerful cloud computers to process data rapidly, all without sacrificing usability or reproducibility-thus ensuring that big data are not hard-to-(re)use data. We evaluate our approach via a user study, and show that 91% of participants were able to replicate a complex analysis involving considerable data volumes

Reproducible big data science: A case study in continuous FAIRness

Big biomedical data create exciting opportunities for discovery, but make it difficult to capture analyses and outputs in forms that are findable, accessible, interoperable, and reusable (FAIR). In response, we describe tools that make it easy to capture, and assign identifiers to, data and code throughout the data lifecycle. We illustrate the use of these tools via a case study involving a multi-step analysis that creates an atlas of putative transcription factor binding sites from terabytes of ENCODE DNase I hypersensitive sites sequencing data. We show how the tools automate routine but complex tasks, capture analysis algorithms in understandable and reusable forms, and harness fast networks and powerful cloud computers to process data rapidly, all without sacrificing usability or reproducibility—thus ensuring that big data are not hard-to-(re)use data. We evaluate our approach via a user study, and show that 91% of participants were able to replicate a complex analysis involving considerable data volumes

Faint High Latitude Carbon Stars Discovered by the Sloan Digital Sky Survey: Methods and Initial Results

We report the discovery of 39 Faint High Latitude Carbon Stars (FHLCs) from Sloan Digital Sky Survey commissioning data. The objects, each selected photometrically and verified spectroscopically, range over 16.6 < r* < 20.0, and show a diversity of temperatures as judged by both colors and NaD line strengths. At the completion of the Sloan Survey, there will be many hundred homogeneously selected and observed FHLCs in this sample. We present proper motion measures for each object, indicating that the sample is a mixture of extremely distant (>100 kpc) halo giant stars, useful for constraining halo dynamics, plus members of the recently-recognized exotic class of very nearby dwarf carbon (dC) stars. Motions, and thus dC classification, are inferred for 40-50 percent of the sample, depending on the level of statistical significance invoked. The new list of dC stars presented here, although selected from only a small fraction of the final SDSS, doubles the number of such objects found by all previous methods. (Abstract abridged).Comment: Accepted for publication in The Astronomical Journal, Vol. 124, Sep. 2002, 40 pages, 7 figures, AASTeX v5.

Technical and economic feasibility of centralized facilities for solar hydrogen production via photocatalysis and photoelectrochemistry

Photoelectrochemical water splitting is a promising route for the renewable production of hydrogen fuel. This work presents the results of a technical and economic feasibility analysis conducted for four hypothetical, centralized, large-scale hydrogen production plants based on this technology. The four reactor types considered were a single bed particle suspension system, a dual bed particle suspension system, a fixed panel array, and a tracking concentrator array. The current performance of semiconductor absorbers and electrocatalysts were considered to compute reasonable solar-to-hydrogen conversion efficiencies for each of the four systems. The U.S. Department of Energy H2A model was employed to calculate the levelized cost of hydrogen output at the plant gate at 300 psi for a 10 tonne per day production scale. All capital expenditures and operating costs for the reactors and auxiliaries (compressors, control systems, etc.) were considered. The final cost varied from $1.60–$10.40 per kg H2 with the particle bed systems having lower costs than the panel-based systems. However, safety concerns due to the cogeneration of O_2 and H_2 in a single bed system and long molecular transport lengths in the dual bed system lead to greater uncertainty in their operation. A sensitivity analysis revealed that improvement in the solar-to-hydrogen efficiency of the panel-based systems could substantially drive down their costs. A key finding is that the production costs are consistent with the Department of Energy's targeted threshold cost of $2.00–$4.00 per kg H_2 for dispensed hydrogen, demonstrating that photoelectrochemical water splitting could be a viable route for hydrogen production in the future if material performance targets can be met

Abundance of unknots in various models of polymer loops

A veritable zoo of different knots is seen in the ensemble of looped polymer chains, whether created computationally or observed in vitro. At short loop lengths, the spectrum of knots is dominated by the trivial knot (unknot). The fractional abundance of this topological state in the ensemble of all conformations of the loop of $N$ segments follows a decaying exponential form, $\sim \exp (-N/N_0)$, where $N_0$ marks the crossover from a mostly unknotted (ie topologically simple) to a mostly knotted (ie topologically complex) ensemble. In the present work we use computational simulation to look closer into the variation of $N_0$ for a variety of polymer models. Among models examined, $N_0$ is smallest (about 240) for the model with all segments of the same length, it is somewhat larger (305) for Gaussian distributed segments, and can be very large (up to many thousands) when the segment length distribution has a fat power law tail.Comment: 13 pages, 6 color figure