Deep shower interpretation of the cosmic ray events observed in excess of the Greisen-Zatsepin-Kuzmin energy

We consider the possibility that the ultra-high-energy cosmic ray flux has a small component of exotic particles which create showers much deeper in the atmosphere than ordinary hadronic primaries. It is shown that applying the conventional AGASA/HiRes/Auger data analysis procedures to such exotic events results in large systematic biases in the energy spectrum measurement. SubGZK exotic showers may be mis-reconstructed with much higher energies and mimick superGZK events. Alternatively, superGZK exotic showers may elude detection by conventional fluorescence analysis techniques.Comment: 22 pages, 5 figure

On the Stress Tensor of Kerr/CFT

The recently-conjectured Kerr/CFT correspondence posits a field theory dual to dynamics in the near-horizon region of an extreme Kerr black hole with certain boundary conditions. We construct a boundary stress tensor for this theory via covariant phase space techniques. The structure of the stress tensor indicates that any dual theory is a discrete light cone quantum theory, in agreement with recent arguments by Balasubramanian et al. The key technical step in our construction is the addition of an appropriate counter-term to the symplectic structure, which is necessary to make the theory fully covariant and to resolve a subtle problem involving the integrability of charges.Comment: 19 page

The Weak Gravity Conjecture and the Viscosity Bound with Six-Derivative Corrections

The weak gravity conjecture and the shear viscosity to entropy density bound place constraints on low energy effective field theories that may help to distinguish which theories can be UV completed. Recently, there have been suggestions of a possible correlation between the two constraints. In some interesting cases, the behavior was precisely such that the conjectures were mutually exclusive. Motivated by these works, we study the mass to charge and shear viscosity to entropy density ratios for charged AdS5 black branes, which are holographically dual to four-dimensional CFTs at finite temperature. We study a family of four-derivative and six-derivative perturbative corrections to these backgrounds. We identify the region in parameter space where the two constraints are satisfied and in particular find that the inclusion of the next-to-leading perturbative correction introduces wider possibilities for the satisfaction of both constraints.Comment: 24 pages, 6 figures, v2: published version, refs added, minor clarificatio

Global Kidney Exchange: Analysis and Background Papers from the Perspective of Medical Anthropology

Global Kidney Exchange (GKE) is a program aimed at facilitating trans-national kidney donation. Although its proponents aim at reducing the unmet demand of kidneys in the United States through the trans-nationalization of kidney exchange programs, the World Health Organization (WHO) and The Transplantation Society (TTS) have expressed concerns about its potential effect on black markets of organs and transnational organ trafficking, as well as on low- or middle-income countries health systems. For GKE to be implemented, it would need to be permitted to operate in at least some low- or middle-income countries. Should a low- or middle-income country allow GKE’s implementation? With the aim of answering this question, the eighteen University of Denver students in the Medical Anthropology course I [Alejandro Cerón] taught in autumn 2017, identified and researched the different aspects that would affect this issue, and delved in a holistic analysis we present in this report. Based on our analysis, health authorities in low- or middle-income countries faced with decisions about GKE need to consider the following aspects: the country’s current and projected needs related to kidney transplant, as well as the capacity for addressing those needs; the country’s current situation related to organ trafficking, transplant tourism and black markets of organs; the current and projected legislation related to both organ donation and human trafficking; the prevailing ethical considerations that inform the practice of all professionals related to organ transplant in the country; analyze end-stage renal failure as a preventable disease needing public health measures; and the sociocultural aspects that surround organ donation in the country. We consider that the concrete configuration of these aspects would influence the effects of implementing GKE. Additionally, we identified some issues of concern that are beyond the level of influence of local authorities: the unmet demand of kidneys in high-income countries is a reality that incentivizes organ trade and transplant tourism, and this is a problem in need of solutions; transnational organ trafficking as well as human trafficking with the purpose of organ donation are problems that need more visibility; for a global exchange of organs to be implemented, it would need to rely on supranational or transnational regulation and oversight; and the global epidemic of chronic kidney disease needs to be addressed through a public health perspective that emphasizes prevention

Effect of Thermal Phase Fluctuations on the Inductances of Josephson Junctions, Arrays of Junctions, and Superconducting Films

We calculate the factor by which thermal phase fluctuations, as distinct from phase-slip fluctuations, increase the inductance, LJ, of a resistively-shunted Josephson junction (JJ) above its mean-field value, L0. We find that quantum mechanics suppresses fluctuations when T drops below a temperature, TQ = h/kBGL0, where G is the shunt conductance. Examination of the calculated sheet inductance, LA(T)/L0(T), of arrays of JJ's reveals that 2-D interconnections halve fluctuation effects, while reducing phase-slip effects by a much larger factor. Guided by these results, we calculate the sheet inductance, LF(T)/L0(T), of 2-D films by treating each plasma oscillation mode as an overdamped JJ. In disordered s-wave superconductors, quantum suppression is important for LF(0)/LF(T) > 0.14, (or, T/TC0 < 0.94). In optimally doped YBCO and BSCCO quantum suppression is important for l2(0)/l2(T) > 0.25, where l is the penetration depth.Comment: 15 pages; 4 figures. Submitted to Physical Review B, May 199

XSTREAM: A practical algorithm for identification and architecture modeling of tandem repeats in protein sequences

<p>Abstract</p> <p>Background</p> <p>Biological sequence repeats arranged in tandem patterns are widespread in DNA and proteins. While many software tools have been designed to detect DNA tandem repeats (TRs), useful algorithms for identifying protein TRs with varied levels of degeneracy are still needed.</p> <p>Results</p> <p>To address limitations of current repeat identification methods, and to provide an efficient and flexible algorithm for the detection and analysis of TRs in protein sequences, we designed and implemented a new computational method called XSTREAM. Running time tests confirm the practicality of XSTREAM for analyses of multi-genome datasets. Each of the key capabilities of XSTREAM (e.g., merging, nesting, long-period detection, and TR architecture modeling) are demonstrated using anecdotal examples, and the utility of XSTREAM for identifying TR proteins was validated using data from a recently published paper.</p> <p>Conclusion</p> <p>We show that XSTREAM is a practical and valuable tool for TR detection in protein and nucleotide sequences at the multi-genome scale, and an effective tool for modeling TR domains with diverse architectures and varied levels of degeneracy. Because of these useful features, XSTREAM has significant potential for the discovery of naturally-evolved modular proteins with applications for engineering novel biostructural and biomimetic materials, and identifying new vaccine and diagnostic targets.</p

How a Diverse Research Ecosystem Has Generated New Rehabilitation Technologies: Review of NIDILRR’s Rehabilitation Engineering Research Centers

Over 50 million United States citizens (1 in 6 people in the US) have a developmental, acquired, or degenerative disability. The average US citizen can expect to live 20% of his or her life with a disability. Rehabilitation technologies play a major role in improving the quality of life for people with a disability, yet widespread and highly challenging needs remain. Within the US, a major effort aimed at the creation and evaluation of rehabilitation technology has been the Rehabilitation Engineering Research Centers (RERCs) sponsored by the National Institute on Disability, Independent Living, and Rehabilitation Research. As envisioned at their conception by a panel of the National Academy of Science in 1970, these centers were intended to take a “total approach to rehabilitation”, combining medicine, engineering, and related science, to improve the quality of life of individuals with a disability. Here, we review the scope, achievements, and ongoing projects of an unbiased sample of 19 currently active or recently terminated RERCs. Specifically, for each center, we briefly explain the needs it targets, summarize key historical advances, identify emerging innovations, and consider future directions. Our assessment from this review is that the RERC program indeed involves a multidisciplinary approach, with 36 professional fields involved, although 70% of research and development staff are in engineering fields, 23% in clinical fields, and only 7% in basic science fields; significantly, 11% of the professional staff have a disability related to their research. We observe that the RERC program has substantially diversified the scope of its work since the 1970’s, addressing more types of disabilities using more technologies, and, in particular, often now focusing on information technologies. RERC work also now often views users as integrated into an interdependent society through technologies that both people with and without disabilities co-use (such as the internet, wireless communication, and architecture). In addition, RERC research has evolved to view users as able at improving outcomes through learning, exercise, and plasticity (rather than being static), which can be optimally timed. We provide examples of rehabilitation technology innovation produced by the RERCs that illustrate this increasingly diversifying scope and evolving perspective. We conclude by discussing growth opportunities and possible future directions of the RERC program

Heavy quarkonium: progress, puzzles, and opportunities

A golden age for heavy quarkonium physics dawned a decade ago, initiated by the confluence of exciting advances in quantum chromodynamics (QCD) and an explosion of related experimental activity. The early years of this period were chronicled in the Quarkonium Working Group (QWG) CERN Yellow Report (YR) in 2004, which presented a comprehensive review of the status of the field at that time and provided specific recommendations for further progress. However, the broad spectrum of subsequent breakthroughs, surprises, and continuing puzzles could only be partially anticipated. Since the release of the YR, the BESII program concluded only to give birth to BESIII; the $B$-factories and CLEO-c flourished; quarkonium production and polarization measurements at HERA and the Tevatron matured; and heavy-ion collisions at RHIC have opened a window on the deconfinement regime. All these experiments leave legacies of quality, precision, and unsolved mysteries for quarkonium physics, and therefore beg for continuing investigations. The plethora of newly-found quarkonium-like states unleashed a flood of theoretical investigations into new forms of matter such as quark-gluon hybrids, mesonic molecules, and tetraquarks. Measurements of the spectroscopy, decays, production, and in-medium behavior of c\bar{c}, b\bar{b}, and b\bar{c} bound states have been shown to validate some theoretical approaches to QCD and highlight lack of quantitative success for others. The intriguing details of quarkonium suppression in heavy-ion collisions that have emerged from RHIC have elevated the importance of separating hot- and cold-nuclear-matter effects in quark-gluon plasma studies. This review systematically addresses all these matters and concludes by prioritizing directions for ongoing and future efforts.Comment: 182 pages, 112 figures. Editors: N. Brambilla, S. Eidelman, B. K. Heltsley, R. Vogt. Section Coordinators: G. T. Bodwin, E. Eichten, A. D. Frawley, A. B. Meyer, R. E. Mitchell, V. Papadimitriou, P. Petreczky, A. A. Petrov, P. Robbe, A. Vair

Jak2V617F Reversible Activation Shows Its Essential Requirement in Myeloproliferative Neoplasms

Gain-of-function mutations activating JAK/STAT signaling are seen in the majority of patients with myeloproliferative neoplasms (MPN), most commonly JAK2V617F. Although clinically approved JAK inhibitors improve symptoms and outcomes in MPNs, remissions are rare, and mutant allele burden does not substantively change with chronic therapy. We hypothesized this is due to limitations of current JAK inhibitors to potently and specifically abrogate mutant JAK2 signaling. We therefore developed a conditionally inducible mouse model allowing for sequential activation, and then inactivation, of Jak2V617F from its endogenous locus using a combined Dre-rox/Cre-lox dual-recombinase system. Jak2V617F deletion abrogates MPN features, induces depletion of mutant-specific hematopoietic stem/progenitor cells, and extends overall survival to an extent not observed with pharmacologic JAK inhibition, including when cooccurring with somatic Tet2 loss. Our data suggest JAK2V617F represents the best therapeutic target in MPNs and demonstrate the therapeutic relevance of a dual-recombinase system to assess mutant-specific oncogenic dependencies in vivo

ResBoost: characterizing and predicting catalytic residues in enzymes

Abstract Background Identifying the catalytic residues in enzymes can aid in understanding the molecular basis of an enzyme's function and has significant implications for designing new drugs, identifying genetic disorders, and engineering proteins with novel functions. Since experimentally determining catalytic sites is expensive, better computational methods for identifying catalytic residues are needed. Results We propose ResBoost, a new computational method to learn characteristics of catalytic residues. The method effectively selects and combines rules of thumb into a simple, easily interpretable logical expression that can be used for prediction. We formally define the rules of thumb that are often used to narrow the list of candidate residues, including residue evolutionary conservation, 3D clustering, solvent accessibility, and hydrophilicity. ResBoost builds on two methods from machine learning, the AdaBoost algorithm and Alternating Decision Trees, and provides precise control over the inherent trade-off between sensitivity and specificity. We evaluated ResBoost using cross-validation on a dataset of 100 enzymes from the hand-curated Catalytic Site Atlas (CSA). Conclusion ResBoost achieved 85% sensitivity for a 9.8% false positive rate and 73% sensitivity for a 5.7% false positive rate. ResBoost reduces the number of false positives by up to 56% compared to the use of evolutionary conservation scoring alone. We also illustrate the ability of ResBoost to identify recently validated catalytic residues not listed in the CSA