Design and optimization of enzymatic activity in a de novo β-barrel scaffold

While native scaffolds offer a large diversity of shapes and topologies for enzyme engineering, their often unpredictable behavior in response to sequence modification makes de novo generated scaffolds an exciting alternative. Here we explore the customization of the backbone and sequence of a de novo designed eight stranded β-barrel protein to create catalysts for a retro-aldolase model reaction. We show that active and specific catalysts can be designed in this fold and use directed evolution to further optimize activity and stereoselectivity. Our results support previous suggestions that different folds have different inherent amenability to evolution and this property could account, in part, for the distribution of natural enzymes among different folds

Geotechnical Field Reconnaissance: Gorkha (Nepal) Earthquake of April 25, 2015 and Related Shaking Sequence

The April 25, 2015 Gorkha (Nepal) Earthquake and its related aftershocks had a devastating impact on Nepal. The earthquake sequence resulted in nearly 9,000 deaths, tens of thousands of injuries, and has left hundreds of thousands of inhabitants homeless. With economic losses estimated at several billion US dollars, the financial impact to Nepal is severe and the rebuilding phase will likely span many years. The Geotechnical Extreme Events Reconnaissance (GEER) Association assembled a reconnaissance team under the leadership of D. Scott Kieffer, Binod Tiwari and Youssef M.A. Hashash to evaluate geotechnical impacts of the April 25, 2015 Gorkha Earthquake and its related aftershocks. The focus of the reconnaissance was on time-sensitive (perishable) data, and the GEER team included a large group of experts in the areas of Geology, Engineering Geology, Seismology, Tectonics, Geotechnical Engineering, Geotechnical Earthquake Engineering, and Civil and Environmental Engineering. The GEER team worked in close collaboration with local and international organizations to document earthquake damage and identify targets for detailed follow up investigations. The overall distribution of damage relative to the April 25, 2015 epicenter indicates significant ground motion directivity, with pronounced damage to the east and comparatively little damage to the west. In the Kathmandu Basin, characteristics of recorded strong ground motion data suggest that a combination of directivity and deep basin effects resulted in significant amplification at a period of approximately five seconds. Along the margins of Kathmandu Basin structural damage and ground failures are more pronounced than in the basin interior, indicating possible basin edge motion amplification. Although modern buildings constructed within the basin generally performed well, local occurrences of heavy damage and collapse of reinforced concrete structures were observed. Ground failures in the basin included cyclic failure of silty clay, lateral spreading and liquefaction. Significant landsliding was triggered over a broad area, with concentrated activity east of the April 25, 2015 epicenter and between Kathmandu and the Nepal-China border. The distribution of concentrated landsliding partially reflects directivity in the ground motion. Several landslides have dammed rivers and many of these features have already been breached. Hydropower is a primary source of electric power in Nepal, and several facilities were damaged due to earthquake-induced landsliding. Powerhouses and penstocks experienced significant damage, and an intake structure currently under construction experienced significant dynamic settlement during the earthquake. Damage to roadways, bridges and retaining structures was also primarily related to landsliding. The greater concentration of infrastructure damage along steep hillsides, ridges and mountain peaks offers a proxy for the occurrence of topographic amplification. The lack of available strong motion records has severely limited the GEER team’s ability to understand how strong motions were distributed and how they correlate to distributions of landsliding, ground failure and infrastructure damage. It is imperative that the engineering and scientific community continues to install strong motion stations so that such data is available for future earthquake events. Such information will benefit the people of Nepal through improved approaches to earthquake resilient design

Geotechnical Effects of the 2015 Magnitude 7.8 Gorkha, Nepal, Earthquake and Aftershocks

This article summarizes the geotechnical effects of the 25 April 2015 M 7.8 Gorkha, Nepal, earthquake and aftershocks, as documented by a reconnaissance team that undertook a broad engineering and scientific assessment of the damage and collected perishable data for future analysis. Brief descriptions are provided of ground shaking, surface fault rupture, landsliding, soil failure, and infrastructure performance. The goal of this reconnaissance effort, led by Geotechnical Extreme Events Reconnaissance, is to learn from earthquakes and mitigate hazards in future earthquakes

Primary Xenografts of Human Prostate Tissue as a Model to Study Angiogenesis Induced by Reactive Stroma

Characterization of the mechanism(s) of androgen-driven human angiogenesis could have significant implications for modeling new forms of anti-angiogenic therapies for CaP and for developing targeted adjuvant therapies to improve efficacy of androgen-deprivation therapy. However, models of angiogenesis by human endothelial cells localized within an intact human prostate tissue architecture are until now extremely limited. This report characterizes the burst of angiogenesis by endogenous human blood vessels in primary xenografts of fresh surgical specimens of benign prostate or prostate cancer (CaP) tissue that occurs between Days 6–14 after transplantation into SCID mice pre-implanted with testosterone pellets. The wave of human angiogenesis was preceded by androgen-mediated up-regulation of VEGF-A expression in the stromal compartment. The neo-vessel network anastomosed to the host mouse vascular system between Days 6–10 post-transplantation, the angiogenic response ceased by Day 15, and by Day 30 the vasculature had matured and stabilized, as indicated by a lack of leakage of serum components into the interstitial tissue space and by association of nascent endothelial cells with mural cells/pericytes. The angiogenic wave was concurrent with the appearance of a reactive stroma phenotype, as determined by staining for α-SMA, Vimentin, Tenascin, Calponin, Desmin and Masson's trichrome, but the reactive stroma phenotype appeared to be largely independent of androgen availability. Transplantation-induced angiogenesis by endogenous human endothelial cells present in primary xenografts of benign and malignant human prostate tissue was preceded by induction of androgen-driven expression of VEGF by the prostate stroma, and was concurrent with and the appearance of a reactive stroma phenotype. Androgen-modulated expression of VEGF-A appeared to be a causal regulator of angiogenesis, and possibly of stromal activation, in human prostate xenografts

Geotechnical Effects of the 2015 Magnitude 7.8 Gorkha, Nepal, Earthquake and Aftershocks

This article summarizes the geotechnical effects of the 25 April 2015 M 7.8 Gorkha, Nepal, earthquake and aftershocks, as documented by a reconnaissance team that undertook a broad engineering and scientific assessment of the damage and collected perishable data for future analysis. Brief descriptions are provided of ground shaking, surface fault rupture, landsliding, soil failure, and infrastructure performance. The goal of this reconnaissance effort, led by Geotechnical Extreme Events Reconnaissance, is to learn from earthquakes and mitigate hazards in future earthquakes.This is the publisher’s final pdf. The published article is copyrighted by Seismological Society of America and can be found at: http://www.seismosoc.org/publications/srl

International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors

BACKGROUND: Sinonasal neoplasms, whether benign and malignant, pose a significant challenge to clinicians and represent a model area for multidisciplinary collaboration in order to optimize patient care. The International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors (ICSNT) aims to summarize the best available evidence and presents 48 thematic and histopathology-based topics spanning the field. METHODS: In accordance with prior International Consensus Statement on Allergy and Rhinology documents, ICSNT assigned each topic as an Evidence-Based Review with Recommendations, Evidence-Based Review, and Literature Review based on the level of evidence. An international group of multidisciplinary author teams were assembled for the topic reviews using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses format, and completed sections underwent a thorough and iterative consensus-building process. The final document underwent rigorous synthesis and review prior to publication. RESULTS: The ICSNT document consists of four major sections: general principles, benign neoplasms and lesions, malignant neoplasms, and quality of life and surveillance. It covers 48 conceptual and/or histopathology-based topics relevant to sinonasal neoplasms and masses. Topics with a high level of evidence provided specific recommendations, while other areas summarized the current state of evidence. A final section highlights research opportunities and future directions, contributing to advancing knowledge and community intervention. CONCLUSION: As an embodiment of the multidisciplinary and collaborative model of care in sinonasal neoplasms and masses, ICSNT was designed as a comprehensive, international, and multidisciplinary collaborative endeavor. Its primary objective is to summarize the existing evidence in the field of sinonasal neoplasms and masses

Azimuthal anisotropy of charged jet production in root s(NN)=2.76 TeV Pb-Pb collisions

We present measurements of the azimuthal dependence of charged jet production in central and semi-central root s(NN) = 2.76 TeV Pb-Pb collisions with respect to the second harmonic event plane, quantified as nu(ch)(2) (jet). Jet finding is performed employing the anti-k(T) algorithm with a resolution parameter R = 0.2 using charged tracks from the ALICE tracking system. The contribution of the azimuthal anisotropy of the underlying event is taken into account event-by-event. The remaining (statistical) region-to-region fluctuations are removed on an ensemble basis by unfolding the jet spectra for different event plane orientations independently. Significant non-zero nu(ch)(2) (jet) is observed in semi-central collisions (30-50% centrality) for 20 <p(T)(ch) (jet) <90 GeV/c. The azimuthal dependence of the charged jet production is similar to the dependence observed for jets comprising both charged and neutral fragments, and compatible with measurements of the nu(2) of single charged particles at high p(T). Good agreement between the data and predictions from JEWEL, an event generator simulating parton shower evolution in the presence of a dense QCD medium, is found in semi-central collisions. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

Production of He-4 and (4) in Pb-Pb collisions at root(NN)-N-S=2.76 TeV at the LHC

Results on the production of He-4 and (4) nuclei in Pb-Pb collisions at root(NN)-N-S = 2.76 TeV in the rapidity range vertical bar y vertical bar <1, using the ALICE detector, are presented in this paper. The rapidity densities corresponding to 0-10% central events are found to be dN/dy4(He) = (0.8 +/- 0.4 (stat) +/- 0.3 (syst)) x 10(-6) and dN/dy4 = (1.1 +/- 0.4 (stat) +/- 0.2 (syst)) x 10(-6), respectively. This is in agreement with the statistical thermal model expectation assuming the same chemical freeze-out temperature (T-chem = 156 MeV) as for light hadrons. The measured ratio of (4)/He-4 is 1.4 +/- 0.8 (stat) +/- 0.5 (syst). (C) 2018 Published by Elsevier B.V.Peer reviewe

Forward-central two-particle correlations in p-Pb collisions at root s(NN)=5.02 TeV

Two-particle angular correlations between trigger particles in the forward pseudorapidity range (2.5 2GeV/c. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B. V.Peer reviewe

Event-shape engineering for inclusive spectra and elliptic flow in Pb-Pb collisions at root(NN)-N-S=2.76 TeV

Peer reviewe