Improved protein structure prediction using potentials from deep learning

Protein structure prediction can be used to determine the three-dimensional shape of a protein from its amino acid sequence1. This problem is of fundamental importance as the structure of a protein largely determines its function2; however, protein structures can be difficult to determine experimentally. Considerable progress has recently been made by leveraging genetic information. It is possible to infer which amino acid residues are in contact by analysing covariation in homologous sequences, which aids in the prediction of protein structures3. Here we show that we can train a neural network to make accurate predictions of the distances between pairs of residues, which convey more information about the structure than contact predictions. Using this information, we construct a potential of mean force4 that can accurately describe the shape of a protein. We find that the resulting potential can be optimized by a simple gradient descent algorithm to generate structures without complex sampling procedures. The resulting system, named AlphaFold, achieves high accuracy, even for sequences with fewer homologous sequences. In the recent Critical Assessment of Protein Structure Prediction5 (CASP13)—a blind assessment of the state of the field—AlphaFold created high-accuracy structures (with template modelling (TM) scores6 of 0.7 or higher) for 24 out of 43 free modelling domains, whereas the next best method, which used sampling and contact information, achieved such accuracy for only 14 out of 43 domains. AlphaFold represents a considerable advance in protein-structure prediction. We expect this increased accuracy to enable insights into the function and malfunction of proteins, especially in cases for which no structures for homologous proteins have been experimentally determined7

Effects of whole-body vibration or resistive-vibration exercise on blood clotting and related biomarkers: a systematic review

Whole-body vibration (WBV) and resistive vibration exercise (RVE) are utilized as countermeasures against bone loss, muscle wasting, and physical deconditioning. The safety of the interventions, in terms of the risk of inducing undesired blood clotting and venous thrombosis, is not clear. We therefore performed the present systematic review of the available scientific literature on the issue. The review was conducted following the guidelines by the Space Biomedicine Systematic Review Group, based on Cochrane review guidelines. The relevant context or environment of the studies was “ground-based environment”; space analogs or diseased conditions were not included. The search retrieved 801 studies; 77 articles were selected for further consideration after an initial screening. Thirty-three studies met the inclusion criteria. The main variables related to blood markers involved angiogenic and endothelial factors, fibrinolysis and coagulation markers, cytokine levels, inflammatory and plasma oxidative stress markers. Functional and hemodynamic markers involved blood pressure measurements, systemic vascular resistance, blood flow and microvascular and endothelial functions. The available evidence suggests neutral or potentially positive effects of short- and long-term interventions with WBV and RVE on variables related to blood coagulation, fibrinolysis, inflammatory status, oxidative stress, cardiovascular, microvascular and endothelial functions. No significant warning signs towards an increased risk of undesired clotting and venous thrombosis were identified. If confirmed by further studies, WBV and RVE could be part of the countermeasures aimed at preventing or attenuating the muscular and cardiovascular deconditioning associated with spaceflights, permanence on planetary habitats and ground-based simulations of microgravity

The Duality between IIB String Theory on PP-wave and N=4 SYM: a Status Report

The aim of this report is to give an overview of the duality between type IIB string theory on the maximally supersymmetric PP-wave and the BMN sector of N=4 Super Yang-Mills theory. The general features of the string and the field theory descriptions are reviewed, but the main focus of this report is on the comparison between the two sides of the duality. In particular, it is first explained how free IIB strings emerge on the gauge theory side and then the generalizations of this relation to the full interacting theory are considered. An ``historical'' approach is taken and the various proposals presented in the literature are described.Comment: 35 pages, 5 figures; Contribution to the proceedings of the Copenhagen RTN workshop, 15-20 September 2003; v3, few comments added, misprints correcte

Protein structure prediction using multiple deep neural networks in the 13th Critical Assessment of Protein Structure Prediction (CASP13)

We describe AlphaFold, the protein structure prediction system that was entered by the group A7D in CASP13 Submissions were made by three free-modelling methods which combine the predictions of three neural networks. All three systems were guided by predictions of distances between pairs of residues produced by a neural network. Two systems assembled fragments produced by a generative neural network, one using scores from a network trained to regress GDT_TS. The third system shows that simple gradient descent on a properly constructed potential is able to perform on-par with more expensive traditional search techniques and without requiring domain segmentation. In the CASP13 free-modelling assessors' ranking by summed z-scores, this system scored highest with 68.3 vs 48.2 for the next closest group. (An average GDT_TS of 61.4.) The system produced high-accuracy structures (with GDT_TS scores of 70 or higher) for 11 out of 43 free-modelling domains. Despite not explicitly using template information, the results in the template category were comparable to the best performing template-based methods

Promoting Transparency in Social Science Research

There is growing appreciation for the advantages of experimentation in the social sciences. Policy-relevant claims that in the past were backed by theoretical arguments and inconclusive correlations are now being investigated using more credible methods. Changes have been particularly pronounced in development economics, where hundreds of randomized trials have been carried out over the last decade. When experimentation is difficult or impossible, researchers are using quasi-experimental designs. Governments and advocacy groups display a growing appetite for evidence-based policy-making. In 2005, Mexico established an independent government agency to rigorously evaluate social programs, and in 2012, the U.S. Office of Management and Budget advised federal agencies to present evidence from randomized program evaluations in budget requests (1, 2)

Sunscreens - Which and what for?

It is well established that sun exposure is the main cause for the development of skin cancer. Chronic continuous UV radiation is believed to induce malignant melanoma, whereas intermittent high-dose UV exposure contributes to the occurrence of actinic keratosis as precursor lesions of squamous cell carcinoma as well as basal cell carcinoma. Not only photocarcinogenesis but also the mechanisms of photoaging have recently become apparent. In this respect the use of sunscreens seemed to prove to be more and more important and popular within the last decades. However, there is still inconsistency about the usefulness of sunscreens. Several studies show that inadequate use and incomplete UV spectrum efficacy may compromise protection more than previously expected. The sunscreen market is crowded by numerous products. Inorganic sunscreens such as zinc oxide and titanium oxide have a wide spectral range of activity compared to most of the organic sunscreen products. It is not uncommon for organic sunscreens to cause photocontact allergy, but their cosmetic acceptability is still superior to the one given by inorganic sunscreens. Recently, modern galenic approaches such as micronization and encapsulation allow the development of high-quality inorganic sunscreens. The potential systemic toxicity of organic sunscreens has lately primarily been discussed controversially in public, and several studies show contradictory results. Although a matter of debate, at present the sun protection factor (SPF) is the most reliable information for the consumer as a measure of sunscreen filter efficacy. In this context additional tests have been introduced for the evaluation of not only the protective effect against erythema but also protection against UV-induced immunological and mutational effects. Recently, combinations of UV filters with agents active in DNA repair have been introduced in order to improve photoprotection. This article reviews the efficacy of sunscreens in the prevention of epithelial and nonepithelial skin cancer, the effect on immunosuppression and the value of the SPF as well as new developments on the sunscreen market. Copyright (C) 2005 S. Karger AG, Basel

Cryogenic testing of the TPC superconducting solenoid

This report describes the results of a series of tests on the TPC superconducting magnet cryogenic system which occurred during the winter and spring of 1983. The tests occurred at interaction region 2 of the PEP colliding beam facility at the Stanford Linear Accelerator Center (SLAC). The TPC Magnet Cryogenic System which was tested includes the following major components: a remote helium compressor with a full flow liquid nitrogen purification station, 400 meters of high pressure supply and low pressure return lines; and locally a CTi Model 2800 refrigerator with two Sulzer gas bearing turbines, the TPC magnet control dewar, 70 meters of transfer lines, and the TPC thin superconducting solenoid magnet. In addition, there is a conditioner (liquid nitrogen heat exchangers and gas heaters) system for cooldown and warmup of the magnet. This report describes the local cryogenic system and describes the various steps in the cooldown and operation of the TPC magnet. The tests were successful in that they showed that the TPC magnet could be cooled down in 24 hours and the magnet could be operated on the refrigerator or a helium pump with adequate cooling margin. The tests identified problems with the cryogenic system and the 2800 refrigerator. Procedures for successful operation and quenching of the superconducting magnet were developed. 19 references

Results industry questionnaire SEAFOODsense

The aim of this research was to define sensory quality, and determine how this can be measured, at each point where quality decision-making is carried out in the chain of seafood handling from catch or slaughter to consumer. This was carried out by taking interviews with the industry to obtain knowledge about their sensory quality evaluation procedures and the descriptive terms they used. In four different countries, Ireland, Iceland, Denmark and The Netherlands, 8-17 companies throughout the fish production chain were selected

Pathophysiology, risk, diagnosis, and management of venous thrombosis in space: where are we now?

The recent incidental discovery of an asymptomatic venous thrombosis (VT) in the internal jugular vein of an astronaut on the International Space Station prompted a necessary, immediate response from the space medicine community. The European Space Agency formed a topical team to review the pathophysiology, risk and clinical presentation of venous thrombosis and the evaluation of its prevention, diagnosis, mitigation, and management strategies in spaceflight. In this article, we discuss the findings of the ESA VT Topical Team over its 2-year term, report the key gaps as we see them in the above areas which are hindering understanding VT in space. We provide research recommendations in a stepwise manner that build upon existing resources, and highlight the initial steps required to enable further evaluation of this newly identified pertinent medical risk