Measurements of the material bucklings of lattices of natural uranium rods in D₂O

"NYO-9660.""AEC Research and development report UC-34 physics (TID-4500, 16th edition)."Originally issued as the first author's Ph. D. thesis, Massachusetts Institute of Technology, Dept. of Nuclear Engineering, 1962U.S. Atomic Energy Commission AT(30-1)234

Enhancing Evolutionary Couplings with Deep Convolutional Neural Networks

While genes are defined by sequence, in biological systems a protein's function is largely determined by its three-dimensional structure. Evolutionary information embedded within multiple sequence alignments provides a rich source of data for inferring structural constraints on macromolecules. Still, many proteins of interest lack sufficient numbers of related sequences, leading to noisy, error-prone residue-residue contact predictions. Here we introduce DeepContact, a convolutional neural network (CNN)-based approach that discovers co-evolutionary motifs and leverages these patterns to enable accurate inference of contact probabilities, particularly when few related sequences are available. DeepContact significantly improves performance over previous methods, including in the CASP12 blind contact prediction task where we achieved top performance with another CNN-based approach. Moreover, our tool converts hard-to-interpret coupling scores into probabilities, moving the field toward a consistent metric to assess contact prediction across diverse proteins. Through substantially improving the precision-recall behavior of contact prediction, DeepContact suggests we are near a paradigm shift in template-free modeling for protein structure prediction. Many protein structures of interest remain out of reach for both computational prediction and experimental determination. DeepContact learns patterns of co-evolution across thousands of experimentally determined structures, identifying conserved local motifs and leveraging this information to improve protein residue-residue contact predictions. DeepContact extracts additional information from the evolutionary couplings using its knowledge of co-evolution and structural space, while also converting coupling scores into probabilities that are comparable across protein sequences and alignments. Keywords: contact prediction; convolutional neural networks; deep learning; protein structure prediction; structure prediction; co-evolution; evolutionary couplingsNational Institutes of Health (U.S.) (Grant R01GM081871

Structured States of Disordered Proteins from Genomic Sequences

Protein flexibility ranges from simple hinge movements to functional disorder. Around half of all human proteins contain apparently disordered regions with little 3D or functional information, and many of these proteins are associated with disease. Building on the evolutionary couplings approach previously successful in predicting 3D states of ordered proteins and RNA, we developed a method to predict the potential for ordered states for all apparently disordered proteins with sufficiently rich evolutionary information. The approach is highly accurate (79%) for residue interactions as tested in more than 60 known disordered regions captured in a bound or specific condition. Assessing the potential for structure of more than 1,000 apparently disordered regions of human proteins reveals a continuum of structural order with at least 50% with clear propensity for three-or two-dimensional states. Co-evolutionary constraints reveal hitherto unseen structures of functional importance in apparently disordered proteins. Keywords: Evolutionary couplings disorder; conformational flexibility; statistical physics; maximum entropy; EVfold; bioinformatics; computational biology; structure predictionNational Institutes of Health (U.S.) (Grant R01GM081871

R&D Spending and Patenting in the Technology Hardware Sector in Nations With and Without Fair Use

This working paper uses two common indicators of innovation to see how the technology hardware sector compares in countries with and without fair use. It illustrates that research and development spending by firms in these industries has been higher in countries with fair use, controlling for other firm- and country-level factors. It then shows more patents have been granted to the technology sector in countries that have adopted fair use, relative to patents granted to firms in the same industries in other countries, controlling for other country-level factors

Korea’s 2011 Copyright Act Amendments and Innovation by Online Service Providers

In 2011, Korea amended its Copyright Act to comply with the U.S.-Korea Free Trade Agreement’s intellectual property chapter, which included an obligation to enact a safe harbor for secondary copyright infringement in the online environment. Safe harbors protect internet firms from legal liability when their users post infringing content online, on the condition that the firms maintain a system to efficiently remove infringing content when notified of the infringement by rightholders. This paper tests whether the newly established safe harbors had an impact on innovation by Korean internet firms. I hypothesize that the amendments alleviated litigation risks faced by internet firms, incentivizing the development of new products and services. I test this by estimating difference-in-differences regressions on a panel of Korean internet and software producers between 2008 and 2015. Using R&D spending as a share of sales and patent metrics as measures of innovation inputs and outputs, respectively, I find that internet firms increased both R&D/sales and patent applications relative to the control group of software firms after the introduction of safe harbors. I find small changes in the direction of innovation as well: both internet and software firms expanded the set of technologies in which they applied for patents, though this was greater for the internet firms

R&D Spending and Patenting in the Technology Hardware Sector in Nations With and Without Fair Use

This working paper uses two common indicators of innovation to see how the technology hardware sector compares in countries with and without fair use. It illustrates that research and development spending by firms in these industries has been higher in countries with fair use, controlling for other firm- and country-level factors. It then shows more patents have been granted to the technology sector in countries that have adopted fair use, relative to patents granted to firms in the same industries in other countries, controlling for other country-level factors

The Impact of Copyright Exceptions for Researchers on Scholarly Output

High prices restrict access to academic journals and books that scholars rely upon to author new research. One possible solution is the expansion of copyright exceptions allowing unauthorized access to copyrighted works for researchers. I test the link between copyright exceptions for health and science researchers and their publishing output at the country-subject level. I find that scientists residing in countries that implement more robust research exceptions publish more papers and books in subsequent years. This relationship between copyright exceptions and publishing is stronger in lower-income countries, and stronger where there is stricter copyright protection of existing works

The U.S. Posture on Global Access to Medication & The Case for Change

The year 2020 marks the 25th anniversary of including intellectual property rights within the larger agenda of trade. While the marriage between trade and intellectual property was always uncomfortable, COVID-19 exposed the flaws, failures and the inadequacy of the trade agenda to harmonise intellectual property rights, particularly for patents in pharmaceuticals. Typically, the United States through its questionable United States Trade Representative (USTR) process exposed the vulnerabilities of the intellectual property systems of the rest of the world. COVID-19 exposed the manner in which the so-called ‘superior’ intellectual property regime of the US left the country with a weak health-care system. Testing, cost of medical care, lack of treatment, lack of quick access to doctors are all barriers that generally place the United States as having one of the worst health care systems compared to other developed economies. The onset of COVID-19 merely exacerbated the existing flaws to expose these vulnerabilities

The User Rights Database: Measuring the Impact of Copyright Balance

International and domestic copyright law reform around the world is increasingly focused on how copyright user rights should be expanded to promote maximum creativity and access to knowledge in the digital age. These efforts are guided by a relatively rich theoretical literature. However, few empirical studies explore the social and economic impact of expanding user rights in the digital era. One reason for this gap has been the absence of a tool measuring the key independent variable – changes in copyright user rights over time and between countries. We developed such a tool, which we call the “User Rights Database.” This paper describes the methodology used to create the Database and the results of empirical tests using it. We find that all of the countries in our study are trending toward more open copyright user rights over time, but the wealthy countries in our sample are about thirty years ahead of developing countries on this measure. We find evidence of benefits that more open copyright user rights generate, including the development of high technology industries and scholarly publication. We do not find evidence that opening user rights causes harm to revenue of copyright intensive industries like publishing and entertainment

Sinonasal mucosal melanoma: Molecular profile and therapeutic implications from a series of 32 cases

BACKGROUND: Primary sinonasal mucosal melanomas are aggressive tumors with a poor clinical control by current treatments, raising the urgent need of novel strategies. METHODS: By fluorescence in situ hybridization (FISH), direct sequencing, and immunohistochemistry, we investigate the spectrum of molecular abnormalities in a cohort of 32 cases of primary sinonasal mucosal melanomas. RESULTS: We found that all primary sinonasal mucosal melanomas lack BRAF V600E mutation; in addition, they are characterized by somatic mutations of NRAS (22%) and KIT (12.5%), together with amplification of RREB1 (100%) and loss of MYB (76%). The large majority of cases showed KIT protein expression (96.9%). Among tumor suppressor genes, primary sinonasal mucosal melanomas showed loss of PTEN (48.1%) and p16/INK4a (55.2%). All tested cases showed expression of pAkt and pErk, suggesting a combined activation of PI3K/Akt and RAS-mitogen-activated protein kinase (MAPK) pathways. CONCLUSIONS: This molecular fingerprint strongly argues against the clinical efficacy of BRAF-inhibitors, but could candidate primary sinonasal mucosal melanomas to therapeutic strategies targeting RAS and KIT mutations or inhibiting PI3K-Akt-mTOR pathway