Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Gas recognition based on the physicochemical parameters determined by monitoring diffusion rates in microfluidic channels

This paper was presented at the 4th Micro and Nano Flows Conference (MNF2014), which was held at University College, London, UK. The conference was organised by Brunel University and supported by the Italian Union of Thermofluiddynamics, IPEM, the Process Intensification Network, the Institution of Mechanical Engineers, the Heat Transfer Society, HEXAG - the Heat Exchange Action Group, and the Energy Institute, ASME Press, LCN London Centre for Nanotechnology, UCL University College London, UCL Engineering, the International NanoScience Community, www.nanopaprika.eu.Monitoring the diffusion progress rates of different gases in a microfluidic channel affords their discrimination by the comparison of their temporal profiles in a high-dimensional feature space. Here, we demonstrate gas recognition by determination of their three important physicochemical parameters via a model-based examination of the experimentally determined diffusion rates in two different cross-section channels. The system utilized comprises two channels with respective cross-sectional diameters of 1000 μm and 50 μm. The open end of both channels are simultaneously exposed to the analyte, and the temporal profiles of the diffusion rates are recorded by continuous resistance measurements on the chemoresistive sensors spliced to the channels at their other ends. Fitting the solutions of the diffusion equation to the experimental profiles obtained from the large cross-section channel results in the diffusivity of the analyte. The results of small cross-section channel, however, fit the solutions of a modified diffusion equation which accounts for the adsorption of the analyte molecules to the channel walls, as well. The latter fitting process results in the adsorption parameter for the analyte-channel wall interactions and the population of the effective adsorption sites on the unit area of the walls. The allocation of these three meaningful parameters to an unknown gaseous analyte affords its recognition

Aerospace medicine and biology: A continuing bibliography with indexes (supplement 352)

This bibliography lists 147 reports, articles and other documents introduced into the NASA Scientific and Technical Information System during July 1991. Subject coverage includes: aerospace medicine and psychology, life support systems and controlled environments, safety equipment, exobiology and extraterrestrial life, and flight crew behavior and performance

Aerospace medicine and biology. A continuing bibliography with indexes, supplement 224

This bibliography lists 127 reports, articles, and other documents introduced into the NASA scientific and technical information system in September 1981

Patent Landscape of Influenza A Virus Prophylactic Vaccines and Related Technologies

Executive Summary: This report focuses on patent landscape analysis of technologies related to prophylactic vaccines targeting pandemic strains of influenza. These technologies include methods of formulating vaccine, methods of producing of viruses or viral subunits, the composition of complete vaccines, and other technologies that have the potential to aid in a global response to this pathogen. The purpose of this patent landscape study was to search, identify, and categorize patent documents that are relevant to the development of vaccines that can efficiently promote the development of protective immunity against pandemic influenza virus strains. The search strategy used keywords which the team felt would be general enough to capture (or “recall”) the majority of patent documents which were directed toward vaccines against influenza A virus. After extensive searching of patent literature databases, approximately 33,500 publications were identified and collapsed to about 3,800 INPADOC families. Relevant documents, almost half of the total, were then identified and sorted into the major categories of vaccine compositions (about 570 families), technologies which support the development of vaccines (about 750 families), and general platform technologies that could be useful but are not specific to the problems presented by pandemic influenza strains (about 560 families). The first two categories, vaccines and supporting technologies, were further divided into particular subcategories to allow an interested reader to rapidly select documents relevant to the particular technology in which he or she is focused. This sorting process increased the precision of the result set. The two major categories (vaccines and supporting technologies) were subjected to a range of analytics in order to extract as much information as possible from the dataset. First, patent landscape maps were generated to assess the accuracy of the sorting procedure and to reveal the relationships between the various technologies that are involved in creating an effective vaccine. Then, filings trends are analyzed for the datasets. The country of origin for the technologies was determined, and the range of distribution to other jurisdictions was assessed. Filings were also analyzed by year, by assignee, and by inventor. Finally, the various patent classification systems were mapped to find which particular classes tend to hold influenza vaccine-related technologies. Besides the keywords developed during the searches and the landscape map generation, the classifications represent an alternate way for further researchers to identify emerging influenza technologies. The analysis included creation of a map of keywords, as shown above, describing the relationship of the various technologies involved in the development of prophylactic influenza A vaccines. The map has regions corresponding to live attenuated virus vaccines, subunit vaccines composed of split viruses or isolated viral polypeptides, and plasmids used in DNA vaccines. Important technologies listed on the map include the use of reverse genetics to create reassortant viruses, the growth of viruses in modified cell lines as opposed to the traditional methods using eggs, the production of recombinant viral antigens in various host cells, and the use of genetically-modified plants to produce virus-like particles. Another major finding was that the number of patent documents related to influenza being published has been steadily increasing in the last decade, as shown in the figure below. Until the mid-1990s, there were only a few influenza patent documents being published each year. The number of publications increased noticeably when TRIPS took effect, resulting in publication of patent applications. However, since 2006 the number of vaccine publications has exploded. In each of 2011 and 2012, about 100 references disclosing influenza vaccine technologies were published. Thus, interest in developing new and more efficacious influenza vaccines has been growing in recent years. This interest is probably being driven by recent influenza outbreaks, such as the H5N1 (bird flu) epidemic that began in the late 1990s and the 2009 H1N1 (swine flu) pandemic. The origins of the vaccine-related inventions were also analyzed. The team determined the country in which the priority application was filed, which was taken as an indication of the country where the invention was made or where the inventors intended to practice the invention. By far, most of the relevant families originated with patent applications filed in the United States. Other prominent priority countries were the China and United Kingdom, followed by Japan, Russia, and South Korea. France was a significant priority country only for supporting technologies, not for vaccines. Top assignees for these families were mostly large pharmaceutical companies, with the majority of patent families coming from Novartis, followed by GlaxoSmithKline, Pfizer, U.S. Merck (Merck, Sharpe, & Dohme), Sanofi, and AstraZeneca. Governmental and nonprofit institutes in China, Japan, Russia, South Korea and the United States also are contributing heavily to influenza vaccine research. Lastly, the jurisdictions were inventors have sought protection for their vaccine technologies were determined, and the number of patent families filing in a given country is plotted on the world map shown on page seven. The United States, Canada, Australia, Japan, South Korea and China have the highest level of filings, followed by Germany, Brazil, India, Mexico and New Zealand. However, although there are a significant number of filings in Brazil, the remainder of Central and South America has only sparse filings. Of concern, with the exception of South Africa, few other African nations have a significant number of filings. In summary, the goal of this report is to provide a knowledge resource for making informed policy decisions and for creating strategic plans concerning the assembly of efficacious vaccines against a rapidly-spreading, highly virulent influenza strain. The team has defined the current state of the art of technologies involved in the manufacture of influenza vaccines, and the important assignees, inventors, and countries have been identified. This document should reveal both the strengths and weaknesses of the current level of preparedness for responding to an emerging pandemic influenza strain. The effects of H5N1 and H1N1 epidemics have been felt across the globe in the last decade, and future epidemics are very probable in the near future, so preparations are necessary to meet this global health threat

Aerospace medicine and biology: A continuing bibliography with indexes (supplement 349)

This bibliography lists 149 reports, articles and other documents introduced into the NASA Scientific and Technical Information System during April, 1991. Subject coverage includes: aerospace medicine and psychology, life support systems and controlled environments, safety equipment, exobiology and extraterrestrial life, and flight crew behavior and performance

Preliminary Report on Patent Literature, Search Methodology and Patent Status of Medicines on the WHO EML 2009

Over the past several decades the World Health Organization (WHO) has produced the Essential Medicines List (EML) to assist countries in deciding what medicines should be essential and available in National Essential Medicine Lists.1 WHO, through the work of regional offices, supports nations using the EML to ensure the quality, availability, and affordability of pharmaceuticals required to promote and advance public health in nations across the globe. However in some cases, access to EML pharmaceuticals might be complicated by existing patents, i.e., where issued, patent rights might pose obstacles to access and inclusion in national EMLs. Indeed, in developed and emerging economy national jurisdictions patent protection may be in effect for a not insignificant number of the WHO EML pharmaceuticals (Figure 2A). However, in developing countries, it is uncertain whether these patents have been filed or issued. Without patent data predicated on an established, reproducible protocol for accessing and assembling patent information on the EML pharmaceuticals, discussions, debates and strategic approaches to understanding and managing patents with regard to access and delivery to developing countries remain in the dark. Indeed, it is absurd to make policy and formulate strategy without solid patent information: the critical foundation for rational debate. To analyze the degree and scope of patenting of EML pharmaceuticals, WIPO (with WHO) approached the Franklin Pierce Center for Intellectual Property at the University of New Hampshire School of Law, specifically the International Technology Transfer Institute (ITTI) to generate a preliminary overview of patents appurtenant to recently added pharmaceutical updates to the EML.2 As part of this work, with inputs from WHO and WIPO, ITTI developed novel methodology and a detailed protocol for identifying EML pharmaceutical patents in national jurisdictions, with an easily reproducible yet cost effective template. Herein is described the development of such a protocol and a preliminary pool of patent information that illustrates its utility. The protocol yields data in a layered approach thereby allowing a user to quickly and effectively obtain both broad and detailed patent information for medications on the WHO EML. In addition, the protocol can be used as an initial path for targeted strategic analysis of potentially relevant patent information in national jurisdictions. In sum, the objectives for this project were: To develop a robust methodology to assess the patent status of medicines on the WHO Model List of Essential Medicines; To place in the public domain a detailed report on the present (2010) patent status of medicines that were on patent in 2003 and those medicines added to the Model List since 2003 by country and level of development; and To analyze the patent status of these Essential Medicines by the development status of countries. The report describes the development of the protocol and presents a preliminary list of EML and corresponding patents in certain jurisdictions to illustrate the utility of the approach. Results will be discussed both in terms of global access and patents, and in the context of establishing standard, systematic, protocols for periodic patent searches related to EML content. 1 WORLD HEALTH ORGANIZATION, CONTINUITY AND CHANGE IMPLEMENTING THE THIRD WHO MEDICINES STRATEGY 2008--‐2013 20 (WHO Press, 3rd ed. 2009). 2 This report covers the EML up to and including updates until 2009