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

Pendokumentasian Aplikasi Ragam Hias Budaya Bali, sebagai Upaya Konservasi Budaya Bangsa Khususnya pada Perancangan Interior

Various ornament of Indonesian people comes from the ethnic groups from all over the archipelago. As a tangible cultural ornament has a specific purpose and it does not change throughout the ages. Bali is one of the ethnic group in archipelago that has beautiful decorative art and one of the most popular tourism destination in Indonesia. Bali\u27s ornament generally seen as decorative carving on the column, window or even in door. The beauty of Bali is not only as an inspiration for their colors and sculpture but also the variety of forms that have been simplified in the ornament. Moreover, floral & fauna forms are easy to apply as an interior element in modern buildings. Generally the value of these ornament has a specific purpose related to the cultural and social custom in Bali people. So that the application need to consider more about the purpose of the symbol of the ornament

Using data science as a community advocacy tool to promote equity in urban renewal programs: An analysis of Atlanta's Anti-Displacement Tax Fund

Cities across the United States are undergoing great transformation and urban growth. Data and data analysis has become an essential element of urban planning as cities use data to plan land use and development. One great challenge is to use the tools of data science to promote equity along with growth. The city of Atlanta is an example site of large-scale urban renewal that aims to engage in development without displacement. On the Westside of downtown Atlanta, the construction of the new Mercedes-Benz Stadium and the conversion of an underutilized rail-line into a multi-use trail may result in increased property values. In response to community residents' concerns and a commitment to development without displacement, the city and philanthropic partners announced an Anti-Displacement Tax Fund to subsidize future property tax increases of owner occupants for the next twenty years. To achieve greater transparency, accountability, and impact, residents expressed a desire for a tool that would help them determine eligibility and quantify this commitment. In support of this goal, we use machine learning techniques to analyze historical tax assessment and predict future tax assessments. We then apply eligibility estimates to our predictions to estimate the total cost for the first seven years of the program. These forecasts are also incorporated into an interactive tool for community residents to determine their eligibility for the fund and the expected increase in their home value over the next seven years.Comment: Presented at the Data For Good Exchange 201

Diversifying selection and host adaptation in two endosymbiont genomes

Background: The endosymbiont Wolbachia pipientis infects a broad range of arthropod and filarial nematode hosts. These diverse associations form an attractive model for understanding host: symbiont coevolution. Wolbachia's ubiquity and ability to dramatically alter host reproductive biology also form the foundation of research strategies aimed at controlling insect pests and vector-borne disease. The Wolbachia strains that infect nematodes are phylogenetically distinct, strictly vertically transmitted, and required by their hosts for growth and reproduction. Insects in contrast form more fluid associations with Wolbachia. In these taxa, host populations are most often polymorphic for infection, horizontal transmission occurs between distantly related hosts, and direct fitness effects on hosts are mild. Despite extensive interest in the Wolbachia system for many years, relatively little is known about the molecular mechanisms that mediate its varied interactions with different hosts. We have compared the genomes of the Wolbachia that infect Drosophila melanogaster, wMel and the nematode Brugia malayi, wBm to that of an outgroup Anaplasma marginale to identify genes that have experienced diversifying selection in the Wolbachia lineages. The goal of the study was to identify likely molecular mechanisms of the symbiosis and to understand the nature of the diverse association across different hosts. Results: The prevalence of selection was far greater in wMel than wBm. Genes contributing to DNA metabolism, cofactor biosynthesis, and secretion were positively selected in both lineages. In wMel there was a greater emphasis on DNA repair, cell division, protein stability, and cell envelope synthesis. Conclusion: Secretion pathways and outer surface protein encoding genes are highly affected by selection in keeping with host: parasite theory. If evidence of selection on various cofactor molecules reflects possible provisioning, then both insect as well as nematode Wolbachia may be providing substances to hosts. Selection on cell envelope synthesis, DNA replication and repair machinery, heat shock, and two component switching suggest strategies insect Wolbachia may employ to cope with diverse host and intra-host environments

Proportionally Representative Clustering

In recent years, there has been a surge in effort to formalize notions of fairness in machine learning. We focus on clustering -- one of the fundamental tasks in unsupervised machine learning. We propose a new axiom ``proportional representation fairness'' (PRF) that is designed for clustering problems where the selection of centroids reflects the distribution of data points and how tightly they are clustered together. Our fairness concept is not satisfied by existing fair clustering algorithms. We design efficient algorithms to achieve PRF both for unconstrained and discrete clustering problems. Our algorithm for the unconstrained setting is also the first known polynomial-time approximation algorithm for the well-studied Proportional Fairness (PF) axiom (Chen, Fain, Lyu, and Munagala, ICML, 2019). Our algorithm for the discrete setting also matches the best known approximation factor for PF.Comment: Revised version includes a new author (Jeremy Vollen) and new results: Our algorithm for the unconstrained setting is also the first known polynomial-time approximation algorithm for the well-studied Proportional Fairness (PF) axiom (Chen, Fain, Lyu, and Munagala, ICML, 2019). Our algorithm for the discrete setting also matches the best known approximation factor for P

On the Feasibility of Detecting Spacecraft Charging and Arcing by Remote Sensing

t is a sad fact that more than 50 years after the dawn of the space age, most spacecraft still do not have sensors onboard capable of detecting whether they are at potentials likely to put them at risk of severe charging and the concomitant arcing, or indeed, even capable of detecting when or if they undergo arcing. As a result, anomaly resolution has often been hit or miss, and false diagnoses are probably common. Until spacecraft are routinely launched with charging and arcing monitors, the best that can be achieved is detection through remote sensing, from the ground or by satellites. In this paper we examine a few remote sensing techniques that could be applied for detecting spacecraft charging and/or arcing.The first technique considered depends on the fact that when bombarded by high energy electrons, many types of dielectrics emit a glow that could be observed remotely, and would change with the degree of spacecraft charging. Only kilovolt electron strikes are effective at producing the glow. Thus, under geomagnetically calm conditions, if the glow were detected, high energy electron fluxes capable of spacecraft surface charging to kilovolt levels would be indicated. If the space plasma were disturbed, and the spacecraft were thus being charged negatively by a multitude of multi-kilovolt electrons, the ongoing charging would be seen as an enhanced surface glow. Although easily seen in the laboratory, this glow is likely to be too weak to be detected in space except for a satellite in eclipse. However, GEO satellites charge more in eclipse anyway. We will estimate whether the glow can be detected from both Earth and space. The second technique depends on the fact that when electrons above about 20 keV strike a surface, x-rays are produced (through bremsstrahlung). If immersed in a very high-temperature plasma (like that of the famous Galaxy 15 event or the ATS-6 record charging event) a spacecraft may thus be seen by the x-rays that are produced. It is generally conceded that in eclipse a spacecraft will charge negatively (in volts) up to the electron temperature of the surrounding plasma (in eV). Again, detection in eclipse is probably necessary, since solar x-rays reflected by spacecraft surfaces might make daytime detection impossible. This method would likely only indicate when the most severe charging conditions were ongoing, and would of necessity require detection by an orbiting satellite. Finally, when spacecraft arc, the arcs produce electromagnetic radiation. On PASP Plus and other scientific satellites, radio waves produced by arcs were used to determine the arc location, for instance. Arcs in laboratory conditions have been detected solely by radio emission, and oftentimes the visible light emitted is used to determine arc location and timing. While the radio noise produced is severe enough close by to produce radio interference in sensitive spacecraft electronics, it is likely to drop off rapidly, and most probably could only be detected by satellites orbiting nearby. However, the light produced may be substantial, and might be detected by a suitably filtered telescope even on Earth. Also, shortly after an arc, solar array surfaces glow for two reasons – firstly, while the arc is progressing, the coverglass surface is positively charged, and glows from electron excitation at its surface. If the arc does not completely discharge the surface, the glow may continue until ambient electrons collected completely neutralize it. Secondly, some of the cells in the array circuit are back-biased by the arc, and act as light emitting diodes. Both of these missions are broadband and may last for hundreds of microseconds. Possibilities for arc detection from Earth-bound optical and radio telescopes will be discussed

Faces in Places: Humans and Machines Make Similar Face Detection Errors

The human visual system seems to be particularly efficient at detecting faces. This efficiency sometimes comes at the cost of wrongfully seeing faces in arbitrary patterns, including famous examples such as a rock configuration on Mars or a toast's roast patterns. In machine vision, face detection has made considerable progress and has become a standard feature of many digital cameras. The arguably most wide-spread algorithm for such applications (“Viola-Jones” algorithm) achieves high detection rates at high computational efficiency. To what extent do the patterns that the algorithm mistakenly classifies as faces also fool humans? We selected three kinds of stimuli from real-life, first-person perspective movies based on the algorithm's output: correct detections (“real faces”), false positives (“illusory faces”) and correctly rejected locations (“non faces”). Observers were shown pairs of these for 20 ms and had to direct their gaze to the location of the face. We found that illusory faces were mistaken for faces more frequently than non faces. In addition, rotation of the real face yielded more errors, while rotation of the illusory face yielded fewer errors. Using colored stimuli increases overall performance, but does not change the pattern of results. When replacing the eye movement by a manual response, however, the preference for illusory faces over non faces disappeared. Taken together, our data show that humans make similar face-detection errors as the Viola-Jones algorithm, when directing their gaze to briefly presented stimuli. In particular, the relative spatial arrangement of oriented filters seems of relevance. This suggests that efficient face detection in humans is likely to be pre-attentive and based on rather simple features as those encoded in the early visual system

The complement of protein kinases of the microsporidium Encephalitozoon cuniculi in relation to those of Saccharomyces cerevisiae and Schizosaccharomyces pombe.

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.BACKGROUND: Microsporidia, parasitic fungi-related eukaryotes infecting many cell types in a wide range of animals (including humans), represent a serious health threat in immunocompromised patients. The 2.9 Mb genome of the microsporidium Encephalitozoon cuniculi is the smallest known of any eukaryote. Eukaryotic protein kinases are a large superfamily of enzymes with crucial roles in most cellular processes, and therefore represent potential drug targets. We report here an exhaustive analysis of the E. cuniculi genomic database aimed at identifying and classifying all protein kinases of this organism with reference to the kinomes of two highly-divergent yeast species, Saccharomyces cerevisiae and Schizosaccharomyces pombe. RESULTS: A database search with a multi-level protein kinase family hidden Markov model library led to the identification of 29 conventional protein kinase sequences in the E. cuniculi genome, as well as 3 genes encoding atypical protein kinases. The microsporidian kinome presents striking differences from those of other eukaryotes, and this minimal kinome underscores the importance of conserved protein kinases involved in essential cellular processes. Approximately 30% of its kinases are predicted to regulate cell cycle progression while another approximately 28% have no identifiable homologues in model eukaryotes and are likely to reflect parasitic adaptations. E. cuniculi lacks MAP kinase cascades and almost all protein kinases that are involved in stress responses, ion homeostasis and nutrient signalling in the model fungi S. cerevisiae and S. pombe, including AMPactivated protein kinase (Snf1), previously thought to be ubiquitous in eukaryotes. A detailed database search and phylogenetic analysis of the kinomes of the two model fungi showed that the degree of homology between their kinomes of approximately 85% is much higher than that previously reported. CONCLUSION: The E. cuniculi kinome is by far the smallest eukaryotic kinome characterised to date. The difficulty in assigning clear homology relationships for nine out of the twentynine microsporidian conventional protein kinases despite its compact genome reflects the phylogenetic distance between microsporidia and other eukaryotes. Indeed, the E. cuniculi genome presents a high proportion of genes in which evolution has been accelerated by up to four-fold. There are no orthologues of the protein kinases that constitute MAP kinase pathways and many other protein kinases with roles in nutrient signalling are absent from the E. cuniculi kinome. However, orthologous kinases can nonetheless be identified that correspond to members of the yeast kinomes with roles in some of the most fundamental cellular processes. For example, E. cuniculi has clear orthologues of virtually all the major conserved protein kinases that regulate the core cell cycle machinery (Aurora, Polo, DDK, CDK and Chk1). A comprehensive comparison of the homology relationships between the budding and fission yeast kinomes indicates that, despite an estimated 800 million years of independent evolution, the two model fungi share approximately 85% of their protein kinases. This will facilitate the annotation of many of the as yet uncharacterised fission yeast kinases, and also those of novel fungal genomes.Published versio