PATENTS, R&D AND LAG EFFECTS: EVIDENCE FROM FLEXIBLE METHODS FOR COUNT PANEL DATA ON MANUFACTURING FIRMS

Hausman, Hall and Griliches (1984) and Hall, Griliches and Hausman (1986) investigated whether there was a lag in the patent-R&D relationship for the U.S. manufacturing sector using 1970¿s data. They found that there was little evidence of anything but contemporaneous movement of patents and R&D. We reexamine this important issue employing new longitudinal patent data at the firm level for the U.S. manufacturing sector from 1982 to 1992. To address unique features of the data, we estimate various distributed lag and dynamic multiplicative panel count data models. The paper also develops a new class of count panel data models based on series expansion of the distribution of individual effects. The empirical analyses show that, although results are somewhat sensitive to different estimation methods, the contemporaneous relationship between patenting and R&D expenditures continues to be rather strong, accounting for over 60% of the total R&D elasticity. Regarding the lag structure of the patents-R&D relationship, we do find a significant lag in all empirical specifications. Moreover, the estimated lag effects are higher than have previously been found, suggesting that the contribution of R&D history to current patenting has increased from the 1970¿s to the 1980¿s.Innovative activity, Patents and R&D, Individual effects, count panel data methods.

Competition among Sellers in Securities Auctions

We study simultaneous security-bid second-price auctions with competition among sellers for potential bidders. The sellers compete by designing ordered sets of securities that the bidders can offer as payment for the assets. Upon observing auction designs, potential bidders decide which auctions to enter. We characterize all symmetric equilibria and show that there always exist equilibria in which auctions are in standard securities or their combinations. In large markets the unique equilibrium is auctions in pure cash. We extend the model for competition in reserve prices and show that binding reserve prices never constitute equilibrium as long as equilibrium security designs are not call options. (JEL D44, D82, G10)

Increasing HPV Vaccination in a Network of Pediatric Clinics using a Multi-component Approach

Background: Despite continued public health efforts to increase human papillomavirus (HPV) vaccination among adolescents, initiation remains below the level needed to reach the Healthy People 2020 goal of 80% series completion by age 13. Methods: We developed, implemented, and evaluated a multi-component program that used evidence-based strategies to increase HPV vaccine initiation in a network of 51 pediatric clinics in Houston, Texas. Our target populations were the clinic network, healthcare providers, male and female patients ages 11-17, and their parents. The program, called the Adolescent Vaccination Program (AVP), was conducted from March 2016 through March 2019 and contained strategies to increase vaccination including: HPV immunization champions; provider assessment and feedback; provider continuing education; provider reminders; and patient reminders. We used a single group pre/post design with an external comparison – NIS-Teen. Our primary outcome was initiation of the HPV vaccine based on the electronic health record. We used interrupted time series analysis (ITSA) to measure change in initiation over time. We calculated monthly, quarterly, and annual rates of initiation for each physician, clinic, and the network. We examined patterns of initiation by patient age, sex, race/ethnicity, and type of insurance. Results: By the end of the project, the 51 clinics averaged 77.4% initiation. Rates increased annually from September 2015 through March 2019. ITSA analysis over 75 months showed an increase in vaccine initiation of 0.396% per month from the introduction of the program in March 2016. Average individual clinic improvement was 0.37% per month ranging from -0.04% to 0.68% through March 2019. Data for the 11-12 year olds, the target age group for initiating the vaccine, showed a greater percentage increase (54.2%) compared with the 13-17 year olds (29.6%). Hispanics and African Americans had the highest initiation rates in all years while non-Hispanic whites had the lowest. Families without insurance had the lowest rates while those with Medicaid/Medicare had the highest. Conclusions: We observed a secular trend upward in both the network and NIS-Teen data; however, the network showed a steeper increase. The AVP is a promising program of strategies to increase HPV vaccination in a clinic setting

Characterization of the acidic cold seep emplaced jarositic Golden Deposit, NWT, Canada, as an analogue for jarosite deposition on Mars

Surficial deposits of the OH-bearing iron sulfate mineral jarosite have been observed in several places on Mars, such as Meridiani Planum and Mawrth Vallis. The specific depositional conditions and mechanisms are not known, but by comparing martian sites to analogous locations on Earth, the conditions of formation and, thus, the martian depositional paleoenvironments may be postulated. Located in a cold semi-arid desert ~100 km east of Norman Wells, Northwest Territories, Canada, the Golden Deposit (GD) is visible from the air as a brilliant golden-yellow patch of unvegetated soil, approximately 140 m x 50 m. The GD is underlain by permafrost and consists of yellow sediment, which is precipitating from seeps of acidic, iron-bearing groundwater. On the surface, the GD appears as a patchwork of raised polygons, with acidic waters flowing from seeps in troughs between polygonal islands. Although UV-Vis-NIR spectral analysis detects only jarosite, mineralogy, as determined by X-Ray Diffraction and Inductively Coupled Plasma Emission Spectrometry, is predominantly natrojarosite and jarosite, with hydronium jarosite, goethite, quartz, clays, and small amounts of hematite. Water pH varies significantly over short distances depending on proximity to acid seeps, from 2.3 directly above seeps, to 5.7 several m downstream from seeps within the deposit, and up to 6.5 in ponds proximal to the deposit. Visual observations of microbial filament communities and phospholipid fatty acid analyses confirm that the GD is capable of supporting life for at least part of the year. Jarositic-bearing sediments extend beneath vegetation up to 70 m out from the deposit and are mixed with plant debris and minerals presumably weathered from bedrock and glacial till. This site is of particular interest because mineralogy (natrojarosite, jarosite, hematite, and goethite) and environmental conditions (permafrost and arid conditions) at the time of deposition are conceivably analogous to jarosite deposits on Mars. Most terrestrial analogues for Mars jarosites have been identified in temperate environments, where evaporation rates are very high and jarosites form along with other sulfates due to rapid evaporation (e.g. Rio Tinto, Spain; Western Australian acidic saline lake deposits). The GD is a rare example of an analogue site where jarosite precipitates under dominant freezing processes similar to those which could have prevailed on early Mars. Thus, the GD offers a new perspective on jarosite deposition by the upwelling of acidic waters through permafrost at Meridiani Planum and Mawrth Vallis, Mars. The GD also demonstrates that martian deposits may show considerably more chemical and mineral variability than indicated by the current remote sensing data sets

A Compensatory Mutation Provides Resistance to Disparate HIV Fusion Inhibitor Peptides and Enhances Membrane Fusion

Fusion inhibitors are a class of antiretroviral drugs used to prevent entry of HIV into host cells. Many of the fusion inhibitors being developed, including the drug enfuvirtide, are peptides designed to competitively inhibit the viral fusion protein gp41. With the emergence of drug resistance, there is an increased need for effective and unique alternatives within this class of antivirals. One such alternative is a class of cyclic, cationic, antimicrobial peptides known as θ-defensins, which are produced by many non-human primates and exhibit broad-spectrum antiviral and antibacterial activity. Currently, the θ-defensin analog RC-101 is being developed as a microbicide due to its specific antiviral activity, lack of toxicity to cells and tissues, and safety in animals. Understanding potential RC-101 resistance, and how resistance to other fusion inhibitors affects RC-101 susceptibility, is critical for future development. In previous studies, we identified a mutant, R5-tropic virus that had evolved partial resistance to RC-101 during in vitro selection. Here, we report that a secondary mutation in gp41 was found to restore replicative fitness, membrane fusion, and the rate of viral entry, which were compromised by an initial mutation providing partial RC-101 resistance. Interestingly, we show that RC-101 is effective against two enfuvirtide-resistant mutants, demonstrating the clinical importance of RC-101 as a unique fusion inhibitor. These findings both expand our understanding of HIV drug-resistance to diverse peptide fusion inhibitors and emphasize the significance of compensatory gp41 mutations. © 2013 Wood et al

Conjunctival fibrosis and the innate barriers to Chlamydia trachomatis intracellular infection: a genome wide association study.

Chlamydia trachomatis causes both trachoma and sexually transmitted infections. These diseases have similar pathology and potentially similar genetic predisposing factors. We aimed to identify polymorphisms and pathways associated with pathological sequelae of ocular Chlamydia trachomatis infections in The Gambia. We report a discovery phase genome-wide association study (GWAS) of scarring trachoma (1090 cases, 1531 controls) that identified 27 SNPs with strong, but not genome-wide significant, association with disease (5 × 10(-6) > P > 5 × 10(-8)). The most strongly associated SNP (rs111513399, P = 5.38 × 10(-7)) fell within a gene (PREX2) with homology to factors known to facilitate chlamydial entry to the host cell. Pathway analysis of GWAS data was significantly enriched for mitotic cell cycle processes (P = 0.001), the immune response (P = 0.00001) and for multiple cell surface receptor signalling pathways. New analyses of published transcriptome data sets from Gambia, Tanzania and Ethiopia also revealed that the same cell cycle and immune response pathways were enriched at the transcriptional level in various disease states. Although unconfirmed, the data suggest that genetic associations with chlamydial scarring disease may be focussed on processes relating to the immune response, the host cell cycle and cell surface receptor signalling

Antivirals Reduce the Formation of Key Alzheimer's Disease Molecules in Cell Cultures Acutely Infected with Herpes Simplex Virus Type 1

Alzheimer's disease (AD) afflicts around 20 million people worldwide and so there is an urgent need for effective treatment. Our research showing that herpes simplex virus type 1 (HSV1) is a risk factor for AD for the brains of people who possess a specific genetic factor and that the virus causes accumulation of key AD proteins (β-amyloid (Aβ) and abnormally phosphorylated tau (P-tau)), suggests that anti-HSV1 antiviral agents might slow AD progression. However, currently available antiviral agents target HSV1 DNA replication and so might be successful in AD only if Aβ and P-tau accumulation depend on viral DNA replication. Therefore, we investigated firstly the stage(s) of the virus replication cycle required for Aβ and P-tau accumulation, and secondly whether antiviral agents prevent these changes using recombinant strains of HSV1 that progress only partly through the replication cycle and antiviral agents that inhibit HSV1 DNA replication. By quantitative immunocytochemistry we demonstrated that entry, fusion and uncoating of HSV1, are insufficient to induce Aβ and P-tau production. We showed also that none of the “immediate early” viral proteins is directly responsible, and that Aβ and P-tau are produced at a subsequent stage of the HSV1 replication cycle. Importantly, the anti-HSV1 antiviral agents acyclovir, penciclovir and foscarnet reduced Aβ and P-tau accumulation, as well as HSV1, with foscarnet being less effective in each case. P-tau accumulation was found to depend on HSV1 DNA replication, whereas Aβ accumulation was not. The antiviral-induced decrease in Aβ is attributable to the reduced number of new viruses, and hence the reduction in viral spread. Since antiviral agents reduce greatly Aβ and P-tau accumulation in HSV1-infected cells, they would be suitable for treating AD with great advantage unlike current AD therapies, only the virus, not the host cell, would be targeted

Modulation of Drosophila Retinal Epithelial Integrity by the Adhesion Proteins Capricious and Tartan

Background The development of the Drosophila eye imaginal disc requires complex epithelial rearrangements. Cells of the morphogenetic furrow are apically constricted and this leads to a physical indentation in the epithelium. Posterior to the furrow, cells start to rearrange into distinct clusters and eventually form a precisely patterned array of ommatidia. These morphogenetic processes include regulated changes of adhesion between cells. Methodology/Principal Findings Here, we show that two transmembrane adhesion proteins, Capricious and Tartan, have dynamic and complementary expression patterns in the eye imaginal disc. We also describe novel null mutations in capricious and double null mutations in capricious and tartan. We report that they have redundant functions in regulating the architecture of the morphogenetic furrow and ommatidial spacing. Conclusions/Significance We conclude that Capricious and Tartan contribute to the adhesive properties of the cells in the morphogenetic furrow and that this regulated adhesion participates in the control of spacing ommatidial clusters

The 2016 UK Space Agency Mars Utah Rover Field Investigation (MURFI)

The 2016 Mars Utah Rover Field Investigation (MURFI) was a Mars rover field trial run by the UK Space Agency in association with the Canadian Space Agency's 2015/2016 Mars Sample Return Analogue Deployment mission. MURFI had over 50 participants from 15 different institutions around the UK and abroad. The objectives of MURFI were to develop experience and leadership within the UK in running future rover field trials; to prepare the UK planetary community for involvement in the European Space Agency/Roscosmos ExoMars 2020 rover mission; and to assess how ExoMars operations may differ from previous rover missions. Hence, the wider MURFI trial included a ten-day (or ten-‘sol’) ExoMars rover-like simulation. This comprised an operations team and control centre in the UK, and a rover platform in Utah, equipped with instruments to emulate the ExoMars rovers remote sensing and analytical suite. The operations team operated in ‘blind mode’, where the only available data came from the rover instruments, and daily tactical planning was performed under strict time constraints to simulate real communications windows. The designated science goal of the MURFI ExoMars rover-like simulation was to locate in-situ bedrock, at a site suitable for sub-surface core-sampling, in order to detect signs of ancient life. Prior to “landing”, the only information available to the operations team were Mars-equivalent satellite remote sensing data, which were used for both geologic and hazard (e.g., slopes, loose soil) characterisation of the area. During each sol of the mission, the operations team sent driving instructions and imaging/analysis targeting commands, which were then enacted by the field team and rover-controllers in Utah. During the ten-sol mission, the rover drove over 100 m and obtained hundreds of images and supporting observations, allowing the operations team to build up geologic hypotheses for the local area and select possible drilling locations. On sol 9, the team obtained a subsurface core sample that was then analyzed by the Raman spectrometer. Following the conclusion of the ExoMars-like component of MURFI, the operations and field team came together to evaluate the successes and failures of the mission, and discuss lessons learnt for ExoMars rover and future field trials. Key outcomes relevant to ExoMars rover included a key recognition of the importance of field trials for (i) understanding how to operate the ExoMars rover instruments as a suite, (ii) building an operations planning team that can work well together under strict time-limited pressure, (iii) developing new processes and workflows relevant to the ExoMars rover, (iv) understanding the limits and benefits of satellite mapping and (v) practicing efficient geological interpretation of outcrops and landscapes from rover-based data, by comparing the outcomes of the simulated mission with post-trial, in-situ field observations. In addition, MURFI was perceived by all who participated as a vital learning experience, especially for early and mid-career members of the team, and also demonstrated the UK capability of implementing a large rover field trial. The lessons learnt from MURFI are therefore relevant both to ExoMars rover, and to future rover field trials

The Science of Sungrazers, Sunskirters, and Other Near-Sun Comets

This review addresses our current understanding of comets that venture close to the Sun, and are hence exposed to much more extreme conditions than comets that are typically studied from Earth. The extreme solar heating and plasma environments that these objects encounter change many aspects of their behaviour, thus yielding valuable information on both the comets themselves that complements other data we have on primitive solar system bodies, as well as on the near-solar environment which they traverse. We propose clear definitions for these comets: We use the term near-Sun comets to encompass all objects that pass sunward of the perihelion distance of planet Mercury (0.307 AU). Sunskirters are defined as objects that pass within 33 solar radii of the Sun’s centre, equal to half of Mercury’s perihelion distance, and the commonly-used phrase sungrazers to be objects that reach perihelion within 3.45 solar radii, i.e. the fluid Roche limit. Finally, comets with orbits that intersect the solar photosphere are termed sundivers. We summarize past studies of these objects, as well as the instruments and facilities used to study them, including space-based platforms that have led to a recent revolution in the quantity and quality of relevant observations. Relevant comet populations are described, including the Kreutz, Marsden, Kracht, and Meyer groups, near-Sun asteroids, and a brief discussion of their origins. The importance of light curves and the clues they provide on cometary composition are emphasized, together with what information has been gleaned about nucleus parameters, including the sizes and masses of objects and their families, and their tensile strengths. The physical processes occurring at these objects are considered in some detail, including the disruption of nuclei, sublimation, and ionisation, and we consider the mass, momentum, and energy loss of comets in the corona and those that venture to lower altitudes. The different components of comae and tails are described, including dust, neutral and ionised gases, their chemical reactions, and their contributions to the near-Sun environment. Comet-solar wind interactions are discussed, including the use of comets as probes of solar wind and coronal conditions in their vicinities. We address the relevance of work on comets near the Sun to similar objects orbiting other stars, and conclude with a discussion of future directions for the field and the planned ground- and space-based facilities that will allow us to address those science topics