7,444 research outputs found

    Intellectual Property Rights in Data?

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    The international intellectual property system founded on the Paris and Berne Conventions in the late nineteenth century has been dominated by the patent and copyright paradigms, which articulate the legal protection of technological inventions and of literary and artistic works, respectively. Although this patent-copyright dichotomy was never as strictly observed abroad as in the United States, it nonetheless charted a relatively clear theoretical line of demarcation between legal incentives to create and the public interest in free competition. Any publicly disclosed technologies or information products that failed to meet the eligibility requirements of the domestic patent and copyright laws became public domain matter that anyone could freely appropriate. By the end of the twentieth century, in contrast, this line of demarcation had empirically broken down. The developed market economies, including the United States, enacted numerous special purpose intellectual property laws to protect industrial designs, plant varieties, integrated circuit designs, and other matter that typically failed to meet the eligibility requirements of either the patent or copyright models. The latest, and arguably most deviant, examples of this trend toward sui generis intellectual property rights are the European - and United States-sponsored initiatives in both national and international forums calling for creation of a new form of legal protection for the contents of databases. These initiatives aim to rescue database producers from the threat of market-destructive appropriations by free-riding competitors who contributed nothing to the costs of collecting or distributing the relevant data

    The Human Cytomegalovirus Fc Receptor gp68 Binds the Fc CH2-CH3 Interface of Immunoglobulin G

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    Recognition of immunoglobulin G (IgG) by surface receptors for the Fc domain of immunoglobulin G (Fc{gamma}), Fc{gamma}Rs, can trigger both humoral and cellular immune responses. Two human cytomegalovirus (HCMV)-encoded type I transmembrane receptors with Fc{gamma}-binding properties (vFc{gamma}Rs), gp34 and gp68, have been identified on the surface of HCMV-infected cells and are assumed to confer protection against IgG-mediated immunity. Here we show that Fc{gamma} recognition by both vFc{gamma}Rs occurs independently of N-linked glycosylation of Fc{gamma}, in contrast with the properties of host Fc{gamma}Rs. To gain further insight into the interaction with Fc{gamma}, truncation mutants of the vFc{gamma}R gp68 ectodomain were probed for Fc{gamma} binding, resulting in localization of the Fc{gamma} binding site on gp68 to residues 71 to 289, a region including an immunoglobulin-like domain. Gel filtration and biosensor binding experiments revealed that, unlike host Fc{gamma}Rs but similar to the herpes simplex virus type 1 (HSV-1) Fc receptor gE-gI, gp68 binds to the CH2-CH3 interdomain interface of the Fc{gamma} dimer with a nanomolar affinity and a 2:1 stoichiometry. Unlike gE-gI, which binds Fc{gamma} at the slightly basic pH of the extracellular milieu but not at the acidic pH of endosomes, the gp68/Fc{gamma} complex is stable at pH values from 5.6 to pH 8.1. These data indicate that the mechanistic details of Fc binding by HCMV gp68 differ from those of host Fc{gamma}Rs and from that of HSV-1 gE-gI, suggesting distinct functional and recognition properties

    Relationship Between Static Mobility of the First Ray and First Ray, Midfoot, and Hindfoot Motion During Gait

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    The relationship between a static measure of dorsal first ray mobility and dynamic motion of the first ray, midfoot, and hindfoot during the stance phase of walking was investigated in healthy, asymptomatic subjects who represented the spectrum of static flexibility. Static first ray mobility of 15 subjects was measured by a load cell device and ranged from stiff (3.1 mm) to lax (8.0 mm). Using three-dimensional motion analysis, mean first ray dorsiflexion/eversion and mid-/hindfoot eversion peak motion, time-to-peak, and eversion excursion were evaluated. Subjects with greater static dorsal mobility of the first ray demonstrated significantly greater time-topeak hindfoot eversion and eversion excursion (p \u3c .01), and midfoot peak eversion and eversion excursion (p \u3c .01). No significant association was found between static first ray mobility and first ray motion during gait. This research provides evidence that the dynamic response of the foot may modulate the consequences of first ray mobility and that compensory strategies are most effective when static measures of dorsal mobility are most extreme

    Dislodged teeth in four intact child mummies from Graeco/Roman Egypt (332 BCE – c. 395 CE) – child abuse, accident or careless embalmers?

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    In a computerised tomographic (CT) scanning and x-ray imaging of four ancient Egyptian Graeco/Roman child mummies, it was observed that deciduous teeth had been dislodged and that the cervical spines were flexed. The objective of this study was to determine whether the cause of the tooth loss and spinal flexion were linked or whether they related to ante-mortem accident or abuse.Three mummies were examined using high speed helical CT scanners and the fourth mummy was examined using x-ray film. The images were loaded into an advanced visualisation workstation for further examination and to provide accurate data to identify exfoliated teeth and the flexion of the cervical spine.The age range of the children was approximately eighteen months to six years. The study showed that in two cases the dislodged teeth were within the oral cavity and in the third case the dislodged teeth were found close to empty sockets. In the fourth mummy two upper teeth were dislodged but could not be identified in the oral cavity due to the lack of clarity in the x-ray films.In all cases natural exfoliation or dental extraction as a cause of tooth loss was rejected due to the age of each child and identification of dislodged teeth which lacked evidence of root resorption. The reason for the dislodgement of teeth appeared to be due rough post-mortem handling by embalmers when grasping the mandible to flex the cervical spine and manipulate the head towards the chest. Ante-mortem accident, child abuse, periodontal disease or extractions were rejected as the cause of tooth loss

    Modulation of Natural Killer Cell Cytotoxicity in Human Cytomegalovirus Infection: The Role of Endogenous Class I Major Histocompatibility Complex and a Viral Class I Homolog

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    Natural killer (NK) cells have been implicated in early immune responses against certain viruses, including cytomegalovirus (CMV). CMV causes downregulation of class I major histocompatibility complex (MHC) expression in infected cells; however, it has been proposed that a class I MHC homolog encoded by CMV, UL18, may act as a surrogate ligand to prevent NK cell lysis of CMV-infected cells. In this study, we examined the role of UL18 in NK cell recognition and lysis using fibroblasts infected with either wild-type or UL18 knockout CMV virus, and by using cell lines transfected with the UL18 gene. In both systems, the expression of UL18 resulted in the enhanced killing of target cells. We also show that the enhanced killing is due to both UL18-dependent and -independent mechanisms, and that the killer cell inhibitory receptors (KIRs) and CD94/NKG2A inhibitory receptors for MHC class I do not play a role in affecting susceptibility of CMV-infected fibroblasts to NK cell–mediated cytotoxicity

    Entitlement Reform and the Future of Pensions

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    Reform of retirement and health care entitlements is inevitable, but its ultimate format remains uncertain. Any entitlement reform should take advantage of the additional resources provided by economic growth and the rise in demand for and supply of older workers. Recognizing the potential from those two forces argues for constructing reforms aimed largely at three goals: better orientation of public-sector retirement resources to needier and older populations; removal of obstacles to increased employment of older workers; and private-pension reform that provides the long-sought second tier of support in older ages

    Science-based restoration monitoring of coastal habitats, Volume One: A framework for monitoring plans under the Estuaries and Clean Waters Act of 2000 (Public Law 160-457)

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    Executive Summary: The Estuary Restoration Act of 2000 (ERA), Title I of the Estuaries and Clean Waters Act of 2000, was created to promote the restoration of habitats along the coast of the United States (including the US protectorates and the Great Lakes). The NOAA National Centers for Coastal Ocean Science was charged with the development of a guidance manual for monitoring plans under this Act. This guidance manual, titled Science-Based Restoration Monitoring of Coastal Habitats, is written in two volumes. It provides technical assistance, outlines necessary steps, and provides useful tools for the development and implementation of sound scientific monitoring of coastal restoration efforts. In addition, this manual offers a means to detect early warnings that the restoration is on track or not, to gauge how well a restoration site is functioning, to coordinate projects and efforts for consistent and successful restoration, and to evaluate the ecological health of specific coastal habitats both before and after project completion (Galatowitsch et al. 1998). The following habitats have been selected for discussion in this manual: water column, rock bottom, coral reefs, oyster reefs, soft bottom, kelp and other macroalgae, rocky shoreline, soft shoreline, submerged aquatic vegetation, marshes, mangrove swamps, deepwater swamps, and riverine forests. The classification of habitats used in this document is generally based on that of Cowardin et al. (1979) in their Classification of Wetlands and Deepwater Habitats of the United States, as called for in the ERA Estuary Habitat Restoration Strategy. This manual is not intended to be a restoration monitoring “cookbook” that provides templates of monitoring plans for specific habitats. The interdependence of a large number of site-specific factors causes habitat types to vary in physical and biological structure within and between regions and geographic locations (Kusler and Kentula 1990). Monitoring approaches used should be tailored to these differences. However, even with the diversity of habitats that may need to be restored and the extreme geographic range across which these habitats occur, there are consistent principles and approaches that form a common basis for effective monitoring. Volume One, titled A Framework for Monitoring Plans under the Estuaries and Clean Waters Act of 2000, begins with definitions and background information. Topics such as restoration, restoration monitoring, estuaries, and the role of socioeconomics in restoration are discussed. In addition, the habitats selected for discussion in this manual are briefly described. (PDF contains 116 pages

    Climate Change and the Integrity of Science

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    We are deeply disturbed by the recent escalation of political assaults on scientists in general and on climate scientists in particular. All citizens should understand some basic scientific facts. There is always some uncertainty associated with scientific conclusions; science never absolutely proves anything. When someone says that society should wait until scientists are absolutely certain before taking any action, it is the same as saying society should never take action. For a problem as potentially catastrophic as climate change, taking no action poses a dangerous risk for our planet

    The Herpes Virus Fc Receptor gE-gI Mediates Antibody Bipolar Bridging to Clear Viral Antigens from the Cell Surface

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    The Herpes Simplex Virus 1 (HSV-1) glycoprotein gE-gI is a transmembrane Fc receptor found on the surface of infected cells and virions that binds human immunoglobulin G (hIgG). gE-gI can also participate in antibody bipolar bridging (ABB), a process by which the antigen-binding fragments (Fabs) of the IgG bind a viral antigen while the Fc binds to gE-gI. IgG Fc binds gE-gI at basic, but not acidic, pH, suggesting that IgG bound at extracellular pH by cell surface gE-gI would dissociate and be degraded in acidic endosomes/lysosomes if endocytosed. The fate of viral antigens associated with gE-gI–bound IgG had been unknown: they could remain at the cell surface or be endocytosed with IgG. Here, we developed an in vitro model system for ABB and investigated the trafficking of ABB complexes using 4-D confocal fluorescence imaging of ABB complexes with transferrin or epidermal growth factor, well-characterized intracellular trafficking markers. Our data showed that cells expressing gE-gI and the viral antigen HSV-1 gD endocytosed anti-gD IgG and gD in a gE-gI–dependent process, resulting in lysosomal localization. These results suggest that gE-gI can mediate clearance of infected cell surfaces of anti-viral host IgG and viral antigens to evade IgG-mediated responses, representing a general mechanism for viral Fc receptors in immune evasion and viral pathogenesis
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