PATSTAT revisited

This study provides a comprehensive summary of and guidance for using the EPO Worldwide Patent Statistical Database (PATSTAT), one of the most widely used patent databases for researchers. We highlight the three most important issues that PATSTAT users must consider when performing patent data analyses and suggest ways to deal with those issues. Although PATSTAT is chosen in this study, the issues that we discuss are also applicable to other patent databases.

p53-independent apoptosis induced by paclitaxel through an indirect mechanism

The efficacy of chemotherapeutic agents may be determined by a number of different factors, including the genotype of the tumor cell. The p53 tumor suppressor gene frequently is mutated in human tumors, and this may contribute to chemotherapeutic resistance. We tested the requirement for wild-type p53 in the response of tumor cells to treatment with paclitaxel (trade name Taxol), an antineoplastic agent that stabilizes cellular microtubules. Although paclitaxel is broadly effective against human tumor xenografts in mice, including some known to carry p53 mutations, we found that p53-containing mouse tumor cells were significantly more sensitive to direct treatment with this drug than were p53-deficient tumor cells. In an attempt to reconcile this apparent discrepancy, we examined the requirement for p53 in the cytotoxic effects of tumor necrosis factor α (TNF-α), a cytokine released from murine macrophages upon paclitaxel treatment. Conditioned medium from paclitaxel-treated macrophages was capable of inducing p53-independent apoptosis when applied to transformed mouse embryonic fibroblasts and was inhibitable by antibodies against TNF-α. Furthermore, in response to direct treatment with TNF-α, both wild-type and p53-deficient tumor cells underwent apoptosis to similar extents and with similar kinetics. Our results suggest that the efficacy of paclitaxel in vivo may be due not only to its microtubule-stabilizing activity, but its ability to activate local release of an apoptosis-inducing cytokine.

The road not taken*

The annual Janet Doe Lecture was established in l966 to honor Janet Doe, emerita librarian of the New York Academy of Medicine. The lecture focuses on either the history or philosophy of health sciences librarianship. This lecture addresses three fundamental values of the field, highlighting basic beliefs of the profession that are at risk: privacy, intellectual property rights, and access to quality information. It calls upon readers to make the everyday choices required to keep the value system of health sciences librarianship in place. Robert Frost's poignant poem ”The Road Not Taken” provides the metaphor for examining choices in an information economy.

Genome projects and gene pools: New germplasm for plant breeding?

Crop gene pools have adapted to and sustained the demands of agricultural systems for thousands of years. Yet, very little is known about their content, distribution, architecture, or circuitry. The presumably shallow elite gene pools often continue to yield genetic gains while the exotic pools remain mostly untapped, uncharacterized, and underutilized. The concept and content of a crop’s gene pools are being changed by advancements in plant science and technology. In the first generation of plant genomics, DNA markers have refined some perceptions of genetic variation by providing a glimpse of a primary source, DNA polymorphism. The markers have provided new and more powerful ways of assessing genetic relationships, diversity, and merit by infusing genetic information for the first time in many scenarios or in a more comprehensive manner for others. As a result, crop gene pools may be supplemented through more rapid and directed methods from a greater variety of sources. Previously limited by the barriers of sexual reproduction, the native gene pools will soon be complemented by another gene pool (transgenes) and perhaps by other native exotic gene pools through comparative analyses of plants’ biological repertoire. Plant genomics will be an important force of change for crop improvement. The plant science community and crop gene pools may be united and enriched as never before. Also, the genomes and gene pools, the products of evolution and crop domestication, will be reduced and subjected to the vagaries and potential divisiveness of intellectual property considerations. Let the gains begin.

Poder da marca: interações entre direito antitruste e direito industrial

O presente trabalho busca analisar os diferentes tratamentos dispensados à marca no âmbito do controle preventivo e no controle repressivo de condutas. A análise da função social das marcas demonstrou que esta é uma propriedade que se realiza na concorrência e pela concorrência. Nesse sentido, não há dúvidas de que está sujeita aos princípios do Direito Concorrencial. Todavia, a maneira como esses princípios balizam a marca no controle de atos de concentração, de um lado, e no controle repressivo de condutas, de outro, difere. No âmbito do controle de atos de concentração, a atuação da autoridade concorrencial é orientada por uma variante do princípio da precaução, o que a autoriza a tomar decisões e impor restrições aos direitos marcários mesmo em um contexto de incerteza. No âmbito do controle repressivo de condutas, todavia, a intervenção do CADE está sujeita aos princípios do Processo Administrativo Sancionador. Neste contexto, as condutas que envolvem o uso de direitos de propriedade intelectual, incluindo as marcas, devem ser analisadas à luz do princípio da estrita legalidade. Um critério jurídico objetivo é necessário para distinguir o lícito do ilícito, sobretudo em um cenário no qual estão em jogo duas políticas públicas distintas: a de proteção à concorrência e a de proteção à direitos de propriedade industrial. Sendo essas duas políticas instrumentais e parciais, voltadas a um fim maior de política econômica, devem harmonizar-se, e não sobrepor-se uma a outra. Ademais, o escopo de atuação da autoridade concorrencial em processos que investiguem o uso abusivo de direitos marcários e atos de concorrência desleal deve ser esclarecido. O direito concorrencial, enquanto ramo autônomo do direito, com princípios e métodos interpretativos próprios, pode analisar institutos e figuras de outros ramos que com ele guardem relação sem ter de ficar adstrito ao posicionamento de outras instâncias.

Da patenteabilidade de genes humanos

São inegáveis o caráter universal e a importância dos avanços tecnológicos e científicos originados das pesquisas genéticas. O sequenciamento do genoma humano, a identificação das principais sequências de DNA contidas nos seus genes e suas respectivas funções biológicas, bem como suas possíveis aplicações biomédicas, são de incalculável importância. Os genes, muito embora possam ser biologicamente caracterizados como compostos químicos, possuem um conteúdo informacional que se revela indispensável ao desenvolvimento da engenharia genética, figurando como elemento básico e central de suporte às inovações biotecnológicas. Desta forma, importante analisar a relevância da aplicação de mecanismos jurídicos como forma de fomento à contínua evolução biotecnológica sob a ótica do desenvolvimento econômico e social do país, princípios constitucionais justificadores da proteção de referidos desenvolvimentos técnicos por meio do intelecto e intervenção humanos na natureza. Para tanto, deve-se levar em consideração que a inexistência de tutela jurídica específica pode gerar desincentivo aos investimentos capazes de possibilitar o desenvolvimento de tais tecnologias, ao passo que uma tutela jurídica muito ampla poderá ocasionar indevida restrição ao acesso a tais insumos biológicos, de modo a gerar um efeito adverso àquele buscado. Assim, deve-se compatibilizar a proteção dos resultados obtidos através do desenvolvimento biotecnológico em relação à potencial dificuldade originada de uma eventual restrição ao acesso a tais elementos fundamentais à pesquisa e desenvolvimento genéticos. É neste contexto que se procura um balizamento entre os diferentes interesses e posicionamentos a respeito da patenteabilidade dos genes humanos, visando solução jurídica que permita um ambiente seguro e propício ao desenvolvimento da engenharia genética, e dos inúmeros benefícios que poderão daí se originar. O presente estudo se voltará, portanto, à análise da necessidade, condições, suficiência e extensão da tutela jurídica a ser conferida pela outorga de direitos patentários aos genes humanos.

Identity Entrepreneurs

In my previous article Racial Capitalism, I examined the ways in which white individuals and predominantly white institutions derive value from non-white racial identity. This process flows from our intense social and legal preoccupation with diversity. And it results in the commodification of non-white racial identity, with negative implications for both individuals and society. This Article picks up where Racial Capitalism left off in three ways. As a foundation, it first expands the concept of racial capitalism to identity categories more generally, explaining that individual in-group members and predominantly in-group institutions — usually individuals or institutions that are white, male, straight, wealthy, and so on — can and do derive value from out-group identities. Second, the Article turns from the overarching system of identity capitalism to the myriad ways that individual out-group members actively participate in that system. In particular, I examine how out-group members leverage their out-group status to derive social and economic value for themselves. I call such out-group participants identity entrepreneurs. Identity entrepreneurship is neither inherently good nor inherently bad. Rather, it is a complicated phenomenon with both positive and negative consequences. Finally, the Article considers the appropriate response to identity entrepreneurship. We should design laws and policies to maximize both individual agency and access to information for out-group members. Such reforms would protect individual choice while making clear the consequences of identity entrepreneurship both for individual identity entrepreneurs and for the out-group as a whole. A range of legal doctrines interact with and influence identity entrepreneurship, including employment discrimination under Title VII, rights of privacy and publicity, and intellectual property. Modifying these doctrines to take account of identity entrepreneurship will further progress toward an egalitarian society in which in-group and out-group identities are valued equally.

An Introduction to Conservation Easements in the United States: A Simple Concept and a Complicated Mosaic of Law

The idea of a conservation easement – restrictions on the development and use of land designed to protect the land’s conservation or historic values – can be relatively easily understood. More significant and more challenging is the complex body of state and federal laws that shapes the creation, funding, tax treatment, enforcement, modification, and termination of conservation easements. The explosion in the number of conservation easements over the past four decades has made them one of the most popular land protection mechanisms in the United States. The National Conservation Easement Database estimates that the total number of acres encumbered by conservation easements exceeds 40 million.Because conservation easements are both novel and ubiquitous, understanding how they actual work is essential for practicing lawyers, policymakers, land trust professionals, and students of conservation. This article provides a “quick tour” through some of the most important aspects of the developing mosaic of conservation easement law. It gives the reader a sense of the complex inter-jurisdictional dynamics that shape conservation transactions and disputes about conservation easements. Professors of property law, environmental law, tax law, and environmental studies who wish to cover conservation easements in the context of a more general course can use the article to provide their students with a broad but comprehensive overview of the relevant legal and policy issues.

Causation and Harm in a Multicomponent World

On September 17, 2015, the Federal Circuit issued another decision in the epic Apple v. Samsung smartphone war. This was the fourth court decision in the ongoing saga to deal with injunctions. Apple IV explained the level of proof necessary to satisfy the "causal nexus" requirement. This requirement had emerged as a response to patent litigations involving products with thousands of features, the vast majority of which are unrelated to the asserted patent. To prove a causal nexus, patentees seeking an injunction have to do more than just show that the infringing product caused the patentee irreparable harm. The harm must be specifically attributable to the infringing feature. In Apple IV, the Federal Circuit noted that proving causation was "nearly impossible" in these multicomponent cases. So it decided to water down the causal nexus requirement saying that it was enough for Apple to show that the infringing features were "important"and customer sought these particular features. This lower standard is an ill-advised mistake that leaves multicomponent product manufacturers more susceptible to patent holdup. My critique takes two parts. First, I argue that a single infringing feature rarely, if ever, "causes" consumers to buy the infringer’s multicomponent products. The minor features at issue in Apple IV illustrate this point vividly. Thus, the new causal nexus standard does not accurately reflect how causation and harm operate in a multicomponent world. Second, I explain why the court was so willing to accept such little evidence of real injury. It improperly applied notions of traditional property law to patents. Specifically, the court viewed patent infringement as harmful regardless of any concrete consequences. This view may resonate for other forms of property where an owner's rights are paramount and a trespass is considered offensive in and of itself. But the same concepts do not apply to patent law where the Supreme Court has consistently said that private interests must take a back seat to the public good. Based on these principles, the courts should restore the "causal nexus" requirement and not presume causation.

THE DESIGN AND SYNTHESIS OF SILOXANE PRECURSORS FOR CHIRAL PERIODIC MESOPOROUS ORGANOSILICA MATERIALS

The development of cost-effective and reliable methods for the synthesis and separation of asymmetric compounds is paramount in helping to meet society’s ever-growing demand for chiral small molecules. Of these methods, chiral heterogeneous supports are particularly appealing as they allow for the reuse of the chiral source. One such support, based on the synergy between chiral organic units and structurally stable inorganic silicon scaffolds are periodic mesoporous organosilicas (PMOs). In the work described herein, I examine some of the factors governing the transmission of chirality between chiral dopants and prochiral bulk phases in chiral PMO materials. In particular, the exploration of 1,1’-binaphthalene-bridged chiral dopants with a focus on the point of attachment into the materials. Moreover, the effects of ordering in the materials are examined and reveal that chirality transfer is more facile in materials with molecular-scale order then those containing amorphous walls. Secondly, the issues surrounding the synthesis and purification of aryl-triethoxysilanes as siloxane precursors are addressed. Both the introduction of a two-carbon linker and the direct attachment of allyl and mixed allyldiethoxysilane species are explored. This work demonstrates that allyldiethoxysilanes are ideal, in that they are stable enough to permit facile synthesis, while still being able to hydrolyze completely to produce well-ordered materials. Lastly, the production of new bulk phases for chiral PMO materials is examined by introducing new prochiral nitrogen-containing siloxane precursors. Biphenyldiamine and bipyridine-bridged siloxane precursors are readily synthesized on reasonable scales. Their use as the bulk siloxane precursor in the production of PMO materials however, is precluded by insufficient gelation and additional siloxane precursors are necessary for the production of ordered materials. In addition to the research detailed above that forms the body of this thesis, two short works are appended. The first details the production of polythiophene assemblies mediated through coordination nanospaces, while the second explores the production of N-heterocyclic carbene functionalized gold nanoparticles through ligand exchange.

ROCK OUTCROPS IN THE CANADIAN SHIELD: AN INVESTIGATION OF CONTAMINANT TRANSPORT FROM SURFACE SOURCES IN FRACTURED ROCK AQUIFERS

Flow, recharge and transport dynamics in fractured rock aquifers with low lying rock outcrops is a largely unexplored area of study in hydrogeology. The purpose of this thesis is to examine these topics in an agricultural area in Eastern Ontario. The study consists of a regional scale groundwater quality study, an infiltration experiment that considers bacteria transport from the ground surface to a well, and a numerical modelling study that tests the parameters that affect surface infiltration of a tracer from a rock outcrop to a deeper horizontal fracture. In the water quality study, approximately 65% of the samples contained total coliform, 16% contained E. coli, and 1% contained nitrate-N at greater than 5 mg/L. Occurrence of E. coli increased when considering seasonality, where wells were drilled on rock outcrops, and for shallow well intervals. Nitrate-N did not occur above the Guidelines for Canadian Drinking Water Quality (Health Canada, 2012) of 10 mg/L. Rapid arrival times were observed in the infiltration study for both the microspheres (30 minutes) and a dye tracer (45 minutes) in a well approximately 6.0 m in horizontal and 2.8 m in vertical distance from the tracer source. Transport velocities were approximately 38.9 m/day for the dye tracer and 115.2 m/day for the colloidal tracer. Results of the model runs indicate that overburden can provide an effective protective layer to transport in fractures, that high groundwater velocities occur in larger fracture apertures and higher gradients dilute tracer concentrations, and that lower groundwater velocities occur with smaller fracture apertures and lower gradients result in elevated tracer concentrations. Lower rainfall rates, larger fracture apertures, early tracer time, larger gradients, and lower water levels maintained unsaturated conditions for longer time periods such that tracer transport was delayed until saturated conditions were attained. The overall heterogeneity of this aquifer environment creates a source water protection conundrum where the water quality is generally good, while transport can occur very quickly in proximity to rock outcrops and in areas with limited overburden.

"Fit Cradle of the Reviving Art": An inquiry into the the Evolving Material Reality of the Murals in the Camposanto of Pisa from the Perspective of their British Reception from the 17th to the 19th century

The Camposanto of Pisa is an extraordinarily complex and evocative monument, which has captured the imagination of pilgrims, both religious and secular, for centuries. The late Medieval and early Renaissance wall paintings that line the perimeter of the portico surrounding a vast inner courtyard, are unparalleled in early Italian art, not only for their striking variety of composition and narrative complexity, but also for the sheer grandeur of their proportion. However, the passage of time has scarred the structure of the Camposanto and inflicted terrible damage on its wall paintings. This thesis explores the material reality of the Camposanto as experienced over three centuries through the eyes of British travelers. In order to situate the Camposanto mural cycle within an historical and cultural context, the first chapter provides an overview of the construction and decoration of the monument. Notably, Giorgio Vasari (1511-1574), the Italian Humanist often recognized as the father of art history, included numerous descriptions of the Camposanto murals in his highly influential text Vite de' più eccellenti pittori, scultori, ed architettori. Accordingly, the second chapter provides an analysis of Vasari’s descriptions and reflects upon the influence that the Renaissance author may have had upon the subsequent British reception of the Camposanto murals. The third chapter utilizes three centuries of travel writing in order to investigate the aesthetic impact of the Camposanto mural cycle upon British tourists from the seventeenth through to the nineteenth century.

SOCIAL, EMOTIONAL, COGNITIVE, AND PHYSIOLOGICAL CORRELATES OF ELECTRONIC SOCIAL BEHAVIOR

There has been very little research that has studied the capacities that can be fostered to mitigate the risk for involvement in electronic bullying or victimization and almost no research examining positive electronic behavior. The primary goal of this dissertation was to use the General Aggression Model and Anxious Apprehension Model of Trauma to explore the underlying cognitive, emotional, and self-regulation processes that are related to electronic bullying, victimization, and prosocial behavior. In Study 1, we explored several potential interpretations of the General Aggression Model that would accurately describe the relationship that electronic self-conscious appraisal, cognitive reappraisal, and activational control may have with electronic bullying and victimization. In Study 2, we used the Anxious Apprehension Model of Trauma to explore rejection cognitions as the mediator of the relationships among emotionality (emotionality, shame, state emotion responses, and physiological arousal) and electronic bullying and victimization using structural equation modelling. In addition, we explored the role of rejection cognitions in mediating the relationship of moral disengagement with electronic bullying. In Study 3, we examined predictors of electronic prosocial behavior, such as bullying, victimization, time online, electronic proficiency, electronic self-conscious appraisals, emotionality, and self-regulation. All three studies supported the General Aggression Model as a framework to guide the study of electronic behavior, and suggest the importance of cognitive, emotional, and behavioral means of regulation in shaping electronic behavior. In addition, each study has implications for the development of high quality electronic bullying prevention and intervention research.

Identification of YAP as sperm-PAWP’s predominant binding partner in MII-arrested oocytes and the relevance of this WWI domain modular interaction to oocyte activation

PAWP, a candidate sperm-borne oocyte activating factor, induces oocyte activation and acts upstream of the calcium signalling pathway, however, PAWP’s downstream signalling pathway in oocyte cytoplasm remains to be uncovered. Data from our lab suggested that the interacting partner of PAWP, at least in the frog (Xenopus laevis) model may be YAP, a highly expressed protein in amphibian and mammalian oocytes. Therefore, the objectives of this study were to confirm that PAWP’s predominant binding partner in Xenopus laevis oocyte is YAP; to determine if mammalian oocyte activation is also dependent on PAWP-YAP interaction; and to verify that the PAWP-YAP interaction during oocyte activation is dependent on the WWI domain module. By immunohistochemistry, YAP was localized predominantly in the cytosol of metaphase II-arrested Xenopus laevis oocytes, where presumably the PAWP-YAP interaction occurs. Utilizing Far Western blotting, YAP was identified as the predominant binding partner of PAWP, in metaphase II-arrested frog (Xenopus laevis), swine (Sus scrofa) and mouse (mus musculus) oocytes. The specificity of this interaction was then tested on Far Western blotting of mouse ovarian and oocyte cytosolic extracts, by competition with both wild-type and point-mutated recombinant WWI domains derived from YAP. The removal of GST from the wild-type WWI-GST fusion protein was a requirement for effective blockage of WWI module interaction between PAWP and YAP. As expected, the mutated WWI domain was ineffective in inhibiting the PAWP-YAP interaction. To conclude, this study identified YAP as the predominant binding partner of PAWP in both amphibian and mammalian oocytes, and showed this interaction is dependent on the WWI modular interaction. The results allow us to test the functional relevance of this WWI modular interaction during oocyte activation in vivo, in the future.

Investigating the Role of cAMP-Signaling in the Regulation of Vascular Endothelial Cell Adaptive Responses to Fluid Shear Stress

The circulating blood exerts a force on the vascular endothelium, termed fluid shear stress (FSS), which directly impacts numerous vascular endothelial cell (VEC) functions. For example, high rates of linear and undisturbed (i.e. laminar) blood flow maintains a protective and quiescent VEC phenotype. Meanwhile, deviations in blood flow, which can occur at vascular branchpoints and large curvatures, create areas of low, and/or oscillatory FSS, and promote a pro-inflammatory, pro-thrombotic and hyperpermeable phenotype. Indeed, it is known that these areas are prone to the development of atherosclerotic lesions. Herein, we show that cyclic nucleotide phosphodiesterase (PDE) 4D (PDE4D) activity is increased by FSS in human arterial endothelial cells (HAECs) and that this activation regulates the activity of cAMP-effector protein, Exchange Protein-activated by cAMP-1 (EPAC1), in these cells. Importantly, we also show that these events directly and critically impact HAEC responses to FSS, especially when FSS levels are low. Both morphological events induced by FSS, as measured by changes in cell alignment and elongation in the direction of FSS, and the expression of critical FSS-regulated genes, including Krüppel-like factor 2 (KLF2), endothelial nitric oxide synthase (eNOS) and thrombomodlin (TM), are mediated by EPAC1/PDE4D signaling. At a mechanistic level, we show that EPAC1/PDE4D acts through the vascular endothelial-cadherin (VECAD)/ platelet-cell adhesion molecule-1 (PECAM1)/vascular endothelial growth factor receptor 2 (VEGFR2) mechanosensor to activate downstream signaling though Akt. Given the critical role of PDE4D in mediating these effects, we also investigated the impact of various patterns of FSS on the expression of individual PDE genes in HAECs. Notably, PDE2A was significantly upregulated in response to high, laminar FSS, while PDE3A was upregulated under low, oscillatory FSS conditions only. These data may provide novel therapeutic targets to limit FSS-dependent endothelial cell dysfunction (ECD) and atherosclerotic development.