i4i Makes the Patent World Blind

All patents receive a presumption of validity pursuant to 35 USC § 282. Courts have traditionally put this presumption into practice by requiring invalidity to be established by clear and convincing evidence. The Supreme Court reaffirmed this understanding of the presumption in Microsoft Corp v i4i Ltd Partnership. District courts have divided, however, on whether to require clear and convincing evidence when the challenger seeks to invalidate a patent for covering ineligible subject matter. The conflict originates from a concurrence written by Justice Stephen Breyer in i4i, in which he stated that a heightened standard of proof—like the clear and convincing standard—can apply only to issues of fact, not issues of law. Because subject-matter eligibility has traditionally presented an issue of law, some courts hold that subject-matter-eligibility challenges cannot be subjected to the clear and convincing standard. Other courts agree with that sentiment but would apply the clear and convincing standard to resolve any underlying issues of fact. Still others maintain that subject-matter-eligibility challenges must be established by clear and convincing evidence. This Comment resolves this ambiguity by showing that subject-mattereligibility challenges must be established by clear and convincing evidence. It compares subject-matter-eligibility challenges to two other patent validity challenges: the on-sale bar and nonobviousness. These two comparisons show that patent law has consistently failed to confine the clear and convincing standard to issues of law. In fact, the standard has been imposed without regard for the distinction between issues of law and fact. Accordingly, judges should impose the clear and convincing standard on subject-matter-eligibility challenges

Relaxed Bell inequalities and Kochen-Specker theorems

The combination of various physically plausible properties, such as no signaling, determinism, and experimental free will, is known to be incompatible with quantum correlations. Hence, these properties must be individually or jointly relaxed in any model of such correlations. The necessary degrees of relaxation are quantified here, via natural distance and information-theoretic measures. This allows quantitative comparisons between different models in terms of the resources, such as the number of bits, of randomness, communication, and/or correlation, that they require. For example, measurement dependence is a relatively strong resource for modeling singlet state correlations, with only 1/15 of one bit of correlation required between measurement settings and the underlying variable. It is shown how various 'relaxed' Bell inequalities may be obtained, which precisely specify the complementary degrees of relaxation required to model any given violation of a standard Bell inequality. The robustness of a class of Kochen-Specker theorems, to relaxation of measurement independence, is also investigated. It is shown that a theorem of Mermin remains valid unless measurement independence is relaxed by 1/3. The Conway-Kochen 'free will' theorem and a result of Hardy are less robust, failing if measurement independence is relaxed by only 6.5% and 4.5%, respectively. An appendix shows the existence of an outcome independent model is equivalent to the existence of a deterministic model.Comment: 19 pages (including 3 appendices); v3: minor clarifications, to appear in PR

Musculoskeletal specialist community outreach patterns : a pilot study

This poster presents the findings of a pilot study examining volunteerism among musculoskeletal specialty physicians

Tracing the water-energy-food nexus : description, theory and practice

The ‘nexus’ between water, energy and food (WEF) has gained increasing attention globally in research, business and policy spheres. We review the premise of recent initiatives framed around the nexus, examine the challenge of achieving the type of disciplinary boundary crossing promoted by the nexus agenda and consider how to operationalise what has to date been a largely paper exercise. The WEF nexus has been promoted through international meetings and calls for new research agendas. It is clear from the literature that many aims of nexus approaches pre-date the recent nexus agenda; these have encountered significant barriers to progress, including challenges to cross-disciplinary collaboration, complexity, political economy (often perceived to be under-represented in nexus research) and incompatibility of current institutional structures. Indeed, the ambitious aims of the nexus—the desire to capture multiple interdependencies across three major sectors, across disciplines and across scales—could become its downfall. However, greater recognition of interdependencies across state and non-state actors, more sophisticated modelling systems to assess and quantify WEF linkages and the sheer scale of WEF resource use globally, could create enough momentum to overcome historical barriers and establish nexus approaches as part of a wider repertoire of responses to global environmental change

Electrical coupling between ventricular myocytes and myofibroblasts in the infarcted mouse heart

Aims: Recent studies have demonstrated electrotonic coupling between scar tissue and the surrounding myocardium in cryoinjured hearts. However, the electrical dynamics occurring at the myocyte-nonmyocyte interface in the fibrotic heart remain undefined. Here, we sought to develop an assay to interrogate the nonmyocyte cell type contributing to heterocellular coupling and to characterize, on a cellular scale, its voltage response in the infarct border zone of living hearts. Methods and results: We used two-photon laser scanning microscopy in conjunction with a voltage-sensitive dye to record transmembrane voltage changes simultaneously from cardiomyocytes and adjoined nonmyocytes in Langendorff-perfused mouse hearts with healing myocardial infarction. Transgenic mice with cardiomyocyte-restricted expression of a green fluorescent reporter protein underwent permanent coronary artery ligation and their hearts were subjected to voltage imaging 7-10 days later. Reporter-negative cells, i.e. nonmyocytes, in the infarct border zone exhibited depolarizing transients at a 1:1 coupling ratio with action potentials recorded simultaneously from adjacent, reporter-positive ventricular myocytes. The electrotonic responses in the nonmyocytes exhibited slower rates of de- and repolarization compared to the action potential waveform of juxtaposed myocytes. Voltage imaging in infarcted hearts expressing a fluorescent reporter specifically in myofibroblasts revealed that the latter were electrically coupled to border zone myocytes. Their voltage transient properties were indistinguishable from those of nonmyocytes in hearts with cardiomyocyte-restricted reporter expression. The density of connexin43 expression at myofibroblast-cardiomyocyte junctions was ∼5% of that in the intercalated disc regions of paired ventricular myocytes in the remote, uninjured myocardium, whereas the ratio of connexin45 to connexin43 expression levels at heterocellular contacts was ∼1%. Conclusion: Myofibroblasts contribute to the population of electrically coupled nonmyocytes in the infarct border zone. The slower kinetics of myofibroblast voltage responses may reflect low electrical conductivity across heterocellular junctions, in accordance with the paucity of connexin expression at myofibroblast-cardiomyocyte contacts

Comparison of histomorphology and DNA preservation produced by fixatives in the veterinary diagnostic laboratory setting

Histopathology is the most useful tool for diagnosis of a number of diseases, especially cancer. To be effective, histopathology requires that tissues be fixed prior to processing. Formalin is currently the most common histologic fixative, offering many advantages: it is cheap, readily available, and pathologists are routinely trained to examine tissues fixed in formalin. However, formalin fixation substantially degrades tissue DNA, hindering subsequent use in diagnostics and research. We therefore evaluated three alternative fixatives, TissueTek® Xpress® Molecular Fixative, modified methacarn, and PAXgene®, all of which have been proposed as formalin alternatives, to determine their suitability for routine use in a veterinary diagnostic laboratory. This was accomplished by examining the histomorphology of sections produced from fixed tissues as well as the ability to amplify fragments from extracted DNA. Tissues were sampled from two dogs and four cats, fixed for 24–48 h, and processed routinely. While all fixatives produced acceptable histomorphology, formalin had significantly better morphologic characteristics than the other three fixatives. Alternative fixatives generally had better DNA amplification than formalin, although results varied somewhat depending on the tissue examined. While no fixative is yet ready to replace formalin, the alternative fixatives examined may be useful as adjuncts to formalin in diagnostic practices