Unnecessary Indeterminacy: Process Patent Protection After Kinik v. ITC

In Kinik v. International Trade Commission, the U.S. Court of Appeals for the Federal Circuit suggested in dicta that the defenses available to foreign manufacturers in infringement actions under 35 U.S.C. § 271(g) in Federal district courts do not apply to exclusion actions before the International Trade Commission. This iBrief argues that this decision is problematic for three reasons: (1) the Federal Circuit’s decision is inconsistent with the ITC’s longstanding tradition of consulting the patent statute when adjudicating exclusion actions under 19 U.S.C. § 1337, (2) the court’s suggestion that the ITC should be given broad discretion to resolve conflicts between the patent statute and the Tariff Act is at odds with the Chevron doctrine, and (3) if the ITC employs the broad discretion that Kinik confers to it by excluding more foreign art than Federal district courts could lawfully exclude under the patent statute, the enforcement of domestic patent policy in the United States could conceivably violate obligations of non-discrimination (Article 27.1) and burden-shifting (Article 34) imposed by the TRIPS Agreement

Multistate Assessment of Public Health Surveillance Relevant to American Indians and Alaska Natives, 2007

Improving the health of American Indian and Alaska Native (AI/AN) populations involves multiple agencies, levels of government, and jurisdictions. We assessed collaboration between state health departments and AI/AN Tribes and agencies through an online survey of State Epidemiologists. Frequencies and percentages of responses were examined by univariate and bivariate analyses. Among 39 states with federally recognized or state-recognized Tribes or federally funded urban Indian health centers, 25 (64%) participated. Nineteen had discussed public health surveillance with an AI/ AN government or nongovernment entity in the past 2 years (10 (53%) of these had ongoing, regular discussions about public health surveillance; nine (47%) had these discussions as needed). Nine (36%) responding states have a point person for working with AI/AN communities and/or agencies on public health surveillance. Four (16%) states have an active memorandum of understanding or other formal agreement with an AI/AN government or nongovernment entity regarding surveillance. To prepare for public health emergencies, six (24%) states involve the Indian Health Service, and eight (47%) involve another AI/AN entity. Functional relationships between state health departments and AI/AN agencies have not been consistently established. Strengthening these relationships will facilitate surveillance and response capacity to address continuing and emerging public health problems

Psychedelics Promote Structural and Functional Neural Plasticity.

Atrophy of neurons in the prefrontal cortex (PFC) plays a key role in the pathophysiology of depression and related disorders. The ability to promote both structural and functional plasticity in the PFC has been hypothesized to underlie the fast-acting antidepressant properties of the dissociative anesthetic ketamine. Here, we report that, like ketamine, serotonergic psychedelics are capable of robustly increasing neuritogenesis and/or spinogenesis both in vitro and in vivo. These changes in neuronal structure are accompanied by increased synapse number and function, as measured by fluorescence microscopy and electrophysiology. The structural changes induced by psychedelics appear to result from stimulation of the TrkB, mTOR, and 5-HT2A signaling pathways and could possibly explain the clinical effectiveness of these compounds. Our results underscore the therapeutic potential of psychedelics and, importantly, identify several lead scaffolds for medicinal chemistry efforts focused on developing plasticity-promoting compounds as safe, effective, and fast-acting treatments for depression and related disorders

Making a journey in knowledge management strategy

This paper reports results from an ongoing project examining what managers think about knowledge management in the context of their organisation. This was done in a facilitated computerassisted group workshop environment. Here we compare the outcomes of workshops held for two relatively large UK organisations, one public sector and the other private. Our conclusions are that there are relatively few differences between the perceptions of these two groups of managers, and that these differences stem more from the stage of the knowledge management life cycle that the two organisations have reached, rather than from the difference in context between public and private sector. © iKMS & World Scientific Publishing Co

A noise-reduction GWAS analysis implicates altered regulation of neurite outgrowth and guidance in autism

<p>Abstract</p> <p>Background</p> <p>Genome-wide Association Studies (GWAS) have proved invaluable for the identification of disease susceptibility genes. However, the prioritization of candidate genes and regions for follow-up studies often proves difficult due to false-positive associations caused by statistical noise and multiple-testing. In order to address this issue, we propose the novel GWAS noise reduction (GWAS-NR) method as a way to increase the power to detect true associations in GWAS, particularly in complex diseases such as autism.</p> <p>Methods</p> <p>GWAS-NR utilizes a linear filter to identify genomic regions demonstrating correlation among association signals in multiple datasets. We used computer simulations to assess the ability of GWAS-NR to detect association against the commonly used joint analysis and Fisher's methods. Furthermore, we applied GWAS-NR to a family-based autism GWAS of 597 families and a second existing autism GWAS of 696 families from the Autism Genetic Resource Exchange (AGRE) to arrive at a compendium of autism candidate genes. These genes were manually annotated and classified by a literature review and functional grouping in order to reveal biological pathways which might contribute to autism aetiology.</p> <p>Results</p> <p>Computer simulations indicate that GWAS-NR achieves a significantly higher classification rate for true positive association signals than either the joint analysis or Fisher's methods and that it can also achieve this when there is imperfect marker overlap across datasets or when the closest disease-related polymorphism is not directly typed. In two autism datasets, GWAS-NR analysis resulted in 1535 significant linkage disequilibrium (LD) blocks overlapping 431 unique reference sequencing (RefSeq) genes. Moreover, we identified the nearest RefSeq gene to the non-gene overlapping LD blocks, producing a final candidate set of 860 genes. Functional categorization of these implicated genes indicates that a significant proportion of them cooperate in a coherent pathway that regulates the directional protrusion of axons and dendrites to their appropriate synaptic targets.</p> <p>Conclusions</p> <p>As statistical noise is likely to particularly affect studies of complex disorders, where genetic heterogeneity or interaction between genes may confound the ability to detect association, GWAS-NR offers a powerful method for prioritizing regions for follow-up studies. Applying this method to autism datasets, GWAS-NR analysis indicates that a large subset of genes involved in the outgrowth and guidance of axons and dendrites is implicated in the aetiology of autism.</p

Generic multiloop methods and application to N=4 super-Yang-Mills

We review some recent additions to the tool-chest of techniques for finding compact integrand representations of multiloop gauge-theory amplitudes - including non-planar contributions - applicable for N=4 super-Yang-Mills in four and higher dimensions, as well as for theories with less supersymmetry. We discuss a general organization of amplitudes in terms of purely cubic graphs, review the method of maximal cuts, as well as some special D-dimensional recursive cuts, and conclude by describing the efficient organization of amplitudes resulting from the conjectured duality between color and kinematic structures on constituent graphs.Comment: 42 pages, 18 figures, invited review for a special issue of Journal of Physics A devoted to "Scattering Amplitudes in Gauge Theories", v2 minor corrections, v3 added reference

Targeted massively parallel sequencing of autism spectrum disorder-associated genes in a case control cohort reveals rare loss-of-function risk variants

BACKGROUND: Autism spectrum disorder (ASD) is highly heritable, yet genome-wide association studies (GWAS), copy number variation screens, and candidate gene association studies have found no single factor accounting for a large percentage of genetic risk. ASD trio exome sequencing studies have revealed genes with recurrent de novo loss-of-function variants as strong risk factors, but there are relatively few recurrently affected genes while as many as 1000 genes are predicted to play a role. As such, it is critical to identify the remaining rare and low-frequency variants contributing to ASD. METHODS: We have utilized an approach of prioritization of genes by GWAS and follow-up with massively parallel sequencing in a case-control cohort. Using a previously reported ASD noise reduction GWAS analyses, we prioritized 837 RefSeq genes for custom targeting and sequencing. We sequenced the coding regions of those genes in 2071 ASD cases and 904 controls of European white ancestry. We applied comprehensive annotation to identify single variants which could confer ASD risk and also gene-based association analysis to identify sets of rare variants associated with ASD. RESULTS: We identified a significant over-representation of rare loss-of-function variants in genes previously associated with ASD, including a de novo premature stop variant in the well-established ASD candidate gene RBFOX1. Furthermore, ASD cases were more likely to have two damaging missense variants in candidate genes than controls. Finally, gene-based rare variant association implicates genes functioning in excitatory neurotransmission and neurite outgrowth and guidance pathways including CACNAD2, KCNH7, and NRXN1. CONCLUSIONS: We find suggestive evidence that rare variants in synaptic genes are associated with ASD and that loss-of-function mutations in ASD candidate genes are a major risk factor, and we implicate damaging mutations in glutamate signaling receptors and neuronal adhesion and guidance molecules. Furthermore, the role of de novo mutations in ASD remains to be fully investigated as we identified the first reported protein-truncating variant in RBFOX1 in ASD. Overall, this work, combined with others in the field, suggests a convergence of genes and molecular pathways underlying ASD etiology. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13229-015-0034-z) contains supplementary material, which is available to authorized users

In vitro bond strength of treated direct-bonding metal bases

Three types of direct-bonding metal bases were used to determine the effect of five commercial surface treatments on in vitro tensile bond strength. The proprietary treatments were etching, silanation, surface activation, etching plus silanation, and etching plus surface activation. Nontreatment was used as a control. The bases were of the mesh, photo-etched, and grooved types. Bases were loaded with a no-mix adhesive to plastic substrates. The grooved base had the highest bond strength with no treatment. Etching improved the bond strength of the grooved bracket by 56%. Silanation improved the bond strength of the mesh bracket by 28%. Surface treatments did not improve the bond strength of the photo-etched bracket.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25602/1/0000149.pd

An X chromosome-wide association study in autism families identifies TBL1X as a novel autism spectrum disorder candidate gene in males

<p>Abstract</p> <p>Background</p> <p>Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with a strong genetic component. The skewed prevalence toward males and evidence suggestive of linkage to the X chromosome in some studies suggest the presence of X-linked susceptibility genes in people with ASD.</p> <p>Methods</p> <p>We analyzed genome-wide association study (GWAS) data on the X chromosome in three independent autism GWAS data sets: two family data sets and one case-control data set. We performed meta- and joint analyses on the combined family and case-control data sets. In addition to the meta- and joint analyses, we performed replication analysis by using the two family data sets as a discovery data set and the case-control data set as a validation data set.</p> <p>Results</p> <p>One SNP, rs17321050, in the transducin β-like 1X-linked (<it>TBL1X</it>) gene [OMIM:300196] showed chromosome-wide significance in the meta-analysis (<it>P </it>value = 4.86 × 10^-6) and joint analysis (<it>P </it>value = 4.53 × 10^-6) in males. The SNP was also close to the replication threshold of 0.0025 in the discovery data set (<it>P </it>= 5.89 × 10^-3) and passed the replication threshold in the validation data set (<it>P </it>= 2.56 × 10^-4). Two other SNPs in the same gene in linkage disequilibrium with rs17321050 also showed significance close to the chromosome-wide threshold in the meta-analysis.</p> <p>Conclusions</p> <p><it>TBL1X </it>is in the Wnt signaling pathway, which has previously been implicated as having a role in autism. Deletions in the Xp22.2 to Xp22.3 region containing <it>TBL1X </it>and surrounding genes are associated with several genetic syndromes that include intellectual disability and autistic features. Our results, based on meta-analysis, joint analysis and replication analysis, suggest that <it>TBL1X </it>may play a role in ASD risk.</p