The Cloak of Copyright: How Costco v. Omega Enabled Price Discrimination

In December of 2010, Costco v. Omega came down from the Supreme Court. The Switzerland-based watchmaker Omega sold Seamaster Collection watches, which were affixed with its copyrighted logo, in the United States as well as in foreign markets. Omega priced watches in the United States market higher than elsewhere. Costco obtained Omega’s watches from a third party that had purchased the watches abroad, then sold them at its membership warehouses for cheaper prices than authorized Omega dealers in the United States. Consequently, Omega sued Costco for copyright infringement. Costco pursued a defense based on the first sale doctrine in response. While from a legal perspective the case was a copyright dispute, this categorization does not make sense from an economic view. Rather, the application of economic models reveals that the core issue in Costco centers about price discrimination, not copyright. This thesis uses a law and economics framework to analyze the facts of and the decision in Costco to determine whether the outcome was welfare maximizing and to assess the implications that the case will have on copyright law in the future

Co-designing an Adaption of a Mobile App to Enhance Communication, Safety, and Well-being Among People Living at Home With Early-Stage Dementia: Protocol for an Exploratory Multiple Case Study

Background There is a growing interest in using mobile apps to support communication, safety, and well-being. Evidence directly from people with dementia regarding the usability, usefulness, and relevance of mobile apps is limited. Objective This paper describes the protocol of a study that will evaluate an app designed for supporting communication, safety, and well-being among people living with dementia. The study aims to understand if the app can enhance safety through improved communication among users. Methods The study will use participatory qualitative methods over 3 cycles of evaluation with co-designers (service users, their families, and care practitioners). The study will be developed in partnership with a specialist home care service in England. Purposive case selection will be performed to ensure that the cases exemplify differences in experiences. The app will be evaluated in a walk-through workshop by people living with early-stage dementia and then trialed at home by up to 12 families in a try-out cycle. An amended version will be evaluated in a final walk-through workshop during cycle 3. Data will be collected from at least 4 data sources during the try-out phase and analyzed thematically. An explanatory multiple case study design will be used to synthesize and present the evidence from the three cycles, drawing on the Normalization Process Theory to support the interpretation of the findings. Results The study is ready to be implemented, but it was paused to protect vulnerable individuals during the COVID-19 pandemic in 2020. The findings will be particularly relevant for understanding how to support vulnerable people living in the community during social distancing and the period following the pandemic as well as for providing insight into the challenges of social isolation that arise from living with dementia. Conclusions Evaluating a mobile app for enhancing communication, safety, and well-being among people living with dementia contributes to the key ambitions enshrined in policy and practice—championing the use of digital technology and supporting people with dementia to live safely in their own homes. The study will involve co-designers living with dementia, so that the voices of service users can be used to highlight the benefits and challenges of assistive technology and shape the future development of apps that enhance safety by improving communication. International Registered Report Identifier (IRRID) PRR1-10.2196/19543 </jats:sec

Australian climate-carbon cycle feedback reduced by soil black carbon

Annual emissions of carbon dioxide from soil organic carbon are an order of magnitude greater than all anthropogenic carbon dioxide emissions taken together1. Global warming is likely to increase the decomposition of soil organic carbon, and thus the release of carbon dioxide from soils2,3,4,5, creating a positive feedback6,7,8,9. Current models of global climate change that recognize this soil carbon feedback are inaccurate if a larger fraction of soil organic carbon than postulated has a very slow decomposition rate. Here we show that by including realistic stocks of black carbon in prediction models, carbon dioxide emissions are reduced by 18.3 and 24.4% in two Australian savannah regions in response to a warming of 3 ∘C over 100 years1. This reduction in temperature sensitivity, and thus the magnitude of the positive feedback, results from the long mean residence time of black carbon, which we estimate to be approximately 1,300 and 2,600 years, respectively. The inclusion of black carbon in climate models is likely to require spatially explicit information about its distribution, given that the black carbon content of soils ranged from 0 to 82% of soil organic carbon in a continental-scale analysis of Australia. We conclude that accurate information about the distribution of black carbon in soils is important for projections of future climate change

Receptor-targeted iron oxide nanoparticles for molecular MR imaging of inflamed atherosclerotic plaques

In a number of literature reports iron oxide nanoparticles have been investigated for use in imaging atherosclerotic plaques and found to accumulate in plaques via uptake by macrophages, which are critical in the process of atheroma initiation, propagation, and rupture. However, the uptake of these agents is non-specific; thus the labeling efficiency for plaques in vivo is not ideal. We have developed targeted agents to improve the efficiency for labeling macrophage-laden plaques. These probes are based on iron oxide nanoparticles coated with dextran sulfate, a ligand of macrophage scavenger receptor type A (SR-A). We have sulfated dextran-coated iron oxide nanoparticles (DIO) with sulfur trioxide, thereby targeting our nanoparticle imaging agents to SR-A. The sulfated DIO (SDIO) remained mono-dispersed and had an average hydrodynamic diameter of 62 nm, an r_1 relaxivity of 18.1 mM^(−1) s^(−1), and an r_2 relaxivity of 95.8 mM^(−1) s^(−1) (37 °C, 1.4 T). Cell studies confirmed that these nanoparticles were nontoxic and specifically targeted to macrophages. In vivo MRI after intravenous injection of the contrast agent into an atherosclerotic mouse injury model showed substantial signal loss on the injured carotid at 4 and 24 h post-injection of SDIO. No discernable signal decrease was seen at the control carotid and only mild signal loss was observed for the injured carotid post-injection of non-sulfated DIO, indicating preferential uptake of the SDIO particles at the site of atherosclerotic plaque. These results indicate that SDIO can facilitate MRI detection and diagnosis of vulnerable plaques in atherosclerosis

High-bandwidth AFM-based rheology is a sensitive indicator of early cartilage aggrecan degradation relevant to mouse models of osteoarthritis

Murine models of osteoarthritis (OA) and post-traumatic OA have been widely used to study the development and progression of these diseases using genetically engineered mouse strains along with surgical or biochemical interventions. However, due to the small size and thickness of murine cartilage, the relationship between mechanical properties, molecular structure and cartilage composition has not been well studied. We adapted a recently developed AFM-based nano-rheology system to probe the dynamic nanomechanical properties of murine cartilage over a wide frequency range of 1 Hz to 10 kHz, and studied the role of glycosaminoglycan (GAG) on the dynamic modulus and poroelastic properties of murine femoral cartilage. We showed that poroelastic properties, highlighting fluid–solid interactions, are more sensitive indicators of loss of mechanical function compared to equilibrium properties in which fluid flow is negligible. These fluid-flow-dependent properties include the hydraulic permeability (an indicator of the resistance of matrix to fluid flow) and the high frequency modulus, obtained at high rates of loading relevant to jumping and impact injury in vivo. Utilizing a fibril-reinforced finite element model, we estimated the poroelastic properties of mouse cartilage over a wide range of loading rates for the first time, and show that the hydraulic permeability increased by a factor ~16 from k[subscript normal] = 7.80 × 10[superscript −16] ± 1.3 × 10[superscript −16] m[superscript 4]/N s to k[subscript GAG-depleted] = 1.26 × 10[superscript −14] ± 6.73 × 10[superscript −15] m[superscript 4]/N s after GAG depletion. The high-frequency modulus, which is related to fluid pressurization and the fibrillar network, decreased significantly after GAG depletion. In contrast, the equilibrium modulus, which is fluid-flow independent, did not show a statistically significant alteration following GAG depletion.National Institutes of Health (U.S.) (Grant 060331)Whitaker Foundation (Health Sciences Fund Fellowship)Arthritis Australi

A synthetic mechanogenetic gene circuit for autonomous drug delivery in engineered tissues

Mechanobiologic signals regulate cellular responses under physiologic and pathologic conditions. Using synthetic biology and tissue engineering, we developed a mechanically responsive bioartificial tissue that responds to mechanical loading to produce a preprogrammed therapeutic biologic drug. By deconstructing the signaling networks induced by activation of the mechanically sensitive ion channel transient receptor potential vanilloid 4 (TRPV4), we created synthetic TRPV4-responsive genetic circuits in chondrocytes. We engineered these cells into living tissues that respond to mechanical loading by producing the anti-inflammatory biologic drug interleukin-1 receptor antagonist. Chondrocyte TRPV4 is activated by osmotic loading and not by direct cellular deformation, suggesting that tissue loading is transduced into an osmotic signal that activates TRPV4. Either osmotic or mechanical loading of tissues transduced with TRPV4-responsive circuits protected constructs from inflammatory degradation by interleukin-1α. This synthetic mechanobiology approach was used to develop a mechanogenetic system to enable long-term, autonomously regulated drug delivery driven by physiologically relevant loading

Effects of Protein Deficiency on Perinatal and Postnatal Health Outcomes

There are a variety of environmental insults that can occur during pregnancy which cause low birth weight and poor fetal health outcomes. One such insult is maternal malnutrition, which can be further narrowed down to a low protein diet during gestation. Studies show that perinatal protein deficiencies can impair proper organ growth and development, leading to long-term metabolic dysfunction. Understanding the molecular mechanisms that underlie how this deficiency leads to adverse developmental outcomes is essential for establishing better therapeuticstrategies that may alleviate or prevent diseases in later life. This chapter reviews how perinatal protein restriction in humans and animals leads to metabolic disease, and it identifies the mechanisms that have been elucidated, to date. These include alterations in transcriptional and epigenetic mechanisms, as well as indirect means such as endoplasmic reticulum (ER) stress and oxidative stress. Furthermore, nutritional and pharmaceutical interventions are highlighted to illustrate that the plasticity of the underdeveloped organs during perinatal life can be exploited to prevent onset of long-term metabolic disease

Admixture mapping implicates 13q33.3 as ancestry-of-origin locus for Alzheimer disease in Hispanic and Latino populations

Alzheimer disease (AD) is the most common form of senile dementia, with high incidence late in life in many populations including Caribbean Hispanic (CH) populations. Such admixed populations, descended from more than one ancestral population, can present challenges for genetic studies, including limited sample sizes and unique analytical constraints. Therefore, CH populations and other admixed populations have not been well represented in studies of AD, and much of the genetic variation contributing to AD risk in these populations remains unknown. Here, we conduct genome-wide analysis of AD in multiplex CH families from the Alzheimer Disease Sequencing Project (ADSP). We developed, validated, and applied an implementation of a logistic mixed model for admixture mapping with binary traits that leverages genetic ancestry to identify ancestry-of-origin loci contributing to AD. We identified three loci on chromosome 13q33.3 associated with reduced risk of AD, where associations were driven by Native American (NAM) ancestry. This AD admixture mapping signal spans the FAM155A, ABHD13, TNFSF13B, LIG4, and MYO16 genes and was supported by evidence for association in an independent sample from the Alzheimer's Genetics in Argentina—Alzheimer Argentina consortium (AGA-ALZAR) study with considerable NAM ancestry. We also provide evidence of NAM haplotypes and key variants within 13q33.3 that segregate with AD in the ADSP whole-genome sequencing data. Interestingly, the widely used genome-wide association study approach failed to identify associations in this region. Our findings underscore the potential of leveraging genetic ancestry diversity in recently admixed populations to improve genetic mapping, in this case for AD-relevant loci.Fil: Horimoto, Andrea R.V.R.. University of Washington; Estados UnidosFil: Boyken, Lisa A.. University of Washington; Estados UnidosFil: Blue, Elizabeth E.. University of Washington; Estados Unidos. Brotman Baty Institute for Precision Medicine; Estados UnidosFil: Grinde, Kelsey E.. University of Washington; Estados Unidos. Macalester College; Estados UnidosFil: Nafikov, Rafael A.. University of Washington; Estados UnidosFil: Sohi, Harkirat K.. University of Washington; Estados UnidosFil: Nato, Alejandro Q.. University of Washington; Estados Unidos. Marshall University; Estados UnidosFil: Bis, Joshua C.. University of Washington; Estados UnidosFil: Brusco, Luis Ignacio. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Morelli, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Ramirez, Alfredo Jose. University Of Cologne; Alemania. Universitat Bonn; Alemania. German Center for Neurodegenerative Diseases; Alemania. University Of Texas Health Science Center At San Antonio (ut Health San Antonio) ; University Of Texas At San Antonio; . Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; ArgentinaFil: Dalmasso, Maria Carolina. Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; Argentina. University Of Cologne; AlemaniaFil: Temple, Seth. University of Washington; Estados UnidosFil: Satizabal, Claudia. University Of Texas Health Science Center At San Antonio (ut Health San Antonio) ; University Of Texas At San Antonio; . University of Texas at San Antonio; Estados UnidosFil: Browning, Sharon R.. University of Washington; Estados UnidosFil: Seshadri, Sudha. University Of Texas Health Science Center At San Antonio (ut Health San Antonio) ; University Of Texas At San Antonio; . University of Texas at San Antonio; Estados UnidosFil: Wijsman, Ellen M.. University of Washington; Estados UnidosFil: Thornton, Timothy A.. University of Washington; Estados Unido