Would Global Patent Protection be too Weak without International Coordination?

This paper analyzes the setting of national patent policies in the global economy. In the standard model with free trade and social-welfare-maximizing governments à la Grossman and Lai (2004), cross-border positive policy externalities induce individual countries to select patent strengths that are weaker than is optimal from a global perspective. The paper introduces three new features to the analysis: trade barriers, firm heterogeneity in terms of productivity and political economy considerations in setting patent policies. The first two features (trade barriers interacting with firm heterogeneity) tend to reduce the size of cross-border externalities in patent protection and therefore make national IPR policies closer to the global optimum. With firm lobbying creating profit-bias of the government, it is even possible that the equilibrium strength of global patent protection is greater than the globally efficient level. Thus, the question of under-protection or not is an empirical one. Based on calibration exercises, we find that there would be global under-protection of patent rights when there is no international policy coordination. Furthermore, requiring all countries to harmonize their patent standards with the equilibrium standard of the most innovative country (the US) does not lead to global over-protection of patent rights.intellectual property rights, patents, TRIPS, harmonization

Targeting EZH2-mediated methylation of H3K27 inhibits proliferation and migration of Synovial Sarcoma in vitro.

Synovial sarcoma is an aggressive soft tissue sarcoma genetically defined by the fusion oncogene SS18-SSX. It is hypothesized that either SS18-SSX disrupts SWI/SNF complex inhibition of the polycomb complex 2 (PRC2) methyltransferase Enhancer of Zeste Homologue 2 (EZH2), or that SS18-SSX is able to directly recruit PRC2 to aberrantly silence target genes. This is of potential therapeutic value as several EZH2 small molecule inhibitors are entering early phase clinical trials. In this study, we first confirmed EZH2 expression in the 76% of human synovial sarcoma samples. We subsequently investigated EZH2 as a therapeutic target in synovial sarcoma in vitro. Knockdown of EZH2 by shRNA or siRNA resulted in inhibition of cell growth and migration across a series of synovial sarcoma cell lines. The EZH2 selective small-molecule inhibitor EPZ005687 similarly suppressed cell proliferation and migration. These data support the hypothesis that targeting EZH2 may be a promising therapeutic strategy in the treatment of synovial sarcoma; clinical trials are initiating enrollment currently

Cross-modal Hashing with Semantic Deep Embedding

Cross-modal hashing has demonstrated advantages on fast retrieval tasks. It improves the quality of hash coding by exploiting semantic correlation across different modalities. In supervised cross-modal hashing, the learning of hash function replies on the quality of extracted features, for which deep learning models have been adopted to replace the traditional models based on handcraft features. All deep methods, however, have not sufficiently explored semantic correlation of modalities for the hashing process. In this paper, we introduce a novel end-to-end deep cross-modal hashing framework which integrates feature and hash-code learning into the same network. We take both between and within modalities data correlation into consideration, and propose a novel network structure and a loss function with dual semantic supervision for hash learning. This method ensures that the generated binary codes keep the semantic relationship of the original data points. Cross-modal retrieval experiments on commonly used benchmark datasets show that our method yields substantial performance improvement over several state-of-the-art hashing methods

The Key Role of Heavy Precipitation Events in Climate Model Disagreements of Future Annual Precipitation Changes in California

Climate model simulations disagree on whether future precipitation will increase or decrease over California, which has impeded efforts to anticipate and adapt to human-induced climate change. This disagreement is explored in terms of daily precipitation frequency and intensity. It is found that divergent model projections of changes in the incidence of rare heavy (\u3e60 mm day−1) daily precipitation events explain much of the model disagreement on annual time scales, yet represent only 0.3% of precipitating days and 9% of annual precipitation volume. Of the 25 downscaled model projections examined here, 21 agree that precipitation frequency will decrease by the 2060s, with a mean reduction of 6–14 days yr−1. This reduces California\u27s mean annual precipitation by about 5.7%. Partly offsetting this, 16 of the 25 projections agree that daily precipitation intensity will increase, which accounts for a model average 5.3% increase in annual precipitation. Between these conflicting tendencies, 12 projections show drier annual conditions by the 2060s and 13 show wetter. These results are obtained from 16 global general circulation models downscaled with different combinations of dynamical methods [Weather Research and Forecasting (WRF), Regional Spectral Model (RSM), and version 3 of the Regional Climate Model (RegCM3)] and statistical methods [bias correction with spatial disaggregation (BCSD) and bias correction with constructed analogs (BCCA)], although not all downscaling methods were applied to each global model. Model disagreements in the projected change in occurrence of the heaviest precipitation days (\u3e60 mm day−1) account for the majority of disagreement in the projected change in annual precipitation, and occur preferentially over the Sierra Nevada and Northern California. When such events are excluded, nearly twice as many projections show drier future conditions

Probabilistic estimates of future changes in California temperature and precipitation usingstatistical and dynamical downscaling

Sixteen global general circulation models were used to develop probabilistic projections of temperature (T) and precipitation (P) changes over California by the 2060s. The global models were downscaled with two statistical techniques and three nested dynamical regional climate models, although not all global models were downscaled with all techniques. Both monthly and daily timescale changes in T and P are addressed, the latter being important for a range of applications in energy use, water management, and agriculture. The T changes tend to agree more across downscaling techniques than the P changes. Year-to-year natural internal climate variability is roughly of similar magnitude to the projected T changes. In the monthly average, July temperatures shift enough that that the hottest July found in any simulation over the historical period becomes a modestly cool July in the future period. Januarys as cold as any found in the historical period are still found in the 2060s, but the median and maximum monthly average temperatures increase notably. Annual and seasonal P changes are small compared to interannual or intermodel variability. However, the annual change is composed of seasonally varying changes that are themselves much larger, but tend to cancel in the annual mean. Winters show modestly wetter conditions in the North of the state, while spring and autumn show less precipitation. The dynamical downscaling techniques project increasing precipitation in the Southeastern part of the state, which is influenced by the North American monsoon, a feature that is not captured by the statistical downscaling

Post-traumatic hypoxia exacerbates neurological deficit, neuroinflammation and cerebral metabolism in rats with diffuse traumatic brain injury

<p>Abstract</p> <p>Background</p> <p>The combination of diffuse brain injury with a hypoxic insult is associated with poor outcomes in patients with traumatic brain injury. In this study, we investigated the impact of post-traumatic hypoxia in amplifying secondary brain damage using a rat model of diffuse traumatic axonal injury (TAI). Rats were examined for behavioral and sensorimotor deficits, increased brain production of inflammatory cytokines, formation of cerebral edema, changes in brain metabolism and enlargement of the lateral ventricles.</p> <p>Methods</p> <p>Adult male Sprague-Dawley rats were subjected to diffuse TAI using the Marmarou impact-acceleration model. Subsequently, rats underwent a 30-minute period of hypoxic (12% O₂/88% N₂) or normoxic (22% O₂/78% N₂) ventilation. Hypoxia-only and sham surgery groups (without TAI) received 30 minutes of hypoxic or normoxic ventilation, respectively. The parameters examined included: 1) behavioural and sensorimotor deficit using the Rotarod, beam walk and adhesive tape removal tests, and voluntary open field exploration behavior; 2) formation of cerebral edema by the wet-dry tissue weight ratio method; 3) enlargement of the lateral ventricles; 4) production of inflammatory cytokines; and 5) real-time brain metabolite changes as assessed by microdialysis technique.</p> <p>Results</p> <p>TAI rats showed significant deficits in sensorimotor function, and developed substantial edema and ventricular enlargement when compared to shams. The additional hypoxic insult significantly exacerbated behavioural deficits and the cortical production of the pro-inflammatory cytokines IL-6, IL-1β and TNF but did not further enhance edema. TAI and particularly TAI+Hx rats experienced a substantial metabolic depression with respect to glucose, lactate, and glutamate levels.</p> <p>Conclusion</p> <p>Altogether, aggravated behavioural deficits observed in rats with diffuse TAI combined with hypoxia may be induced by enhanced neuroinflammation, and a prolonged period of metabolic dysfunction.</p