Harmonization Without Consensus: Critical Reflections on Drafting a Substantive Patent Law Treaty

In this Article, we contend that the World Intellectual Property Organization\u27s proposed Substantive Patent Law Treaty (SPLT) is premature. Developing countries are struggling to adjust to the heightened standards of intellectual property protection required by the TRIPS Agreement of 1994. With TRIPS, at least, these countries obtained side payments (in the form of trade concessions) to offset the rising costs of knowledge products. A free-standing instrument, such as the SPLT, would shrink the remaining flexibilities in the TRIPS Agreement with no side payments and no concessions to the catch-up strategies of developing countries at different stages of technological advancement. More controversially, we argue that a deep harmonization would boomerang against even its developed country promoters by creating more problems than it would solve. There is no vision of a properly functioning patent system for the developed world that commands even the appearance of a consensus. The evidence shows, instead, that the worldwide intellectual property system has entered a brave new scientific epoch, in which experts have only tentative, divergent ideas about how best to treat a daunting array of new technologies. The proposals for reconciling the needs of different sectors, such as information technology and biotechnology, pose hard, unresolved issues at a time when the costs of litigation are rising at the expense of profits from innovation. These difficulties are compounded by the tendency of universities to push patenting up stream, generating new rights to core methodologies and research tools. As new approaches to new technologies emerge in different jurisdictions, there is a need to gather empirical evidence to determine which, if any, of these still experimental solutions are preferable over time. Our argument need not foreclose other less intrusive options and measures surveyed in the Article that can reduce the costs of delaying harmonization. However, the international community should not rush to freeze legal obligations regarding the protection of intellectual property. It should wait until economists and policymakers better understand the dynamics of innovation and the role that patent rights play in promoting progress and until there are mechanisms in place to keep international obligations responsive to developments in science, technology, and the organization of the creative community

Reflectivity and topography of cells grown on glass-coverslips measured with phase-shifted laser feedback interference microscopy

In spite of the advantages associated with the molecular specificity of fluorescence imaging, there is still a significant need to augment these approaches with label-free imaging. Therefore, we have implemented a form of interference microscopy based upon phase-shifted, laser-feedback interferometry and developed an algorithm that can be used to separate the contribution of the elastically scattered light by sub-cellular structures from the reflection at the coverslip-buffer interface. The method offers an opportunity to probe protein aggregation, index of refraction variations and structure. We measure the topography and reflection from calibration spheres and from stress fibers and adhesions in both fixed and motile cells. Unlike the data acquired with reflection interference contrast microscopy, where the reflection from adhesions can appear dark, our approach demonstrates that these regions have high reflectivity. The data acquired from fixed and live cells show the presence of a dense actin layer located ≈ 100 nm above the coverslip interface. Finally, the measured dynamics of filopodia and the lamella in a live cell supports retrograde flow as the dominate mechanism responsible for filopodia retraction

ZikaPLAN: Zika Preparedness Latin American Network

The ongoing Zika virus (ZIKV) outbreak in Latin America, the Caribbean, and the Pacific Islands has underlined the need for a coordinated research network across the whole region that can respond rapidly to address the current knowledge gaps in Zika and enhance research preparedness beyond Zika. The European Union under its Horizon 2020 Research and Innovation Programme awarded three research consortia to respond to this need. Here we present the ZikaPLAN (Zika Preparedness Latin American Network) consortium. ZikaPLAN combines the strengths of 25 partners in Latin America, North America, Africa, Asia, and various centers in Europe. We will conduct clinical studies to estimate the risk and further define the full spectrum and risk factors of congenital Zika virus syndrome (including neurodevelopmental milestones in the first 3 years of life), delineate neurological complications associated with ZIKV due to direct neuroinvasion and immune-mediated responses in older children and adults, and strengthen surveillance for birth defects and Guillain-Barré Syndrome. Laboratory-based research to unravel neurotropism and investigate the role of sexual transmission, determinants of severe disease, and viral fitness will underpin the clinical studies. Social messaging and engagement with affected communities, as well as development of wearable repellent technologies against Aedes mosquitoes will enhance the impact. Burden of disease studies, data-driven vector control, and vaccine modeling as well as risk assessments on geographic spread of ZIKV will form the foundation for evidence-informed policies. While addressing the research gaps around ZIKV, we will engage in capacity building in laboratory and clinical research, collaborate with existing and new networks to share knowledge, and work with international organizations to tackle regulatory and other bottlenecks and refine research priorities. In this way, we can leverage the ZIKV response toward building a long-term emerging infectious diseases response capacity in the region to address future challenges

Morphological, photosynthetic and water relations traits underpin the contrasting success of two tropical lichen groups at the interior and edge of forest fragments

Microclimatic edge effects and morpho-physiological characteristics are shaping lichen functional group distribution. Thus, lichen functional groups may be used as indicator for forest disturbanc

Conformational Changes during Potassium-Channel Gating

Voltage-gated ion channels have a paramount importance in many physiological processes such as cell-to-cell communication, action potential-propagation, and cell motility. Voltage-gated ion channels are characterized by their ability to sense membrane voltage and to greatly change channel activity in response to small changes in the voltage. The ability to sense voltage resides in the four voltage-sensor domains (VSDs) surrounding the central ion-conducting pore. Membrane depolarization causes the inside of the membrane to become positively charged, electrostatically repelling the positively charged fourth transmembrane segment (S4), or voltage sensor, in the VSD, causing the voltage sensor to move outwards. This motion provides necessary energy to open the pore and allow ion conductivity. Prolonged channel activation leads to alterations in the selectivity filter which cease ion conductivity, in a process called slow inactivation. In this thesis, we investigated the movement of S4 during activation of the channel. We also studied the communication between the four subunits during activation as well as the communication between the pore domain and VSD during slow inactivation. We have shown that voltage sensors move approximately 12 Å outwards during activation. The positively charged amino acid residues in S4 create temporary salt bridges with negative counter-charges in the other segments of the VSD as it moves through a membrane. We have also shown that the movement of one of the four voltage sensors can affect the movement of the neighboring voltage sensors. When at least one voltage sensor has moved to an up-position, it stabilizes other voltage sensors in the up-position, increasing the energy required for the voltage sensor to return to the down position. We have also shown reciprocal communication between the pore domain and the VSDs. Alterations in the VSD or the interface between the pore and the VSD cause changes in the rate of slow inactivation. Likewise, modifications in the pore domain cause changes to the voltage-sensor movement. This indicates communication between the pore and the VSD during slow inactivation. The information from our work could be used to find new approaches when designing channel-modifying drugs for the treatment of diseases caused by increased neuronal excitability, such as chronic pain and epilepsy