Bolstering Global Trade: Governance A Work Program for the WTO presented by the High-Level Board of Experts on the Future of Global Trade Governance

The WTO provides the foundation of the rules-based global trading system that has played a critical role in sup- porting growth in global GDP during recent decades. Preserving the salience of the WTO is vital in managing the adjustment pressures from globalization and sustaining the cooperation needed to govern trade relations in a world in which the transformation towards a global digital economy and associated servicification of production creates new policy challenges. Efforts to address these challenges are stymied by disagreements between WTO members regarding the priorities for the multilateral trading system. These disagreements reflect differences in views on the extent to which national policies have adverse international effects and the costs and benefits of ne- gotiating additional trade policy rules. The result has been to impede progress on rule-making for both long- standing core policies of concern to many WTO members (e.g., agriculture) as well as new policy areas. Matters have been compounded by dissatisfaction by some Members regarding the functioning of the WTO dispute set- tlement body and transparency mechanisms. While preferential trade agreements are important complementary vehicles for countries to pursue deeper coop- eration on trade policy matters than has been possible in the WTO, such initiatives depend on the strong foundation of basic rules provided by the WTO. Moreover, they only offer partial solutions – many of the emerging policy areas of concern to business and civil society call for multilateral cooperation. Re-vitalizing such coopera- tion does not require major changes in the organization. What is needed is willingness to engage in candid, substantive discussion of perceived problems and possible solutions. The recent Agreement on Trade Facilitation, with its positive approach to addressing development concerns, and the success of Members in incrementally deepening cooperation on some matters under the purview of some WTO agreements – e.g., addressing specific trade concerns arising from proposed new product regulations – show that WTO Members can innovate and agree to common approaches towards trade policies while recogniz- ing differences in social preferences and national circumstances

Cerebellar-Dependent Learning in Larval Zebrafish

Understanding how neuronal network activity contributes to memory formation is challenged by the complexity of most brain circuits and the restricted ability to monitor the activity of neuronal populations in vivo. The developing zebrafish (Danio rerio) is an animal model that circumvents these problems, because zebrafish larvae possess a rich behavioral repertoire and an accessible brain. Here, we developed a classical conditioning paradigm in which 6- to 8-d-old larvae develop an enhanced motor response to a visual stimulus (conditioned stimulus, CS) when it is paired with touch (unconditioned stimulus, US). Using in vivo calcium imaging we demonstrate that CS and US activate different subsets of neurons in the cerebellum; their activity, modulated by learning two-photon laser ablation, revealed that the cerebellum is involved in acquisition and extinction, but not the retention, of this memory

Protein synthesis at synaptic sites on dendrites

Studies over the past 20 years have revealed that gene expression in neurons is carried out by a distributed network of translational machinery. One component of this network is localized in dendrites, where polyribosomes and associated membranous elements are positioned beneath synapses and translate a particular population of dendritic mRNAs. The localization of translation machinery and mRNAs at synapses endows individual synapses with the capability to independently control synaptic strength through the local synthesis of proteins. The present review discusses recent studies linking synaptic plasticity to dendritic protein synthesis and mRNA trafficking and considers how these processes are regulated. We summarize recent information about how synaptic signaling is coupled to local translation and to the delivery of newly transcribed mRNAs to activated synaptic sites and how local translation may play a role in activity-dependent synaptic modification

Nitric oxide and synaptic function

The free radical gas nitric oxide (NO) is a recently identified neuronal messenger that carries out diverse signaling tasks in both the central and peripheral nervous systems. Whereas most neurotransmitters are packaged in synaptic vesicles and secreted in a Ca2+-dependent manner from specialized nerve endings, NO is an unconventional transmitter which is not packaged in vesicles, but rather diffuses from its site of production in the absence of any specialized release machinery. The lack of a requirement for release apparatus raises the possibility that NO can be released from both pre- and postsynaptic neuronal elements. In addition, because NO is gaseous and extremely membrane permeant, it can bypass normal signal transduction routes involving interactions with synaptic membrane receptors. Although the targets of NO have not yet been completely described, it is known that NO can bind to the iron contained in heine groups, leading to conformational changes in associated proteins, such as guanylyl cyclase

Elasto-plastic response of reversibly crosslinked biopolymer bundles

We study the response of F-actin bundles to driving forces through a simple analytical model. We consider two filaments connected by reversibly bound crosslinks and driven by an external force. Two failure modes under load can be defined. \textit{Brittle failure} is observed when crosslinks suddenly and collectively unbind, leading to catastrophic loss of bundle integrity. During \textit{ductile failure}, on the other hand, bundle integrity is maintained, however at the cost of crosslink reorganization and defect formation. We present phase diagrams for the onset of failure, highlighting the importance of the crosslink stiffness for these processes. Crossing the phase boundaries, force-deflection curves display (frequency-dependent) hysteresis loops, reflecting the first-order character of the failure processes. We evidence how the introduction of defects can lead to complex elasto-plastic relaxation processes, once the force is switched off. Depending on, both, the time-scale for defect motion as well as the crosslink stiffness, bundles can remain in a quasi-permanent plastically deformed state for a very long time.Comment: 9 pages, 15 figure

IFEMS, an Interactive Finite Element Modeling System Using a CAD/CAM System

A method of coupling a CAD/CAM system with a general purpose finite element mesh generator is described. The three computer programs which make up the interactive finite element graphics system are discussed

Further analysis of the effects of baffles on combustion instability

A computerized analytical model, developed to predict the effects of baffles on combustion instability, was modified in an effort to improve the ability to properly predict stability effects. The model was modified: (1) to replace a single spatially-averaged response factor by separate values for each baffle compartment; (2) to calculate the axial component of the acoustic energy flux, and (3) to permit analysis of traveling waves in a thin annular chamber. Allowance for separate average response factors in each baffle compartment was found to significantly affect the predicted results. With this modification, an optimum baffle length was predicted which gave maximum stability

Activity of human hippocampal and amygdala neurons during retrieval of declarative memories

Episodic memories allow us to remember not only that we have seen an item before but also where and when we have seen it (context). Sometimes, we can confidently report that we have seen something (familiarity) but cannot recollect where or when it was seen. Thus, the two components of episodic recall, familiarity and recollection, can be behaviorally dissociated. It is not clear, however, whether these two components of memory are represented separately by distinct brain structures or different populations of neurons in a single anatomical structure. Here, we report that the spiking activity of single neurons in the human hippocampus and amygdala [the medial temporal lobe (MTL)] contain information about both components of memory. We analyzed a class of neurons that changed its firing rate to the second presentation of a previously novel stimulus. We found that the neuronal activity evoked by the presentation of a familiar stimulus (during retrieval) distinguishes stimuli that will be successfully recollected from stimuli that will not be recollected. Importantly, the ability to predict whether a stimulus is familiar is not influenced by whether the stimulus will later be recollected. We thus conclude that human MTL neurons contain information about both components of memory. These data support a continuous strength of memory model of MTL function: the stronger the neuronal response, the better the memory

OCT for glaucoma diagnosis, screening and detection of glaucoma progression.

Optical coherence tomography (OCT) is a commonly used imaging modality in the evaluation of glaucomatous damage. The commercially available spectral domain (SD)-OCT offers benefits in glaucoma assessment over the earlier generation of time domain-OCT due to increased axial resolution, faster scanning speeds and has been reported to have improved reproducibility but similar diagnostic accuracy. The capabilities of SD-OCT are rapidly advancing with 3D imaging, reproducible registration, and advanced segmentation algorithms of macular and optic nerve head regions. A review of the evidence to date suggests that retinal nerve fibre layer remains the dominant parameter for glaucoma diagnosis and detection of progression while initial studies of macular and optic nerve head parameters have shown promising results. SD-OCT still currently lacks the diagnostic performance for glaucoma screening

Single-trial learning of novel stimuli by individual neurons of the human hippocampus-amygdala complex

The ability to distinguish novel from familiar stimuli allows nervous systems to rapidly encode significant events following even a single exposure to a stimulus. This detection of novelty is necessary for many types of learning. Neurons in the medial temporal lobe (MTL) are critically involved in the acquisition of long-term declarative memories. During a learning task, we recorded from individual MTL neurons in vivo using microwire electrodes implanted in human epilepsy surgery patients. We report here the discovery of two classes of neurons in the hippocampus and amygdala that exhibit single-trial learning: novelty and familiarity detectors, which show a selective increase in firing for new and old stimuli, respectively. The neurons retain memory for the stimulus for 24 hr. Thus, neurons in the MTL contain information sufficient for reliable novelty-familiarity discrimination and also show rapid plasticity as a result of single-trial learning