Loss of hippocampal serine protease BSP1/neuropsin predisposes to global seizure activity

Serine proteases in the adult CNS contribute both to activity-dependent structural changes accompanying learning and to the regulation of excitotoxic cell death. Brain serine protease 1 (BSP1)/neuropsin is a trypsin-like serine protease exclusively expressed, within the CNS, in the hippocampus and associated limbic structures. To explore the role of this enzyme, we have used gene targeting to disrupt this gene in mice. Mutant mice were viable and overtly normal; they displayed normal hippocampal long-term synaptic potentiation (LTP) and exhibited no deficits in spatial navigation (water maze). Nevertheless, electrophysiological studies revealed that the hippocampus of mice lacking this specifically expressed protease possessed an increased susceptibility for hyperexcitability (polyspiking) in response to repetitive afferent stimulation. Furthermore, seizure activity on kainic acid administration was markedly increased in mutant mice and was accompanied by heightened immediate early gene (c-fos) expression throughout the brain. In view of the regional selectivity of BSP1/neuropsin brain expression, the observed phenotype may selectively reflect limbic function, further implicating the hippocampus and amygdala in controlling cortical activation. Within the hippocampus, our data suggest that BSP1/neuropsin, unlike other serine proteases, has little effect on physiological synaptic remodeling and instead plays a role in limiting neuronal hyperexcitability induced by epileptogenic insult

Learn your opponent's strategy (in polynomial time)!

Agents that interact in a distributed environment might increase their utility by behaving optimally given the strategies of the other agents. To do so, agents need to learn about those with whom they share the same world. This paper examines interactions among agents from a game theoretic perspective. In this context, learning has been assumed as a means to reach equilibrium. We analyze the complexity of this learning process. We start with a restricted two-agent model, in which agents are represented by finite automata, and one of the agents plays a fixed strategy. We show that even with this restrictions, the learning process may be exponential in time. We then suggest a criterion of simplicity, that induces a class of automata that are learnable in polynomial time

Rational bidding using reinforcement learning: an application in automated resource allocation

The application of autonomous agents by the provisioning and usage of computational resources is an attractive research field. Various methods and technologies in the area of artificial intelligence, statistics and economics are playing together to achieve i) autonomic resource provisioning and usage of computational resources, to invent ii) competitive bidding strategies for widely used market mechanisms and to iii) incentivize consumers and providers to use such market-based systems. The contributions of the paper are threefold. First, we present a framework for supporting consumers and providers in technical and economic preference elicitation and the generation of bids. Secondly, we introduce a consumer-side reinforcement learning bidding strategy which enables rational behavior by the generation and selection of bids. Thirdly, we evaluate and compare this bidding strategy against a truth-telling bidding strategy for two kinds of market mechanisms – one centralized and one decentralized

Cooperation and Contagion in Web-Based, Networked Public Goods Experiments

A longstanding idea in the literature on human cooperation is that cooperation should be reinforced when conditional cooperators are more likely to interact. In the context of social networks, this idea implies that cooperation should fare better in highly clustered networks such as cliques than in networks with low clustering such as random networks. To test this hypothesis, we conducted a series of web-based experiments, in which 24 individuals played a local public goods game arranged on one of five network topologies that varied between disconnected cliques and a random regular graph. In contrast with previous theoretical work, we found that network topology had no significant effect on average contributions. This result implies either that individuals are not conditional cooperators, or else that cooperation does not benefit from positive reinforcement between connected neighbors. We then tested both of these possibilities in two subsequent series of experiments in which artificial seed players were introduced, making either full or zero contributions. First, we found that although players did generally behave like conditional cooperators, they were as likely to decrease their contributions in response to low contributing neighbors as they were to increase their contributions in response to high contributing neighbors. Second, we found that positive effects of cooperation were contagious only to direct neighbors in the network. In total we report on 113 human subjects experiments, highlighting the speed, flexibility, and cost-effectiveness of web-based experiments over those conducted in physical labs

The Anti-Inflammatory Reliever (AIR) Algorithm Study: a protocol for a single-group study of an AIR stepwise approach to the treatment of adult asthma

Background The stepwise approach to long-term asthma management, which traditionally incorporates short-acting β2-agonist reliever therapy, has been a core feature of asthma guidelines for over 30 years. There have been no studies, however, directly investigating the use of an entire guideline-recommended track. Recently, inhaled corticosteroid–formoterol has been recommended as the preferred reliever therapy in adult asthma, in accordance with a stepwise “Anti-Inflammatory Reliever” (AIR) treatment track. Objective The aim of this study was to evaluate the AIR stepwise approach recommended by the New Zealand adolescent and adult asthma guidelines, in combination with a novel algorithm for transitioning between treatment steps. Methods This 52-week, open-label, single-group study will recruit 100 adults aged 18 to 75 years with mild, moderate and moderate–severe asthma (ACTRN12620001010987). Participants will be allocated to budesonide–formoterol 200/6 µg, one actuation as needed (Step 1), one actuation twice daily and as needed (Step 2), or two actuations twice daily and one as needed (Step 3). Treatment steps will be adjusted throughout the study, in response to reliever use and asthma attacks, according to a stepwise AIR algorithm. Following a 26-week period of investigator-led transitions, participants will adjust their own treatment step. The primary outcome is participant satisfaction as measured by the Global Satisfaction score of the Treatment Satisfaction Questionnaire for Medication. Secondary outcomes will assess efficacy and safety, and describe patterns of medication use and participant flow through the treatment steps. Conclusion This is the first trial to assess the AIR treatment track and algorithm. The results will provide knowledge to guide the clinical use of this approach

Elucidation of the bonding of a near infrared dye to hollow gold nanospheres : a chalcogen tripod

Infrared surface enhanced Raman scattering (SERS) is an attractive technique for the in situ detection of nanoprobes in biological samples due to the greater depth of penetration and reduced interference compared to SERS in the visible region. A key challenge is to understand the surface layer formed in suspension when a specific label is added to the SERS substrate in aqueous suspension. SERS taken at different wavelengths, theoretical calculations, and surface-selective sum frequency generation vibrational spectroscopy (SFG-VS) were used to define the surface orientation and manner of attachment of a new class of infrared SERS label with a thiopyrylium core and four pendant 2-selenophenyl rings. Hollow gold nanospheres (HGNs) were used as the enhancing substrate and two distinct types of SERS spectra were obtained. With excitation close to resonance with both the near infrared electronic transition in the label (max 826 nm) and the plasmon resonance maximum (690 nm), surface enhanced resonance Raman scattering (SERRS) was obtained. SERRS indicates that the major axis of the core is near to perpendicular to the surface plane and SFG-VS obtained from a dried gold film gave a similar orientation with the major axis at an angle 64°-85° from the surface plane. Longer excitation wavelengths give SERS with little or no molecular resonance contribution and new vibrations appeared with significant displacements between the thiopyrylium core and the pendant selenophene rings. Analysis using calculated spectra with one or two rings rotated indicates that two rings on one end are rotated towards the metal surface to give an arrangement of two selenium and one sulphur atoms directly facing the gold structure. The spectra, together with a space filled model, indicate that the molecule is strongly adsorbed to the surface through the selenium and sulphur atoms in an arrangement which will facilitate layer formation

Place attachment in deprived neighbourhoods: The impacts of population turnover and social mix

This paper examines the determinants of individual place attachment, focussing in particular on differences between deprived and others neighbourhoods, and on the impacts of population turnover and social mix. It uses a multi-level modelling approach to take account of both individual- and neighbourhood-level determinants. Data are drawn from a large sample government survey, the Citizenship Survey 2005, to which a variety of neighbourhood-level data have been attached. The paper argues that attachment is significantly lower in more deprived neighbourhoods primarily because these areas have weaker social cohesion but that, in other respects, the drivers of attachment are the same. Turnover has modest direct impacts on attachment through its effect on social cohesion. Social mix has very limited impacts on attachment and the effects vary between social groups. In general, higher status or more dominant groups appear less tolerant of social mix

The decline and rise of neighbourhoods: the importance of neighbourhood governance

There is a substantial literature on the explanation of neighbourhood change. Most of this literature concentrates on identifying factors and developments behind processes of decline. This paper reviews the literature, focusing on the identification of patterns of neighbourhood change, and argues that the concept of neighbourhood governance is a missing link in attempts to explain these patterns. Including neighbourhood governance in the explanations of neighbourhood change and decline will produce better explanatory models and, finally, a better view about what is actually steering neighbourhood change

Physics at a Neutrino Factory

In response to the growing interest in building a Neutrino Factory to produce high intensity beams of electron- and muon-neutrinos and antineutrinos, in October 1999 the Fermilab Directorate initiated two six-month studies. The first study, organized by N. Holtkamp and D. Finley, was to investigate the technical feasibility of an intense neutrino source based on a muon storage ring. This design study has produced a report in which the basic conclusion is that a Neutrino Factory is technically feasible, although it requires an aggressive R&D program. The second study, which is the subject of this report, was to explore the physics potential of a Neutrino Factory as a function of the muon beam energy and intensity, and for oscillation physics, the potential as a function of baseline.Comment: 133 pages, 64 figures. Report to the Fermilab Directorate. Available from http://www.fnal.gov/projects/muon_collider/ This version fixes some printing problem