Functional Dysregulations in CA1 Hippocampal Networks of a 3-Hit Mouse Model of Schizophrenia

For a better translation from treatment designs of schizophrenia to clinical efficiency, there is a crucial need to refine preclinical animal models. In order to consider the multifactorial nature of the disorder, a new mouse model associating three factors (genetic susceptibility—partial deletion of the MAP6 gene, early-life stress—maternal separation, and pharmacological treatment—chronic Δ-9-tetrahydrocannabinol during adolescence) has recently been described. While this model depicts a schizophrenia-like phenotype, the neurobiological correlates remain unknown. Synaptic transmission and functional plasticity of the CA1 hippocampal region of male and female 3-hit mice were therefore investigated using electrophysiological recordings on the hippocampus slice. While basal excitatory transmission remained unaffected, NMDA receptor (NMDAr)-mediated long-term potentiation (LTP) triggered by theta-burst (TBS) but not by high-frequency (HFS) stimulation was impaired in 3-hit mice. Isolated NMDAr activation was not affected or even increased in female 3-hit mice, revealing a sexual dimorphism. Considering that the regulation of LTP is more prone to inhibitory tone if triggered by TBS than by HFS, the weaker potentiation in 3-hit mice suggests a deficiency of intrinsic GABA regulatory mechanisms. Indeed, NMDAr activation was increased by GABA_A receptor blockade in wild-type but not in 3-hit mice. This electrophysiological study highlights dysregulations of functional properties and plasticity in hippocampal networks of 3-hit mice, one of the mechanisms suspected to contribute to the pathophysiology of schizophrenia. It also shows differences between males and females, supporting the sexual dimorphism observed in the disorder. Combined with the previously reported study, the present data reinforce the face validity of the 3-hit model that will help to consider new therapeutic strategies for psychosis.     

Probabilistic reliable dissemination in large-scale systems

The growth of the Internet raises new challenges for the design of distributed systems and applications. In the context of group communication protocols, gossip-based schemes have attracted interest as they are scalable, easy to deploy, and resilient to network and process failures. However, traditional gossip-based protocols have two major drawbacks: 1) they rely on each peer having knowledge of the global membership; and 2) being oblivious to the network topology, they can impose a high load on network links when applied to wide-area settings. In this paper, we provide a theoretical analysis of gossip-based protocols which relates their reliability to key system parameters (the system size, failure rates, and number of gossip targets). The results provide guidelines for the design of practical protocols. In particular, they show how reliability can be maintained while alleviating drawback by: 1) providing each peer with only a small subset of the total membership information and drawback; and 2) organizing members into a hierarchical structure that reflects their proximity according to some network-related metric. We validate the analytical results by simulations and verify that the hierarchical gossip protocol considerably reduces the load on the network compared to the original, non-hierarchical protocol.     

A low cost and low power silicon npn bipolar process with NMOS transistors (ADRF) for RF and microwave applications

A silicon bipolar process for RF and microwave applications, which features 25-GHz double-polysilicon self-aligned npn bipolar transistors with 5.5-V BV/sub CEO/, optional 0.7-/spl mu/m (L/sub eff/) NMOS transistors with p/sup +/ polysilicon gates for switch applications, lateral pnp transistors, high and low valued resistors, p/sup +/ polysilicon-to-n/sup +/ plug capacitors, and inductors is described. The npn transistors utilize nitride-oxide composite spacers formed using sacrificial TEOS spacers, a process which is simpler than the previously reported composite spacer processes. Use of the composite spacer structure virtually eliminates problems relating to the extrinsic-intrinsic base link-up and reduces plasma induced damage associated with the conventional spacer process. Microwave and RF capabilities of the process up to several GHz are demonstrated by fabricating and characterizing RF amplifiers, low noise amplifiers, and RF switches.<>     

Impact of inhaled nitric oxide on platelet aggregation and fibrinolysis in rats with endotoxic lung injury. Role of cyclic guanosine 5'-monophosphate

As inhaled nitric oxide (iNO) may differently increase bleeding time (BT) and inhibit platelet aggregation in normal and lung-injured patients or experimental models, we studied the effects of iNO on hemostasis in presence and absence of an endotoxic lung injury in the rat. Eight hours after intratracheal administration of endotoxin (lipopolysaccharide [LPS]) or its solvent (phosphate-buffered solution [PBS]), four groups of rats were randomized according to the presence or absence of 15 ppm iNO added for an additional 10 h. We measured BT, ex vivo platelet aggregation, plasma fibrinogen, euglobulin clot lysis time (ECLT), and platelet and aortic cyclic guanosine 5'-monophosphate (cGMP) contents. Acute lung inflammation did not influence BT, but increased platelet aggregability, fibrinogen levels, and platelet and aortic cGMP. In control and endotoxic rats, iNO increased BT, reduced platelet aggregability, and increased platelet cGMP. iNO increased aortic cGMP only in healthy rats. ECLT was increased by LPS and unchanged with iNO. These results suggest that the extrapulmonary "systemic" effects induced by iNO on hemostasis were not strictly similar in healthy and LPS rats, inflammation inducing proper changes in coagulation parameters. However, iNO attenuated the procoagulant activity induced by acute lung inflammation, suggesting a potentially beneficial effect of this therapy.     

Transfer of learning in virtual environments: a new challenge?

The aim of all education is to apply what we learn in different contexts and to recognise and extend this learning to new situations. Virtual learning environments can be used to build skills. Recent research in cognitive psychology and education has shown that acquisitions are linked to the initial context. This provides a challenge for virtual reality in education or training. A brief overview of transfer issues highlights five main ideas: (1) the type of transfer enables the virtual environment (VE) to be classified according to what is learned; (2) the transfer process can create conditions within the VE to facilitate transfer of learning; (3) specific features of VR must match and comply with transfer of learning; (4) transfer can be used to assess a VE’s effectiveness; and (5) future research on transfer of learning must examine the singular context of learning. This paper discusses how new perspectives in cognitive psychology influence and promote transfer of learning through the use of VEs.     

Stable monolithic GaAs FET oscillator

A monolithic X-band GaAs FET oscillator has been developed. Passive circuit components are lumped capacitors and inductors on semi-insulating GaAs; the chip size is 1.2 × 1.4 mm2. Stabilised with a Ba2Ti9O20 dielectric resonator, the oscillator delivers more than 30 mW output power at 10.8 GHz with a maximum chip efficiency of 20%. The frequency drift is better than 1 × 10?6/K from ?20°C to 80°C.     

Estimation of the exposure of the French population to the BSE agent: comparison of the 1980-95 consumption of beef products containing mechanically recovered meat in France and the UK,by birth cohort and gender

Assuming that human exposure to BSE was through beef mechanically recovered meat (MRM) consumed as burgers and other meat products, we estimated the French consumption of different food items containing beef MRM, and compared these consumptions for French and British populations. To estimate consumption of meat products containing bovine MRM, we used dietary data from national individual and household food surveys conducted between 1980 and 1995. After reconciliation of consumption data between the available surveys and calendar year adjustments, we simulated consumption of one-thousandth of the French population. Consumption was estimated by birth cohort and gender, and for the periods 1980-89 and 1990-95 separately. Data showed that burgers (including manufactured minced meat) represented around 75-80% of the individual consumption of meat products containing MRM, and that consumption of burgers increased by 40% over the 1980-95 period. In all age groups, consumption was higher in males than in females. In both genders, the 1940-69 birth cohort had the highest mean consumption of burgers and other beef products containing MRM. Similar findings have been reported for the UK population. Estimated consumption of bovine MRM per calendar year increased markedly over the study period, concomitantly with an increase of bovine carcasses imported from the UK. Comparison of the 1980-1995 pattern of bovine MRM consumption in the UK and France indicated thatthis consumption peaked later in France than in the UK. This difference might result in different temporal pattern of vCJD incidence.     

Efficient and adaptive epidemic-style protocols for reliable and scalable multicast

Epidemic-style (gossip-based) techniques have recently emerged as a class of scalable and reliable protocols for peer-to-peer multicast dissemination in large process groups. However, popular implementations of epidemic-style dissemination suffer from two major drawbacks: 1) Network overhead: when deployed on a WAN-wide or VPN-wide scale, they generate a large number of packets that transit across the boundaries of multiple network domains (e.g., LANs, subnets, ASs), causing an overload on core network elements such as bridges, routers, and associated links. 2) Lack of adaptivity: they impose the same load on process group members and the network even under reduced failure rates (viz., packet losses, process failures). In this paper, we describe two protocols to address these problems: 1) a hierarchical gossiping protocol and 2) an adaptive dissemination framework (for multicasts) that allows use of any gossiping primitive within it. These protocols work within a virtual peer-to-peer hierarchy called the leaf box hierarchy. Processes can be allocated in a topologically aware manner to the leaf boxes of this structure, so that protocols 1 and 2 produce low traffic across domain boundaries in the network and induce minimal overhead when there are no failures.     

Epidemic information dissemination in distributed systems

Easy to deploy, robust, and highly resilient to failures, epidemic algorithms are a potentially effective mechanism for propagating information in large peer-to-peer systems deployed on Internet or ad hoc networks. It is possible to adjust the parameters of epidemic algorithm to achieve high reliability despite process crashes and disconnections, packet losses, and a dynamic network topology. Although researchers have used epidemic algorithms in applications such as failure detection, data aggregation, resource discovery and monitoring, and database replication, their general applicability to practical, Internet-wide systems remains open to question. We describe four key problems: membership maintenance, network awareness, buffer management, and message filtering, and suggest some preliminary approaches to address them.