The striatal dopamine transporter in first-episode, drug-naive schizophrenic patients: evaluation by the new SPECT-ligand[99mTc]TRODAT-1

Following the current hypothesis that acute schizophrenic psychotic illness is associated with a triatal ‘hyperdopaminergic state’, presynaptic integrity and dopamine transporter (DAT) density in first-episode, neuroleptic-naive schizophrenic patients was measured by single-photonemission- tomography (SPECT) and compared with that in healthy control subjects. A new SPECT-ligand for assessment of the striatal DAT, the Technetium-99m-labelled tropane TRODAT-1 ([99mTc]TRODAT-1), was used. Ten inpatients suffering from a first acute schizophrenic episode and 10 age- and sex-matched healthy control subjects underwent SPECT with [99mTc]TRODAT-1. On the day of SPECT, psychopathological ratings were performed with the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Syndrome Scale (PANSS) and Schedule for Assessment of Negative Symptoms (SANS). Patients had not previously received any neuroleptic or antidepressant medication. Mean specific TRODAT-1 binding in the striatum did not differ significantly between the patient and the age- and sex-matched control group (1.25 vs. 1.28). Variance was significantly higher in the patient group. The data obtained with the new ligand in first-episode, drug-naive schizophrenic patients are in line with the PET results from the group of Laakso et al. in a comparable patient sample. [99mTc]TRODAT-1 seems to be a valuable new SPECTligand in the evaluation of the presynaptic site of the striatal dopaminergic synapse in schizophrenia

A comparative study of arbitration algorithms for the Alpha 21364 pipelined router

Interconnection networks usually consist of a fabric of interconnected routers, which receive packets arriving at their input ports and forward them to appropriate output ports. Unfortunately, network packets moving through these routers are often delayed due to conflicting demand for resources, such as output ports or buffer space. Hence, routers typically employ arbiters that resolve conflicting resource demands to maximize the number of matches between packets waiting at input ports and free output ports. Efficient design and implementation of the algorithm running on these arbiters is critical to maximize network performance.This paper proposes a new arbitration algorithm called SPAA (Simple Pipelined Arbitration Algorithm), which is implemented in the Alpha 21364 processor's on-chip router pipeline. Simulation results show that SPAA significantly outperforms two earlier well-known arbitration algorithms: PIM (Parallel Iterative Matching) and WFA (Wave-Front Arbiter) implemented in the SGI Spider switch. SPAA outperforms PIM and WFA because SPAA exhibits matching capabilities similar to PIM and WFA under realistic conditions when many output ports are busy, incurs fewer clock cycles to perform the arbitration, and can be pipelined effectively. Additionally, we propose a new prioritization policy called the Rotary Rule, which prevents the network's adverse performance degradation from saturation at high network loads by prioritizing packets already in the network over new packets generated by caches or memory.Mukherjee, S.; Silla Jiménez, F.; Bannon, P.; Emer, J.; Lang, S.; Webb, D. (2002). A comparative study of arbitration algorithms for the Alpha 21364 pipelined router. ACM SIGPLAN Notices. 37(10):223-234. doi:10.1145/605432.605421S223234371

Satellite data for the offshore renewable energy sector: Synergies and innovation opportunities

Can satellite data be used to address challenges currently faced by the Offshore Renewable Energy (ORE) sector? What benefit can satellite observations bring to resource assessment and maintenance of ORE farms? Can satellite observations be used to assess the environmental impact of offshore renewables leading towards a more sustainable ORE sector? This review paper faces these questions presenting a holistic view of the current interactions between satellite and ORE sectors, and future needs to make this partnership grow. The aim of the work is to start the conversation between these sectors by establishing a common ground. We present offshore needs and satellite technology limitations, as well as potential opportunities and areas of growth. To better understand this, the reader is guided through the history, current developments, challenges and future of offshore wind, tidal and wave energy technologies. Then, an overview on satellite observations for ocean applications is given, covering types of instruments and how they are used to provide different metocean variables, satellite performance, and data processing and integration. Past, present and future satellite missions are also discussed. Finally, the paper focuses on innovation opportunities and the potential of synergies between the ORE and satellite sectors. Specifically, we pay attention to improvements that satellite observations could bring to standard measurement techniques: assessing uncertainty, wind, tidal and wave conditions forecast, as well as environmental monitoring from space. Satellite–enabled measurement of ocean physical processes and applications for fisheries, mammals and birds, and habitat change, are also discussed in depth

Should digestion assays be used to estimate persistence of potential allergens in tests for safety of novel food proteins?

Food allergies affect an estimated 3 to 4% of adults and up to 8% of children in developed western countries. Results from in vitro simulated gastric digestion studies with purified proteins are routinely used to assess the allergenic potential of novel food proteins. The digestion of purified proteins in simulated gastric fluid typically progresses in an exponential fashion allowing persistence to be quantified using pseudo-first-order rate constants or half lives. However, the persistence of purified proteins in simulated gastric fluid is a poor predictor of the allergenic status of food proteins, potentially due to food matrix effects that can be significant in vivo. The evaluation of the persistence of novel proteins in whole, prepared food exposed to simulated gastric fluid may provide a more correlative result, but such assays should be thoroughly validated to demonstrate a predictive capacity before they are accepted to predict the allergenic potential of novel food proteins

Human-computer interaction to human-computer-context interaction : towards a conceptual framework for conducting user studies for shifting interfaces

Computer interfaces have been diversifying: from mobile and wearable technologies to the human body as an interface. Moreover, new sensing possibilities have allowed input to interfaces to go beyond the traditional mouse- and keyboard. This has resulted in a shift from manifest to latent interactions, where interactions between the human and the computer are becoming less visible. Currently, there is no framework available that fully captures the complexity of the multidimensional, multimodal, often latent interactions with these constantly shifting interfaces. In this manuscript, the Hu-man-Computer-Context Interaction (HCCI) framework is proposed. This framework defines 5 relevant interaction levels to be considered during user research in all stages of the new product development process in order to optimize user experience. More specifically, the interaction context is defined in terms of user-object, user-user, user-content, user-platform and user-context interactions. The HCCI framework serves as a concrete tool to use in a new product development process by HCI researchers, design-ers, and developers and aims to be technology independent and future-proof. This framework is a preliminary suggestion to be matched against other innovation devel-opment projects and needs to be further validated

Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress

In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse

Bottom-up Infrastructures: Aligning Politics and Technology in building a Wireless Community Network

Contemporary innovation in infrastructures is increasingly characterized by a close relationship between experts and lay people. This phenomenon has attracted the attention from a wide range of disciplines, including computer-supported cooperative work (CSCW), science and technology studies (S&TS), organization studies and participatory design (PD). Connecting to this broad area of research, the article presents a qualitative case study concerning the building and maintenance of a grassroots, bottom-up information infrastructure in Italy, defined as wireless community network (WCN). Methodologically, the research is based on qualitative interviews with participants to the WCN, ethnographic observations and document analysis. The aim of the article is to understand the alignment between the technical work implied in building this bottom-up infrastructure and the political and cultural frameworks that move people to participate to this project. Relying on the field of science & technology studies, and in particular on the notions of ‘inverse infrastructure’ and ‘research in the wild’, we disclose the WCN’s peculiar innovation trajectory, localized outside conventional spaces of research and development. Overall, the presentation of the qualitative and ethnographic data allows to point out a more general reflection on bottom-up infrastructures and to enrich the academic debate concerning bottom-up infrastructuring work and other similar typologies of collaborative design projects in the domain of infrastructures

A genetic network model of cellular responses to lithium treatment and cocaine abuse in bipolar disorder

<p>Abstract</p> <p>Background</p> <p>Lithium is an effective treatment for Bipolar Disorder (BD) and significantly reduces suicide risk, though the molecular basis of lithium's effectiveness is not well understood. We seek to improve our understanding of this effectiveness by posing hypotheses based on new experimental data as well as published data, testing these hypotheses in silico, and posing new hypotheses for validation in future studies. We initially hypothesized a gene-by-environment interaction where lithium, acting as an environmental influence, impacts signal transduction pathways leading to differential expression of genes important in the etiology of BD mania.</p> <p>Results</p> <p>Using microarray and rt-QPCR assays, we identified candidate genes that are differentially expressed with lithium treatment. We used a systems biology approach to identify interactions among these candidate genes and develop a network of genes that interact with the differentially expressed candidates. Notably, we also identified cocaine as having a potential influence on the network, consistent with the observed high rate of comorbidity for BD and cocaine abuse. The resulting network represents a novel hypothesis on how multiple genetic influences on bipolar disorder are impacted by both lithium treatment and cocaine use. Testing this network for association with BD and related phenotypes, we find that it is significantly over-represented for genes that participate in signal transduction, consistent with our hypothesized-gene-by environment interaction. In addition, it models related pharmacogenomic, psychiatric, and chemical dependence phenotypes.</p> <p>Conclusions</p> <p>We offer a network model of gene-by-environment interaction associated with lithium's effectiveness in treating BD mania, as well as the observed high rate of comorbidity of BD and cocaine abuse. We identified drug targets within this network that represent immediate candidates for therapeutic drug testing. Posing novel hypotheses for validation in future work, we prioritized SNPs near genes in the network based on functional annotation. We also developed a "concept signature" for the genes in the network and identified additional candidate genes that may influence the system because they are significantly associated with the signature.</p