Varenicline decreases ethanol intake and increases dopamine release via neuronal nicotinic acetylcholine receptors in the nucleus accumbens

BACKGROUND AND PURPOSE Varenicline, a neuronal nicotinic acetylcholine receptor (nAChR) modulator, decreases ethanol consumption in rodents and humans. The proposed mechanism of action for varenicline to reduce ethanol consumption has been through modulation of dopamine (DA) release in the nucleus accumbens (NAc) via α4*-containing nAChRs in the ventral tegmental area (VTA). However, presynaptic nAChRs on dopaminergic terminals in the NAc have been shown to directly modulate dopaminergic signalling independently of neuronal activity from the VTA. In this study, we determined whether nAChRs in the NAc play a role in varenicline’s effects on ethanol consumption. EXPERIMENTAL APPROACH Rats were trained to consume ethanol using the intermittent-access two-bottle choice protocol for 10 weeks. Ethanol intake was measured after varenicline or vehicle was microinfused into the NAc (core, shell or core-shell border) or the VTA (anterior or posterior). The effect of varenicline treatment on DA release in the NAc was measured using both in vivo microdialysis and in vitro fast-scan cyclic voltammetry (FSCV). KEY RESULTS Microinfusion of varenicline into the NAc core and core-shell border, but not into the NAc shell or VTA, reduced ethanol intake following long-term ethanol consumption. During microdialysis, a significant enhancement in accumbal DA release occurred following systemic administration of varenicline and FSCV showed that varenicline also altered the evoked release of DA in the NAc. CONCLUSION AND IMPLICATIONS Following long-term ethanol consumption, varenicline in the NAc reduces ethanol intake, suggesting that presynaptic nAChRs in the NAc are important for mediating varenicline’s effects on ethanol consumption.

Modelling the intention to adopt cloud computing services : a transaction cost theory perspective

This paper uses transaction cost theory to study cloud computing adoption. A model is developed and tested with data from an Australian survey. According to the results, perceived vendor opportunism and perceived legislative uncertainty around cloud computing were significantly associated with perceived cloud computing security risk. There was also a significant negative relationship between perceived cloud computing security risk and the intention to adopt cloud services. This study also reports on adoption rates of cloud computing in terms of applications, as well as the types of services used.

Design and implementation of unified communications as a service based on the OpenStack cloud environment

Cloud Computing, based on early virtual computer concepts and technologies, is now itself a maturing technology in the marketplace and it has revolutionized the IT industry, being the powerful platform that many businesses are choosing to migrate their in-premises IT services onto. Cloud solution has the potential to reduce the capital and operational expenses associated with deploying IT services on their own. In this study, we have implemented our own private cloud solution, infrastructure as a service (IaaS), using the OpenStack platform with high availability and a dynamic resource allocation mechanism. Besides, we have hosted unified communication as a service (UCaaS) in the underlying IaaS and successfully tested voice over IP (VoIP), video conferencing, voice mail and instant messaging (IM) with clients located at the remote site. The proposed solution has been developed in order to give advice to bussinesses that want to build their own cloud environment, IaaS and host cloud services and applicatons in the cloud. This paper also aims at providing an alternate option for proprietary cloud solutions for service providers to consider.

On secure outsourcing of cryptographic computations to cloud

For the past few years, research works on the topic of secure outsourcing of cryptographic computations has drawn significant attention from academics in security and cryptology disciplines as well as information security practitioners. One main reason for this interest is their application for resource constrained devices such as RFID tags. While there has been significant progress in this domain since Hohenberger and Lysyanskaya have provided formal security notions for secure computation delegation, there are some interesting challenges that need to be solved that can be useful towards a wider deployment of cryptographic protocols that enable secure outsourcing of cryptographic computations. This position paper brings out these challenging problems with RFID technology as the use case together with our ideas, where applicable, that can provide a direction towards solving the problems.

Extinction risk in cloud forest fragments under climate change and habitat loss

Aim: To quantify the consequences of major threats to biodiversity, such as climate and land-use change, it is important to use explicit measures of species persistence, such as extinction risk. The extinction risk of metapopulations can be approximated through simple models, providing a regional snapshot of the extinction probability of a species. We evaluated the extinction risk of three species under different climate change scenarios in three different regions of the Mexican cloud forest, a highly fragmented habitat that is particularly vulnerable to climate change. Location: Cloud forests in Mexico. Methods: Using Maxent, we estimated the potential distribution of cloud forest for three different time horizons (2030, 2050 and 2080) and their overlap with protected areas. Then, we calculated the extinction risk of three contrasting vertebrate species for two scenarios: (1) climate change only (all suitable areas of cloud forest through time) and (2) climate and land-use change (only suitable areas within a currently protected area), using an explicit patch-occupancy approximation model and calculating the joint probability of all populations becoming extinct when the number of remaining patches was less than five. Results: Our results show that the extent of environmentally suitable areas for cloud forest in Mexico will sharply decline in the next 70 years. We discovered that if all habitat outside protected areas is transformed, then only species with small area requirements are likely to persist. With habitat loss through climate change only, high dispersal rates are sufficient for persistence, but this requires protection of all remaining cloud forest areas. Main conclusions: Even if high dispersal rates mitigate the extinction risk of species due to climate change, the synergistic impacts of changing climate and land use further threaten the persistence of species with higher area requirements. Our approach for assessing the impacts of threats on biodiversity is particularly useful when there is little time or data for detailed population viability analyses. © 2013 John Wiley & Sons Ltd.

Performance evaluation of cloud-based parallel computing

As computational models in fields such as medicine and engineering get more refined, resource requirements are increased. In a first instance, these needs have been satisfied using parallel computing and HPC clusters. However, such systems are often costly and lack flexibility. HPC users are therefore tempted to move to elastic HPC using cloud services. One difficulty in making this transition is that HPC and cloud systems are different, and performance may vary. The purpose of this study is to evaluate cloud services as a means to minimise both cost and computation time for large-scale simulations, and to identify which system properties have the most significant impact on performance. Our simulation results show that, while the performance of Virtual CPU (VCPU) is satisfactory, network throughput may lead to difficulties.

Reliable, cloud-based communication for multi-robot systems

In contrast to single robotic agent, multi-robot systems are highly dependent on reliable communication. Robots have to synchronize tasks or to share poses and sensor readings with other agents, especially for co-operative mapping task where local sensor readings are incorporated into a global map. The drawback of existing communication frameworks is that most are based on a central component which has to be constantly within reach. Additionally, they do not prevent data loss between robots if a failure occurs in the communication link. During a distributed mapping task, loss of data is critical because it will corrupt the global map. In this work, we propose a cloud-based publish/subscribe mechanism which enables reliable communication between agents during a cooperative mission using the Data Distribution Service (DDS) as a transport layer. The usability of our approach is verified by several experiments taking into account complete temporary communication loss.

How the energy sector could get it wrong with cloud computing

Cloud computing has significantly impacted a broad range of industries, but these technologies and services have been absorbed throughout the marketplace unevenly. Some industries have moved aggressively towards cloud computing, while others have moved much more slowly. For the most part, the energy sector has approached cloud computing in a measured and cautious way, with progress often in the form of private cloud solutions rather than public ones, or hybridized information technology systems that combine cloud and existing non-cloud architectures. By moving towards cloud computing in a very slow and tentative way, however, the energy industry may prevent itself from reaping the full benefit that a more complete migration to the public cloud has brought about in several other industries. This short communication is accordingly intended to offer a high-level overview of cloud computing, and to put forward the argument that the energy sector should make a more complete migration to the public cloud in order to unlock the major system-wide efficiencies that cloud computing can provide. Also, assets within the energy sector should be designed with as much modularity and flexibility as possible so that they are not locked out of cloud-friendly options in the future.

A new approach to the cloud-based heterogeneous MapReduce placement problem

Guaranteeing Quality of Service (QoS) with minimum computation cost is the most important objective of cloud-based MapReduce computations. Minimizing the total computation cost of cloud-based MapReduce computations is done through MapReduce placement optimization. MapReduce placement optimization approaches can be classified into two categories: homogeneous MapReduce placement optimization and heterogeneous MapReduce placement optimization. It is generally believed that heterogeneous MapReduce placement optimization is more effective than homogeneous MapReduce placement optimization in reducing the total running cost of cloud-based MapReduce computations. This paper proposes a new approach to the heterogeneous MapReduce placement optimization problem. In this new approach, the heterogeneous MapReduce placement optimization problem is transformed into a constrained combinatorial optimization problem and is solved by an innovative constructive algorithm. Experimental results show that the running cost of the cloud-based MapReduce computation platform using this new approach is 24:3%-44:0% lower than that using the most popular homogeneous MapReduce placement approach, and 2:0%-36:2% lower than that using the heterogeneous MapReduce placement approach not considering the spare resources from the existing MapReduce computations. The experimental results have also demonstrated the good scalability of this new approach.

EphB4 localises to the nucleus of prostate cancer cells

The EphB4 receptor tyrosine kinase is over-expressed in a variety of different epithelial cancers including prostate where it has been shown to be involved in survival, migration and angiogenesis. We report here that EphB4 also resides in the nucleus of prostate cancer cell lines. We used in silico methods to identify a bipartite nuclear localisation signal (NLS) in the extracellular domain and a monopartite NLS sequence in the intracellular kinase domain of EphB4. To determine whether both putative NLS sequences were functional, fragments of the EphB4 sequence containing each NLS were cloned to create EphB4NLS-GFP fusion proteins. Localisation of both NLS-GFP proteins to the nuclei of transfected cells was observed, demonstrating that EphB4 contains two functional NLS sequences. Mutation of the key amino residues in both NLS sequences resulted in diminished nuclear accumulation. As nuclear translocation is often dependent on importins we confirmed that EphB4 and importin-α can interact. To assess if nuclear EphB4 could be implicated in gene regulatory functions potential EphB4-binding genomic loci were identified using chromatin immunoprecipitation and Lef1 was confirmed as a potential target of EphB4-mediated gene regulation. These novel findings add further complexity to the biology of this important cancer-associated receptor.

Genome-wide association identifies genetic variants associated with lentiform nucleus volume in N = 1345 young and elderly subjects

Deficits in lentiform nucleus volume and morphometry are implicated in a number of genetically influenced disorders, including Parkinson's disease, schizophrenia, and ADHD. Here we performed genome-wide searches to discover common genetic variants associated with differences in lentiform nucleus volume in human populations. We assessed structural MRI scans of the brain in two large genotyped samples: the Alzheimer's Disease Neuroimaging Initiative (ADNI; N = 706) and the Queensland Twin Imaging Study (QTIM; N = 639). Statistics of association from each cohort were combined meta-analytically using a fixed-effects model to boost power and to reduce the prevalence of false positive findings. We identified a number of associations in and around the flavin-containing monooxygenase (FMO) gene cluster. The most highly associated SNP, rs1795240, was located in the FMO3 gene; after meta-analysis, it showed genome-wide significant evidence of association with lentiform nucleus volume (PMA = 4. 79 × 10-8). This commonly-carried genetic variant accounted for 2. 68 % and 0. 84 % of the trait variability in the ADNI and QTIM samples, respectively, even though the QTIM sample was on average 50 years younger. Pathway enrichment analysis revealed significant contributions of this gene to the cytochrome P450 pathway, which is involved in metabolizing numerous therapeutic drugs for pain, seizures, mania, depression, anxiety, and psychosis. The genetic variants we identified provide replicated, genome-wide significant evidence for the FMO gene cluster's involvement in lentiform nucleus volume differences in human populations.

The fight for fair use in Australia: Copyright law in an age of cloud computing

Fair Use Week has celebrated the evolution and development of the defence of fair use under copyright law in the United States. As Krista Cox noted, ‘As a flexible doctrine, fair use can adapt to evolving technologies and new situations that may arise, and its long history demonstrates its importance in promoting access to information, future innovation, and creativity.’ While the defence of fair use has flourished in the United States, the adoption of the defence of fair use in other jurisdictions has often been stymied. Professor Peter Jaszi has reflected: ‘We can only wonder (with some bemusement) why some of our most important foreign competitors, like the European Union, haven’t figured out that fair use is, to a great extent, the “secret sauce” of U.S. cultural competitiveness.’ Jurisdictions such as Australia have been at a dismal disadvantage, because they lack the freedoms and flexibilities of the defence of fair use.

A penalty-based genetic algorithm for the migration cost-aware virtual machine placement problem in cloud data centers

In the past few years, the virtual machine (VM) placement problem has been studied intensively and many algorithms for the VM placement problem have been proposed. However, those proposed VM placement algorithms have not been widely used in today's cloud data centers as they do not consider the migration cost from current VM placement to the new optimal VM placement. As a result, the gain from optimizing VM placement may be less than the loss of the migration cost from current VM placement to the new VM placement. To address this issue, this paper presents a penalty-based genetic algorithm (GA) for the VM placement problem that considers the migration cost in addition to the energy-consumption of the new VM placement and the total inter-VM traffic flow in the new VM placement. The GA has been implemented and evaluated by experiments, and the experimental results show that the GA outperforms two well known algorithms for the VM placement problem.