The effect of lipophilicity on the antibacterial activity of some 1-benzylbenzimidazole derivatives

In the present paper, the antibacterial activity of some 1-benzylbenzimidazole derivatives were evaluated against the Gram-negative bacteria Escherichia coli. The minimum inhibitory concentration was determined for all the compounds. Quantitative structure–activity relationship (QSAR) was employed to study the effect of the lipophilicity parameters (log P) on the inhibitory activity. Log P values for the target compounds were experimentally determined by the “shake-flask” method and calculated by using eight different software products. Multiple linear regression was used to correlate the log P values and antibacterial activity of the studied benzimidazole derivatives. The results are discussed based on statistical data. The most acceptable QSAR models for the prediction of the antibacterial activity of the investigated series of benzimidazoles were developed. High agreement between the experimental and predicted inhibitory values was obtained. The results of this study indicate that the lipophilicity parameter has a significant effect on the antibacterial activity of this class of compounds, which simplifies the design of new biologically active molecules

Experimental Assessment of BitTorrent Completion Time in Heterogeneous TCP/uTP swarms

BitTorrent, one of the most widespread used P2P application for file-sharing, recently got rid of TCP by introducing an application-level congestion control protocol named uTP. The aim of this new protocol is to efficiently use the available link capacity, while minimizing its interference with the rest of user traffic (e.g., Web, VoIP and gaming) sharing the same access bottleneck. In this paper we perform an experimental study of the impact of uTP on the torrent completion time, the metric that better captures the user experience. We run BitTorrent applications in a flash crowd scenario over a dedicated cluster platform, under both homogeneous and heterogeneous swarm population. Experiments show that an all-uTP swarms have shorter torrent download time with respect to all-TCP swarms. Interestingly, at the same time, we observe that even shorter completion times can be achieved under careful mixtures of TCP and uTP traffic.Comment: 14 pages, under submissio

Denial-of-service resilience in peer-to-peer file sharing systems

Peer-to-peer (p2p) file sharing systems are characterized by highly replicated content distributed among nodes with enormous aggregate resources for storage and communication. These properties alone are not sufficient, however, to render p2p networks immune to denial-of-service (DoS) attack. In this paper, we study, by means of analytical modeling and simulation, the resilience of p2p file sharing systems against DoS attacks, in which malicious nodes respond to queries with erroneous responses. We consider the filetargeted attacks in current use in the Internet, and we introduce a new class of p2p-network-targeted attacks. In file-targeted attacks, the attacker puts a large number of corrupted versions of a single file on the network. We demonstrate that the effectiveness of these attacks is highly dependent on the clients’ behavior. For the attacks to succeed over the long term, clients must be unwilling to share files, slow in removing corrupted files from their machines, and quick to give up downloading when the system is under attack. In network-targeted attacks, attackers respond to queries for any file with erroneous information. Our results indicate that these attacks are highly scalable: increasing the number of malicious nodes yields a hyperexponential decrease in system goodput, and a moderate number of attackers suffices to cause a near-collapse of the entire system. The key factors inducing this vulnerability are (i) hierarchical topologies with misbehaving “supernodes,” (ii) high path-length networks in which attackers have increased opportunity to falsify control information, and (iii) power-law networks in which attackers insert themselves into high-degree points in the graph. Finally, we consider the effects of client counter-strategies such as randomized reply selection, redundant and parallel download, and reputation systems. Some counter-strategies (e.g., randomized reply selection) provide considerable immunity to attack (reducing the scaling from hyperexponential to linear), yet significantly hurt performance in the absence of an attack. Other counter-strategies yield little benefit (or penalty). In particular, reputation systems show little impact unless they operate with near perfection

Origins and genetic legacy of prehistoric dogs

Dogs were the first domestic animal, but little is known about their population history and to what extent it was linked to humans. We sequenced 27 ancient dog genomes and found that all dogs share a common ancestry distinct from present-day wolves, with limited gene flow from wolves since domestication but substantial dog-to-wolf gene flow. By 11,000 years ago, at least five major ancestry lineages had diversified, demonstrating a deep genetic history of dogs during the Paleolithic. Coanalysis with human genomes reveals aspects of dog population history that mirror humans, including Levant-related ancestry in Africa and early agricultural Europe. Other aspects differ, including the impacts of steppe pastoralist expansions in West and East Eurasia and a near-complete turnover of Neolithic European dog ancestry

Atypical emotional anticipation in high-functioning autism

"Background: Understanding and anticipating others’ mental or emotional states relies on the processing of social cues, such as dynamic facial expressions. Individuals with high-functioning autism (HFA) may process these cues differently from individuals with typical development (TD) and purportedly use a ‘mechanistic’ rather than a ‘mentalistic’ approach, involving rule- and contingency-based interpretations of the stimuli. The study primarily aimed at examining whether the judgments of facial expressions made by individuals with TD and HFA would be similarly affected by the immediately preceding dynamic perceptual history of that face. A second aim was to explore possible differences in the mechanisms underpinning the perceptual judgments in the two groups. Methods: Twenty-two adults with HFA and with TD, matched for age, gender and IQ, were tested in three experiments in which dynamic, ‘ecologically valid’ offsets of happy and angry facial expressions were presented. Participants evaluated the expression depicted in the last frame of the video clip by using a 5-point scale ranging from slightly angry via neutral to slightly happy. Specific experimental manipulations prior to the final facial expression of the video clip allowed examining contributions of bottom-up mechanisms (sequential contrast/ context effects and representational momentum) and a top-down mechanism (emotional anticipation) to distortions in the perception of the final expression. Results: In experiment 1, the two groups showed a very similar perceptual bias for the final expression of joy-to-neutral and anger-to-neutral videos (overshoot bias). In experiment 2, a change in the actor’s identity during the clip removed the bias in the TD group, but not in the HFA group. In experiment 3, neutral-to-joy/anger-to-neutral sequences generated an undershoot bias (opposite to the overshoot) in the TD group, whereas no bias was observed in the HFA group. Conclusions: We argue that in TD individuals the perceptual judgments of other’s facial expressions were underpinned by an automatic emotional anticipation mechanism. In contrast, HFA individuals were primarily influenced by visual features, most notably the contrast between the start and end expressions, or pattern extrapolation. We critically discuss the proposition that automatic emotional anticipation may be induced by motor simulation of the perceived dynamic facial expressions and discuss its implications for autism.

The potential risks and impact of the start of the 2015–2016 influenza season in the WHO European Region: a rapid risk assessment

Background: Countries in the World Health Organization (WHO) European Region are reporting more severe influenza activity in the 2015–2016 season compared to previous seasons. Objectives: To conduct a rapid risk assessment to provide interim information on the severity of the current influenza season. Methods: Using the WHO manual for rapid risk assessment of acute public health events and surveillance data available from Flu News Europe, an assessment of the current influenza season from 28 September 2015 (week 40/2015) up to 31 January 2016 (week 04/2016) was made compared with the four previous seasons. Results: The current influenza season started around week 51/2015 with higher influenza activity reported in Eastern Europe compared to Western Europe. There is a strong predominance of influenza A(H1N1)pdm09 compared to previous seasons, but the virus is antigenically similar to the strain included in the seasonal influenza vaccine. Compared to the 2014/2015 season, there was a rapid increase in the number of severe cases in Eastern European countries with the majority of such cases occurring among adults aged < 65 years. Conclusions: The current influenza season is characterized by an early start in Eastern European countries, with indications of a more severe season. Currently circulating influenza A(H1N1)pdm09 viruses are antigenically similar to those included in the seasonal influenza vaccine, and the vaccine is expected to be effective. Authorities should provide information to the public and health providers about the current influenza season, recommendations for the treatment of severe disease and effective public health measures to prevent influenza transmission

GFAP-Driven GFP Expression in Activated Mouse Muller Glial Cells Aligning Retinal Blood Vessels Following Intravitreal Injection of AAV2/6 Vectors

Background: Muller cell gliosis occurs in various retinal pathologies regardless of the underlying cellular defect. Because activated Muller glial cells span the entire retina and align areas of injury, they are ideal targets for therapeutic strategies, including gene therapy.Methodology/Principal Findings: We used adeno-associated viral AAV2/6 vectors to transduce mouse retinas. The transduction pattern of AAV2/6 was investigated by studying expression of the green fluorescent protein (GFP) transgene using scanning-laser ophthalmoscopy and immuno-histochemistry. AAV2/6 vectors transduced mouse Muller glial cells aligning the retinal blood vessels. However, the transduction capacity was hindered by the inner limiting membrane (ILM) and besides Muller glial cells, several other inner retinal cell types were transduced. To obtain Muller glial cell-specific transgene expression, the cytomegalovirus (CMV) promoter was replaced by the glial fibrillary acidic protein (GFAP) promoter. Specificity and activation of the GFAP promoter was tested in a mouse model for retinal gliosis. Mice deficient for Crumbs homologue 1 (CRB1) develop gliosis after light exposure. Light exposure of Crb1(-/-) retinas transduced with AAV2/6-GFAP-GFP induced GFP expression restricted to activated Muller glial cells aligning retinal blood vessels.Conclusions/Significance: Our experiments indicate that AAV2 vectors carrying the GFAP promoter are a promising tool for specific expression of transgenes in activated glial cells

Mechanical and Assembly Units of Viral Capsids Identified via Quasi-Rigid Domain Decomposition

Key steps in a viral life-cycle, such as self-assembly of a protective protein container or in some cases also subsequent maturation events, are governed by the interplay of physico-chemical mechanisms involving various spatial and temporal scales. These salient aspects of a viral life cycle are hence well described and rationalised from a mesoscopic perspective. Accordingly, various experimental and computational efforts have been directed towards identifying the fundamental building blocks that are instrumental for the mechanical response, or constitute the assembly units, of a few specific viral shells. Motivated by these earlier studies we introduce and apply a general and efficient computational scheme for identifying the stable domains of a given viral capsid. The method is based on elastic network models and quasi-rigid domain decomposition. It is first applied to a heterogeneous set of well-characterized viruses (CCMV, MS2, STNV, STMV) for which the known mechanical or assembly domains are correctly identified. The validated method is next applied to other viral particles such as L-A, Pariacoto and polyoma viruses, whose fundamental functional domains are still unknown or debated and for which we formulate verifiable predictions. The numerical code implementing the domain decomposition strategy is made freely available

Sympathetic involvement in time-constrained sequential foraging

Appraising sequential offers relative to an unknown future opportunity and a time cost requires an optimization policy that draws on a learned estimate of an environment’s richness. Converging evidence points to a learning asymmetry, whereby estimates of this richness update with a bias toward integrating positive information. We replicate this bias in a sequential foraging (prey selection) task and probe associated activation within the sympathetic branch of the autonomic system, using trial-by-trial measures of simultaneously recorded cardiac autonomic physiology. We reveal a unique adaptive role for the sympathetic branch in learning. It was specifically associated with adaptation to a deteriorating environment: it correlated with both the rate of negative information integration in belief estimates and downward changes in moment-to-moment environmental richness, and was predictive of optimal performance on the task. The findings are consistent with a framework whereby autonomic function supports the learning demands of prey selection