Evidence both L-type and non-L-type voltage-dependent calcium channels contribute to cerebral artery vasospasm following loss of NO in the rat

We recently found block of NO synthase in rat middle cerebral artery caused spasm, associated with depolarizing oscillations in membrane potential (Em) similar in form but faster in frequency (circa 1 Hz) to vasomotion. T-type voltage-gated Ca2+ channels contribute to cerebral myogenic tone and vasomotion, so we investigated the significance of T-type and other ion channels for membrane potential oscillations underlying arterial spasm. Smooth muscle cell membrane potential (Em) and tension were measured simultaneously in rat middle cerebral artery. NO synthase blockade caused temporally coupled depolarizing oscillations in cerebrovascular Em with associated vasoconstriction. Both events were accentuated by block of smooth muscle BKCa. Block of T-type channels or inhibition of Na+/K+-ATPase abolished the oscillations in Em and reduced vasoconstriction. Oscillations in Em were either attenuated or accentuated by reducing [Ca2+]o or block of KV, respectively. TRAM-34 attenuated oscillations in both Em and tone, apparently independent of effects against KCa3.1. Thus, rapid depolarizing oscillations in Em and tone observed after endothelial function has been disrupted reflect input from T-type calcium channels in addition to L-type channels, while other depolarizing currents appear to be unimportant. These data suggest that combined block of T and L-type channels may represent an effective approach to reverse cerebral vasospasm.

Hobbes, history, and non-domination

Pettit's and Skinner's stimulating books are open to historically-minded objections. Pettit's reading of Hobbes is Rousseauian, but he rejects the Hobbesian/Rousseauian belief that some modern people are driven by amour-propre/“glory”. If Hobbes is right, there is, in Pettit's sense, no “common good”. Skinner's treatment of the neo-Roman “theorists” over-estimates their self-consciousness and their consistency. Leviathan chapter 21 is not a response to neo-Romanism; it treats civil liberty as non-obligation, not as non-interference.

Performance analysis of data transmissions in MPLS and non-MPLS networks

Basic Network transactions specifies that datagram from source to destination is routed through numerous routers and paths depending on the available free and uncongested paths which results in the transmission route being too long, thus incurring greater delay, jitter, congestion and reduced throughput. One of the major problems of packet switched networks is the cell delay variation or jitter. This cell delay variation is due to the queuing delay depending on the applied loading conditions. The effect of delay, jitter accumulation due to the number of nodes along transmission routes and dropped packets adds further complexity to multimedia traffic because there is no guarantee that each traffic stream will be delivered according to its own jitter constraints therefore there is the need to analyze the effects of jitter. IP routers enable a single path for the transmission of all packets. On the other hand, Multi-Protocol Label Switching (MPLS) allows separation of packet forwarding and routing characteristics to enable packets to use the appropriate routes and also optimize and control the behavior of transmission paths. Thus correcting some of the shortfalls associated with IP routing. Therefore MPLS has been utilized in the analysis for effective transmission through the various networks. This paper analyzes the effect of delay, congestion, interference, jitter and packet loss in the transmission of signals from source to destination. In effect the impact of link failures, repair paths in the various physical topologies namely bus, star, mesh and hybrid topologies are all analyzed based on standard network conditions.

Response theory for equilibrium and non-equilibrium statistical mechanics: causality and generalized Kramers-Kronig relations

We consider the general response theory recently proposed by Ruelle for describing the impact of small perturbations to the non-equilibrium steady states resulting from Axiom A dynamical systems. We show that the causality of the response functions entails the possibility of writing a set of Kramers-Kronig (K-K) relations for the corresponding susceptibilities at all orders of nonlinearity. Nonetheless, only a special class of directly observable susceptibilities obey K-K relations. Specific results are provided for the case of arbitrary order harmonic response, which allows for a very comprehensive K-K analysis and the establishment of sum rules connecting the asymptotic behavior of the harmonic generation susceptibility to the short-time response of the perturbed system. These results set in a more general theoretical framework previous findings obtained for optical systems and simple mechanical models, and shed light on the very general impact of considering the principle of causality for testing self-consistency: the described dispersion relations constitute unavoidable benchmarks that any experimental and model generated dataset must obey. The theory exposed in the present paper is dual to the time-dependent theory of perturbations to equilibrium states and to non-equilibrium steady states, and has in principle similar range of applicability and limitations. In order to connect the equilibrium and the non equilibrium steady state case, we show how to rewrite the classical response theory by Kubo so that response functions formally identical to those proposed by Ruelle, apart from the measure involved in the phase space integration, are obtained. These results, taking into account the chaotic hypothesis by Gallavotti and Cohen, might be relevant in several fields, including climate research. In particular, whereas the fluctuation-dissipation theorem does not work for non-equilibrium systems, because of the non-equivalence between internal and external fluctuations, K-K relations might be robust tools for the definition of a self-consistent theory of climate change.

Communities of practice in UK large contracting firms: contrasting application and non-utilized merits

The idea of a community of practice (CoP) has been offered as the engine to unlock the potential of organizational resources, mainly knowledge and people, to achieve the strategic goal of sustained competitiveness. The relevance and application of CoPs in large UK contracting companies was investigated using two case studies. Contrasting variations in the understanding of the concept between the two contracting companies were observed. While a CoP was applied in one company with strategic intent, the concept was not fully understood in the other. In one company, only a third of CoP members surveyed agreed that CoPs were a vehicle for driving best practice and innovation throughout the business; this compared with more than 60% in agreement in the other contracting firm. The higher agreement and satisfaction of CoP members in the latter case study was the result of the management's understanding and commitment. CoPs require time and organizational support to mature. The strategic inception and management support of CoP application is vital for their maturation and progress. Although the construction industry change discourses portray CoPs as fostering an environment of trust, and hence serving as innovation and competiveness enablers, their potential contribution to contracting firms does not provide a compelling case and hence merits further research studies.

Identification of genetic and phenotypic differences associated with prevalent and non-prevalent Salmonella Enteritidis phage types: analysis of variation in amino acid transport

In this study, differences at the genetic level of 37 Salmonella Enteritidis strains from five phage types (PTs) were compared using comparative genomic hybridization (CGH) to assess differences between PTs. There were approximately 400 genes that differentiated prevalent (4, 6, 8 and 13a) and sporadic (11) PTs, of which 35 were unique to prevalent PTs, including six plasmid-borne genes, pefA, B, C, D, srgC and rck, and four chromosomal genes encoding putative amino acid transporters. Phenotype array studies also demonstrated that strains from prevalent PTs were less susceptible to urea stress and utilized L-histidine, L-glutamine, L-proline, L-aspartic acid, gly-asn and gly-gln more efficiently than PT11 strains. Complementation of a PT11 strain with the transporter genes from PT4 resulted in a significant increase in utilization of the amino acids and reduced susceptibility to urea stress. In epithelial cell association assays, PT11 strains were less invasive than other prevalent PTs. Most strains from prevalent PTs were better biofilm formers at 37 degrees C than at 28 degrees C, whilst the converse was true for PT11 strains. Collectively, the results indicate that genetic and corresponding phenotypic differences exist between strains of the prevalent PTs 4, 6, 8 and 13a and non-prevalent PT11 strains that are likely to provide a selective advantage for strains from the former PTs and could help them to enter the food chain and cause salmonellosis.

Improving insight and non-insight problem solving with brief interventions

Developing brief training interventions that benefit different forms of problem solving is challenging. In earlier research, Chrysikou (2006) showed that engaging in a task requiring generation of alternative uses of common objects improved subsequent insight problem solving. These benefits were attributed to a form of implicit transfer of processing involving enhanced construction of impromptu, on-the-spot or ‘ad hoc’ goal-directed categorizations of the problem elements. Following this, it is predicted that the alternative uses exercise should benefit abilities that govern goal-directed behaviour, such as fluid intelligence and executive functions. Similarly, an indirect intervention – self-affirmation (SA) – that has been shown to enhance cognitive and executive performance after self-regulation challenge and when under stereotype threat, may also increase adaptive goal-directed thinking and likewise should bolster problem-solving performance. In Experiment 1, brief single-session interventions, involving either alternative uses generation or SA, significantly enhanced both subsequent insight and visual–spatial fluid reasoning problem solving. In Experiment 2, we replicated the finding of benefits of both alternative uses generation and SA on subsequent insight problem-solving performance, and demonstrated that the underlying mechanism likely involves improved executive functioning. Even brief cognitive– and social–psychological interventions may substantially bolster different types of problem solving and may exert largely similar facilitatory effects on goal-directed behaviours.

Speech-like and non-speech lip kinematics and coordination in aphasia

Background and aims: In addition to the well-known linguistic processing impairments in aphasia, oro-motor skills and articulatory implementation of speech segments are reported to be compromised to some degree in most types of aphasia. This study aimed to identify differences in the characteristics and coordination of lip movements in the production of a bilabial closure gesture between speech-like and nonspeech tasks in individuals with aphasia and healthy control subjects. Method and procedure: Upper and lower lip movement data were collected for a speech-like and a nonspeech task using an AG 100 EMMA system from five individuals with aphasia and five age and gender matched control subjects. Each task was produced at two rate conditions (normal and fast), and in a familiar and a less-familiar manner. Single articulator kinematic parameters (peak velocity, amplitude, duration, and cyclic spatio-temporal index) and multi-articulator coordination indices (average relative phase and variability of relative phase) were measured to characterize lip movements. Outcome and results: The results showed that when the two lips had similar task goals (bilabial closure) in speech-like versus nonspeech task, kinematic and coordination characteristics were not found to be different. However, when changes in rate were imposed on the bilabial gesture, only speech-like task showed functional adaptations, indicated by a greater decrease in amplitude and duration at fast rates. In terms of group differences, individuals with aphasia showed smaller amplitudes and longer movement durations for upper lip, higher spatio-temporal variability for both lips, and higher variability in lip coordination than the control speakers. Rate was an important factor in distinguishing the two groups, and individuals with aphasia were limited in implementing the rate changes. Conclusion and implications: The findings support the notion of subtle but robust differences in motor control characteristics between individuals with aphasia and the control participants, even in the context of producing bilabial closing gestures for a relatively simple speech-like task. The findings also highlight the functional differences between speech-like and nonspeech tasks, despite a common movement coordination goal for bilabial closure.

Dynamical control of the mesosphere by orographic and non-orographic gravity wave drag during the extended northern winters of 2006 and 2009

A version of the Canadian Middle Atmosphere Model (CMAM) that is nudged toward reanalysis data up to 1 hPa is used to examine the impacts of parameterized orographic and non-orographic gravity wave drag (OGWD and NGWD) on the zonal-mean circulation of the mesosphere during the extended northern winters of 2006 and 2009 when there were two large stratospheric sudden warmings. The simulations are compared to Aura Microwave Limb Sounder (MLS) observations of mesospheric temperature, carbon monoxide (CO) and derived zonal winds. The control simulation, which uses both OGWD and NGWD, is shown to be in good agreement with MLS. The impacts of OGWD and NGWD are assessed using simulations in which those sources of wave drag are removed. In the absence of OGWD the mesospheric zonal winds in the months preceding the warmings are too strong, causing increased mesospheric NGWD, which drives excessive downwelling, resulting in overly large lower mesospheric values of CO prior to the warming. NGWD is found to be most important following the warmings when the underlying westerlies are too weak to allow much vertical propagation of the orographic gravity waves to the mesosphere. NGWD is primarily responsible for driving the circulation that results in the descent of CO from the thermosphere following the warmings. Zonal mean mesospheric winds and temperatures in all simulations are shown to be strongly constrained by (i.e. slaved to) the stratosphere. Finally, it is demonstrated that the responses to OGWD and NGWD are non-additive due to their dependence and influence on the background winds and temperatures.

Self-ratings and observer-ratings of social skill: a manipulation of state social anxiety in anxious and non-anxious children

The role of state and trait anxiety on observer ratings of social skill and negatively biased self-perception of social skill was examined. Participants were aged between 7 and 13 years (mean=9.65; sd=1.77; N=102), 47 had a current anxiety diagnosis and 55 were non-anxious controls. Participants were randomly allocated to a high or low anxiety condition and asked to complete social tasks. Task instructions were adjusted across conditions to manipulate participants’ state anxiety. Observers rated anxious participants as having poorer social skills than non-anxious controls but there was no evidence that anxious participants exhibited a negative self-perception bias, relative to controls. However, as participants’ ratings of state anxiety increased, their perception of their performance became more negatively biased. The results suggest that anxious children may exhibit real impairments in social skill and that high levels of state anxiety can lead to biased judgements of social skills in anxious and non-anxious children.

Dysregulation of REST-regulated coding and non-coding RNAs in a cellular model of Huntington's disease

Huntingtin (Htt) protein interacts with many transcriptional regulators, with widespread disruption to the transcriptome in Huntington's disease (HD) brought about by altered interactions with the mutant Htt (muHtt) protein. Repressor Element-1 Silencing Transcription Factor (REST) is a repressor whose association with Htt in the cytoplasm is disrupted in HD, leading to increased nuclear REST and concomitant repression of several neuronal-specific genes, including brain-derived neurotrophic factor (Bdnf). Here, we explored a wide set of HD dysregulated genes to identify direct REST targets whose expression is altered in a cellular model of HD but that can be rescued by knock-down of REST activity. We found many direct REST target genes encoding proteins important for nervous system development, including a cohort involved in synaptic transmission, at least two of which can be rescued at the protein level by REST knock-down. We also identified several microRNAs (miRNAs) whose aberrant repression is directly mediated by REST, including miR-137, which has not previously been shown to be a direct REST target in mouse. These data provide evidence of the contribution of inappropriate REST-mediated transcriptional repression to the widespread changes in coding and non-coding gene expression in a cellular model of HD that may affect normal neuronal function and survival.