2,626 research outputs found
Robust damping controller design in power systems with superconducting magnetic energy storage devices
Published versio
Cancer and systemic inflammation: treat the tumour and treat the host
Determinants of cancer progression and survival are multifactorial and host responses are increasingly appreciated to have a major role. Indeed, the development and maintenance of a systemic inflammatory response has been consistently observed to confer poorer outcome, in both early and advanced stage disease. For patients, cancer-associated symptoms are of particular importance resulting in a marked impact on day-to-day quality of life and are also associated with poorer outcome. These symptoms are now recognised to cluster with one another with anorexia, weight loss and physical function forming a recognised cluster whereas fatigue, pain and depression forming another. Importantly, it has become apparent that these symptom clusters are associated with presence of a systemic inflammatory response in the patient with cancer. Given the understanding of the above, there is now a need to intervene to moderate systemic inflammatory responses, where present. In this context the rationale for therapeutic intervention using nonselective anti-inflammatory agents is clear and compelling and likely to become a part of routine clinical practice in the near future. The published literature on therapeutic intervention using anti-inflammatory agents for cancer-associated symptoms was reviewed. There are important parallels with the development of useful treatments for the systemic inflammatory response in patients with rheumatological disease and cardiovascular disease
Optogenetic and potassium channel gene therapy in a rodent model of focal neocortical epilepsy.
Neocortical epilepsy is frequently drug-resistant. Surgery to remove the epileptogenic zone is only feasible in a minority of cases, leaving many patients without an effective treatment. We report the potential efficacy of gene therapy in focal neocortical epilepsy using a rodent model in which epilepsy is induced by tetanus toxin injection in the motor cortex. By applying several complementary methods that use continuous wireless electroencephalographic monitoring to quantify epileptic activity, we observed increases in high frequency activity and in the occurrence of epileptiform events. Pyramidal neurons in the epileptic focus showed enhanced intrinsic excitability consistent with seizure generation. Optogenetic inhibition of a subset of principal neurons transduced with halorhodopsin targeted to the epileptic focus by lentiviral delivery was sufficient to attenuate electroencephalographic seizures. Local lentiviral overexpression of the potassium channel Kv1.1 reduced the intrinsic excitability of transduced pyramidal neurons. Coinjection of this Kv1.1 lentivirus with tetanus toxin fully prevented the occurrence of electroencephalographic seizures. Finally, administration of the Kv1.1 lentivirus to an established epileptic focus progressively suppressed epileptic activity over several weeks without detectable behavioral side effects. Thus, gene therapy in a rodent model can be used to suppress seizures acutely, prevent their occurrence after an epileptogenic stimulus, and successfully treat established focal epilepsy
Non-thermal emission processes in massive binaries
In this paper, I present a general discussion of several astrophysical
processes likely to play a role in the production of non-thermal emission in
massive stars, with emphasis on massive binaries. Even though the discussion
will start in the radio domain where the non-thermal emission was first
detected, the census of physical processes involved in the non-thermal emission
from massive stars shows that many spectral domains are concerned, from the
radio to the very high energies.
First, the theoretical aspects of the non-thermal emission from early-type
stars will be addressed. The main topics that will be discussed are
respectively the physics of individual stellar winds and their interaction in
binary systems, the acceleration of relativistic electrons, the magnetic field
of massive stars, and finally the non-thermal emission processes relevant to
the case of massive stars. Second, this general qualitative discussion will be
followed by a more quantitative one, devoted to the most probable scenario
where non-thermal radio emitters are massive binaries. I will show how several
stellar, wind and orbital parameters can be combined in order to make some
semi-quantitative predictions on the high-energy counterpart to the non-thermal
emission detected in the radio domain.
These theoretical considerations will be followed by a census of results
obtained so far, and related to this topic... (see paper for full abstract)Comment: 47 pages, 5 postscript figures, accepted for publication in Astronomy
and Astrophysics Review. Astronomy and Astrophysics Review, in pres
Speaking and Listening with the Eyes: Gaze Signaling during Dyadic Interactions
Cognitive scientists have long been interested in the role that eye gaze plays in social interactions. Previous research suggests that gaze acts as a signaling mechanism and can be used to control turn-taking behaviour. However, early research on this topic employed methods of analysis that aggregated gaze information across an entire trial (or trials), which masks any temporal dynamics that may exist in social interactions. More recently, attempts have been made to understand the temporal characteristics of social gaze but little research has been conducted in a natural setting with two interacting participants. The present study combines a temporally sensitive analysis technique with modern eye tracking technology to 1) validate the overall results from earlier aggregated analyses and 2) provide insight into the specific moment-to-moment temporal characteristics of turn-taking behaviour in a natural setting. Dyads played two social guessing games (20 Questions and Heads Up) while their eyes were tracked. Our general results are in line with past aggregated data, and using cross-correlational analysis on the specific gaze and speech signals of both participants we found that 1) speakers end their turn with direct gaze at the listener and 2) the listener in turn begins to speak with averted gaze. Convergent with theoretical models of social interaction, our data suggest that eye gaze can be used to signal both the end and the beginning of a speaking turn during a social interaction. The present study offers insight into the temporal dynamics of live dyadic interactions and also provides a new method of analysis for eye gaze data when temporal relationships are of interest
Effect of temperature anisotropy on various modes and instabilities for a magnetized non-relativistic bi-Maxwellian plasma
Using kinetic theory for homogeneous collisionless magnetized plasmas, we
present an extended review of the plasma waves and instabilities and discuss
the anisotropic response of generalized relativistic dielectric tensor and
Onsager symmetry properties for arbitrary distribution functions. In general,
we observe that for such plasmas only those electromagnetic modes whose
magnetic field perturbations are perpendicular to the ambient magneticeld,
i.e.,B1 \perp B0, are effected by the anisotropy. However, in oblique
propagation all modes do show such anisotropic effects. Considering the
non-relativistic bi-Maxwellian distribution and studying the relevant
components of the general dielectric tensor under appropriate conditions, we
derive the dispersion relations for various modes and instabilities. We show
that only the electromagnetic R- and L- waves, those derived from them and the
O-mode are affected by thermal anisotropies, since they satisfy the required
condition B1\perpB0. By contrast, the perpendicularly propagating X-mode and
the modes derived from it (the pure transverse X-mode and Bernstein mode) show
no such effect. In general, we note that the thermal anisotropy modifies the
parallel propagating modes via the parallel acoustic effect, while it modifies
the perpendicular propagating modes via the Larmor-radius effect. In oblique
propagation for kinetic Alfven waves, the thermal anisotropy affects the
kinetic regime more than it affects the inertial regime. The generalized fast
mode exhibits two distinct acoustic effects, one in the direction parallel to
the ambient magnetic field and the other in the direction perpendicular to it.
In the fast-mode instability, the magneto-sonic wave causes suppression of the
firehose instability. We discuss all these propagation characteristics and
present graphic illustrations
Effects of deletion of the Streptococcus pneumoniae lipoprotein diacylglyceryl transferase gene lgt on ABC transporter function and on growth in vivo
Lipoproteins are an important class of surface associated proteins that have diverse roles and frequently are involved in the virulence of bacterial pathogens. As prolipoproteins are attached to the cell membrane by a single enzyme, prolipoprotein diacylglyceryl transferase (Lgt), deletion of the corresponding gene potentially allows the characterisation of the overall importance of lipoproteins for specific bacterial functions. We have used a Δlgt mutant strain of Streptococcus pneumoniae to investigate the effects of loss of lipoprotein attachment on cation acquisition, growth in media containing specific carbon sources, and virulence in different infection models. Immunoblots of triton X-114 extracts, flow cytometry and immuno-fluorescence microscopy confirmed the Δlgt mutant had markedly reduced lipoprotein expression on the cell surface. The Δlgt mutant had reduced growth in cation depleted medium, increased sensitivity to oxidative stress, reduced zinc uptake, and reduced intracellular levels of several cations. Doubling time of the Δlgt mutant was also increased slightly when grown in medium with glucose, raffinose and maltotriose as sole carbon sources. These multiple defects in cation and sugar ABC transporter function for the Δlgt mutant were associated with only slightly delayed growth in complete medium. However the Δlgt mutant had significantly reduced growth in blood or bronchoalveolar lavage fluid and a marked impairment in virulence in mouse models of nasopharyngeal colonisation, sepsis and pneumonia. These data suggest that for S. pneumoniae loss of surface localisation of lipoproteins has widespread effects on ABC transporter functions that collectively prevent the Δlgt mutant from establishing invasive infection
Non-Equilibrium Edge Channel Spectroscopy in the Integer Quantum Hall Regime
Heat transport has large potentialities to unveil new physics in mesoscopic
systems. A striking illustration is the integer quantum Hall regime, where the
robustness of Hall currents limits information accessible from charge
transport. Consequently, the gapless edge excitations are incompletely
understood. The effective edge states theory describes them as prototypal
one-dimensional chiral fermions - a simple picture that explains a large body
of observations and calls for quantum information experiments with quantum
point contacts in the role of beam splitters. However, it is in ostensible
disagreement with the prevailing theoretical framework that predicts, in most
situations, additional gapless edge modes. Here, we present a setup which gives
access to the energy distribution, and consequently to the energy current, in
an edge channel brought out-of-equilibrium. This provides a stringent test of
whether the additional states capture part of the injected energy. Our results
show it is not the case and thereby demonstrate regarding energy transport, the
quantum optics analogy of quantum point contacts and beam splitters. Beyond the
quantum Hall regime, this novel spectroscopy technique opens a new window for
heat transport and out-of-equilibrium experiments.Comment: 13 pages including supplementary information, Nature Physics in prin
Histone deacetylases as new therapy targets for platinum-resistant epithelial ovarian cancer
Introduction: In developed countries, ovarian cancer is the fourth most common cancer in women. Due to the nonspecific symptomatology associated with the disease many patients with ovarian cancer are diagnosed late, which leads to significantly poorer prognosis. Apart from surgery and radiotherapy, a substantial number of ovarian cancer patients will undergo chemotherapy and platinum based agents are the mainstream first-line therapy for this disease. Despite the initial efficacy of these therapies, many women relapse; therefore, strategies for second-line therapies are required. Regulation of DNA transcription is crucial for tumour progression, metastasis and chemoresistance which offers potential for novel drug targets. Methods: We have reviewed the existing literature on the role of histone deacetylases, nuclear enzymes regulating gene transcription. Results and conclusion: Analysis of available data suggests that a signifant proportion of drug resistance stems from abberant gene expression, therefore HDAC inhibitors are amongst the most promising therapeutic targets for cancer treatment. Together with genetic testing, they may have a potential to serve as base for patient-adapted therapies
Intensive removal of signal crayfish (Pacifastacus leniusculus) from rivers increases numbers and taxon richness of macroinvertebrate species
Invasive species are a major cause of species extinction in freshwater ecosystems, and crayfish species are particularly pervasive. The invasive American signal crayfish Pacifastacus leniusculus has impacts over a range of trophic levels, but particularly on benthic aquatic macroinvertebrates. Our study examined the effect on the macroinvertebrate community of removal trapping of signal crayfish from UK rivers. Crayfish were intensively trapped and removed from two tributaries of the River Thames to test the hypothesis that lowering signal crayfish densities would result in increases in macroinvertebrate numbers and taxon richness. We removed 6181 crayfish over four sessions, resulting in crayfish densities that decreased toward the center of the removal sections. Conversely in control sections (where crayfish were trapped and returned), crayfish density increased toward the center of the section. Macroinvertebrate numbers and taxon richness were inversely correlated with crayfish densities. Multivariate analysis of the abundance of each taxon yielded similar results and indicated that crayfish removals had positive impacts on macroinvertebrate numbers and taxon richness but did not alter the composition of the wider macroinvertebrate community. Synthesis and applications: Our results demonstrate that non‐eradication‐oriented crayfish removal programmes may lead to increases in the total number of macroinvertebrates living in the benthos. This represents the first evidence that removing signal crayfish from riparian systems, at intensities feasible during control attempts or commercial crayfishing, may be beneficial for a range of sympatric aquatic macroinvertebrates
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