1,662 research outputs found
Antipsychotic dose escalation as a trigger for Neuroleptic Malignant Syndrome (NMS): literature review and case series report
Background: “Neuroleptic malignant syndrome” (NMS) is a potentially fatal idiosyncratic reaction to any medication which affects the central dopaminergic system. Between 0.5% and 1% of patients exposed to antipsychotics develop the condition. Mortality rates may be as high as 55% and many risk factors have been reported. Although rapid escalation of antipsychotic dose is thought to be an important risk factor, to date it has not been the focus of a published case series or scientifically defined.
<p/>Aims: To identify cases of NMS and review risk factors for its development with a particular focus on rapid dose escalation in the 30 days prior to onset.
<p/>Methodology: A review of the literature on rapid dose escalation was undertaken and a pragmatic definition of “rapid dose escalation” was made. NMS cases were defined using DSM-IV criteria and systematically identified within a secondary care mental health service. A ratio of titration rate was calculated for each NMS patient and “rapid escalators” and “non rapid escalators” were compared.
<p/>Results: 13 cases of NMS were identified. A progressive mean dose increase 15 days prior to the confirmed episode of NMS was observed (241.7mg/day during days 1-15 to 346.9mg/day during days 16-30) and the mean ratio of dose escalation for NMS patients was 1.4. Rapid dose escalation was seen in 5/13 cases and non rapid escalators had markedly higher daily cumulative antipsychotic dose compared to rapid escalators.
<p/>Conclusions: Rapid dose escalation occurred in less than half of this case series (n=5, 38.5%), although there is currently no consensus on the precise definition of rapid dose escalation. Cumulative antipsychotic dose – alongside other known risk factors - may also be important in the development of NMS
PocketMatch: A new algorithm to compare binding sites in protein structures
Background: Recognizing similarities and deriving relationships among protein molecules is a fundamental
requirement in present-day biology. Similarities can be present at various levels which can be detected through comparison of protein sequences or their structural folds. In some cases similarities obscure at these levels could be present merely in the substructures at their binding sites. Inferring functional similarities between protein molecules by comparing their binding sites is still largely exploratory and not as yet a routine protocol. One of
the main reasons for this is the limitation in the choice of appropriate analytical tools that can compare binding sites with high sensitivity. To benefit from the enormous amount of structural data that is being rapidly accumulated, it is essential to have high throughput tools that enable large scale binding site comparison.

Results: Here we present a new algorithm PocketMatch for comparison of binding sites in a frame invariant
manner. Each binding site is represented by 90 lists of sorted distances capturing shape and chemical nature of the site. The sorted arrays are then aligned using an incremental alignment method and scored to obtain PMScores for pairs of sites. A comprehensive sensitivity analysis and an extensive validation of the algorithm have been carried out. Perturbation studies where the geometry of a given site was retained but the residue types were changed randomly, indicated that chance similarities were virtually non-existent. Our analysis also demonstrates that shape information alone is insufficient to discriminate between diverse binding sites, unless
combined with chemical nature of amino acids.

Conclusions: A new algorithm has been developed to compare binding sites in accurate, efficient and
high-throughput manner. Though the representation used is conceptually simplistic, we demonstrate that along
with the new alignment strategy used, it is sufficient to enable binding comparison with high sensitivity. Novel methodology has also been presented for validating the algorithm for accuracy and sensitivity with respect to geometry and chemical nature of the site. The method is also fast and takes about 1/250th second for one comparison on a single processor. A parallel version on BlueGene has also been implemented
Energy spectra of quantum rings
Ring geometries have fascinated experimental and theoretical physicists over
many years. Open rings connected to leads allow the observation of the
Aharonov-Bohm effect, a paradigm of quantum mechanical phase coherence. The
phase coherence of transport through a quantum dot embedded in one arm of an
open ring has been demonstrated. The energy spectrum of closed rings has only
recently been analysed by optical experiments and is the basis for the
prediction of persistent currents and related experiments. Here we report
magnetotransport experiments on a ring-shaped semiconductor quantum dot in the
Coulomb blockade regime. The measurements allow us to extract the discrete
energy levels of a realistic ring, which are found to agree well with
theoretical expectations. Such an agreement, so far only found for few-electron
quantum dots, is here extended to a many-electron system. In a semiclassical
language our results indicate that electron motion is governed by regular
rather than chaotic motion, an unexplored regime in many-electron quantum dots.Comment: 10 pages, 4 figure
Strong Interactions of Single Atoms and Photons near a Dielectric Boundary
Modern research in optical physics has achieved quantum control of strong
interactions between a single atom and one photon within the setting of cavity
quantum electrodynamics (cQED). However, to move beyond current
proof-of-principle experiments involving one or two conventional optical
cavities to more complex scalable systems that employ N >> 1 microscopic
resonators requires the localization of individual atoms on distance scales <
100 nm from a resonator's surface. In this regime an atom can be strongly
coupled to a single intracavity photon while at the same time experiencing
significant radiative interactions with the dielectric boundaries of the
resonator. Here, we report an initial step into this new regime of cQED by way
of real-time detection and high-bandwidth feedback to select and monitor single
Cesium atoms localized ~100 nm from the surface of a micro-toroidal optical
resonator. We employ strong radiative interactions of atom and cavity field to
probe atomic motion through the evanescent field of the resonator. Direct
temporal and spectral measurements reveal both the significant role of
Casimir-Polder attraction and the manifestly quantum nature of the atom-cavity
dynamics. Our work sets the stage for trapping atoms near micro- and
nano-scopic optical resonators for applications in quantum information science,
including the creation of scalable quantum networks composed of many
atom-cavity systems that coherently interact via coherent exchanges of single
photons.Comment: 8 pages, 5 figures, Supplemental Information included as ancillary
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Physicochemical conditions and timing of rodingite formation: evidence from rodingite-hosted fluid inclusions in the JM Asbestos mine, Asbestos, Québec
Fluid inclusions and geological relationships indicate that rodingite formation in the Asbestos ophiolite, Québec, occurred in two, or possibly three, separate episodes during thrusting of the ophiolite onto the Laurentian margin, and that it involved three fluids. The first episode of rodingitization, which affected diorite, occurred at temperatures of between 290 and 360°C and pressures of 2.5 to 4.5 kbar, and the second episode, which affected granite and slate, occurred at temperatures of between 325 and 400°C and pressures less than 3 kbar. The fluids responsible for these episodes of alteration were moderately to strongly saline (~1.5 to 6.3 m eq. NaCl), rich in divalent cations and contained appreciable methane. A possible third episode of alteration is suggested by primary fluid inclusions in vesuvianite-rich bodies and secondary inclusions in other types of rodingite, with significantly lower trapping temperatures, salinity and methane content. The association of the aqueous fluids with hydrocarbon-rich fluids containing CH4 and higher order alkanes, but no CO2, suggests strongly that the former originated from the serpentinites. The similarities in the composition of the fluids in all rock types indicate that the ophiolite had already been thrust onto the slates when rodingitization occurred
Gorlin syndrome associated with small bowel carcinoma and mesenchymal proliferation of the gastrointestinal tract: case report and review of literature
<p>Abstract</p> <p>Background and Case Presentation</p> <p>A patient with nevoid basal cell carcinoma syndrome (Gorlin syndrome) presented with two unusual clinical features, i.e. adenocarcinoma of the small bowel and extensive mesenchymal proliferation of the lower gastrointestinal tract.</p> <p>Conclusions</p> <p>We discuss the possibility that these two features are pathogenetically linked to the formerly undescribed patient's <it>PTCH </it>germ line mutation.</p
Matrix theory origins of non-geometric fluxes
We explore the origins of non-geometric fluxes within the context of M theory
described as a matrix model. Building upon compactifications of Matrix theory
on non-commutative tori and twisted tori, we formulate the conditions which
describe compactifications with non-geometric fluxes. These turn out to be
related to certain deformations of tori with non-commutative and
non-associative structures on their phase space. Quantization of flux appears
as a natural consequence of the framework and leads to the resolution of
non-associativity at the level of the unitary operators. The quantum-mechanical
nature of the model bestows an important role on the phase space. In
particular, the geometric and non-geometric fluxes exchange their properties
when going from position space to momentum space thus providing a duality among
the two. Moreover, the operations which connect solutions with different fluxes
are described and their relation to T-duality is discussed. Finally, we provide
some insights on the effective gauge theories obtained from these matrix
compactifications.Comment: 1+31 pages, reference list update
Formation of regulatory modules by local sequence duplication
Turnover of regulatory sequence and function is an important part of
molecular evolution. But what are the modes of sequence evolution leading to
rapid formation and loss of regulatory sites? Here, we show that a large
fraction of neighboring transcription factor binding sites in the fly genome
have formed from a common sequence origin by local duplications. This mode of
evolution is found to produce regulatory information: duplications can seed new
sites in the neighborhood of existing sites. Duplicate seeds evolve
subsequently by point mutations, often towards binding a different factor than
their ancestral neighbor sites. These results are based on a statistical
analysis of 346 cis-regulatory modules in the Drosophila melanogaster genome,
and a comparison set of intergenic regulatory sequence in Saccharomyces
cerevisiae. In fly regulatory modules, pairs of binding sites show
significantly enhanced sequence similarity up to distances of about 50 bp. We
analyze these data in terms of an evolutionary model with two distinct modes of
site formation: (i) evolution from independent sequence origin and (ii)
divergent evolution following duplication of a common ancestor sequence. Our
results suggest that pervasive formation of binding sites by local sequence
duplications distinguishes the complex regulatory architecture of higher
eukaryotes from the simpler architecture of unicellular organisms
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Minimal regulation of platelet activity by PECAM-1
PECAM-1 is a member of the superfamily of immunoglobulins (Ig) and is expressed on platelets at moderate level. PECAM-1 has been reported to have contrasting effects on platelet activation by the collagen receptor GPVI and the integrin, αIIbβ3, even though both receptors signal through Src-kinase regulation of PLCγ2. The present study compares the role of PECAM-1 on platelet activation by these two receptors and by the lectin receptor, CLEC-2, which also signals via PLCγ2. Studies using PECAM-1 knockout-mice and cross-linking of PECAM-1 using specific antibodies demonstrated a minor inhibitory role on platelet responses to the above three receptors and also under some conditions to the G-protein agonist thrombin. The degree of inhibition was considerably less than that produced by PGI2, which elevates cAMP. There was no significant difference in thrombus formation on collagen in PECAM-1-/- platelets relative to litter-matched controls. The very weak inhibitory effect of PECAM-1 on platelet activation relative to that of PGI2 indicate that the Ig-receptor is not a major regulator of platelet activation. PECAM-1 has been reported to have contrasting effects on platelet activation. The present study demonstrates a very mild or negligible effect on platelet activation in response to stimulation by a variety of agonists, thereby questioning the physiological role of the immunoglobulin receptor as a major regulator of platelet activation
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