1,277 research outputs found
Pathwise Sensitivity Analysis in Transient Regimes
The instantaneous relative entropy (IRE) and the corresponding instanta-
neous Fisher information matrix (IFIM) for transient stochastic processes are
pre- sented in this paper. These novel tools for sensitivity analysis of
stochastic models serve as an extension of the well known relative entropy rate
(RER) and the corre- sponding Fisher information matrix (FIM) that apply to
stationary processes. Three cases are studied here, discrete-time Markov
chains, continuous-time Markov chains and stochastic differential equations. A
biological reaction network is presented as a demonstration numerical example
Trace anomalies in chiral theories revisited
Motivated by the search for possible CP violating terms in the trace of the
energy-momentum tensor in theories coupled to gravity we revisit the problem of trace
anomalies in chiral theories. We recalculate the latter and ascertain that in the trace of
the energy-momentum tensor of theories with chiral fermions at one-loop the Pontryagin
density appears with an imaginary coefficient. We argue that this may break unitarity, in
which case the trace anomaly has to be used as a selective criterion for theories, analogous
to the chiral anomalies in gauge theories. We analyze some remarkable consequences of
this fact, that seem to have been overlooked in the literature
General Messenger Gauge Mediation
We discuss theories of gauge mediation in which the hidden sector consists of
two subsectors which are weakly coupled to each other. One sector is made up of
messengers and the other breaks supersymmetry. Each sector by itself may be
strongly coupled. We provide a unifying framework for such theories and discuss
their predictions in different settings. We show how this framework
incorporates all known models of messengers. In the case of weakly-coupled
messengers interacting with spurions through the superpotential, we prove that
the sfermion mass-squared is positive, and furthermore, that there is a lower
bound on the ratio of the sfermion mass to the gaugino mass.Comment: 37 pages; minor change
Tissue print of prostate biopsy: a novel tool in the diagnostic procedure of prostate cancer
<p>Abstract</p> <p>Background</p> <p>Nowadays, the histological examination of prostate core needle biopsies is still regarded as the gold standard in the diagnosis of prostate cancer (PCa). We investigated if the tissue print of core needle biopsy (biopsy print) could be used as adjunctive molecular investigative procedures in conjunction with routine histological examination of biopsy to improve PCa diagnosis.</p> <p>Methods</p> <p>The direct contact of PCa core biopsy to nitrocellulose membrane resulted in the release of a cellular micropeel that was used for downstream analytical procedures.</p> <p>Results</p> <p>By zymogram print-phoresis we demonstrated that matrix metalloproteases MMP-2 and MMP-9 could be visualized in biopsy prints and that the gelatinolytic activity was positively correlated with immunohistochemistry analysis of the same markers in matched bioptic specimens. Moreover, we compared the ability to detect the PCa-associated hypermethylation of GSTP1 promoter in DNA extracted from biopsy prints with those of the corresponding core needle biopsies. Biopsy prints demonstrated the same specificity of biopsies in detecting PCa (50%) while the sensitivity and the positive predictive value were lower than biopsies (56% vs 78% and 63% vs 70%, respectively).</p> <p>Conclusions</p> <p>Biopsy print, combining a molecular point of view to the routinely hystopathological analysis of prostate biopsies, should be a useful tool to improve the diagnosis of PCa.</p
Expression and DNA methylation of TNF, IFNG and FOXP3 in colorectal cancer and their prognostic significance.
BACKGROUND: Colorectal cancer (CRC) progression is associated with suppression of host cell-mediated immunity and local immune escape mechanisms. Our aim was to assess the immune function in terms of expression of TNF, IFNG and FOXP3 in CRC.
METHODS: Sixty patients with CRC and 15 matched controls were recruited. TaqMan quantitative PCR and methylation-specific PCR was performed for expression and DNA methylation analysis of TNF, IFNG and FOXP3. Survival analysis was performed over a median follow-up of 48 months.
RESULTS: TNF was suppressed in tumour and IFNG was suppressed in peripheral blood mononuclear cells (PBMCs) of patients with CRC. Tumours showed enhanced expression of FOXP3 and was significantly higher when tumour size was >38βmm (median tumour size; P=0.006, Mann-Whitney U-test). Peripheral blood mononuclear cell IFNG was suppressed in recurrent CRC (P=0.01). Methylated TNFpromoter (P=0.003) and TNFexon1 (P=0.001) were associated with significant suppression of TNF in tumours. Methylated FOXP3cpg was associated with significant suppression of FOXP3 in both PBMC (P=0.018) and tumours (P=0.010). Reduced PBMC FOXP3 expression was associated with significantly worse overall survival (HR=8.319, P=0.019).
CONCLUSIONS: We have detected changes in the expression of immunomodulatory genes that could act as biomarkers for prognosis and future immunotherapeutic strategies
Serotonin Augments Gut Pacemaker Activity via 5-HT3 Receptors
Serotonin (5-hydroxytryptamine: 5-HT) affects numerous functions in the gut, such as secretion, muscle contraction, and enteric nervous activity, and therefore to clarify details of 5-HT's actions leads to good therapeutic strategies for gut functional disorders. The role of interstitial cells of Cajal (ICC), as pacemaker cells, has been recognised relatively recently. We thus investigated 5-HT actions on ICC pacemaker activity. Muscle preparations with myenteric plexus were isolated from the murine ileum. Spatio-temporal measurements of intracellular Ca2+ and electric activities in ICC were performed by employing fluorescent Ca2+ imaging and microelectrode array (MEA) systems, respectively. Dihydropyridine (DHP) Ca2+ antagonists and tetrodotoxin (TTX) were applied to suppress smooth muscle and nerve activities, respectively. 5-HT significantly enhanced spontaneous Ca2+ oscillations that are considered to underlie electric pacemaker activity in ICC. LY-278584, a 5-HT3 receptor antagonist suppressed spontaneous Ca2+ activity in ICC, while 2-methylserotonin (2-Me-5-HT), a 5-HT3 receptor agonist, restored it. GR113808, a selective antagonist for 5-HT4, and O-methyl-5-HT (O-Me-5-HT), a non-selective 5-HT receptor agonist lacking affinity for 5-HT3 receptors, had little effect on ICC Ca2+ activity. In MEA measurements of ICC electric activity, 5-HT and 2-Me-5-HT caused excitatory effects. RT-PCR and immunostaining confirmed expression of 5-HT3 receptors in ICC. The results indicate that 5-HT augments ICC pacemaker activity via 5-HT3 receptors. ICC appear to be a promising target for treatment of functional motility disorders of the gut, for example, irritable bowel syndrome
Searching for faces differs from categorization: Evidence from scenes and eye movements
This study examined whether the detection of frontal, ΒΎ and profile face views differs from their categorization as faces. Experiment 1 compared three tasks that required observers to determine the presence or absence of a face but varied in the extent to which they had to search for faces in simple displays and small or large scenes to make this decision. Performance was equivalent for all face views in simple displays and small scenes, but was notably slower for profile views when this required the search for faces in extended scene displays. This search effect was confirmed in Experiment 2, which compared observersβ eye movements with their response times to faces in visual scenes. These results demonstrate that the categorization of faces at fixation is dissociable from the detection of faces in space. Consequently, we suggest that face detection should be studied with extended visual displays, such as natural scenes
Hidden conformal symmetry of extreme and non-extreme Einstein-Maxwell-Dilaton-Axion black holes
The hidden conformal symmetry of extreme and non-extreme
Einstein-Maxwell-Dilaton-Axion (EMDA) black holes is addressed in this paper.
For the non-extreme one, employing the wave equation of massless scalars, the
conformal symmetry with left temperature and right
temperature in the near region is
found. The conformal symmetry is spontaneously broken due to the periodicity of
the azimuthal angle. The microscopic entropy is derived by the Cardy formula
and is fully in consistence with the Bekenstein-Hawking area-entropy law. The
absorption cross section in the near region is calculated and exactly equals
that in a 2D CFT. For the extreme case, by redefining the conformal
coordinates, the duality between the solution space and CFT is studied. The
microscopic entropy is found to exactly agree with the area-entropy law.Comment: V3, typos corrected, version to appear in JHE
Three-dimensional kinematic motion analysis of a daily activity drinking from a glass: a pilot study
BACKGROUND: Development of reliable and objective evaluation methods is required, particularly for natural and goal-oriented upper-extremity tasks. Three-dimensional imaging measurement techniques have turned out to be a powerful tool for a quantitative and qualitative assessment of multijoint movements. The purpose of this study was to develop and test a method of three-dimensional motion analysis for the activity "drinking from a glass" and describe the drinking task with kinematic variables in control subjects. METHODS: A protocol was developed for the drinking activity including the set-up of cameras and positions of the markers and the subject. The drinking task included reaching, forward transport with glass, drinking, back transport and returning the hand to the initial position. An optoelectronic system was used for the three-dimensional kinematic motion capture. Movement times, velocities, joint angles and interjoint coordination for shoulder and elbow were computed and analyzed for twenty control subjects. Test-retest consistency was evaluated for six subjects. RESULTS: The test protocol showed good consistency in test-retest. Phase definitions for the drinking task were defined and verified. Descriptive kinematic variables were obtained for movement times, positions, velocities and joint angles for shoulder and elbow joint. Interjoint coordination between shoulder and elbow joint in reaching phase showed a high correlation. CONCLUSION: This study provides a detailed description of the three-dimensional kinematic analysis of the drinking task. Our approach to investigate and analyze a goal-oriented daily activity has a great clinical potential. Consequently, the next step is to use and test this protocol on persons with impairments and disabilities from upper extremities
Ischaemic strokes in patients with pulmonary arteriovenous malformations and hereditary hemorrhagic telangiectasia: associations with iron deficiency and platelets.
<div><p>Background</p><p>Pulmonary first pass filtration of particles marginally exceeding βΌ7 Β΅m (the size of a red blood cell) is used routinely in diagnostics, and allows cellular aggregates forming or entering the circulation in the preceding cardiac cycle to lodge safely in pulmonary capillaries/arterioles. Pulmonary arteriovenous malformations compromise capillary bed filtration, and are commonly associated with ischaemic stroke. Cohorts with CT-scan evident malformations associated with the highest contrast echocardiographic shunt grades are known to be at higher stroke risk. Our goal was to identify within this broad grouping, which patients were at higher risk of stroke.</p><p>Methodology</p><p>497 consecutive patients with CT-proven pulmonary arteriovenous malformations due to hereditary haemorrhagic telangiectasia were studied. Relationships with radiologically-confirmed clinical ischaemic stroke were examined using logistic regression, receiver operating characteristic analyses, and platelet studies.</p><p>Principal Findings</p><p>Sixty-one individuals (12.3%) had acute, non-iatrogenic ischaemic clinical strokes at a median age of 52 (IQR 41β63) years. In crude and age-adjusted logistic regression, stroke risk was associated not with venous thromboemboli or conventional neurovascular risk factors, but with low serum iron (adjusted odds ratio 0.96 [95% confidence intervals 0.92, 1.00]), and more weakly with low oxygen saturations reflecting a larger right-to-left shunt (adjusted OR 0.96 [0.92, 1.01]). For the same pulmonary arteriovenous malformations, the stroke risk would approximately double with serum iron 6 Β΅mol/L compared to mid-normal range (7β27 Β΅mol/L). Platelet studies confirmed overlooked data that iron deficiency is associated with exuberant platelet aggregation to serotonin (5HT), correcting following iron treatment. By MANOVA, adjusting for participant and 5HT, iron or ferritin explained 14% of the variance in log-transformed aggregation-rate (pβ=β0.039/pβ=β0.021).</p><p>Significance</p><p>These data suggest that patients with compromised pulmonary capillary filtration due to pulmonary arteriovenous malformations are at increased risk of ischaemic stroke if they are iron deficient, and that mechanisms are likely to include enhanced aggregation of circulating platelets.</p></div
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