1,110 research outputs found
Progressive internal gravity waves with bounded upper surface climbing a triangular obstacle
In this paper we discuss a theoretical model for the interfacial profiles of
progressive non-linear waves which result from introducing a triangular
obstacle, of finite height, attached to the bottom below the flow of a
stratified, ideal, two layer fluid, bounded from above by a rigid boundary. The
derived equations are solved by using a nonlinear perturbation method. The
dependence of the interfacial profile on the triangular obstacle size, as well
as its dependence on some flow parameters, such as the ratios of depths and
densities of the two fluids, have been studied
Multidimensional reconciliation for continuous-variable quantum key distribution
We propose a method for extracting an errorless secret key in a
continuous-variable quantum key distribution protocol, which is based on
Gaussian modulation of coherent states and homodyne detection. The crucial
feature is an eight-dimensional reconciliation method, based on the algebraic
properties of octonions. Since the protocol does not use any postselection, it
can be proven secure against arbitrary collective attacks, by using
well-established theorems on the optimality of Gaussian attacks. By using this
new coding scheme with an appropriate signal to noise ratio, the distance for
secure continuous-variable quantum key distribution can be significantly
extended.Comment: 8 pages, 3 figure
Estimating large-scale signaling networks through nested effect models with intervention effects from microarray data
Motivation: Targeted interventions using RNA interference in combination with the measurement of secondary effects with DNA microarrays can be used to computationally reverse engineer features of upstream non-transcriptional signaling cascades based on the nested structure of effects
Loss of epidermal Evi/Wls results in a phenotype resembling psoriasiform dermatitis
Cells of the epidermis renew constantly from germinal layer stem cells. Although epithelial cell differentiation has been studied in great detail and the role of Wnt signaling in this process is well described, the contribution of epidermal Wnt secretion in epithelial cell homeostasis remains poorly understood. To analyze the role of Wnt proteins in this process, we created a conditional knockout allele of the Wnt cargo receptor Evi/Gpr177/Wntless and studied mice that lacked Evi expression in the epidermis. We found that K14-Cre, Evi-LOF mice lost their hair during the first hair cycle, showing a reddish skin with impaired skin barrier function. Expression profiling of mutant and wild-type skin revealed up-regulation of inflammation-associated genes. Furthermore, we found that Evi expression in psoriatic skin biopsies is down-regulated, suggesting that Evi-deficient mice developed skin lesions that resemble human psoriasis. Immune cell infiltration was detected in Evi-LOF skin. Interestingly, an age-dependent depletion of dendritic epidermal T cells (DETCs) and an infiltration of gammadelta(low) T cells in Evi mutant epidermis was observed. Collectively, the described inflammatory skin phenotype in Evi-deficient mice revealed an essential role of Wnt secretion in maintaining normal skin homeostasis by enabling a balanced epidermal-dermal cross talk, which affects immune cell recruitment and DETC survival
Cholesterol Levels and Activity of Membrane Bound Proteins: Characterization by Thermal and Electrochemical Methods
The long-term goal of this investigation is to study the effects of increased cholesterol levels on the molecular activity of membrane-bound enzymes such as nitric oxide synthase, that are critical in the functioning of the cardiovascular system. In this particular investigation, we used differential scanning calorimetry (DSC) and dielectric thermal analysis (DETA) to study the effect of added cholesterol on melting/recrystallization and dielectric behavior, respectively, of phosphatidylcholine (PC) bilayered thin films. We also used electrochemical methods to investigate the effect of added cholesterol on the redox behavior of the oxygenase domain of nitric oxide synthase as a probe embedded in the PC films. The results show that added cholesterol in the PC films seems to depress the molecular dynamics as indicated by lowered current responses in the presence of cholesterol as well as a slight increase of the transition temperature in the overall two-phase regime behavior observed in PCâcholesterol films. These results are rationalized in the context of the general DSC and DETA behaviors of the PCâchol films
Quantitative and Qualitative Analysis of Blood-based Liquid Biopsies to Inform Clinical Decision-making in Prostate Cancer
ADN tumoral circulant; Medicina de precisiĂł; CĂ ncer de prĂČstataADN tumoral circulante; Medicina de precisiĂłn; CĂĄncer de prĂłstataCirculating tumor DNA; Precision medicine; Prostate cancerContext
Genomic stratification can impact prostate cancer (PC) care through diagnostic, prognostic, and predictive biomarkers that aid in clinical decision-making. The temporal and spatial genomic heterogeneity of PC together with the challenges of acquiring metastatic tissue biopsies hinder implementation of tissue-based molecular profiling in routine clinical practice. Blood-based liquid biopsies are an attractive, minimally invasive alternative.
Objective
To review the clinical value of blood-based liquid biopsy assays in PC and identify potential applications to accelerate the development of precision medicine.
Evidence acquisition
A systematic review of PubMed/MEDLINE was performed to identify relevant literature on blood-based circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and extracellular vesicles (EVs) in PC.
Evidence synthesis
Liquid biopsy has emerged as a practical tool to profile tumor dynamics over time, elucidating features that evolve (genome, epigenome, transcriptome, and proteome) with tumor progression. Liquid biopsy tests encompass analysis of DNA, RNA, and proteins that can be detected in CTCs, ctDNA, or EVs. Blood-based liquid biopsies have demonstrated promise in the context of localized tumors (diagnostic signatures, risk stratification, and disease monitoring) and advanced disease (response/resistance biomarkers and prognostic markers).
Conclusions
Liquid biopsies have value as a source of prognostic, predictive, and response biomarkers in PC. Most clinical applications have been developed in the advanced metastatic setting, where CTC and ctDNA yields are significantly higher. However, standardization of assays and analytical/clinical validation is necessary prior to clinical implementation
Pregnancy and Fetal Outcomes After Exposure to Mefloquine in the Pre- and Periconception Period and During Pregnancy
Pregnant women who travel to malarious areas and their clinicians need data on the safety of malaria chemoprophylaxis. The drug safety database analysis of mefloquine exposure in pregnancy showed that the birth defect prevalence and fetal loss in maternal, prospectively-monitored cases were comparable to background rate
Adolescent Intermittent Ethanol Exposure Is Associated with Increased Risky Choice and Decreased Dopaminergic and Cholinergic Neuron Markers in Adult Rats
Background:Binge drinking is prevalent during adolescence and may have effects on the adult brain and behavior. The present study investigated whether adolescent intermittent ethanol exposure alters adult risky choice and prefrontal dopaminergic and forebrain cholinergic neuronal marker levels in male Wistar rats.Methods:Adolescent (postnatal day 28â53) rats were administered 5g/kg of 25% (vol/vol) ethanol 3 times/d in a 2-daysâon/2-daysâoff exposure pattern. In adulthood, risky choice was assessed in the probability discounting task with descending and ascending series of large reward probabilities and after acute ethanol challenge. Immunohistochemical analyses assessed tyrosine hydroxylase, a marker of dopamine and norepinephrine in the prelimbic and infralimbic cortices, and choline acetyltransferase, a marker of cholinergic neurons, in the basal forebrain.Results:All of the rats preferred the large reward when it was delivered with high probability. When the large reward became unlikely, control rats preferred the smaller, safe reward, whereas adolescent intermittent ethanol-exposed rats continued to prefer the risky alternative. Acute ethanol had no effect on risky choice in either group of rats. Tyrosine hydroxylase (prelimbic cortex only) and choline acetyltransferase immunoreactivity levels were decreased in adolescent intermittent ethanol-exposed rats compared with controls. Risky choice was negatively correlated with choline acetyltransferase, implicating decreased forebrain cholinergic activity in risky choice.Conclusions:The decreases in tyrosine hydroxylase and choline acetyltransferase immunoreactivity suggest that adolescent intermittent ethanol exposure has enduring neural effects that may lead to altered adult behaviors, such as increased risky decision making. In humans, increased risky decision making could lead to maladaptive, potentially harmful consequences
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