1,684 research outputs found
Caffeine and a selective adenosine A2A receptor antagonist induce sensitization and cross-sensitization behavior associated with increased striatal dopamine in mice
<p>Abstract</p> <p>Background</p> <p>Caffeine, a nonselective adenosine A<sub>1 </sub>and A<sub>2A </sub>receptor antagonist, is the most widely used psychoactive substance in the world. Evidence demonstrates that caffeine and selective adenosine A<sub>2A </sub>antagonists interact with the neuronal systems involved in drug reinforcement, locomotor sensitization, and therapeutic effect in Parkinson's disease (PD). Evidence also indicates that low doses of caffeine and a selective adenosine A<sub>2A </sub>antagonist SCH58261 elicit locomotor stimulation whereas high doses of these drugs exert locomotor inhibition. Since these behavioral and therapeutic effects are mediated by the mesolimbic and nigrostriatal dopaminergic pathways which project to the striatum, we hypothesize that low doses of caffeine and SCH58261 may modulate the functions of dopaminergic neurons in the striatum.</p> <p>Methods</p> <p>In this study, we evaluated the neuroadaptations in the striatum by using reverse-phase high performance liquid chromatography (HPLC) to quantitate the concentrations of striatal dopamine and its metabolites, dihydroxylphenylacetic acid (DOPAC) and homovanilic acid (HVA), and using immunoblotting to measure the level of phosphorylation of tyrosine hydroxylase (TH) at Ser31, following chronic caffeine and SCH58261 sensitization in mice. Moreover, to validate further that the behavior sensitization of caffeine is through antagonism at the adenosine A<sub>2A </sub>receptor, we also evaluate whether chronic pretreatment with a selective adenosine A<sub>2A </sub>antagonist SCH58261 or a selective adenosine A<sub>1 </sub>antagonist DPCPX can sensitize the locomotor stimulating effects of caffeine.</p> <p>Results</p> <p>Chronic treatments with low dose caffeine (10 mg/kg) or SCH58261 (2 mg/kg) increased the concentrations of dopamine, DOPAC and HVA, concomitant with increased TH phosphorylation at Ser31 and consequently enhanced TH activity in the striatal tissues in both caffeine- and SCH58261-sensitized mice. In addition, chronic caffeine or SCH58261 administration induced locomotor sensitization, and locomotor cross-sensitization to caffeine was observed following chronic treatment of mice with SCH58261 but not with DPCPX.</p> <p>Conclusions</p> <p>Our study demonstrated that low dosages of caffeine and a selective adenosine A<sub>2A </sub>antagonist SCH58261 elicited locomotor sensitization and cross-sensitization, which were associated with elevated dopamine concentration and TH phosphorylation at Ser31 in the striatum. Blockade of adenosine A<sub>2A </sub>receptor may play an important role in the striatal neuroadaptations observed in the caffeine-sensitized and SCH58261-sensitized mice.</p
Combustion of the butanol isomers: reaction pathways at elevated pressures from low-to-high temperatures
Experimental procedures for precision measurements of the Casimir force with an Atomic Force Microscope
Experimental methods and procedures required for precision measurements of
the Casimir force are presented. In particular, the best practices for
obtaining stable cantilevers, calibration of the cantilever, correction of
thermal and mechanical drift, measuring the contact separation, sphere radius
and the roughness are discussed.Comment: 14 pages, 7 figure
Auxiliary field approach to dilute Bose gases with tunable interactions
We rewrite the Lagrangian for a dilute Bose gas in terms of auxiliary fields
related to the normal and anomalous condensate densities. We derive the loop
expansion of the effective action in the composite-field propagators. The
lowest-order auxiliary field (LOAF) theory is a conserving mean-field
approximation consistent with the Goldstone theorem without some of the
difficulties plaguing approximations such as the Hartree and Popov
approximations. LOAF predicts a second-order phase transition. We give a set of
Feynman rules for improving results to any order in the loop expansion in terms
of composite-field propagators. We compare results of the LOAF approximation
with those derived using the Popov approximation. LOAF allows us to explore the
critical regime for all values of the coupling constant and we determine
various parameters in the unitarity limit.Comment: 16 pages, 7 figure
Visualizing landscapes of the superconducting gap in heterogeneous superconductor thin films: geometric influences on proximity effects
The proximity effect is a central feature of superconducting junctions as it
underlies many important applications in devices and can be exploited in the
design of new systems with novel quantum functionality. Recently, exotic
proximity effects have been observed in various systems, such as
superconductor-metallic nanowires and graphene-superconductor structures.
However, it is still not clear how superconducting order propagates spatially
in a heterogeneous superconductor system. Here we report intriguing influences
of junction geometry on the proximity effect for a 2D heterogeneous
superconductor system comprised of 2D superconducting islands on top of a
surface metal. Depending on the local geometry, the superconducting gap induced
in the surface metal region can either be confined to the boundary of the
superconductor, in which the gap decays within a short distance (~ 15 nm), or
can be observed nearly uniformly over a distance of many coherence lengths due
to non-local proximity effects.Comment: 17 pages, 4 figure
Molecular diagnostic yield of exome sequencing in patients with congenital hydrocephalus: A systematic review and meta-analysis
IMPORTANCE: Exome sequencing (ES) has been established as the preferred first line of diagnostic testing for certain neurodevelopmental disorders, such as global developmental delay and autism spectrum disorder; however, current recommendations are not specific to or inclusive of congenital hydrocephalus (CH).
OBJECTIVE: To determine the diagnostic yield of ES in CH and whether ES should be considered as a first line diagnostic test for CH.
DATA SOURCES: PubMed, Cochrane Library, and Google Scholar were used to identify studies published in English between January 1, 2010, and April 10, 2023. The following search terms were used to identify studies: congenital hydrocephalus, ventriculomegaly, cerebral ventriculomegaly, primary ventriculomegaly, fetal ventriculomegaly, prenatal ventriculomegaly, molecular analysis, genetic cause, genetic etiology, genetic testing, exome sequencing, whole exome sequencing, genome sequencing, microarray, microarray analysis, and copy number variants.
STUDY SELECTION: Eligible studies included those with at least 10 probands with the defining feature of CH and/or severe cerebral ventriculomegaly that had undergone ES. Studies with fewer than 10 probands, studies of mild or moderate ventriculomegaly, and studies using genetic tests other than ES were excluded. A full-text review of 68 studies was conducted by 2 reviewers. Discrepancies were resolved by consensus.
DATA EXTRACTION AND SYNTHESIS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and Meta-Analysis of Observational Studies in Epidemiology guidelines were used by 2 reviewers to extract data. Data were synthesized using a random-effects model of single proportions. Data analysis occurred in April 2023.
MAIN OUTCOMES AND MEASURES: The primary outcome was pooled diagnostic yield. Additional diagnostic yields were estimated for specific subgroups on the basis of clinical features, syndromic presentation, and parental consanguinity. For each outcome, a 95% CI and estimate of interstudy heterogeneity (I2 statistic) was reported.
RESULTS: From 498 deduplicated and screened records, 9 studies with a total of 538 CH probands were selected for final inclusion. The overall diagnostic yield was 37.9% (95% CI, 20.0%-57.4%; I2 = 90.1). The yield was lower for isolated and/or nonsyndromic cases (21.3%; 95% CI, 12.8%-31.0%; I2 = 55.7). The yield was higher for probands with reported consanguinity (76.3%; 95% CI, 65.1%-86.1%; I2 = 0) than those without (16.2%; 95% CI, 12.2%-20.5%; I2 = 0).
CONCLUSIONS AND RELEVANCE: In this systematic review and meta-analysis of the diagnostic yield of ES in CH, the diagnostic yield was concordant with that of previous recommendations for other neurodevelopmental disorders, suggesting that ES should also be recommended as a routine diagnostic adjunct for patients with CH
Robustness Verification of Support Vector Machines
We study the problem of formally verifying the robustness to adversarial
examples of support vector machines (SVMs), a major machine learning model for
classification and regression tasks. Following a recent stream of works on
formal robustness verification of (deep) neural networks, our approach relies
on a sound abstract version of a given SVM classifier to be used for checking
its robustness. This methodology is parametric on a given numerical abstraction
of real values and, analogously to the case of neural networks, needs neither
abstract least upper bounds nor widening operators on this abstraction. The
standard interval domain provides a simple instantiation of our abstraction
technique, which is enhanced with the domain of reduced affine forms, which is
an efficient abstraction of the zonotope abstract domain. This robustness
verification technique has been fully implemented and experimentally evaluated
on SVMs based on linear and nonlinear (polynomial and radial basis function)
kernels, which have been trained on the popular MNIST dataset of images and on
the recent and more challenging Fashion-MNIST dataset. The experimental results
of our prototype SVM robustness verifier appear to be encouraging: this
automated verification is fast, scalable and shows significantly high
percentages of provable robustness on the test set of MNIST, in particular
compared to the analogous provable robustness of neural networks
Geometric quenching of orbital pair breaking in a single crystalline superconducting nanomesh network
In a superconductor Cooper pairs condense into a single state and in so doing support dissipation free charge flow and perfect diamagnetism. In a magnetic field the minimum kinetic energy of the Cooper pairs increases, producing an orbital pair breaking effect. We show that it is possible to significantly quench the orbital pair breaking effect for both parallel and perpendicular magnetic fields in a thin film superconductor with lateral nanostructure on a length scale smaller than the magnetic length. By growing an ultra-thin (2 nm thick) single crystalline Pb nanowire network, we establish nm scale lateral structure without introducing weak links. Our network suppresses orbital pair breaking for both perpendicular and in-plane fields with a negligible reduction in zero-field resistive critical temperatures. Our study opens a frontier in nanoscale superconductivity by providing a strategy for maintaining pairing in strong field environments in all directions with important technological implications
PU.1 controls fibroblast polarization and tissue fibrosis
Fibroblasts are polymorphic cells with pleiotropic roles in organ morphogenesis, tissue homeostasis and immune responses. In fibrotic diseases, fibroblasts synthesize abundant amounts of extracellular matrix, which induces scarring and organ failure. By contrast, a hallmark feature of fibroblasts in arthritis is degradation of the extracellular matrix because of the release of metalloproteinases and degrading enzymes, and subsequent tissue destruction. The mechanisms that drive these functionally opposing pro-fibrotic and pro-inflammatory phenotypes of fibroblasts remain unknown. Here we identify the transcription factor PU.1 as an essential regulator of the pro-fibrotic gene expression program. The interplay between transcriptional and post-transcriptional mechanisms that normally control the expression of PU.1 expression is perturbed in various fibrotic diseases, resulting in the upregulation of PU.1, induction of fibrosis-associated gene sets and a phenotypic switch in extracellular matrix-producing pro-fibrotic fibroblasts. By contrast, pharmacological and genetic inactivation of PU.1 disrupts the fibrotic network and enables reprogramming of fibrotic fibroblasts into resting fibroblasts, leading to regression of fibrosis in several organs
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