Photoheliograph study for the Apollo telescope mount

Photoheliograph study for Apollo telescope moun

Effects of Frontal Transcranial Direct Current Stimulation on Emotional State and Processing in Healthy Humans

The prefrontal cortex is involved in mood and emotional processing. In patients suffering from depression, the left dorsolateral prefrontal cortex (DLPFC) is hypoactive, while activity of the right DLPFC is enhanced. Counterbalancing these pathological excitability alterations by repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) improves mood in these patients. In healthy subjects, however, rTMS of the same areas has no major effect, and the effects of tDCS are mixed. We aimed to evaluate the effects of prefrontal tDCS on emotion and emotion-related cognitive processing in healthy humans. In a first study, we administered excitability-enhancing anodal, excitability-diminishing cathodal, and placebo tDCS to the left DLPFC, combined with antagonistic stimulation of the right frontopolar cortex, and tested acute emotional changes by an adjective checklist. Subjective emotions were not influenced by tDCS. Emotional face identification, however, which was explored in a second experiment, was subtly improved by a tDCS-driven excitability modulation of the prefrontal cortex, markedly by anodal tDCS of the left DLPFC for positive emotional content. We conclude that tDCS of the prefrontal cortex improves emotion processing in healthy subjects, but does not influence subjective emotional state

Analysis of brain adrenergic receptors in dopamine-β-hydroxylase knockout mice

The biosynthesis of norepinephrine occurs through a multi-enzymatic pathway that includes the enzyme dopamine-β-hydroxylase (DBH). Mice with a homozygous deletion of DBH (Dbh−/−) have a selective and complete absence of norepinephrine. The purpose of this study was to assess the expression of alpha-1, alpha-2 and beta adrenergic receptors (α1-AR, α2-AR and β-AR) in the postnatal absence of norepinephrine by comparing noradrenergic receptors in Dbh−/− mice with those in Dbh heterozygotes (Dbh+/−), which have normal levels of norepinephrine throughout life. The densities of α1-AR, α2-AR and β-AR were assayed with [3H]prazosin, [3H]RX21002 and [125I]-iodo-pindolol autoradiography, respectively. The α2-AR agonist high affinity state was examined with [125I]-paraiodoclonidine autoradiography and α2-AR functionality by α2-AR agonist-stimulated [35S] GTPγS autoradiography. The density of α1-AR in Dbh−/− mice was similar to Dbh+/− mice in most brain regions, with an up-regulation in the hippocampus. Modest decreases in α2-AR were found in septum, hippocampus and amygdala, but these were not reflected in α2-AR functionality. The density of β-AR was up-regulated to varying degrees in many brain regions of Dbh−/− mice compared to the heterozygotes. These findings indicate that regulation of noradrenergic receptors by endogenous norepinephrine depends on receptor type and neuroanatomical region

Spatial interactions in agent-based modeling

Agent Based Modeling (ABM) has become a widespread approach to model complex interactions. In this chapter after briefly summarizing some features of ABM the different approaches in modeling spatial interactions are discussed. It is stressed that agents can interact either indirectly through a shared environment and/or directly with each other. In such an approach, higher-order variables such as commodity prices, population dynamics or even institutions, are not exogenously specified but instead are seen as the results of interactions. It is highlighted in the chapter that the understanding of patterns emerging from such spatial interaction between agents is a key problem as much as their description through analytical or simulation means. The chapter reviews different approaches for modeling agents' behavior, taking into account either explicit spatial (lattice based) structures or networks. Some emphasis is placed on recent ABM as applied to the description of the dynamics of the geographical distribution of economic activities, - out of equilibrium. The Eurace@Unibi Model, an agent-based macroeconomic model with spatial structure, is used to illustrate the potential of such an approach for spatial policy analysis.Comment: 26 pages, 5 figures, 105 references; a chapter prepared for the book "Complexity and Geographical Economics - Topics and Tools", P. Commendatore, S.S. Kayam and I. Kubin, Eds. (Springer, in press, 2014

Defining language impairments in a subgroup of children with autism spectrum disorder

Autism spectrum disorder (ASD) is diagnosed on the basis of core impairments in pragmatic language skills, which are found across all ages and subtypes. In contrast, there is significant heterogeneity in language phenotypes, ranging from nonverbal to superior linguistic abilities, as defined on standardized tests of vocabulary and grammatical knowledge. The majority of children are verbal but impaired in language, relative to age-matched peers. One hypothesis is that this subgroup has ASD and co-morbid specific language impairment (SLI). An experiment was conducted comparing children with ASD to children with SLI and typically developing controls on aspects of language processing that have been shown to be impaired in children with SLI: repetition of nonsense words. Patterns of performance among the children with ASD and language impairment were similar to those with SLI, and contrasted with the children with ASD and no language impairment and typical controls, providing further evidence for the hypothesis that a subgroup of children with ASD has co-morbid SLI. The findings are discussed in the context of brain imaging studies that have explored the neural bases of language impairment in ASD and SLI, and overlap in the genes associated with elevated risk for these disorders.M01 RR00533 - NCRR NIH HHS; R01 DC10290 - NIDCD NIH HHS; U19 DC03610 - NIDCD NIH HH

Cure of ADPKD by Selection for Spontaneous Genetic Repair Events in Pkd1-Mutated iPS Cells

Induced pluripotent stem cells (iPSCs) generated by epigenetic reprogramming of personal somatic cells have limited therapeutic capacity for patients suffering from genetic disorders. Here we demonstrate restoration of a genomic mutation heterozygous for Pkd1 (polycystic kidney disease 1) deletion (Pkd1(+/−) to Pkd1(+/R+)) by spontaneous mitotic recombination. Notably, recombination between homologous chromosomes occurred at a frequency of 1∼2 per 10,000 iPSCs. Southern blot hybridization and genomic PCR analyses demonstrated that the genotype of the mutation-restored iPSCs was indistinguishable from that of the wild-type cells. Importantly, the frequency of cyst generation in kidneys of adult chimeric mice containing Pkd1(+/R+) iPSCs was significantly lower than that of adult chimeric mice with parental Pkd1(+/−) iPSCs, and indistinguishable from that of wild-type mice. This repair step could be directly incorporated into iPSC development programmes prior to cell transplantation, offering an invaluable step forward for patients carrying a wide range of genetic disorders

Impaired Prefrontal Hemodynamic Maturation in Autism and Unaffected Siblings

BACKGROUND: Dysfunctions of the prefrontal cortex have been previously reported in individuals with autism spectrum disorders (ASD). Previous studies reported that first-degree relatives of individuals with ASD show atypical brain activity during tasks associated with social function. However, developmental changes in prefrontal dysfunction in ASD and genetic influences on the phenomena remain unclear. In the present study, we investigated the change in hemoglobin concentration in the prefrontal cortex as measured with near-infrared spectroscopy, in children and adults with ASD during the letter fluency test. Moreover, to clarify the genetic influences on developmental changes in the prefrontal dysfunction in ASD, unaffected siblings of the ASD participants were also assessed. METHODOLOGY/PRINCIPAL FINDINGS: Study participants included 27 individuals with high-functioning ASD, age- and IQ-matched 24 healthy non-affected siblings, and 27 unrelated healthy controls aged 5 to 39 years. The relative concentration of hemoglobin ([Hb]) in the prefrontal cortex was measured during the letter fluency task. For children, neither the [oxy-Hb] change during the task nor task performances differed significantly among three groups. For adults, the [oxy-Hb] increases during the task were significantly smaller in the bilateral prefrontal cortex in ASD than those in control subjects, although task performances were similar. In the adult siblings the [oxy-Hb] change was intermediate between those in controls and ASDs. CONCLUSION/SIGNIFICANCE: Although indirectly due to a cross-sectional design, the results of this study indicate altered age-related change of prefrontal activity during executive processing in ASD. This is a first near-infrared spectroscopy study that implies alteration in the age-related changes of prefrontal activity in ASD and genetic influences on the phenomena

Autism Spectrum Traits in the Typical Population Predict Structure and Function in the Posterior Superior Temporal Sulcus

Autism spectrum disorders (ASDs) are typically characterized by impaired social interaction and communication, narrow interests, and repetitive behaviors. The heterogeneity in the severity of these characteristics across individuals with ASD has led some researchers to suggest that these disorders form a continuum which extends into the general, or “typical,” population, and there is growing evidence that the extent to which typical adults display autistic traits, as measured using the autism-spectrum quotient (AQ), predicts performance on behavioral tasks that are impaired in ASD. Here, we show that variation in autism spectrum traits is related to cortical structure and function within the typical population. Voxel-based morphometry showed that increased AQ scores were associated with decreased white matter volume in the posterior superior temporal sulcus (pSTS), a region important in processing socially relevant stimuli and associated with structural and functional impairments in ASD. In addition, AQ was correlated with the extent of cortical deactivation of an adjacent area of pSTS during a Stroop task relative to rest, reflecting variation in resting state function. The results provide evidence that autism spectrum characteristics are reflected in neural structure and function across the typical (non-ASD) population

Progressive development of augmentation during long-term treatment with levodopa in restless legs syndrome: results of a prospective multi-center study

The European Restless Legs Syndrome (RLS) Study Group performed the first multi-center, long-term study systematically evaluating RLS augmentation under levodopa treatment. This prospective, open-label 6-month study was conducted in six European countries and included 65 patients (85% treatment naive) with idiopathic RLS. Levodopa was flexibly up-titrated to a maximum dose of 600 mg/day. Presence of augmentation was diagnosed independently by two international experts using established criteria. In addition to the augmentation severity rating scale (ASRS), changes in RLS severity (International RLS severity rating scale (IRLS), clinical global impression (CGI)) were analyzed. Sixty patients provided evaluable data, 35 completed the trial and 25 dropped out. Augmentation occurred in 60% (36/60) of patients, causing 11.7% (7/60) to drop out. Median time to occurrence of augmentation was 71 days. The mean maximum dose of levodopa was 311 mg/day (SD: 105). Patients with augmentation compared to those without were significantly more likely to be on higher doses of levodopa (≥300 mg, 83 vs. 54%, P = 0.03) and to show less improvement of symptom severity (IRLS, P = 0.039). Augmentation was common with levodopa, but could be tolerated by most patients during this 6-month trial. Patients should be followed over longer periods to determine if dropout rates increase with time