Data Analysis Techniques for Fan Performance in Highly-Distorted Flows from Boundary Layer Ingesting Inlets

The design of a unique distortion-tolerant fan for a high-bypass ratio boundary-layer ingesting propulsion system has been completed and a rig constructed and tested in the NASA Glenn 8x6 wind tunnel. Processing the data from the experiment presented some interesting challenges because of the complexity of the experimental setup and the flow through the test rig. The experiment was run in three phases, each of which employed a unique complement of inlet throat and fan face instrumentation to avoid the blockage that would have resulted from simultaneously installing all of the rakes. The measurement from the individual test points were subsequently combined to compute the overall stage performance. A CFD model of the experiment was used to gain understanding of the flow field and to test some of the techniques proposed for interpolating and extrapolating the measurements into regions where measurements were not made. This capability became extremely useful when it was discovered that there was an unexpected total temperature distortion in the tunnel. The CFD model was modified by inserting a total temperature profile at the upstream boundary that mimicked the measured distortion where measurements were available and that CFD solution was used to investigate methods to infer the complete total temperature field at the fan face

Peroxisome Turnover and Diurnal Modulation of Antioxidant Activity in Retinal Pigment Epithelia Utilizes Microtubule-Associated Protein 1 Light Chain 3B (LC3B)

The retinal pigment epithelium (RPE) supports the outer retina through essential roles in the retinoid cycle, nutrient supply, ion exchange, and waste removal. Each day the RPE removes the oldest ∼10% of photoreceptor outer segment (OS) disk membranes through phagocytic uptake, which peaks following light onset. Impaired degradation of phagocytosed OS material by the RPE can lead to toxic accumulation of lipids, oxidative tissue damage, inflammation, and cell death. OSs are rich in very long chain fatty acids, which are preferentially catabolized in peroxisomes. Despite the importance of lipid degradation in RPE function, the regulation of peroxisome number and activity relative to diurnal OS ingestion is relatively unexplored. Using immunohistochemistry, immunoblot analysis, and catalase activity assays, we investigated peroxisome abundance and activity at 6 AM, 7 AM (light onset), 8 AM, and 3 PM, in wild-type (WT) mice and mice lacking microtubule-associated protein 1 light chain 3B (Lc3b), which have impaired phagosome degradation. We found that catalase activity, but not the amount of catalase protein, is 50% higher in the morning compared with 3 PM, in RPE of WT, but not Lc3b-/-, mice. Surprisingly, we found that peroxisome abundance was stable during the day in RPE of WT mice; however, numbers were elevated overall in Lc3b-/- mice, implicating LC3B in autophagic organelle turnover in RPE. Our data suggest that RPE peroxisome function is regulated in coordination with phagocytosis, possibly through direct enzyme regulation, and may serve to prepare RPE peroxisomes for daily surges in ingested lipid-rich OS. Copyright © 2019 the American Physiological Society

Color perception and attentional load in dynamic, time-constrained environments

The capacity to perceive color in the peripheral field has attracted research interest for more than a decade. There is evidence that sensitivity to red-green color variations is lower than for yellow-blue in peripheral vision. Whether, and to what extent, color vision affects the visual focus of attention, which is normally much smaller than the visual field, has not yet been examined. We used a sport-specific decision-making task to assess whether the color of the jersey worn by players appearing in the periphery influences decision making by affecting the attentional and perceptual capabilities. Pairs of players wearing chromatic (blue, yellow, red, and green) and achromatic (black, white) colored jerseys were briefly presented across a range of visual angles on a 6 m concave immersive screen. Participants were required to decide to whom to pass and recall relevant information. Findings indicate that color perception changes vary with increasing visual angle, but that the focus of attention is too small to be influenced by jersey color sensitivity. Decision-making performance decreases with increasing visual angle, but is not influenced by color. The implications for decision-making processes in sport and other professional domains are discussed

Risk Factors for Soil-Transmitted Helminth Infections during the First 3 Years of Life in the Tropics; Findings from a Birth Cohort.

Background: Soil-transmitted helminths (STH) infect more than 2 billion humans worldwide, causing significant morbidity in children. There are few data on the epidemiology and risk factors for infection in pre-school children. To investigate risk factors for infection in early childhood, we analysed data prospectively collected in the ECUAVIDA birth cohort in Ecuador. Methods and Findings: Children were recruited at birth and followed up to 3 years of age with periodic collection of stool samples that were examined microscopically for STH parasites. Data on social, demographic, and environmental risk factors were collected from the mother at time of enrolment. Associations between exposures and detection of STH infections were analysed by multivariable logistic regression. Data were analysed from 1,697 children for whom a stool sample was obtained at 3 years. 42.3% had at least one STH infection in the first 3 years of life and the most common infections were caused by A. lumbricoides (33.2% of children) and T. trichiura (21.2%). Hookworm infection was detected in 0.9% of children. Risk of STH infection was associated with factors indicative of poverty in our study population such as Afro-Ecuadorian ethnicity and low maternal educational level. Maternal STH infections during pregnancy were strong risk factors for any childhood STH infection, infections with either A. lumbricoides or T. trichiura, and early age of first STH infection. Children of mothers with moderate to high infections intensities with A. lumbricoides were most at risk. Conclusions: Our data show high rates of infection with STH parasites during the first 3 years of life in an Ecuadorian birth cohort, an observation that was strongly associated with maternal STH infections during pregnancy. The targeted treatment of women of childbearing age, in particular before pregnancy, with anthelmintic drugs could offer a novel approach to the prevention of STH infections in pre-school children

NeuroD2 regulates the development of hippocampal mossy fiber synapses

<p>Abstract</p> <p>Background</p> <p>The assembly of neural circuits requires the concerted action of both genetically determined and activity-dependent mechanisms. Calcium-regulated transcription may link these processes, but the influence of specific transcription factors on the differentiation of synapse-specific properties is poorly understood. Here we characterize the influence of NeuroD2, a calcium-dependent transcription factor, in regulating the structural and functional maturation of the hippocampal mossy fiber (MF) synapse.</p> <p>Results</p> <p>Using NeuroD2 null mice and <it>in vivo </it>lentivirus-mediated gene knockdown, we demonstrate a critical role for NeuroD2 in the formation of CA3 dendritic spines receiving MF inputs. We also use electrophysiological recordings from CA3 neurons while stimulating MF axons to show that NeuroD2 regulates the differentiation of functional properties at the MF synapse. Finally, we find that NeuroD2 regulates PSD95 expression in hippocampal neurons and that PSD95 loss of function <it>in vivo </it>reproduces CA3 neuron spine defects observed in NeuroD2 null mice.</p> <p>Conclusion</p> <p>These experiments identify NeuroD2 as a key transcription factor that regulates the structural and functional differentiation of MF synapses <it>in vivo</it>.</p

Determinants of Dwell Time in Visual Search: Similarity or Perceptual Difficulty?

The present study examined the factors that determine the dwell times in a visual search task, that is, the duration the gaze remains fixated on an object. It has been suggested that an item’s similarity to the search target should be an important determiner of dwell times, because dwell times are taken to reflect the time needed to reject the item as a distractor, and such discriminations are supposed to be harder the more similar an item is to the search target. In line with this similarity view, a previous study shows that, in search for a target ring of thin line-width, dwell times on thin linewidth Landolt C’s distractors were longer than dwell times on Landolt C’s with thick or medium linewidth. However, dwell times may have been longer on thin Landolt C’s because the thin line-width made it harder to detect whether the stimuli had a gap or not. Thus, it is an open question whether dwell times on thin line-width distractors were longer because they were similar to the target or because the perceptual decision was more difficult. The present study de-coupled similarity from perceptual difficulty, by measuring dwell times on thin, medium and thick line-width distractors when the target had thin, medium or thick line-width. The results showed that dwell times were longer on target-similar than target-dissimilar stimuli across all target conditions and regardless of the line-width. It is concluded that prior findings of longer dwell times on thin linewidth-distractors can clearly be attributed to target similarity. As will be discussed towards the end, the finding of similarity effects on dwell times has important implications for current theories of visual search and eye movement control

Electrophysiological network alterations in adults with copy number variants associated with high neurodevelopmental risk

Rare copy number variants associated with increased risk for neurodevelopmental and psychiatric disorders (referred to as ND-CNVs) are characterized by heterogeneous phenotypes thought to share a considerable degree of overlap. Altered neural integration has often been linked to psychopathology and is a candidate marker for potential convergent mechanisms through which ND-CNVs modify risk; however, the rarity of ND-CNVs means that few studies have assessed their neural correlates. Here, we used magnetoencephalography (MEG) to investigate resting-state oscillatory connectivity in a cohort of 42 adults with ND-CNVs, including deletions or duplications at 22q11.2, 15q11.2, 15q13.3, 16p11.2, 17q12, 1q21.1, 3q29, and 2p16.3, and 42 controls. We observed decreased connectivity between occipital, temporal and parietal areas in participants with ND-CNVs. This pattern was common across genotypes and not exclusively characteristic of 22q11.2 deletions, which were present in a third of our cohort. Furthermore, a data-driven graph theory framework enabled us to successfully distinguish participants with ND-CNVs from unaffected controls using differences in node centrality and network segregation. Together, our results point to alterations in electrophysiological connectivity as a putative common mechanism through which genetic factors confer increased risk for neurodevelopmental and psychiatric disorders

Correction: The psychiatric phenotypes of 1q21 distal deletion and duplication.

Copy number variants are amongst the most highly penetrant risk factors for psychopathology and neurodevelopmental deficits, but little information about the detailed clinical phenotype associated with particular variants is available. We present the largest study of the microdeletion and -duplication at the distal 1q21 locus, which has been associated with schizophrenia and intellectual disability, in order to investigate the range of psychiatric phenotypes. Clinical and cognitive data from 68 deletion and 55 duplication carriers were analysed with logistic regression analysis to compare frequencies of mental disorders between carrier groups and controls, and linear mixed models to compare quantitative phenotypes. Both children and adults with copy number variants at 1q21 had high frequencies of psychopathology. In the children, neurodevelopmental disorders were most prominent (56% for deletion, 68% for duplication carriers). Adults had increased prevalence of mood (35% for deletion [OR = 6.6 (95% CI: 1.4–40.1)], 55% for duplication carriers [8.3 (1.4–55.5)]) and anxiety disorders (24% [1.8 (0.4–8.4)] and 55% [10.0 (1.9–71.2)]). The adult group, which included mainly genetically affected parents of probands, had an IQ in the normal range. These results confirm high prevalence of neurodevelopmental disorders associated with CNVs at 1q21 but also reveal high prevalence of mood and anxiety disorders in a high-functioning adult group with these CNVs. Because carriers of neurodevelopmental CNVs who show relevant psychopathology but no major cognitive impairment are not currently routinely receiving clinical genetic services widening of genetic testing in psychiatry may be considered

Endothelial Wnt/β-catenin signaling inhibits glioma angiogenesis and normalizes tumor blood vessels by inducing PDGF-B expression

Endothelial Wnt/β-catenin signaling is necessary for angiogenesis of the central nervous system and blood–brain barrier (BBB) differentiation, but its relevance for glioma vascularization is unknown. In this study, we show that doxycycline-dependent Wnt1 expression in subcutaneous and intracranial mouse glioma models induced endothelial Wnt/β-catenin signaling and led to diminished tumor growth, reduced vascular density, and normalized vessels with increased mural cell attachment. These findings were corroborated in GL261 glioma cells intracranially transplanted in mice expressing dominant-active β-catenin specifically in the endothelium. Enforced endothelial β-catenin signaling restored BBB characteristics, whereas inhibition by Dkk1 (Dickkopf-1) had opposing effects. By overactivating the Wnt pathway, we induced the Wnt/β-catenin–Dll4/Notch signaling cascade in tumor endothelia, blocking an angiogenic and favoring a quiescent vascular phenotype, indicated by induction of stalk cell genes. We show that β-catenin transcriptional activity directly regulated endothelial expression of platelet-derived growth factor B (PDGF-B), leading to mural cell recruitment thereby contributing to vascular quiescence and barrier function. We propose that reinforced Wnt/β-catenin signaling leads to inhibition of angiogenesis with normalized and less permeable vessels, which might prove to be a valuable therapeutic target for antiangiogenic and edema glioma therapy