Site-Specific Effects of PECAM-1 on Atherosclerosis in LDL Receptor-Deficient Mice

Objective—Atherosclerosis is a vascular disease that involves lesion formation at sites of disturbed flow under the influence of genetic and environmental factors. Endothelial expression of adhesion molecules that enable infiltration of immune cells is important for lesion development. Platelet/endothelial cell adhesion molecule-1 (PECAM-1; CD31) is an adhesion and signaling receptor expressed by many cells involved in atherosclerotic lesion development. PECAM-1 transduces signals required for proinflammatory adhesion molecule expression at atherosusceptible sites; thus, it is predicted to be proatherosclerotic. PECAM-1 also inhibits inflammatory responses, on which basis it is predicted to be atheroprotective. Methods and Results—We evaluated herein the effect of PECAM-1 deficiency on development of atherosclerosis in LDL receptor– deficient mice. We found that PECAM-1 has both proatherosclerotic and atheroprotective effects, but that the former dominate in the inner curvature of the aortic arch whereas the latter dominate in the aortic sinus, branching arteries, and descending aorta. Endothelial cell expression of PECAM-1 was sufficient for its atheroprotective effects in the aortic sinus but not in the descending aorta, where the atheroprotective effects of PECAM-1 also required its expression on bone marrow–derived cells. Conclusion—We conclude that PECAM-1 influences initiation and progression of atherosclerosis both positively and negatively, and that it does so in a site-specific manner. (Arterioscler Thromb Vasc Biol. 2008;28:1996-2002

Serious Gordon Using Serious Games To Teach Food Safety in the Kitchen

This paper will describe the development of Serious Gordon, an interactive digital game developed to tech the basics of kitchen food safety to workers in industries dealing with food. The motivations driving the development of the game will be described as will the development process itself. An initial evaluation of the game, from both a technical and pedagogical point of view, will be presented as will conclusions on the viability of using a commercial game engine for the purpose of developing educational games

Tests of the extension and deadbolt models of integrin activation

Despite extensive evidence that integrin conformational changes between bent and extended conformations regulate affinity for ligands, an alternative hypothesis has been proposed in which a deadbolt can regulate affinity for ligand in the absence of extension. Here, we tested both the deadbolt and the extension models. According to the deadbolt model, a hairpin loop in the β3 tail domain could act as a deadbolt to restrain the displacement of the β3 I domain β6-α7 loop and maintain integrin in the low affinity state. We found that mutating or deleting the β3 tail domain loop has no effect on ligand binding by either αIIbβ3 or αVβ3 integrins. In contrast, we found that mutations that lock integrins in the bent conformation with disulfide bonds resist inside-out activation induced by cytoplasmic domain mutation. Furthermore, we demonstrated that extension is required for accessibility to fibronectin but not smaller fragments. The data demonstrate that integrin extension is required for ligand binding during integrin inside-out signaling and that the deadbolt does not regulate integrin activation. © 2007 by The American Society for Biochemistry and Molecular Biology, Inc

Serious Gordon: Using Serious Games to Teach Food Safety in the Kitchen.

This paper will describe the development of Serious Gordon, an interactive digital game developed to tech the basics of kitchen food safety to workers in industries dealing with food. The motivations driving the development of the game will be described as will the development process itself. An initial evaluation of the game, from both a technical and pedagogical point of view, will be presented as will conclusions on the viability of using a commercial game engine for the purpose of developing educational games

The Absolute Age of M92

The \textit{absolute age} of a simple stellar population is of fundamental interest for a wide range of applications but is difficult to measure in practice, as it requires an understanding of the uncertainties in a variety of stellar evolution processes as well as the uncertainty in the distance, reddening and composition. As a result, most studies focus only on the \textit{relative age} by assuming that stellar evolution calculations are accurate and using age determinations techniques that are relatively independent of distance and reddening. Here, we construct $20,000$ sets of theoretical isochrones through Monte Carlo simulation using the Dartmouth Stellar Evolution Program to measure the absolute age of the globular cluster M92. For each model, we vary a range of input physics used in the stellar evolution models, including opacities, nuclear reaction rates, diffusion coefficients, atmospheric boundary conditions, helium abundance, and treatment of convection. We also explore variations in the distance and reddening as well as its overall metallicity and $\alpha$ enhancement. We generate simulated Hess diagrams around the main-sequence turn-off region from each set of isochrones and use a Voronoi binning method to fit the diagrams to HST ACS data. We find the age of M92 to be $13.80 \pm 0.75$ Gyr. The $5.4\%$ error in the absolute age is dominated by the uncertainty in the distance to M92 ($\sim 80\%$ of the error budget); of the remaining parameters, only the total metallicity, $\alpha$ element abundance, and treatment of helium diffusion contribute significantly to the total error.Comment: 15 Pages, 14 Figures, 2 Tables; Accepted for Publication A

Neuro-Specific and Immuno-Inflammatory Biomarkers in Umbilical Cord Blood in Neonatal Hypoxic-Ischemic Encephalopathy

OBJECTIVES: The aim of the study was to evaluate neuronal injury and immuno-inflammatory biomarkers in umbilical cord blood (UCB) at birth, in cases with perinatal asphyxia with or without hypoxic-ischemic encephalopathy (HIE), compared with healthy controls and to assess their ability to predict HIE. STUDY DESIGN: In this case-control study, term infants with perinatal asphyxia were recruited at birth. UCB was stored at delivery for batch analysis. HIE was diagnosed by clinical Sarnat staging at 24 h. Glial fibrillary acidic protein (GFAP), the neuronal biomarkers tau and neurofilament light protein (NFL), and a panel of cytokines were analyzed in a total of 150 term neonates: 50 with HIE, 50 with asphyxia without HIE (PA), and 50 controls. GFAP, tau, and NFL concentrations were measured using ultrasensitive single-molecule array (Simoa) assays, and a cytokine screening panel was applied to analyze the immuno-inflammatory and infectious markers. RESULTS: GFAP, tau, NFL, and several cytokines were significantly higher in newborns with moderate and severe HIE compared to a control group and provided moderate prediction of HIE II/III (AUC: 0.681-0.827). Furthermore, the levels of GFAP, tau, interleukin-6 (IL-6), and interleukin-8 (IL-8) were higher in HIE II/III cases compared with cases with PA/HIE I. IL-6 was also higher in HIE II/III compared with HIE I cases. CONCLUSIONS: Biomarkers of brain injury and inflammation were increased in umbilical blood in cases with asphyxia. Several biomarkers were higher in HIE II/III versus those with no HIE or HIE I, suggesting that they could assist in the prediction of HIE II/III

Impact of therapeutic hypothermia on infantile spasms: an observational cohort study

Aim: To establish the incidence of infantile spasms in children in the southern region of the Republic of Ireland and to compare the incidence of infantile spasms before and after the introduction of therapeutic hypothermia in infants with hypoxic‐ischemic encephalopathy (HIE). Method: Children born between 2003 and 2015 and diagnosed with infantile spasms (epileptic spasms with or without hypsarrhythmia) in the first 2 years of life were identified through audits of electroencephalography reports and paediatric neurology patient lists. Data on live births were obtained from the regional hospital statistics databases. Medical charts of infantile spasm cases were reviewed for demographic information, diagnostic workup results, treatment response, disease course, and developmental outcome. Results: Forty‐two infants with infantile spasms were identified. The cumulative incidence of infantile spasms up to the age of 2 years was 4.01 per 10 000 live births. Difference due to sex was minimal (22 males, 20 females) and most infants were delivered at or near term with gestational ages ranging between 30.0 and 41.8 weeks (median [interquartile range] 39.6wks [38.1–40.0wks]). The aetiology for infantile spasms was identified in almost two‐thirds of cases, with HIE being the single most common cause (n=7). Other causes included chromosomal and monogenetic abnormalities (n=8). Infantile spasms occurred in moderate and severe grades of HIE, with a significantly higher incidence in those with severe HIE (p=0.029). Infants with severe HIE who did not receive therapeutic hypothermia were six times more likely to develop infantile spasms compared to those who did, but the difference was not statistically significant (4 out of 16 vs 1 out of 24, p=0.138). Interpretation: This study provides detailed information about infantile spasms before and after the introduction of therapeutic hypothermia. HIE severity is a risk factor for the development of infantile spasms. The introduction of therapeutic hypothermia may have had an impact, but the effect was hard to ascertain in this cohort due to the small number of infants

UVUDF: UV Luminosity Functions at the Cosmic High Noon

We present the rest-1500 Å UV luminosity functions (LF) for star-forming galaxies during the cosmic high noon—the peak of cosmic star formation rate at 1.5 < z < 3. We use deep NUV imaging data obtained as part of the Hubble Ultra-Violet Ultra Deep Field (UVUDF) program, along with existing deep optical and NIR coverage on the HUDF. We select F225W, F275W, and F336W dropout samples using the Lyman break technique, along with samples in the corresponding redshift ranges selected using photometric redshifts, and measure the rest-frame UV LF at z ~ 1.7, 2.2, 3.0, respectively, using the modified maximum likelihood estimator. We perform simulations to quantify the survey and sample incompleteness for the UVUDF samples to correct the effective volume calculations for the LF. We select galaxies down to M_(UV) = -15.9, -16.3, -16.8 and fit a faint-end slope of α = -1.20^(+0.10)_(-0.13), -1.32^(+0.10)_(-0.14), -1.39^(+0.08)_(-0.12) at 1.4 < z < 1.9, 1.8 < z < 2.6, and 2.4 < z < 3.6, respectively. We compare the star formation properties of z ~ 2 galaxies from these UV observations with results from Hα and UV+IR observations. We find a lack of high-SFR sources in the UV LF compared to the Hα and UV+IR, likely due to dusty SFGs not being properly accounted for by the generic IRX-β relation used to correct for dust. We compute a volume-averaged UV-to-Hα ratio by abundance matching the rest-frame UV LF and Hα LF. We find an increasing UV-to-Hα ratio toward low-mass galaxies (M_∗ ≾ 5 x 10^9 M_⊙). We conclude that this could be due to a larger contribution from starbursting galaxies compared to the high-mass end

Multichannel EEG abnormalities during the first 6 hours in infants with mild hypoxic-ischaemic encephalopathy

Background: Infants with mild HIE are at risk of significant disability at follow-up. In the pre-therapeutic hypothermia (TH) era, electroencephalography (EEG) within 6 hours of birth was most predictive of outcome. This study aims to identify and describe features of early EEG and heart rate variability (HRV) (<6 hours of age) in infants with mild HIE compared to healthy term infants. Methods: Infants >36 weeks with mild HIE, not undergoing TH, with EEG before 6 hours of age were identified from 4 prospective cohort studies conducted in the Cork University Maternity Services, Ireland (2003-2019). Control infants were taken from a contemporaneous study examining brain activity in healthy term infants. EEGs were qualitatively analysed by two neonatal neurophysiologists and quantitatively assessed using multiple features of amplitude, spectral shape and inter-hemispheric connectivity. Quantitative features of HRV were assessed in both the groups. Results: Fifty-eight infants with mild HIE and sixteen healthy term infants were included. Seventy-two percent of infants with mild HIE had at least one abnormal EEG feature on qualitative analysis and quantitative EEG analysis revealed significant differences in spectral features between the two groups. HRV analysis did not differentiate between the groups. Conclusions: Qualitative and quantitative analysis of the EEG before 6 hours of age identified abnormal EEG features in mild HIE, which could aid in the objective identification of cases for future TH trials in mild HIE. Impact: Infants with mild HIE currently do not meet selection criteria for TH yet may be at risk of significant disability at follow-up. In the pre-TH era, EEG within 6 hours of birth was most predictive of outcome; however, TH has delayed this predictive value. 72% of infants with mild HIE had at least one abnormal EEG feature in the first 6 hours on qualitative assessment. Quantitative EEG analysis revealed significant differences in spectral features between infants with mild HIE and healthy term infants. Quantitative EEG features may aid in the objective identification of cases for future TH trials in mild HIE