Neutrino Detection With CLEAN

This article describes CLEAN, an approach to the detection of low-energy solar neutrinos and neutrinos released from supernovae. The CLEAN concept is based on the detection of elastic scattering events (neutrino-electron scattering and neutrino-nuclear scattering) in liquified noble gases such as liquid helium, liquid neon, and liquid xenon, all of which scintillate brightly in the ultraviolet. Key to the CLEAN technique is the use of a thin film of wavelength-shifting fluor to convert the ultraviolet scintillation light to the visible. This allows the same liquid to be used as both a passive shielding medium and an active self-shielding detector, allowing lower intrinsic radioactive backgrounds at low energies. Liquid neon is a particularly promising medium for CLEAN. Because liquid neon has a high scintillation yield, has no long-lived radioactive isotopes, and can be easily purified by use of cold traps, it is an ideal medium for the detection of rare nuclear events. In addition, neon is inexpensive, dense, and transparent to its own scintillation light, making it practical for use in a large self-shielding apparatus. Monte Carlo simulations of gamma ray backgrounds have been performed assuming liquid neon as both shielding and detection medium. Gamma ray events occur with high probability in the outer parts of the detector. In contrast, neutrino scattering events occur uniformly throughout the detector. We discriminate background gamma ray events from events of interest based on a spatial Maximum Likelihood method estimate of event location. Background estimates for CLEAN are presented, as well as an evaluation of the sensitivity of the detector for $p-p$ neutrinos. Given these simulations, the physics potential of the CLEAN approach is evaluated.Comment: 21 pages, 3 figures. Submitted to Astroparticle Physic

Multiscale Modeling and Simulation of Organic Solar Cells

In this article, we continue our mathematical study of organic solar cells (OSCs) and propose a two-scale (micro- and macro-scale) model of heterojunction OSCs with interface geometries characterized by an arbitrarily complex morphology. The microscale model consists of a system of partial and ordinary differential equations in an heterogeneous domain, that provides a full description of excitation/transport phenomena occurring in the bulk regions and dissociation/recombination processes occurring in a thin material slab across the interface. The macroscale model is obtained by a micro-to-macro scale transition that consists of averaging the mass balance equations in the normal direction across the interface thickness, giving rise to nonlinear transmission conditions that are parametrized by the interfacial width. These conditions account in a lumped manner for the volumetric dissociation/recombination phenomena occurring in the thin slab and depend locally on the electric field magnitude and orientation. Using the macroscale model in two spatial dimensions, device structures with complex interface morphologies, for which existing data are available, are numerically investigated showing that, if the electric field orientation relative to the interface is taken into due account, the device performance is determined not only by the total interface length but also by its shape

Body Mass Index, abdominal adiposity, obesity, and cardiovascular reactions to psychological stress in a large community sample

OBJECTIVE: To examine the association between adiposity and the magnitude of cardiovascular reactions to acute psychological stress cross-sectionally and prospectively in a large community sample.\ud \ud METHODS: Blood pressure and heart rate (HR) were measured at rest and in response to a brief time-pressured mental arithmetic stress in 1647 adults. At the same session and 5 years later, height, weight, waist and hip circumference were measured and body mass index (BMI) and waist-hip ratio were computed. Obesity was defined as a body mass index of > or = 30 kg/m(2).\ud \ud RESULTS: Contrary to expectations, the most robust and consistent results to emerge from cross-sectional analyses were negative associations between all three measures of adiposity and HR reactivity; those with greater BMI and waist-hip ratios and those categorized as obese displayed smaller HR reactions to stress. In prospective analyses, high HR reactivity was associated with a reduced likelihood of becoming obese in the subsequent 5 years.\ud \ud CONCLUSIONS: Our analyses suggest that it is low, not high, HR reactivity that is related to adiposity. Low HR reactivity, probably by reflecting generally blunted sympathetic nervous system reactions to challenge, may be a risk marker for developing obesity.\ud \u

Mucin production and hydration responses to mucopurulent materials in normal versus cystic fibrosis airway epithelia

Rationale: Cystic fibrosis (CF) airways disease produces a mucoobstructive lung phenotype characterized by airways mucus plugging, epithelial mucous cell metaplasia/hyperplasia, chronic infection, and inflammation. Simultaneous biochemical and functional in vivo studies of mucin synthesis and secretion from CF airways are not available. In vitro translational models may quantitate differential CF versus normal mucin and fluid secretory responses to infectious/inflammatory stimuli. Objectives: We tested the hypothesis that CF airways exhibit defective epithelial fluid, but not mucin, secretory responses to bacterial/inflammatory host products. Methods: Well-differentiated primary human bronchial epithelial cultures were exposed to supernatant from mucopurulent material (SMM) from human CF airways as a test of bacterial/inflammatory host product stimulus. Human bronchial epithelia (HBE) with normal CF transmembrane conductance regulator function were compared with DF508/DF508 CF HBE. Measurements and Main Results: Acute (up to 60 min) SMM exposure promoted mucin secretion, but mucins were degraded by the proteolytic enzymes present in SMM. Chronic SMM exposure induced upregulation of mucin synthesis and storage and generated absolute increases in basal and stimulated mucin release in normal and CF cultures. These responses were similar in normal and CF cultures. In contrast, SMM produced a coordinated CF transmembrane conductance regulator-mediated Cl secretory response in normal HBE, but not in CF HBE. The absence of the fluid secretory response in CF produced quantitatively more dehydrated mucus. Conclusions: Our study reveals the interplay between regulation of mucin and fluid secretion rates in inflamed versus noninflamed conditions and why a hyperconcentrated mucus is produced in CF airways

Single event and TREE latchup mitigation for a star tracker sensor: An innovative approach to system level latchup mitigation

Electronic packages designed for spacecraft should be fault-tolerant and operate without ground control intervention through extremes in the space radiation environment. If designed for military use, the electronics must survive and function in a nuclear radiation environment. This paper presents an innovative ``blink`` approach rather than the typical ``operate through`` approach to achieve system level latchup mitigation on a prototype star tracker camera. Included are circuit designs, flash x-ray test data, and heavy ion data demonstrating latchup mitigation protecting micro-electronics from current latchup and burnout due to Single Event Latchup (SEL) and Transient Radiation Effects on Electronics (TREE)

Defective postsecretory maturation of MUC5B mucin in cystic fibrosis airways

In cystic fibrosis (CF), airway mucus becomes thick and viscous, and its clearance from the airways is impaired. The gel-forming mucins undergo an ordered "unpacking/maturation" process after granular release that requires an optimum postsecretory environment, including hydration and pH. We hypothesized that this unpacking process is compromised in the CF lung due to abnormal transepithelial fluid transport that reduces airway surface hydration and alters ionic composition. Using human tracheobronchial epithelial cells derived from non-CF and CF donors and mucus samples from human subjects and domestic pigs, we investigated the process of postsecretory mucin unfolding/maturation, how these processes are defective in CF airways, and the probable mechanism underlying defective unfolding. First, we found that mucins released into a normal lung environment transform from a compact granular form to a linear form. Second, we demonstrated that this maturation process is defective in the CF airway environment. Finally, we demonstrated that independent of HCO3- and pH levels, airway surface dehydration was the major determinant of this abnormal unfolding process. This defective unfolding/maturation process after granular release suggests that the CF extracellular environment is ion/water depleted and likely contributes to abnormal mucus properties in CF airways prior to infection and inflammation

Small molecule anionophores promote transmembrane anion permeation matching CFTR activity

Anion selective ionophores, anionophores, are small molecules capable of facilitating the transmembrane transport of anions. Inspired in the structure of natural product prodigiosin, four novel anionophores 1a-d, including a 1,2,3-triazole group, were prepared. These compounds proved highly efficient anion exchangers in model phospholipid liposomes. The changes in the hydrogen bond cleft modified the anion transport selectivity exhibited by these compounds compared to prodigiosin and suppressed the characteristic high toxicity of the natural product. Their activity as anionophores in living cells was studied and chloride efflux and iodine influx from living cells mediated by these derivatives was demonstrated. These compounds were shown to permeabilize cellular membranes to halides with efficiencies close to the natural anion channel CFTR at doses that do not compromise cellular viability. Remarkably, optimal transport efficiency was measured in the presence of pH gradients mimicking those found in the airway epithelia of Cystic Fibrosis patients. These results support the viability of developing small molecule anionophores as anion channel protein surrogates with potential applications in the treatment of conditions such as Cystic Fibrosis derived from the malfunction of natural anion transport mechanisms.European Union’s Horizon 2020 research and innovation programme under grant agreement No. 667079, La Marató de TV3 Foundation (20132730), Consejería de Educación de la Junta de Castilla y León (Projects BU340U13 and BU092U16

Mucus Hydration in Subjects with Stable Chronic Bronchitis: A Comparison of Spontaneous and Induced Sputum

Mucus hydration is important in mucus clearance and lung health. This study sought to test the relative utility of spontaneous sputum (SS) versus the reasonably noninvasive induced sputum (IS) samples for measurement of mucus hydration. SS and IS samples were collected over a 2-day study interval. Sputum was induced with escalating inhaled nebulized 3–5% hypertonic saline. Viscous portions of the samples (“plugs”) were utilized for percent solids and total mucin analyses. Cytokines, nucleotides/nucleosides and cell differentials were measured in plugs diluted into 0.1% Sputolysin. Overall, 61.5% of chronic bronchitis (CB) subjects produced a SS sample and 95.2% an IS sample. Total expectorate sample weights were less for the SS (0.94 ± 0.98 g) than the IS (2.67 ± 2.33 g) samples. Percent solids for the SS samples (3.56% ± 1.95; n = 162) were significantly greater than the IS samples (3.08% ± 1.81; n = 121), p = 0.133. Total mucin concentrations also exhibited a dilution of the IS samples: SS = 4.15 ± 3.23 mg/ml (n = 62) versus IS= 3.34 ± 2.55 mg/ml (n = 71) (p = 0.371). Total mucins (combined SS and IS) but not percent solids, were inversely associated with FEV 1 percent predicted (p = 0.052) and FEV 1 ,/FVC % (p = 0.035). There were no significant differences between sample types in cytokine or differential cell counts. The probability of sample collections was less for SS than IS samples. Measurements of hydration revealed modest dilution of the IS samples compared to SS. Thus for measurements of mucus hydration, both SS and IS samples appear to be largely interchangeable

Chronic e-cigarette exposure alters the human bronchial epithelial proteome

Rationale: E-cigarettes vaporize propylene glycol/vegetable glycerin (PG/VG), nicotine, and flavorings. However, the long-term health effects of exposing lungs to vaped e-liquids are unknown. Objectives: To determine the effects of chronic vaping on pulmonary epithelia. Methods: We performed research bronchoscopies on healthy nonsmokers, cigarette smokers, and e-cigarette users (vapers) and obtained bronchial brush biopsies and lavage samples from these subjects for proteomic investigation. We further employed in vitro and murine exposure models to support our human findings. Measurements and Main Results: Visual inspection by bronchoscopy revealed that vaper airways appeared friable and erythematous. Epithelial cells from biopsy samples revealed approximately 300 proteins that were differentially expressed in smoker and vaper airways, with only 78 proteins being commonly altered in both groups and 113 uniquely altered in vapers. For example, CYP1B1 (cytochrome P450 family 1 subfamily B member 1), MUC5AC (mucin 5 AC), and MUC4 levels were increased in vapers. Aerosolized PG/VG alone significantly increasedMUC5AC protein in human airway epithelial cultures and in murine nasal epithelia in vivo.We also found that e-liquids rapidly entered cells and that PG/VG reduced membrane fluidity and impaired protein diffusion. Conclusions: We conclude that chronic vaping exerts marked biological effects on the lung and that these effects may in part be mediated by the PG/VG base. These changes are likely not harmless and may have clinical implications for the development of chronic lung disease. Further studies will be required to determine the full extent of vaping on the lung

Estrogen aggravates inflammation in Pseudomonas aeruginosa pneumonia in cystic fibrosis mice

<p>Abstract</p> <p>Background</p> <p>Among patients with cystic fibrosis (CF), females have worse pulmonary function and survival than males, primarily due to chronic lung inflammation and infection with <it>Pseudomonas aeruginosa </it>(<it>P. aeruginosa</it>). A role for gender hormones in the causation of the CF "gender gap" has been proposed. The female gender hormone 17β-estradiol (E2) plays a complex immunomodulatory role in humans and in animal models of disease, suppressing inflammation in some situations while enhancing it in others. Helper T-cells were long thought to belong exclusively to either T helper type 1 (Th1) or type 2 (Th2) lineages. However, a distinct lineage named Th17 is now recognized that is induced by interleukin (IL)-23 to produce IL-17 and other pro-inflammatory Th17 effector molecules. Recent evidence suggests a central role for the IL-23/IL-17 pathway in the pathogenesis of CF lung inflammation. We used a mouse model to test the hypothesis that E2 aggravates the CF lung inflammation that occurs in response to airway infection with <it>P. aeruginosa </it>by a Th17-mediated mechanism.</p> <p>Results</p> <p>Exogenous E2 caused adult male CF mice with pneumonia due to a mucoid CF clinical isolate, the <it>P. aeruginosa </it>strain PA508 (PA508), to develop more severe manifestations of inflammation in both lung tissue and in bronchial alveolar lavage (BAL) fluid, with increased total white blood cell counts and differential and absolute cell counts of polymorphonuclear leukocytes (neutrophils). Inflammatory infiltrates and mucin production were increased on histology. Increased lung tissue mRNA levels for IL-23 and IL-17 were accompanied by elevated protein levels of Th17-associated pro-inflammatory mediators in BAL fluid. The burden of PA508 bacteria was increased in lung tissue homogenate and in BAL fluid, and there was a virtual elimination in lung tissue of mRNA for lactoferrin, an antimicrobial peptide active against <it>P. aeruginosa </it>in vitro.</p> <p>Conclusions</p> <p>Our data show that E2 increases the severity of PA508 pneumonia in adult CF male mice, and suggest two potential mechanisms: enhancement of Th17-regulated inflammation and suppression of innate antibacterial defences. Although this animal model does not recapitulate all aspects of human CF lung disease, our present findings argue for further investigation of the effects of E2 on inflammation and infection with <it>P. aeruginosa </it>in the CF lung.</p