Feasibility of nanofluid-based optical filters

In this article we report recent modeling and design work indicating that mixtures of nanoparticles in liquids can be used as an alternative to conventional optical filters. The major motivation for creating liquid optical filters is that they can be pumped in and out of a system to meet transient needs in an application. To demonstrate the versatility of this new class of filters, we present the design of nanofluids for use as long-pass, short-pass, and bandpass optical filters using a simple Monte Carlo optimization procedure. With relatively simple mixtures, we achieve filters with <15% mean-squared deviation in transmittance from conventional filters. We also discuss the current commercial feasibility of nanofluid-based optical filters by including an estimation of today's off-the-shelf cost of the materials. While the limited availability of quality commercial nanoparticles makes it hard to compete with conventional filters, new synthesis methods and economies of scale could enable nanofluid-based optical filters in the near future. As such, this study lays the groundwork for creating a new class of selective optical filters for a wide range of applications, namely communications, electronics, optical sensors, lighting, photography, medicine, and many more

Rhomboid family member 2 regulates cytoskeletal stress-associated Keratin 16.

Keratin 16 (K16) is a cytoskeletal scaffolding protein highly expressed at pressure-bearing sites of the mammalian footpad. It can be induced in hyperproliferative states such as wound healing, inflammation and cancer. Here we show that the inactive rhomboid protease RHBDF2 (iRHOM2) regulates thickening of the footpad epidermis through its interaction with K16. K16 expression is absent in the thinned footpads of irhom2-/- mice compared with irhom2+/+mice, due to reduced keratinocyte proliferation. Gain-of-function mutations in iRHOM2 underlie Tylosis with oesophageal cancer (TOC), characterized by palmoplantar thickening, upregulate K16 with robust downregulation of its type II keratin binding partner, K6. By orchestrating the remodelling and turnover of K16, and uncoupling it from K6, iRHOM2 regulates the epithelial response to physical stress. These findings contribute to our understanding of the molecular mechanisms underlying hyperproliferation of the palmoplantar epidermis in both physiological and disease states, and how this 'stress' keratin is regulated

Generating synthetic data from administrative health records for drug safety and effectiveness studies

Introduction Administrative health records (AHRs) are used to conduct population-based post-market drug safety and comparative effectiveness studies to inform healthcare decision making. However, the cost of data extraction, and the challenges associated with privacy and securing approvals can make it challenging for researchers to conduct methodological research in a timely manner using real data. Generating synthetic AHRs that reasonably represent the real-world data are beneficial for developing analytic methods and training analysts to rapidly implement study protocols. We generated synthetic AHRs using two methods and compared these synthetic AHRs to real-world AHRs. We described the challenges associated with using synthetic AHRs for real-world study. Methods The real-world AHRs comprised prescription drug records for individuals with healthcare insurance coverage in the Population Research Data Repository (PRDR) from Manitoba, Canada for the 10-year period from 2008 to 2017. Synthetic data were generated using the Observational Medical Dataset Simulator II (OSIM2) and a modification (ModOSIM). Synthetic and real-world data were described using frequencies and percentages. Agreement of prescription drug use measures in PRDR, OSIM2 and ModOSIM was estimated with the concordance coefficient. Results The PRDR cohort included 169,586,633 drug records and 1,395 drug types for 1,604,734 individuals. Synthetic data for 1,000,000 individuals were generated using OSIM2 and ModOSIM. Sex and age group distributions were similar in the real-world and synthetic AHRs. However, there were significant differences in the number of drug records and number of unique drugs per person for OSIM2 and ModOSIM when compared with PRDR. For the average number of days of drug use, concordance with the PRDR was 16% (95% confidence interval [CI]: 12%-19%) for OSIM2 and 88% (95% CI: 87%-90%) for ModOSIM. Conclusions ModOSIM data were more similar to PRDR than OSIM2 data on many measures. Synthetic AHRs consistent with those found in real-world settings can be generated using ModOSIM. Synthetic data will benefit rapid implementation of methodological studies and data analyst training

Muramyl Dipeptide Induces NOD2-Dependent Ly6Chigh Monocyte Recruitment to the Lungs and Protects Against Influenza Virus Infection

Bacterial peptidoglycan-derived muramyl dipeptide (MDP) and derivatives have long-recognized antiviral properties but their mechanism of action remains unclear. In recent years, the pattern-recognition receptor NOD2 has been shown to mediate innate responses to MDP. Here, we show that MDP treatment of mice infected with Influenza A virus (IAV) significantly reduces mortality, viral load and pulmonary inflammation in a NOD2-dependent manner. Importantly, the induction of type I interferon (IFN) and CCL2 chemokine was markedly increased in the lungs following MDP treatment and correlated with a NOD2-dependent enhancement in circulating monocytes. Mechanistically, the protective effect of MDP could be explained by the NOD2-dependent transient increase in recruitment of Ly6Chigh “inflammatory” monocytes and, to a lesser extent, neutrophils to the lungs. Indeed, impairment in both Ly6Chigh monocyte recruitment and survival observed in infected Nod2-/- mice treated with MDP was recapitulated in mice deficient for the chemokine receptor CCR2 required for CCL2-mediated Ly6Chigh monocyte migration from the bone marrow into the lungs. MDP-induced pulmonary monocyte recruitment occurred normally in IAV-infected and MDP-treated Ips-1-/- mice. However, IPS-1 was required for improved survival upon MDP treatment. Finally, mycobacterial N-glycolyl MDP was more potent than N-acetyl MDP expressed by most bacteria at reducing viral burden while both forms of MDP restored pulmonary function following IAV challenge. Overall, our work sheds light on the antiviral mechanism of a clinically relevant bacterial-derived compound and identifies the NOD2 pathway as a potential therapeutic target against IAV

Characterizing the Near-infrared Spectra of Flares from TRAPPIST-1 During JWST Transit Spectroscopy Observations

We present the first analysis of JWST near-infrared spectroscopy of stellar flares from TRAPPIST-1 during transits of rocky exoplanets. Four flares were observed from 0.6--2.8 $\mu$m with NIRISS and 0.6--3.5 $\mu$m with NIRSpec during transits of TRAPPIST-1b, f, and g. We discover P$\alpha$ and Br$\beta$ line emission and characterize flare continuum at wavelengths from 1--3.5 $\mu$m for the first time. Observed lines include H$\alpha$, P$\alpha$-P$\epsilon$, Br$\beta$, He I $\lambda$0.7062$\mu$m, two Ca II infrared triplet (IRT) lines, and the He I IRT. We observe a reversed Paschen decrement from P$\alpha$-P$\gamma$ alongside changes in the light curve shapes of these lines. The continuum of all four flares is well-described by blackbody emission with an effective temperature below 5300 K, lower than temperatures typically observed at optical wavelengths. The 0.6--1 $\mu$m spectra were convolved with the TESS response, enabling us to measure the flare rate of TRAPPIST-1 in the TESS bandpass. We find flares of 10$^{30}$ erg large enough to impact transit spectra occur at a rate of 3.6$\substack{+2.1 \\ -1.3}$ flare d$^{-1}$, $\sim$10$\times$ higher than previous predictions from K2. We measure the amount of flare contamination at 2 $\mu$m for the TRAPPIST-1b and f transits to be 500$\pm$450 and 2100$\pm$400 ppm, respectively. We find up to 80% of flare contamination can be removed, with mitigation most effective from 1.0--2.4 $\mu$m. These results suggest transits affected by flares may still be useful for atmospheric characterization efforts.Comment: 29 pages, 17 figures, 3 tables, accepted to The Astrophysical Journa

A segmental genomic duplication generates a functional intron

An intron is an extended genomic feature whose function requires multiple constrained positions—donor and acceptor splice sites, a branch point, a polypyrimidine tract and suitable splicing enhancers—that may be distributed over hundreds or thousands of nucleotides. New introns are therefore unlikely to emerge by incremental accumulation of functional sub-elements. Here we demonstrate that a functional intron can be created de novo in a single step by a segmental genomic duplication. This experiment recapitulates in vivo the birth of an intron that arose in the ancestral jawed vertebrate lineage nearly half-a-billion years ago

Effects of Aflatoxin B1 and Fumonisin B1 on Blood Biochemical Parameters in Broilers

The individual and combined effects of dietary aflatoxin B1 (AFB1) and fumonisin B1 (FB1) on liver pathology, serum levels of aspartate amino-transferase (AST) and plasma total protein (TP) of broilers were evaluated from 8 to 41 days of age. Dietary treatments included a 3 × 3 factorial arrangement with three levels of AFB1 (0, 50 and 200 μg AFB1/kg), and three levels of FB1 (0, 50 and 200 mg FB1/kg). At 33 days post feeding, with the exception of birds fed 50 mg FB1 only, concentrations of AST were higher (p < 0.05) in all other treatment groups when compared with controls. Plasma TP was lower (p < 0.05) at six days post feeding in groups fed 200 μg AFB1/kg alone or in combination with FB1. At day 33 days post feeding, with the exception of birds fed the highest combination of AFB1 and FB1 which had higher plasma TP than control birds, plasma TP of birds fed other dietary treatments were similar to controls. Broilers receiving the highest levels of AFB1 and FB1 had bile duct proliferation and trabecular disorder in liver samples. AFB1 singly or in combination with FB at the levels studied, caused liver damage and an increase in serum levels of AST

Mesenchymal stromal cells inhibit NLRP3 inflammasome activation in a model of Coxsackievirus B3-induced inflammatory cardiomyopathy

Inflammation in myocarditis induces cardiac injury and triggers disease progression to heart failure. NLRP3 inflammasome activation is a newly identified amplifying step in the pathogenesis of myocarditis. We previously have demonstrated that mesenchymal stromal cells (MSC) are cardioprotective in Coxsackievirus B3 (CVB3)-induced myocarditis. In this study, MSC markedly inhibited left ventricular (LV) NOD2, NLRP3, ASC, caspase-1, IL-1β, and IL-18 mRNA expression in CVB3-infected mice. ASC protein expression, essential for NLRP3 inflammasome assembly, increased upon CVB3 infection and was abrogated in MSC-treated mice. Concomitantly, CVB3 infection in vitro induced NOD2 expression, NLRP3 inflammasome activation and IL-1β secretion in HL-1 cells, which was abolished after MSC supplementation. The inhibitory effect of MSC on NLRP3 inflammasome activity in HL-1 cells was partly mediated via secretion of the anti-oxidative protein stanniocalcin-1. Furthermore, MSC application in CVB3-infected mice reduced the percentage of NOD2-, ASC-, p10- and/or IL-1β- positive splenic macrophages, natural killer cells, and dendritic cells. The suppressive effect of MSC on inflammasome activation was associated with normalized expression of prominent regulators of myocardial contractility and fibrosis to levels comparable to control mice. In conclusion, MSC treatment in myocarditis could be a promising strategy limiting the adverse consequences of cardiac and systemic NLRP3 inflammasome activation

Atmospheric Reconnaissance of TRAPPIST-1 b with JWST/NIRISS: Evidence for Strong Stellar Contamination in the Transmission Spectra

TRAPPIST-1 is a nearby system of seven Earth-sized, temperate, rocky exoplanets transiting a Jupiter-sized M8.5V star, ideally suited for in-depth atmospheric studies. Each TRAPPIST-1 planet has been observed in transmission both from space and from the ground, confidently rejecting cloud-free, hydrogen-rich atmospheres. Secondary eclipse observations of TRAPPIST-1 b with JWST/MIRI are consistent with little to no atmosphere given the lack of heat redistribution. Here we present the first transmission spectra of TRAPPIST-1 b obtained with JWST/NIRISS over two visits. The two transmission spectra show moderate to strong evidence of contamination from unocculted stellar heterogeneities, which dominates the signal in both visits. The transmission spectrum of the first visit is consistent with unocculted starspots and the second visit exhibits signatures of unocculted faculae. Fitting the stellar contamination and planetary atmosphere either sequentially or simultaneously, we confirm the absence of cloud-free hydrogen-rich atmospheres, but cannot assess the presence of secondary atmospheres. We find that the uncertainties associated with the lack of stellar model fidelity are one order of magnitude above the observation precision of 89 ppm (combining the two visits). Without affecting the conclusion regarding the atmosphere of TRAPPIST-1 b, this highlights an important caveat for future explorations, which calls for additional observations to characterize stellar heterogeneities empirically and/or theoretical works to improve model fidelity for such cool stars. This need is all the more justified as stellar contamination can affect the search for atmospheres around the outer, cooler TRAPPIST-1 planets for which transmission spectroscopy is currently the most efficient technique.Comment: 26 pages, 11 figures, accepted for publication in The Astrophysical Journal Letter