Optical properties of electrochromic materials can be controlled by the application of an electric field allowing recent development of new applications such as smart windows technology for indoor ...climate control and energy conservation. We report the fabrication of a single-walled nanotube (SWNT) thin film based electro-optical modulator controlled by ionic liquid polarization in which the active electrochromic layer is made of a film of semiconducting (SC-) SWNTs and the counter-electrode is composed of a film of metallic (MT-) SWNTs. Optimization of this electro-optical cell allows the operations with an optical modulation depth of 3.7 dB and a response time in the millisecond range, which is thousands of times faster than typical electrolyte-controlled devices. In addition, a dual electro-optical device was built utilizing electro-optically active SC-SWNT films for each electrode that allowed increasing modulation depth of 6.7 dB while preserving the speed of the response.
A production prototype structures for lossless ion manipulation ion mobility (SLIM IM) platform interfaced to a commercial high-resolution mass spectrometer (MS) is described. The SLIM IM implements ...the traveling wave ion mobility technique across a ∼13m path length for high-resolution IM (HRIM) separations. The resolving power (CCS/ΔCCS) of the SLIM IM stage was benchmarked across various parameters (traveling wave speeds, amplitudes, and waveforms), and results indicated that resolving powers in excess of 200 can be accessed for a broad range of masses. For several cases, resolving powers greater than 300 were achieved, notably under wave conditions where ions transition from a nonselective “surfing” motion to a mobility-selective ion drift, that corresponded to ion speeds approximately 30–70% of the traveling wave speed. The separation capabilities were evaluated on a series of isomeric and isobaric compounds that cannot be resolved by MS alone, including reversed-sequence peptides (SDGRG and GRGDS), triglyceride double-bond positional isomers (TG 3, 6, 9 and TG 6, 9, 12), trisaccharides (melezitose, raffinose, isomaltotriose, and maltotriose), and ganglioside lipids (GD1b and GD1a). The SLIM IM platform resolved the corresponding isomeric mixtures, which were unresolvable using the standard resolution of a drift-tube instrument (∼50). In general, the SLIM IM-MS platform is capable of resolving peaks separated by as little as ∼0.6% without the need to target a specific separation window or drift time. Low CCS measurement biases <0.5% were obtained under high resolving power conditions. Importantly, all the analytes surveyed are able to access high-resolution conditions (>200), demonstrating that this instrument is well-suited for broadband HRIM separations important in global untargeted applications.
Defects in sphingolipid metabolism have emerged as a common link across neurodegenerative disorders, and a deeper understanding of the lipid content in preclinical models and patient specimens offers ...opportunities for development of new therapeutic targets and biomarkers. Sphingolipid metabolic pathways include the formation of glycosphingolipid species that branch into staggeringly complex structural heterogeneity within the globoside and ganglioside sub-lipidomes. Characterization of these sub-lipidomes has typically relied on liquid chromatography-mass spectrometry-based (LC-MS) approaches, but such assays are challenging and resource intensive due to the close structural heterogeneity, the presence of isobaric and isomeric species, and broad dynamic range of endogenous glycosphingolipids. Here, we apply Structures for Lossless Ion Manipulations (SLIM)-based High Resolution Ion Mobility (HRIM)-MS to enable rapid, repeatable, quantitative assays with deep structural information sufficient to resolve endogenous brain gangliosides at the level of individual molecular species. Analyses were performed using a prototype SLIM-MS instrument equipped with a 13-m serpentine path which enabled resolution of closely related isomeric analytes such as GD1a d36:1 and GD1b d36:1 based on recorded mass-to-charge (m/z) and arrival times. To demonstrate the power of our methodology, brain extracts derived from wild-type mice hemi-brains were analyzed by HRIM-MS using flow injection analyses (FIA) without the need for additional separation by liquid chromatography. Endogenous ganglioside species were readily resolved, identified, and quantified by FIA-SLIM-MS analyses within 2 min per sample. Thus, the FIA-SLIM-MS platform enables robust quantification across a broad range of lipid species in biological specimens in a standardized assay format that is readily scalable to support studies with large sample numbers.
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•Structures for Lossless Ion Manipulations (SLIM) based High Resolution Ion Mobility (HRIM) mass spectrometry (MS) permits separation of isomeric gangliosides without liquid chromatography (LC) coupling.•Highly reproducible separation and quantification of ganglioside isomers can be obtained directly from flow-injection analysis (FIA) of total lipid extracts.•Major ganglioside species and isomers are quantified from mouse brain extracts in only 2-min timeframes using FIA-SLIM-MS.
High mucosal and fecal concentrations of the antimicrobial siderophore-binding peptide Lipocalin-2 (Lcn2) are observed in inflammatory bowel disease. However, Lcn2 function in chronic intestinal ...inflammation remains unclear. Here, we demonstrate that Lcn2 protects from early-onset colitis and spontaneous emergence of right-sided colonic tumors resulting from IL-10 deficiency. Exacerbated inflammation in Lcn2–/–/Il10–/– mice is driven by IL-6, which also controls tumorigenesis. Lcn2–/–/Il10–/– mice exhibit profound alterations in gut microbial composition, which contributes to inflammation and tumorigenesis, as demonstrated by the transmissibility of the phenotype and protection conferred by antibiotics. Specifically, facultative pathogenic Alistipes spp. utilize enterobactin as iron source, bloom in Lcn2–/–/Il10–/– mice, and are sufficient to induce colitis and right-sided tumors when transferred into Il10–/– mice. Our results demonstrate that Lcn2 protects against intestinal inflammation and tumorigenesis associated with alterations in the microbiota.
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•Antimicrobial peptide Lipocalin-2 (Lcn2) is strongly induced in Il10–/– colitic mice•Lcn2 deficiency exacerbates Il10–/– colitis and causes spontaneous right-sided tumors•Inflammation and tumorigenesis are due to altered gut microbiota and are transmissible•Alistipes spp. is sufficient to induce colitis and site-specific tumors in Il10–/– mice
Lipocalin-2 is a host defense protein that is upregulated during inflammation. Moschen et al. demonstrate that Lipocalin-2 protects from intestinal inflammation and spontaneous tumor formation in experimental colitis through its impact on microbial composition, specifically Alistipes spp., which induces colitis and tumors when transferred to Il10–/– mice.
Cataracts are the world's leading cause of avoidable blindness. In low-income countries, there are high rates of poor follow-up, which makes it very difficult to monitor surgical outcomes. To address ...this issue, the Better Operative Outcome Software Tool (BOOST Cataract app) predicts outcome on the first postoperative day and provides specific advice to improve outcomes. The aim of the study is to evaluate the ability of the BOOST Cataract app to categorise surgical outcomes and to analyse the possible factors that contribute to its performance. This was a prospective observational study performed at the General Hospital of Hospitalet of Llobregat.
A total of 126 cataracts were included. Patients had a mean SD age of 75.8 12.19 years, and 52% were females. Manual small-incision cataract surgery was involved in 57% and phacoemulsification in 43%. Thirty-eight percent of eyes presented significant corneal oedema on day 1. The BOOST Cataract app succeeded in categorising the final outcome in 65.6% of the eyes and in 93,4% of the eyes with good outcome.The agreement between the BOOST and UDVA outcomes was 0.353 (p< .000). The level of agreement improved to 0.619 (p< .000) in eyes with clear corneas. Success obtained by BOOST for both types of surgery was not statistically different. Eyes that obtained a good outcome on day one after surgery and eyes with clear cornea had 37 times higher odds (95% CI 6.66, 212.83) and 12 times higher odds (95% CI 3.13, 47.66) of being correctly categorised by the BOOST Cataract app than eyes that obtained a suboptimal (moderate and poor) outcome and eyes with corneal oedema on day 1.
The BOOST Cataract app is an e-Health tool designed to address issues of measuring quality in low- and middle-income settings. Although its reliability is limited to eyes that obtain a good outcome and with clear corneas on day 1, the use of the tool on a regular basis facilitates monitoring and reporting outcomes when clinical data collection is challenging due to low postoperative follow-up rates.
Nitric oxide (NO) generated by inducible NO synthase 2 (NOS2) affects cellular iron homeostasis, but the underlying molecular mechanisms and implications for NOS2-dependent pathogen control are ...incompletely understood. In this study, we found that NO up-regulated the expression of ferroportin-1 (Fpn1), the major cellular iron exporter, in mouse and human cells. Nos2(-/-) macrophages displayed increased iron content due to reduced Fpn1 expression and allowed for an enhanced iron acquisition by the intracellular bacterium Salmonella typhimurium. Nos2 gene disruption or inhibition of NOS2 activity led to an accumulation of iron in the spleen and splenic macrophages. Lack of NO formation resulted in impaired nuclear factor erythroid 2-related factor-2 (Nrf2) expression, resulting in reduced Fpn1 transcription and diminished cellular iron egress. After infection of Nos2(-/-) macrophages or mice with S. typhimurium, the increased iron accumulation was paralleled by a reduced cytokine (TNF, IL-12, and IFN-γ) expression and impaired pathogen control, all of which were restored upon administration of the iron chelator deferasirox or hyperexpression of Fpn1 or Nrf2. Thus, the accumulation of iron in Nos2(-/-) macrophages counteracts a proinflammatory host immune response, and the protective effect of NO appears to partially result from its ability to prevent iron overload in macrophages.
Objective
To study the safety and clinical efficacy of rituximab therapy for primary Sjögren's syndrome, as well as to investigate its mechanisms.
Methods
Patients with primary Sjögren's syndrome ...were enrolled in an open‐label trial, were given rituximab (1 gm) infusions on days 1 and 15, and were monitored through week 52. The primary end point was safety, with secondary end points evaluating clinical and biologic efficacy. Blood was obtained for enumeration of lymphocyte subsets, measurement of serum autoantibody and BAFF levels, and analysis of gene expression.
Results
Twelve female patients with primary Sjögren's syndrome were administered rituximab. They had a median age of 51 years (range 34–69 years) and a median disease duration of 8.0 years (range 2–18 years). We observed no unexpected toxicities from the rituximab therapy. Modest improvements were observed at week 26 in patient‐reported symptoms of fatigue and oral dryness, with no significant improvement in the objective measures of lacrimal and salivary gland function. The recovery of blood B cells following the nadir from rituximab therapy was characterized by a predominance of transitional B cells and a lack of memory B cells. While blood B cell depletion was associated with an increase in serum BAFF levels, no significant changes were observed in the levels of serum anti‐Ro/SSA, anti‐La/SSB, and anti–type 3 muscarinic acetylcholine receptor autoantibodies or in the blood interferon signature.
Conclusion
In patients with primary Sjögren's syndrome, a single treatment course of rituximab was not associated with any unexpected toxicities and led to only modest clinical benefits despite effective depletion of blood B cells.
High rates of dispersal can breakdown coadapted gene complexes. However, concentrated genomic architecture (i.e., genomic islands of divergence) can suppress recombination to allow evolution of local ...adaptations despite high gene flow. Pacific lamprey (Entosphenus tridentatus) is a highly dispersive anadromous fish. Observed trait diversity and evidence for genetic basis of traits suggests it may be locally adapted. We addressed whether concentrated genomic architecture could influence local adaptation for Pacific lamprey. Using two new whole genome assemblies and genotypes from 7,716 single nucleotide polymorphism (SNP) loci in 518 individuals from across the species range, we identified four genomic islands of divergence (on chromosomes 01, 02, 04, and 22). We determined robust phenotype‐by‐genotype relationships by testing multiple traits across geographic sites. These trait associations probably explain genomic divergence across the species’ range. We genotyped a subset of 302 broadly distributed SNPs in 2,145 individuals for association testing for adult body size, sexual maturity, migration distance and timing, adult swimming ability, and larval growth. Body size traits were strongly associated with SNPs on chromosomes 02 and 04. Moderate associations also implicated SNPs on chromosome 01 as being associated with variation in female maturity. Finally, we used candidate SNPs to extrapolate a heterogeneous spatiotemporal distribution of these predicted phenotypes based on independent data sets of larval and adult collections. These maturity and body size results guide future elucidation of factors driving regional optimization of these traits for fitness. Pacific lamprey is culturally important and imperiled. This research addresses biological uncertainties that challenge restoration efforts.
The rich information on (sub)millimeter dust continuum emission from distant galaxies in the public Atacama Large Millimeter/submillimeter Array (ALMA) archive is contained in thousands of ...inhomogeneous observations from individual PI-led programs. To increase the usability of these data for studies deepening our understanding of galaxy evolution, we have developed automated mining pipelines for the ALMA archive in the COSMOS field (A3COSMOS) that efficiently exploit the available information for large numbers of galaxies across cosmic time and keep the data products in sync with the increasing public ALMA archive: (a) a dedicated ALMA continuum imaging pipeline, (b) two complementary photometry pipelines for both blind source extraction and prior source fitting, (c) a counterpart association pipeline utilizing the multiwavelength data available (including quality assessment based on machine-learning techniques), (d) an assessment of potential (sub)millimeter line contribution to the measured ALMA continuum, and (e) extensive simulations to provide statistical corrections to biases and uncertainties in the ALMA continuum measurements. Application of these tools yields photometry catalogs with ∼1000 (sub)millimeter detections (spurious fraction ∼8%-12%) from over 1500 individual ALMA continuum images. Combined with ancillary photometric and redshift catalogs and the above quality assessments, we provide robust information on redshift, stellar mass, and star formation rate for ∼700 galaxies at redshifts 0.5-6 in the COSMOS field (with undetermined selection function). The ALMA photometric measurements and galaxy properties are released publicly within our blind extraction, prior fitting, and galaxy property catalogs, plus the images. These products will be updated on a regular basis in the future.
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