gebhart/patrepeval huggingface dataset:
Integrated scRNAseq Analysis of Murine Lung Fibrosis Reveals Patterns in Composition and Gene Expression of Lymphocytes (2021)

Rationale:Lymphocytes are known to aggregate in proximity to lesions in pulmonary fibrosis, but the role for T and innate lymphoid cells in contributing to lung fibrosis remains poorly understood.We aggregated several published scRNAseq datasets of mouse bleomycin fibrosis models, and assessed fibrosis-associated patterns among lymphoid cells. Methods: scRNAseq data from seven published datasets, each consisting of both bleomycin and saline control treated murine whole lung dissociates were downloaded from GEO for aggregation: GSE104154 (control n=3, bleo n=3), GSE111664 (control n=7, bleo n=3), GSE129605 (control n=4, bleo n=4, bleo and nintedanib n=3), GSE132771 (control n=4, bleo n=4), GSE141259 (control n=8, bleo n=8), GSE154031 (control n=2, bleo n=4) and GSE131800 (control n=2, bleo n=2). Genes detected in fewer than 3 datasets were discarded, as were cells with less than 400 transcripts detected. Datasets were integrated using R package Seurat's SCTintegration implementation. Cells were recursively graph-embedded and clustered for cell annotation, beginning at the level of all cells, then among the immune cells, then among T cells. Cells were annotated based on marker expression patterns in accordance with the literature. T cell population composition statistics were performed with R packages lme4 and lmerTest; datasets are treated as random variables with treatment nested underneath; only samples with 10 or more T cells were included in the proportion analysis. Results: 12,375 cells from 85 treatment and control mouse lungs (control n=28, bleomycin n=54, bleomycin and nintedanib n=3) are representative of one of nine distinct types of T or innate lymphoid cells. All datasets and sample treatments are represented among all identified cell types. Among these cells and across all datasets, we observe the proportion of T regulatory (Treg) cells to be significantly over-represented among bleomycin-treated samples when compared to saline, across all datasets (p-value 1.36E-5). The average increase in Treg representation following bleomycin treatment ranges from 37.79% (GSE104154) to 311.80% (GSE129605). The most significantly downregulated gene in Tregs from bleomycin-treated lungs is the TGF-B signaling inhibitor Klf2 (avg log FC: 0.87, Bonferroni adj. p-value 6.42E-25) -suggesting a reduced capacity to mitigate fibrosis when compared to Tregs in control lungs. Conclusions:Integrated analysis of multiple murine pulmonary fibrosis scRNAseq datasets demonstrate patterns in T regulatory cell population expansion and altered gene expression,indicating a role for these cells in the development of pulmonary fibrosis. Further analyses will account for longitudinal sampling times and include cross-validation of patterns with integrated human lung fibrosis data.
Protein Cysteine Modifications: (2) Reactivity Specificity and Topics of Medicinal Chemistry and Protein Engineering (2009)

Cysteine (cysteinyl residue) modifications in proteins result in diversity in protein functions. The reaction specificity of a protein with a modified cysteine residue is determined by the overall conditions of the protein, including the spatial position of the cysteine residue, electrostatic interactions between cysteine residue and other charged residues, spatial interactions between the cysteine residue and a chemical compound, electrophilicity of the chemical compound, and the pH of the solution. In cysteine-dependant enzymes, each specific type of cysteine modification characterizes the catalytic mechanism of the enzyme. Recently, the catalytic mechanisms of peroxiredoxins and cysteine proteases, which contain a cysteine residue(s) in their catalytic sites, have been elucidated. In the catalytic process of peroxiredoxins, a sulfenyl intermediate is formed by oxidation of the catalytic cysteine residue. On the other hand, in cysteine proteases, the catalytic cysteine residue reacts with the carboxyl carbon of a peptide substrate to form an intermediate complex via S-alkylation. In this review, we introduce the most current information on the applications of cysteine thiol chemistry for in vitro glycoprotein synthesis. Recently, a glycoprotein (monocyte chemotactic protein-3), containing an intact human complex-type sialyloligosaccharide has been chemically synthesized. The procedure used for this could have applications in the development of new protein-based drugs, including antineoplastic drugs and antibiotics. It can also potentially be applied for improving the half-life and reducing the toxicity of these drugs, and for preventing the development of multidrug resistance.
Utility of the Arabidopsis FAEI and yeast SLCI-I genes for improvements in erucic acid and oil content in rapeseed (2000)

High-erucic acid (HEA) Brassica napus cultivars are regaining interest in industrial contexts. Erucic acid and its derivatives are important renewable raw materials utilized in the manufacture of plastic films, in the synthesis of Nylon 13,13, and in the lubricant and emollient industries. Theoretically, the highest level of erucic acid that can be achieved by means of classical breeding is 66 mol%; however, using new approaches on the basis of genetic engineering, it might be possible to develop a B. napus cultivar containing levels of erucic acid significantly above 66 mol% (>80 mol%). In an attempt to increase the amounts of very-long-chain fatty acids (VLCFAs), and erucic acid in particular, in Canadian HEA B. napus cultivars, we have focused on two targets using a transgenic approach. We examined both the role/function of the Arabidopsis thaliana FAE1 (fatty acid elongase) gene by expressing it under the control of the seed-specific napin promoter in B. napus germplasm with analysis of the changes in VLCFA content in the seed oil of transgenic lines, and the performance of the yeast SLC1-1 (sphingolipid compensation mutant) in B. napus cv. Hero transgenic progeny in the field. Here, we report analyses of the contents of 22:1, total VLCFAand oil in the seed oil, as well as seed yield of the field-grown FAE1 and SLC1-1 B. napus cv. Hero progeny.
Translational studies of intravenous and intracerebroventricular routes of administration for CNS cellular biodistribution for BMN 250, an enzyme replacement therapy for the treatment of Sanfilippo type B (2020)

BMN 250 is being developed as enzyme replacement therapy for Sanfilippo type B, a primarily neurological rare disease, in which patients have deficient lysosomal alpha-N-acetylglucosaminidase (NAGLU) enzyme activity. BMN 250 is taken up in target cells by the cation-independent mannose 6-phosphate receptor (CI-MPR, insulin-like growth factor 2 receptor), which then facilitates transit to the lysosome. BMN 250 is dosed directly into the central nervous system via the intracerebroventricular (ICV) route, and the objective of this work was to compare systemic intravenous (IV) and ICV delivery of BMN 250 to confirm the value of ICV dosing. We first assess the ability of enzyme to cross a potentially compromised blood-brain barrier in the Naglu<sup>-/-</sup> mouse model and then assess the potential for CI-MPR to be employed for receptor-mediated transport across the blood-brain barrier. In wild-type and Naglu<sup>-/-</sup> mice, CI-MPR expression in brain vasculature is high during the neonatal period but virtually absent by adolescence. In contrast, CI-MPR remains expressed through adolescence in non-affected non-human primate and human brain vasculature. Combined results from IV administration of BMN 250 in Naglu<sup>-/-</sup> mice and IV and ICV administration in healthy juvenile non-human primates suggest a limitation to therapeutic benefit from IV administration because enzyme distribution is restricted to brain vascular endothelial cells: enzyme does not reach target neuronal cells following IV administration, and pharmacological response following IV administration is likely restricted to clearance of substrate in endothelial cells. In contrast, ICV administration enables central nervous system enzyme replacement with biodistribution to target cells.
Phase II Study of Nonmyeloablative Allogeneic Bone Marrow Transplantation for B Cell Lymphoma with Post-Transplantation Rituximab and Donor Selection Based First on Non-HLA Factors (2015)

Outcomes of nonmyeloablative (NMA), HLA-haploidentical (haplo), related-donor allogeneic blood or marrow transplantation (allo-BMT) with high-dose post-transplantation cyclophosphamide (PTCy) appear to be similar to those using HLA-matched donors. Thus, it may be possible to prioritize donor factors other than HLA matching that could enhance antitumor activity. The Fc receptor polymorphism FCGR3A-158VV may confer greater sensitivity to rituximab than FCGR3A-158FF. In a prospective phase II study of NMA, related-donor allo-BMT with PTCy and post-transplantation rituximab for patients with B cell lymphomas, we hypothesized that donor selection that prioritized FCGR3A-158 polymorphism over HLA matching would be feasible, safe, and improve outcomes. The primary endpoint was 1-year progression-free survival (PFS). Of 83 patients transplanted (median age, 59 years), 69 (83%) received haplo grafts. Fifty-four (65%) received a graft that maintained or improved their Fc receptor polymorphism status. With 2.6-year median follow-up, the 1-year PFS and overall survival (OS) probabilities were 71% and 86%, respectively, with 1-year relapse and nonrelapse mortality (NRM) probabilities of 20% and 8%. At 1 year, the probability of acute grades II to IV graft-versus-host disease (GVHD) was 41%, with acute grades III to IV GVHD probability of 5% and chronic GVHD probability of 11%. Among haplo transplants, the 1-year probabilities of PFS, OS, relapse, and NRM were 70%, 83%, 20%, and 10%, respectively. No differences in outcomes were observed based on donor FCGR3A-158 polymorphism. Excess infection risk was not apparent with post-transplantation rituximab. Although donor selection based on FCGR3A-158 polymorphism was not shown to influence PFS, this study suggests that donor selection based on criteria other than best HLA match is feasible and safe. This study opens the way for the future investigation of donor prioritization based on promising non-HLA factors that may improve antitumor activity and decrease relapse after allo-BMT. This study was registered at www.clinicaltrials.gov as NCT00946023.
A real-space navigation system based on ubiquitous technology (2006)

In next-generation networking environments, ubiquitous networks will be available both indoors and outdoors. Various devices will be ubiquitously embedded in the surrounding environment, such as buildings and urban spaces. We will be able to browse digital contents on ubiquitous networks anywhere and at anytime. In our research, we have proposed several content-processing mechanisms for use in environment-enabled collaborative acquisition of embedded digital content in the real world situations. We have developed a network management device that makes it possible to acquire embedded content using coordinated ubiquitous devices. We have also developed two prototype systems using these devices. In this paper, we describe the implementation of a prototype system that can share 3D objects in a virtual 3D space based on a real-space environment. This system can be used not only as a virtual 3D browser in a private area, but also as an interactive digital poster in a public area. We tested our system in real situation, and explore the feasibility of applying our system in a ubiquitous environment.
Phase behavior of inverse microemulsions for the polymerization of acrylamide in near-critical and supercritical continuous phases (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhase behavior of inverse microemulsions for the polymerization of acrylamide in near-critical and supercritical continuous phasesEric J. Beckman and Richard D. SmithCite this: J. Phys. Chem. 1990, 94, 1, 345–350Publication Date (Print):January 1, 1990Publication History Published online1 May 2002Published inissue 1 January 1990https://pubs.acs.org/doi/10.1021/j100364a059https://doi.org/10.1021/j100364a059research-articleACS PublicationsRequest reuse permissionsArticle Views174Altmetric-Citations22LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access options Get e-Alerts
Molecular Layer Deposition for Surface Modification of Lithium‐Ion Battery Electrodes (2016)

Inspired by recent successes in applying molecular layer deposition (MLD) to stabilize lithium‐ion (Li‐ion) electrodes, this review presents the MLD process and its outstanding attributes for electrochemical applications. The review discusses various MLD materials and their implementation in Li‐ion electrodes. The rationale behind these emerging uses of MLD is examined to motivate future efforts on the fundamental understanding of interphase chemistry and the development of new materials for enhanced electrochemical performance.
In Vivo/In Vitro Correlation of Intravitreal Drug Delivery from Biodegradable Polymer Implants. (2002)

An approach for predicting the drug concentration in the vitreous body has been proposed for intravitreal drug delivery by biodegradable polymer implants. The release rates of a model drug, dexamethasone sodium m-sulfobenzoate (DMSB), from poly lactic acid implants were measured under in vitro and in vivo conditions using Japanese albino rabbits. The pharmacokinetic model assuming the cylindrical vitreous body was then solved together with the in vivo release rate and the other model parameters determined separately. The mathematical model successfully described the drug concentration–time profile in the vitreous body. The in vivo concentration–time profile in the rabbit vitreous body agreed with the one predicted on the basis of the in vivo release profile. The in vivo concentration–time profile in the vitrectomized eye was well predicted from the in vitro release profile. These findings may suggest that if the in vivo release profile is known or predicted, the in vivo concentration in the vitreous body can be evaluated by the help of computer simulation without carrying out the in vivo release experiment which is usually time-consuming for controlled release formulations.
Overcoming codon-usage bias in heterologous protein expression in Streptococcus gordonii (2009)

One of the limitations facing the development of Streptococcus gordonii into a successful vaccine vector is the inability of this bacterium to express high levels of heterologous proteins. In the present study, we have identified 12 codons deemed as rare codons in S. gordonii and seven other streptococcal species. tRNA genes encoding 10 of the 12 rare codons were cloned into a plasmid. The plasmid was transformed into strains of S. gordonii expressing the fusion protein SpaP/S1, the anti-complement receptor 1 (CR1) single-chain variable fragment (scFv) antibody, or the Toxoplasma gondii cyclophilin C18 protein. These three heterologous proteins contained high percentages of amino acids encoded by rare codons. The results showed that the production of SpaP/S1, anti-CR1 scFv and C18 increased by 2.7-, 120- and 10-fold, respectively, over the control strains. In contrast, the production of the streptococcal SpaP protein without the pertussis toxin S1 fragment was not affected by tRNA gene supplementation, indicating that the increased production of SpaP/S1 protein was due to the ability to overcome the limitation caused by rare codons required for the S1 fragment. The increase in anti-CR1 scFv production was also observed in Streptococcus mutans following tRNA gene supplementation. Collectively, the findings in the present study demonstrate for the first time, to the best of our knowledge, that codon-usage bias exists in Streptococcus spp. and the limitation of heterologous protein expression caused by codon-usage bias can be overcome by tRNA supplementation.
BARcode DEmixing through Non-negative Spatial Regression (BarDensr) (2021)

Modern spatial transcriptomics methods can target thousands of different types of RNA transcripts in a single slice of tissue. Many biological applications demand a high spatial density of transcripts relative to the imaging resolution, leading to partial mixing of transcript rolonies in many voxels; unfortunately, current analysis methods do not perform robustly in this highly-mixed setting. Here we develop a new analysis approach, BARcode DEmixing through Non-negative Spatial Regression (BarDensr): we start with a generative model of the physical process that leads to the observed image data and then apply sparse convex optimization methods to estimate the underlying (demixed) rolony densities. We apply BarDensr to simulated and real data and find that it achieves state of the art signal recovery, particularly in densely-labeled regions or data with low spatial resolution. Finally, BarDensr is fast and parallelizable. We provide open-source code as well as an implementation for the 'NeuroCAAS' cloud platform.
Graph- and finite element-based total variation models for the inverse problem in diffuse optical tomography (2019)

Total variation (TV) is a powerful regularization method that has been widely applied in different imaging applications, but is difficult to apply to diffuse optical tomography (DOT) image reconstruction (inverse problem) due to complex and unstructured geometries, non-linearity of the data fitting and regularization terms, and non-differentiability of the regularization term. We develop several approaches to overcome these difficulties by: i) defining discrete differential operators for unstructured geometries using both finite element and graph representations; ii) developing an optimization algorithm based on the alternating direction method of multipliers (ADMM) for the non-differentiable and non-linear minimization problem; iii) investigating isotropic and anisotropic variants of TV regularization, and comparing their finite element- and graph-based implementations. These approaches are evaluated on experiments on simulated data and real data acquired from a tissue phantom. Our results show that both FEM and graph-based TV regularization is able to accurately reconstruct both sparse and non-sparse distributions without the over-smoothing effect of Tikhonov regularization and the over-sparsifying effect of L$_1$ regularization. The graph representation was found to out-perform the FEM method for low-resolution meshes, and the FEM method was found to be more accurate for high-resolution meshes.
Immunoglobulin Isotype Determines Pathogenicity in Antibody-Mediated Myocarditis in Naive Mice (2000)

Antimyosin reactivity is associated with cardiac damage in autoimmune myocarditis, an inflammatory heart disease characterized by a cellular infiltrate in the myocardium and myocyte necrosis. We are interested in the pathogenicity of antimyosin antibodies and their ability to cause autoimmune myocarditis. We have shown that antimyosin antibodies of the IgG isotype will induce disease in the DBA/2 mouse. In the present study, we show that IgM antimyosin antibodies do not induce myocarditis; however, these same antibodies become pathogenic when converted to the IgG isotype. Although IgM antibodies can penetrate the myocardium during cardiac inflammation, they are usually less able to leave the vascular compartment and penetrate cardiac tissue, thus accounting for their lack of pathogenicity. Thus, antimyosin B cells may be potentially pathogenic only after antigen activation and heavy chain class switching or under conditions that alter vascular permeability in the heart.
Millimeter-scale chip–based supercontinuum generation for optical coherence tomography (2021)

Supercontinuum sources for optical coherence tomography (OCT) have raised great interest as they provide broad bandwidth to enable high resolution and high power to improve imaging sensitivity. Commercial fiber-based supercontinuum systems require high pump powers to generate broad bandwidth and customized optical filters to shape/attenuate the spectra. They also have limited sensitivity and depth performance. We introduce a supercontinuum platform based on a 1-mm<sup>2</sup> Si<sub>3</sub>N<sub>4</sub> photonic chip for OCT. We directly pump and efficiently generate supercontinuum near 1300 nm without any postfiltering. With a 25-pJ pump pulse, we generate a broadband spectrum with a flat 3-dB bandwidth of 105 nm. Integrating the chip into a spectral domain OCT system, we achieve 105-dB sensitivity and 1.81-mm 6-dB sensitivity roll-off with 300-μW optical power on sample. We image breast tissue to demonstrate strong imaging performance. Our chip will pave the way toward portable OCT and incorporating integrated photonics into optical imaging technologies.
Nitric oxide and respiratory rhythm in mammals: a new modulator of phase transition? (2007)

NO (nitric oxide) modulates several central pattern generators, but its role in respiratory rhythmogenesis and its mode of action on medullary respiratory neurons during normoxia are unknown. We analysed the actions of NO on the mammalian respiratory network at the system and cellular levels. Given systemically, the NO donor diethylamine NONOate increased post-inspiratory duration in vagus, phrenic and hypoglossal nerves, whereas blockade of NO generation with L-NAME (N(G)-nitro-L-arginine methyl ester) produced the opposite response. At the cellular level, we pressure-ejected the NO donor on to respiratory neurons. NO had both inhibitory and excitatory effects on all types of respiratory neurons. Inhibitory effects involved soluble guanylate cyclase, as they were blocked with ODQ (1H-[1,2,4]oxadiazolo[4,3a]quinoxalin-1-one), whereas excitations were antagonized by uric acid and possibly mediated via peroxynitrite. Importantly, NO facilitated both GABA (gamma-aminobutyric acid)- and NMDA (N-methyl-D-aspartate)-induced neuronal responses, but this was restricted to post-inspiratory and pre-inspiratory neurons; other neuron types showed additive effects only. Our results support NO as modulator of centrally generated respiratory activity and specifically of ligand-mediated responses in respiratory neuron types involved in respiratory phase transition.
Characterization of GaInAs/InP Triple-Barrier Resonant Tunneling Diodes Grown by Organo-Metallic Vapor Phase Epitaxy for High-Temperature Estimation of Phase Coherent Length of Electrons (1997)

To estimate the phase coherent length( L C ) of electrons in semiconductor, triple-barrier resonant tunneling diodes (TBRTDs) with GaInAs/InP heterostructures were fabricated by using organo-metallic vapor phase epitaxy (OMVPE). The current density-voltage ( J - V ) characteristics were measured at 4.2 K and 77 K. Moreover method of comparison between experimental and theoretical results is proposed. By comparing experimental result with theoretical result, the coherent lengths are estimated to be longer than 90 nm and 55 nm at 4.2 K and 77 K respectively.