gebhart/patrepeval huggingface dataset:
Dendrimer‐Based Lipid Nanoparticles Deliver Therapeutic FAH mRNA to Normalize Liver Function and Extend Survival in a Mouse Model of Hepatorenal Tyrosinemia Type I (2018)

mRNA-mediated protein replacement represents a promising concept for the treatment of liver disorders. Children born with fumarylacetoacetate hydrolase (FAH) mutations suffer from Hepatorenal Tyrosinemia Type 1 (HT-1) resulting in renal dysfunction, liver failure, neurological impairments, and cancer. Protein replacement therapy using FAH mRNA offers tremendous potential to cure HT-1, but is currently hindered by the development of effective mRNA carriers that can function in diseased livers. Structure-guided, rational optimization of 5A2-SC8 mRNA-loaded dendrimer lipid nanoparticles (mDLNPs) increases delivery potency of FAH mRNA, resulting in functional FAH protein and sustained normalization of body weight and liver function in FAH<sup>-/-</sup> knockout mice. Optimization using luciferase mRNA produces DLNP carriers that are efficacious at mRNA doses as low as 0.05 mg kg<sup>-1</sup> in vivo. mDLNPs transfect > 44% of all hepatocytes in the liver, yield high FAH protein levels (0.5 mg kg<sup>-1</sup> mRNA), and are well tolerated in a knockout mouse model with compromised liver function. Genetically engineered FAH<sup>-/-</sup> mice treated with FAH mRNA mDLNPs have statistically equivalent levels of TBIL, ALT, and AST compared to wild type C57BL/6 mice and maintain normal weight throughout the month-long course of treatment. This study provides a framework for the rational optimization of LNPs to improve delivery of mRNA broadly and introduces a specific and viable DLNP carrier with translational potential to treat genetic diseases of the liver.
Effects of Darwinian Selection and Mutability on Rate of Broadly Neutralizing Antibody Evolution during HIV-1 Infection (2016)

Accumulation of somatic mutations in antibody variable regions is critical for antibody affinity maturation, with HIV-1 broadly neutralizing antibodies (bnAbs) generally requiring years to develop. We recently found that the rate at which mutations accumulate decreases over time, but the mechanism governing this slowing is unclear. In this study, we investigated whether natural selection and/or mutability of the antibody variable region contributed significantly to observed decrease in rate. We used longitudinally sampled sequences of immunoglobulin transcripts of single lineages from each of 3 donors, as determined by next generation sequencing. We estimated the evolutionary rates of the complementarity determining regions (CDRs), which are most significant for functional selection, and found they evolved about 1.5-to 2-fold faster than the framework regions. We also analyzed the presence of AID hotspots and coldspots at different points in lineage development and observed an average decrease in mutability of less than 10 percent over time. Altogether, the correlation between Darwinian selection strength and evolutionary rate trended toward significance, especially for CDRs, but cannot fully explain the observed changes in evolutionary rate. The mutability modulated by AID hotspots and coldspots changes correlated only weakly with evolutionary rates. The combined effects of Darwinian selection and mutability contribute substantially to, but do not fully explain, evolutionary rate change for HIV-1-targeting bnAb lineages.
Matrix Molecule mRNA Levels in the Bursa and Rotator Cuff of Patients With Full‐Thickness Rotator Cuff Tears (2005)

These findings may help clinicians determine what aspects of the repair process can be manipulated to affect optimal ruptured tendon repair.
Identification of type II and type III pyoverdine receptors from Pseudomonas aeruginosa (2003)

Pseudomonas aeruginosa produces, under conditions of iron limitation, a high-affinity siderophore, pyoverdine (PVD), which is recognized at the level of the outer membrane by a specific TonB-dependent receptor, FpvA. So far, for P. aeruginosa, three different PVDs, differing in their peptide chain, have been described (types I-III), but only the FpvA receptor for type I is known. Two PVD-producing P. aeruginosa strains, one type II and one type III, were mutagenized by a mini-TnphoA3 transposon. In each case, one mutant unable to grow in the presence of the strong iron chelator ethylenediaminedihydroxyphenylacetic acid (EDDHA) and the cognate PVD was selected. The first mutant, which had an insertion in the pvdE gene, upstream of fpvA, was unable to take up type II PVD and showed resistance to pyocin S3, which is known to use type II FpvA as receptor. The second mutant was unable to take up type III PVD and had the transposon insertion in fpvA. Cosmid libraries of the respective type II and type III PVD wild-type strains were constructed and screened for clones restoring the capacity to grow in the presence of PVD. From the respective complementing genomic fragments, type II and type III fpvA sequences were determined. When in trans, type II and type III fpvA restored PVD production, uptake, growth in the presence of EDDHA and, in the case of type II fpvA, pyocin S3 sensitivity. Complementation of fpvA mutants obtained by allelic exchange was achieved by the presence of cognate fpvA in trans. All three receptors posses an N-terminal extension of about 70 amino acids, similar to FecA of Escherichia coli, but only FpvAI has a TAT export sequence at its N-terminal end.
Mild, reversible carbon-hydrogen oxidative addition/reductive elimination in a dinuclear iridium complex (1986)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMild, reversible carbon-hydrogen oxidative addition/reductive elimination in a dinuclear iridium complexWilliam D. McGhee and Robert G. BergmanCite this: J. Am. Chem. Soc. 1986, 108, 18, 5621–5622Publication Date (Print):September 1, 1986Publication History Published online1 May 2002Published inissue 1 September 1986https://pubs.acs.org/doi/10.1021/ja00278a041https://doi.org/10.1021/ja00278a041research-articleACS PublicationsRequest reuse permissionsArticle Views229Altmetric-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 optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Preparation of desymmetrised meso-tartrate derivatives—synthesis and utility of (R′,R′,R,S)-2,3-butane diacetal protected dimethyl tartrate (1999)

The synthesis of 2,3-butane diacetal protected dimethyl tartrate (R′,R′,R,S)-1 using a chiral memory protocol and its utility for the preparation of desymmetrised meso-tartrate derivatives through selective transesterification and aminolysis of the spatially different carboxylate termini is described.
Virial Theorem for Plasmas (1960)

ABS>A generalization of the Chandrasekhar-Fermi virial theorem is outlined to include plasmas. From this generalization it may be concluded that in the absence of confining gravitational fields, self-confinement of plasmas cannot be achieved. (B.O.G.)
Polyfluorinated Oxaziridines:  Synthesis and Reactivity (1996)

Oxaziridines are three-membered heterocyclic compounds containing oxygen, nitrogen, and carbon. They were first described in mid-1950s,1-3 but the first perfluorinated example was reported in mid-1970s.4 Some scattered papers in the 1980s have provided evidence of the unusual reactivity and unique properties of these perfluorinated heterocycles. It is only in the last five years, however, that a strong focus on the area allowed the unique properties of polyfluorinated oxaziridines to be recognized. For instance, perfluorinated oxaziridines as oxidants are much closer to dioxiranes than to hydrocarbon oxaziridines. This is a consequence of the dramatic effect of electon-withdrawing perfluoroalkyl groups. While the chemistry of hydrocarbon oxaziridines has been reviewed in several papers,5-10 the current work is the first attempt to provide a comprehensive survey of the synthesis, physical properties, and reactions of poly- and perfluorinated oxaziridines.
Polycrystalline Diamond Film on Si(100) by XPS (1992)

Filament-assisted chemical vapor deposition (CVD) diamond film growth on Si(100) was studied using x-ray photoelectron spectroscopy (XPS) in a system that couples a growth chamber to an ultrahigh vacuum analytical chamber. Diamond nucleates and grows on a SiC layer formed on the Si(100) substrate [D. N. Belton and S. J. Schmieg, Appl. Phys. Lett. 54, 416 (1989)]. After about 17 h growth XPS showed no Si signal from the substrate, no detectable contaminants, and only carbon present in survey scans. Electron energy loss spectroscopy (EELS) spectra obtained by x-ray excitation of the C 1s level can be used as a fingerprint for distinguishing diamond from graphite or carbides [D. N. Belton and S. J. Schmieg, J. Vac. Sci. Technol. A 8, 2353 (1990)]. The identification of a continuous diamond film was confirmed with Raman spectroscopy and scanning electron microscopy (SEM).
Luminescence thermometry for detection of optical cooling from colloidal quantum dots embedded in dielectric waveguides (2021)

We have developed a novel method of pump-probe luminescence thermometry based on the detection of photoluminescence signal phase change versus power of the pumping laser, and applied it to studies of optical cooling from colloidal quantum dots embedded in dielectric waveguides.
Integrated Optofluidic Sensor for Coagulation Risk Monitoring in COVID-19 Patients at Point-of-Care (2020)

While the pathophysiology underlying the COVID-19 infection remains incompletely understood, there is growing evidence to indicate that it is closely correlated to hypercoagulation among severely ill patients. Doctors may choose for use anti-coagulation doses to treat the patients at intensive care units. A rapid, easy, and low-cost solution to monitor the coagulation status at the point-of-care may help with treatment by enabling the administration of controlled doses of medication to patients and to understand the disease's underlying pathophysiology. Thromboelastography, the clinical standard is accurate; it suffers from limited portability and low sensitivity when miniaturized to handheld form factor. In the article, we summarize research helping to advance towards an integrated optofluidic device combining microfluidics and photonic sensor technology. Microfluidics are used to perform blood pre-processing, and a photonic sensor measures blood coagulation status in real-time readout on the device itself. These techniques make it portable and scalable, potentially serving as technology foundation for the development of a disposable sensor for point-of-care diagnostics in COVID-19 patients and coagulopathy in general.
Orthogonal Middle-up Approaches for Characterization of the Glycan Heterogeneity of Etanercept by Hydrophilic Interaction Chromatography Coupled to High-Resolution Mass Spectrometry (2018)

Etanercept is a recombinant Fc fusion protein widely used to treat rheumatic diseases. This protein is highly glycosylated and contains numerous O- and N-glycosylation sites. Since glycosylation is recognized as an important critical quality attribute (CQA) that can affect immunogenicity, solubility, and stability of Fc fusion proteins, it should be thoroughly characterized. In this work, hydrophilic interaction chromatography (HILIC) was combined with high-resolution mass spectrometry (HRMS) by using a quadrupole time-of flight mass spectrometer to assess glycosylation of etanercept at the middle-up level of analysis (fragments of ca. 25-30 kDa). In addition, a combination of different enzymatic digestion procedures (i.e., glycosidase, sialidase, and protease) was systematically employed to facilitate spectra deconvolution. With the developed procedure, the main post-translational modifications (PTMs) of etanercept were assessed, and a global overview of the subunit-specific distribution of the glycosylation pattern was obtained at a middle-up level of analysis.
Expression of L1-CAM and ADAM10 in Human Colon Cancer Cells Induces Metastasis (2007)

L1-CAM, a neuronal cell adhesion receptor, is also expressed in a variety of cancer cells. Recent studies identified L1-CAM as a target gene of beta-catenin-T-cell factor (TCF) signaling expressed at the invasive front of human colon cancer tissue. We found that L1-CAM expression in colon cancer cells lacking L1-CAM confers metastatic capacity, and mice injected in their spleen with such cells form liver metastases. We identified ADAM10, a metalloproteinase that cleaves the L1-CAM extracellular domain, as a novel target gene of beta-catenin-TCF signaling. ADAM10 overexpression in colon cancer cells displaying endogenous L1-CAM enhanced L1-CAM cleavage and induced liver metastasis, and ADAM10 also enhanced metastasis in colon cancer cells stably transfected with L1-CAM. DNA microarray analysis of genes induced by L1-CAM in colon cancer cells identified a cluster of genes also elevated in a large set of human colon carcinoma tissue samples. Expression of these genes in normal colon epithelium was low. These results indicate that there is a gene program induced by L1-CAM in colon cancer cells that is also present in colorectal cancer tissue and suggest that L1-CAM can serve as target for colon cancer therapy.
Table S4 from Enrichment of PI3K-AKT–mTOR Pathway Activation in Hepatic Metastases from Breast Cancer (2023)

&lt;p&gt;AKT S473 distribution based on ER, HER2 expression measured by IHC in for primary and metastatic lesions included in the validation set.&lt;/p&gt;
28-Gb/s Directly Modulated InGaAlAs ACPM DFB Lasers with High Mask Margin of 22% at 55°C (2013)

A 1.3-µm directly modulated InGaAlAs-MQW DFB laser, incorporating an asymmetric corrugation-pitch-modulated (ACPM) grating, operating at 28 Gb/s at 55°C experimentally demonstrated high mask margin of 22% for the first time.
Organic Poultry Pathogen Control from Farm to Fork (2008)

In October 2002, the United States Department of Agriculture issued the framework for the National Organic Program. Under these guidelines, the use of many chemicals and all antibiotics for animals to be labeled organic have been prohibited. There is currently a great demand to find not only organic substances to use as feed additives but also alternative treatment methods for common poultry diseases. This article is intended as a brief introduction to the research presently being pursued to develop suitable additives and treatments for this rapidly growing sector of the food industry.
Index-of-refraction-dependent subcellular light scattering observed with organelle-specific dyes (2007)

Angularly resolved light scattering and wavelength-resolved darkfield scattering spectroscopy measurements were performed on intact, control EMT6 cells and cells stained with high-extinction lysosomal- or mitochondrial-localizing dyes. In the presence of the lysosomal-localizing dye NPe6, we observe changes in the details of light scattering from stained and unstained cells, which have both wavelength- and angular-dependent features. Analysis of measurements performed at several wavelengths reveals a reduced scattering cross section near the absorption maximum of the lysosomal-localizing dye. When identical measurements are made with cells loaded with a similar mitochondrial-localizing dye, HPPH, we find no evidence that staining mitochondria had any effect on the light scattering. Changes in the scattering properties of candidate populations of organelles induced by the addition of an absorber are modeled with Mie theory, and we find that any absorber-induced scattering response is very sensitive to the inherent refractive index of the organelle population. Our measurements and modeling are consistent with EMT6-cell-mitochondria having refractive indices close to those reported in the literature for organelles, approximately 1.4. The reduction in scattering cross section induced by NPe6 constrains the refractive index of lysosomes to be significantly higher. We estimate the refractive index of lysosomes in EMT6 cells to be approximately 1.6.
ITERATIVE SCATTER CORRECTION FOR GRID-LESS BEDSIDE CHEST RADIOGRAPHY: PERFORMANCE FOR A CHEST PHANTOM (2015)

The aim of this work was to experimentally compare the contrast improvement factors (CIFs) of a newly developed software-based scatter correction to the CIFs achieved by an antiscatter grid. To this end, three aluminium discs were placed in the lung, the retrocardial and the abdominal areas of a thorax phantom, and digital radiographs of the phantom were acquired both with and without a stationary grid. The contrast generated by the discs was measured in both images, and the CIFs achieved by grid usage were determined for each disc. Additionally, the non-grid images were processed with a scatter correction software. The contrasts generated by the discs were determined in the scatter-corrected images, and the corresponding CIFs were calculated. The CIFs obtained with the grid and with the software were in good agreement. In conclusion, the experiment demonstrates quantitatively that software-based scatter correction allows restoring the image contrast of a non-grid image in a manner comparable with an antiscatter grid.
Influence of intra‐aortic balloon pump on mortality as a function of cardiogenic shock severity (2021)

Patients with CS who were selected to receive an IABP had lower in-hospital mortality, without differences in this effect across the SCAI shock stages. Future studies should account for the severity and etiology of shock when evaluating the efficacy of IABP for CS.
Relevance of Circulating Hybrid Cells as a Non-Invasive Biomarker for Myriad Solid Tumors (2021)

Abstract Metastatic progression defines the final stages of tumor evolution and underlies the majority of cancer-related deaths. The heterogeneity in disseminated tumor cell populations capable of seeding and growing in distant organ sites contributes to the development of treatment resistant disease. We recently reported the identification of a novel tumor-derived cell population, circulating hybrid cells (CHCs), harboring attributes from both macrophages and neoplastic cells, including functional characteristics important to metastatic spread. These disseminated hybrids outnumber conventionally defined circulating tumor cells (CTCs) in cancer patients. It is unknown if CHCs represent a generalized cancer mechanism for cell dissemination, or if this population is relevant to the metastatic cascade. Herein, we detect CHCs in the peripheral blood of patients with cancer in myriad disease sites encompassing epithelial and non-epithelial malignancies. Further, we demonstrate that in vivo-derived hybrid cells harbor tumor-initiating capacity in murine cancer models and that CHCs from human breast cancer patients express stem cell antigens, features consistent with the ability to seed and grow at metastatic sites. Finally, we reveal heterogeneity of CHC phenotypes reflect key tumor features, including oncogenic mutations and functional protein expression. Importantly, this novel population of disseminated neoplastic cells opens a new area in cancer biology and renewed opportunity for battling metastatic disease. Simple Summary There is an incomplete understanding of circulating neoplastic cell populations and the fundamental mechanisms that drive dissemination, immune evasion, and growth —all critical information to more effectively prevent and treat cancer progression. A novel disseminated tumor cell population, circulating hybrid cells, are detected across many cancer types and carry functional tumor-initiating properties. Additionally, circulating hybrid cells are found at significantly higher levels than conventionally defined circulating tumor cells. Our study demonstrates that neoplastic hybrid cells harbor phenotypic and genetic characteristics of tumor and immune cells, display stem features, and are a generalizable phenomenon in solid tumors. Circulating hybrid cells therefore have relevance as a novel biomarker and open a new field of study in malignancy.
Defect pixel interpolation for lossy compression of camera raw data (2012)

The image processing pipeline of a traditional digital camera is often limited by processing power. A better image quality could be generated only if more complexity was allowed. In a raw data workflow most algorithms are executed off-camera. This allows the use of more sophisticated algorithms for increasing image quality while reducing camera complexity. However, this requires a major change in the processing pipeline: a lossy compression of raw camera images might be used early in the pipeline. Subsequent off-camera algorithms then need to work on modified data. We analyzed this problem for the interpolation of defect pixels. We found that a lossy raw compression spreads the error from uncompensated defects over many pixels. This leads to a problem as this larger error cannot be compensated after compression. The use of high quality, high complexity algorithms in the camera is also not an option. We propose a solution to this problem: Inside the camera only a simple and low complexity defect pixel interpolation is used. This significantly reduces the compression error for neighbors of defects. We then perform a lossy raw compression and compensate for defects afterwards. The high complexity defect pixel interpolation can be used off-camera. This leads to a high image quality while keeping the camera complexity low.