gebhart/patrepeval huggingface dataset:
LKB1 and KEAP1/NRF2 Pathways Cooperatively Promote Metabolic Reprogramming with Enhanced Glutamine Dependence in KRAS -Mutant Lung Adenocarcinoma (2019)

In <i>KRAS</i>-mutant lung adenocarcinoma, tumors with LKB1 loss (KL) are highly enriched for concurrent <i>KEAP1</i> mutations, which activate the KEAP1/NRF2 pathway (KLK). Here, we investigated the biological consequences of these cooccurring alterations and explored whether they conferred specific therapeutic vulnerabilities. Compared with KL tumors, KLK tumors exhibited increased expression of genes involved in glutamine metabolism, the tricarboxylic acid cycle, and the redox homeostasis signature. Using isogenic pairs with knockdown or overexpression of LKB1, KEAP1, and NRF2, we found that LKB1 loss results in increased energetic and redox stress marked by increased levels of intracellular reactive oxygen species and decreased levels of ATP, NADPH/NADP<sup>+</sup> ratio, and glutathione. Activation of the KEAP1/NRF2 axis in LKB1-deficient cells enhanced cell survival and played a critical role in the maintenance of energetic and redox homeostasis in a glutamine-dependent manner. LKB1 and the KEAP1/NRF2 pathways cooperatively drove metabolic reprogramming and enhanced sensitivity to the glutaminase inhibitor CB-839 <i>in vitro</i> and <i>in vivo</i>. Overall, these findings elucidate the adaptive advantage provided by KEAP1/NRF2 pathway activation in KL tumors and support clinical testing of glutaminase inhibitor in subsets of KRAS-mutant lung adenocarcinoma. SIGNIFICANCE: In <i>KRAS</i>-mutant non-small cell lung cancer, LKB1 loss results in enhanced energetic/redox stress, which is tolerated, in part, through cooccurring KEAP1/NRF2-dependent metabolic adaptations, thus enhancing glutamine dependence and vulnerability to glutaminase inhibition.<b>Graphical Abstract:</b> http://cancerres.aacrjournals.org/content/canres/79/13/3251/F1.large.jpg.
Identification of autoantibody clusters that best predict lupus disease activity using glomerular proteome arrays (2005)

Nephrophilic autoantibodies dominate the seroprofile in lupus, but their fine specificities remain ill defined. We constructed a multiplexed proteome microarray bearing about 30 antigens known to be expressed in the glomerular milieu and used it to study serum autoantibodies in lupus. Compared with normal serum, serum from B6.Sle1.lpr lupus mice (C57BL/6 mice homozygous for the NZM2410/NZW allele of Sle1 as well as the FAS defect) exhibited high levels of IgG and IgM antiglomerular as well as anti-double-stranded DNA/chromatin Abs and variable levels of Abs to alpha-actinin, aggrecan, collagen, entactin, fibrinogen, hemocyanin, heparan sulphate, laminin, myosin, proteoglycans, and histones. The use of these glomerular proteome arrays also revealed 5 distinct clusters of IgG autoreactivity in the sera of lupus patients. Whereas 2 of these IgG reactivity clusters (DNA/chromatin/glomeruli and laminin/myosin/Matrigel/vimentin/heparan sulphate) showed association with disease activity, the other 3 reactivity clusters (histones, vitronectin/collagen/chondroitin sulphate, and entactin/fibrinogen/hyaluronic acid) did not. Human lupus sera also displayed 2 distinct IgM autoantibody clusters, one reactive to DNA and the other apparently polyreactive. Interestingly, the presence of IgM polyreactivity in patient sera was associated with reduced disease severity. Hence, the glomerular proteome array promises to be a powerful analytical tool for uncovering novel autoantibody disease associations and for distinguishing patients at high risk for end-organ disease.
A framework for calibration of electromagnetic surgical navigation systems (2004)

In this paper, we present a framework of calibrating an electromagnetic tracker (Northern Digital's Aurora) using an accurate optical tracker (the Optotrak system, also from Northern Digital). First, registration methods for these two navigation systems are developed. Sub millimeter accuracy registration is achieved for both cases. We also address the latency between the two different trackers. The registration accuracy for dynamic acquired data is greatly improved after we compensate for the tracker latency. In our calibration approach, we sample the measurement field of the Aurora and compute the position and orientation error using the Optotrak measurements and previously computed registration results as "ground truth". Then we approximate the error field using Bernstein polynomials. Another comparative technique we use is to decompose the error space using KD tree, and then approximate each atomic cell with local interpolation. Experimental results show significant improvement in tracking accuracy for both position and orientation. Finally we discuss our future directions.
Neurofascin induces neurites by heterophilic interactions with axonal NrCAM while NrCAM requires F11 on the axonal surface to extend neurites. (1996)

Neurofascin and NrCAM are two axon-associated transmembrane glycoproteins belonging to the L1 subgroup of the Ig superfamily. In this study, we have analyzed the interaction of both proteins using neurite outgrowth and binding assays. A neurofascin-Fc chimera was found to stimulate the outgrowth of tectal cells when immobilized on an inert surface but not as a soluble form using polylysine as substrate. Antibody blocking experiments demonstrate that neurite extension on immobilized neurofascin is mediated by NrCAM on the axonal surface. Under the reverse experimental conditions where NrCAM induces neurite extension, F11, and not neurofascin, serves as axonal receptor. Binding studies using transfected COS7 cells and immunoprecipitations reveal a direct interaction between neurofascin and NrCAM. This binding activity was mapped to the Ig domains within neurofascin. The neurofascin-NrCAM binding can be modulated by alternative splicing of specific stretches within neurofascin. These studies indicate that heterophilic interactions between Ig-like proteins implicated in axonal extension underlie a regulation by the neuron.
Establishment of an immortal chicken embryo liver-derived cell line (2013)

A continuously growing immortal cell substrate can be used for virus propagation, diagnostic purposes, and vaccine production. The aim of this study was to develop an immortal chicken cell line for efficient propagation of avian infectious viruses. From the various chicken embryo cells that were tested for life span extension, an immortalized chicken embryo liver (CEL) cell line, named CEL-im, was derived spontaneously without either oncogenic viruses or carcinogenic chemical treatment. Currently, CEL-im cells are growing 0.8 to 1.1 population doublings per day and have reached 120 passages. The CEL-im cell line is permissive for poultry infectious viruses, including avian metapneumovirus (AMPV), Marek's disease virus serotype 1 (MDV-1), and infectious laryngotracheitis virus. The CEL-im cells produced high AMPV titer (>10(5) pfu/mL), whereas very low titers (~10 pfu/mL) for MDV-1 and infectious laryngotracheitis virus were produced. To identify genetic alterations in the immortal CEL-im cell line, telomerase activity and mRNA expression for major cell cycle regulatory genes were determined during the immortalizing process. The CEL-im cell line has negative telomerase activity, and when compared with the primary passage 2 CEL cell counterpart, mRNA expression of tumor suppressor protein p53, mouse double minute 2 (Mdm2), cyclin dependent kinase (CDK) inhibitor p21 (p21(WAF)), and CDK inhibitor p16 (p16(INK4)) were downregulated in the CEL-im cell line, whereas retinoblastoma (Rb), transcription factor E2F, member 1 (E2F-1), and alternative reading frame of p16(INK4) (ARF) were upregulated. These results are similar to genetic alterations found previously in immortal chicken embryo fibroblast (CEF) cell lines that showed efficient propagation of MDV-1. Therefore, this newly established CEL-im cell line can serve as an alternative cell substrate for the propagation of poultry viruses, such as AMPV.
Pressure Ulcer Risk Factors Among Hospitalized Patients With Activity Limitation (1995)

These results suggest that nonblanchable erythema, lymphopenia, immobility, dry skin, and decreased body weight are independent and significant risk factors for pressure ulcers in hospitalized patients whose activity is limited to bed or chair.
A Simple, Efficient Synthesis of Dibenzyl and Di-p-nitrobenzyl 1-Hydroxyalkanephosphonates (1988)

Dibenzyl and di-p-nitrobenzyl 1-hydroxyalkanephosphonates 3a-i are prepared by alkylation of 1-hydroxyalkanephosphonic acids 1 with O-benzyl and O-(p-nitrobenzyl)-N,N′-dicyclohexylisoureas 2.
Ultrahigh dose-rate FLASH irradiation increases the differential response between normal and tumor tissue in mice (2014)

In vitro studies suggested that sub-millisecond pulses of radiation elicit less genomic instability than continuous, protracted irradiation at the same total dose. To determine the potential of ultrahigh dose-rate irradiation in radiotherapy, we investigated lung fibrogenesis in C57BL/6J mice exposed either to short pulses (≤ 500 ms) of radiation delivered at ultrahigh dose rate (≥ 40 Gy/s, FLASH) or to conventional dose-rate irradiation (≤ 0.03 Gy/s, CONV) in single doses. The growth of human HBCx-12A and HEp-2 tumor xenografts in nude mice and syngeneic TC-1 Luc(+) orthotopic lung tumors in C57BL/6J mice was monitored under similar radiation conditions. CONV (15 Gy) triggered lung fibrosis associated with activation of the TGF-β (transforming growth factor-β) cascade, whereas no complications developed after doses of FLASH below 20 Gy for more than 36 weeks after irradiation. FLASH irradiation also spared normal smooth muscle and epithelial cells from acute radiation-induced apoptosis, which could be reinduced by administration of systemic TNF-α (tumor necrosis factor-α) before irradiation. In contrast, FLASH was as efficient as CONV in the repression of tumor growth. Together, these results suggest that FLASH radiotherapy might allow complete eradication of lung tumors and reduce the occurrence and severity of early and late complications affecting normal tissue.
Analysis of progressive deletions of the transmembrane and cytoplasmic domains of influenza hemagglutinin. (1986)

Site-directed oligonucleotide mutagenesis has been used to introduce chain termination codons into the cloned DNA sequences encoding the carboxy-terminal transmembrane (27 amino acids) and cytoplasmic (10 amino acids) domains of influenza virus hemagglutinin (HA). Four mutant genes were constructed which express truncated forms of HA that lack the cytoplasmic domain and terminate at amino acids 9, 14, 17, or 27 of the wild-type hydrophobic domain. Analysis of the biosynthesis and intracellular transport of these mutants shows that the cytoplasmic tail is not needed for the efficient transport of HA to the cell surface; the stop-transfer sequences are located in the hydrophobic domain; 17 hydrophobic amino acids are sufficient to anchor HA stably in the membrane; and mutant proteins with truncated hydrophobic domains show drastic alterations in transport, membrane association, and stability.
Preparation of Autologous Leukemia and Lymphoma Vaccines Expressing α -Gal Epitopes (2001)

This study describes a novel method for increasing the immunogenicity of autologous tumor vaccines in leukemia and lymphoma patients by exploiting the natural anti-Gal antibody for in situ targeting of the vaccinating cells to antigen-presenting cells (APCs). Incubation of leukemia or lymphoma cells with neuraminidase and recombinant alpha 1,3-galactosyltransferase results in the synthesis of many alpha-gal epitopes (Gal alpha 1-3Gal beta 1-4GlcNAc-R) on their cell membranes. Vaccination with such processed tumor cells results in the binding of the natural anti-Gal immunoglobulin G (IgG) antibody to these epitopes and opsonization of these cells for effective phagocytosis by APCs, such as dendritic cells and macrophages. These APCs may transport the vaccine to adjacent draining lymph nodes for subsequent effective processing and presentation of tumor-associated antigens (TAA) peptides to activate TAA-specific helper and cytotoxic T cells. Once the TAA-specific cytotoxic T cells are activated, they can leave the lymph node, circulate in the body, and seek metastatic cells expressing TAA to destroy them. Alternatively, activated helper T cells may provide the help required for B cells to produce antibodies to TAA on the leukemia or lymphoma cells. Because every patient receives his or her own TAA within the vaccinating cells, such vaccines are customized for the patient. These autologous tumor vaccines may be used as an adjuvant treatment that complements currently used treatment regimens by providing the immune system with an additional opportunity to be exposed effectively to autologous TAA.
A Schwann cell-seeded intrinsic framework and its satisfactory biocompatibility for a bioartificial nerve graft (2001)

To optimize the internal environment of a collagen nerve tube, we designed a Schwann cell-seeded intrinsic framework and its biocompatibility was investigated. We fixed 6-0 polyglactin woven filaments (Vicryl) or polydioxanone monofilaments (PDS) on a silicone ring in a net fashion. It was coated with matrigel and then incubated with cultured newborn or adult Schwann cells. Furthermore, we implanted 1.5-cm-long filament-filled collagen tubes in a rat model. Using a live/dead fluorescent assay and electron microscopy, we found that adherent Schwann cells onto filaments remained viable and oriented longitudinally along filaments. The preliminary in vivo study indicated that a mild inflammatory reaction was present around the tube wall. However, nerve regeneration occurred around and between filaments. We concluded that the arrangement of Schwann cell columns onto filaments was achieved, mimicking Bünger bands. It was shown that the biomaterials did not impede nerve regeneration.
Enhanced isobutanol production from acetate by combinatorial overexpression of acetyl-CoA synthetase and anaplerotic enzymes in engineered Escherichia coli (2018)

Acetic acid is an abundant material that can be used as a carbon source by microorganisms. Despite its abundance, its toxicity and low energy content make it hard to utilize as a sole carbon source for biochemical production. To increase acetate utilization and isobutanol production with engineered Escherichia coli, the feasibility of utilizing acetate and metabolic engineering was investigated. The expression of acs, pckA, and maeB increased isobutanol production by up to 26%, and the addition of TCA cycle intermediates indicated that the intermediates can enhance isobutanol production. For isobutanol production from acetate, acetate uptake rates and the NADPH pool were not limiting factors compared to glucose as a carbon source. This work represents the first approach to produce isobutanol from acetate with pyruvate flux optimization to extend the applicability of acetate. This technique suggests a strategy for biochemical production utilizing acetate as the sole carbon source.
Development of Human Protein Reference Database as an Initial Platform for Approaching Systems Biology in Humans (2003)

Human Protein Reference Database (HPRD) is an object database that integrates a wealth of information relevant to the function of human proteins in health and disease. Data pertaining to thousands of protein-protein interactions, posttranslational modifications, enzyme/substrate relationships, disease associations, tissue expression, and subcellular localization were extracted from the literature for a nonredundant set of 2750 human proteins. Almost all the information was obtained manually by biologists who read and interpreted >300,000 published articles during the annotation process. This database, which has an intuitive query interface allowing easy access to all the features of proteins, was built by using open source technologies and will be freely available at http://www.hprd.org to the academic community. This unified bioinformatics platform will be useful in cataloging and mining the large number of proteomic interactions and alterations that will be discovered in the postgenomic era.
In Vitro Binding Analysis of Hepatitis B Virus preS‐derived Putative Helper T‐cell Epitopes to MHC Class II Molecules Using Stable HLA‐DRB1*0405/‐DRA*0101 Transfected Cells (2000)

In designing epitope-based vaccines, the inclusion of a helper T-lymphocyte (HTL) epitope is necessary to elicit both humoral and cellular immune responses. Whereas the preS region of the hepatitis B virus (HBV) surface antigen is well-known to raise protective immunity, the epitopes for activating HTLs are poorly characterized. In an attempt to identify such epitopes, the HBV-preS region was screened for peptide sequences with HLA-DR4 binding motifs, and putative HTL candidate peptides were synthesized in a biotinylated form. Using L929 mouse fibroblasts stably transfected with HLA-DRB1*0405 and HLA-DRA*0101 cDNA, specific binding of the peptides was then detected using fluorescence-conjugated streptavidin. The cell-surface expression of HLA-DR molecules on transfectants was confirmed by confocal microscopy, and quantitative analysis of candidate peptide binding was performed by fluorescence activated cell sorting. Among eight preS-derived peptides, three candidate peptides-namely preS1(23-33), preS1(62-72), and preS1(76-86)-showed good binding characteristics to HLA-DR4 molecules, among which the preS1(23-33) epitope was regarded as the most promising HTL epitope. Further studies with these candidate HTL stimulatory peptides will show their ability to activate the human immune system against HBV.
Cloning and expression in Escherichia coli of a Klebsiella ozaenae plasmid-borne gene encoding a nitrilase specific for the herbicide bromoxynil (1987)

An enzyme (nitrilase) that converts the herbicide bromoxynil (3,5-dibromo-4-hydroxybenzonitrile) to its metabolite 3,5-dibromo-4-hydroxybenzoic acid was shown to be plasmid encoded in the natural soil isolate Klebsiella ozaenae. The bromoxynil-specific nitrilase was expressed in Escherichia coli by direct transfer and stable maintenance in E. coli of a naturally occurring 82-kilobase K. ozaenae plasmid. Irreversible loss of the ability to metabolize bromoxynil both in E. coli and K. ozaenae was associated with the conversion of the 82-kilobase plasmid to a 68-kilobase species. In E. coli this conversion was the result of a host recA+-dependent recombinational event. A gene, designated bxn, encoding the bromoxynil-specific nitrilase was constitutively expressed in K. ozaenae and E. coli and subcloned on a 2.6-kilobase PstI DNA segment. The polarity and the location of the gene were determined by assaying hybrid constructs of the bromoxynil-specific nitrilase gene fused with the heterologous lac promoter.
The wear behavior of ion‐implanted Ti‐6Al‐4V against UHMW polyethylene (1990)

Nitrogen-ion-implanted Ti-6A1-4V against UHMW polyethylene was tested on a joint simulator to evaluate the wear behavior under different conditions. It was concluded that the polymer wear rate was not affected by ion implantation. The metallic wear, on the other hand, was substantially reduced by this treatment. It was also found that ion implantation resulted in good protection of the metal surface against third-body wear by PMMA, while the introduction of C.P. titanium particles in the joint initiated tremendous wear. Although ion implantation improved the wear of titanium alloy against UHMW polyethylene, the durability of the implanted layer needs further study.
Development of an efficient automated docking method. (1993)

An efficient automated method of searching for stable docking structures of protein-ligand complex has been developed. The method outputs several promising docking models in which protein and ligand interact favorably, covering all possible binding modes and ligand conformations. Our search method is excellent in terms of not only ease of use and speed of calculation, but also reliability and reproducibility of the docking results. It should become an indispensable tool for investigating biochemical reaction processes and designing new drug structures based on receptor structure.
Biosynthesis of Natural Products with a PC Bond, X. Incorporation of D‐[1‐2H1]Glucose into 2‐Aminoethylphosphonic Acid in Tetrahymena thermophila and into Fosfomycin in Streptomyces fradiae. — the Stereochemical Course of a Phosphoenolpyruvate Mutase‐Catalyzed Reaction (1992)

Abstract 2‐Aminoethylphosphonic acid and fosfomycin produced on feeding D ‐[1‐ 2 H 1 ]glucose to Tetrahymena thermophila and Streptomyces fradiae , respectively, indicate that the phosphoenolpyruvate mutase catalyzes the stereospecific transfer of the phospho group of ( Z )‐phosphoenol‐[3‐ 2 H 1 ]pyruvate from oxygen to carbon from the si face. 2 H‐NMR spectroscopy was used to determine the configuration at C‐1 of biosynthetically formed 2‐amino‐[1‐ 2 H 1 ]ethylphosphonic acid after derivatization with (—)‐camphanoyl chloride and diazomethane.
<title>Parallel Processing For Computer Vision</title> (1982)

It has been estimated that processor speeds on the order of 1 to 100 billion operations per second will be required to solve some of the current problems in computer vision. This paper overviews the use of parallel processing techniques for various vision tasks using a parallel processing computer architecture known as PASM (partitionable SIMD/MIMD machine). PASM is a large-scale multimicroprocessor system being designed for image processing and pattern recognition. It can be dynamically reconfigured to operate as one or more independent SIMD (single instruction stream-multiple data stream) and/or MIMD (multiple instruction stream-multiple data stream) machines. This paper begins with a discussion of the computational capabilities required for com-puter vision. It is then shown how parallel processing, and in particular PASM, can be used to meet these needs.
Mastering the Complexity of Reactive Systems - The AutoFocusApproach (2006)

In this chapter we apply the AutoFocus approach to the BART case study. In a nutshell, we investigate how a formally-based approach can help to structure the informal requirements, define system boundaries, specify an abstract behavior of the system and the environment, ensure the suitability of the model, and repeatedly enhance the system with design decisions.
Atomic layer controlled deposition of silicon nitride with self-limiting mechanism (1996)

Thin (2–10 nm) silicon nitride films have been grown by repetitive plasma nitridation of Si using a NH3 remote plasma and deposition of Si by a SiH2Cl2 thermal reaction. The deposition rate is self-limited at nearly half-molecular layer (ML) per one deposition cycle. The process window for the half-ML/cycle of growth has been investigated with respect to the NH3 plasma power, SiH2Cl2 exposure time, and substrate temperature. The thickness fluctuation of the film over a 2 in. wafer is within measurement accuracy of the ellipsometer (± 1.9%) for the atomic layer controlled film while it is ± 8.5% for all the remote-plasma chemical vapor deposition film.