gebhart/patrepeval huggingface dataset:
Progesterone Receptor in Non–Small Cell Lung Cancer—A Potent Prognostic Factor and Possible Target for Endocrine Therapy (2005)

Abstract A possible involvement of gender-dependent factors has been postulated in development of human non–small-cell lung cancers (NSCLC), but its details remain unclear. In this study, we examined biological significance of progesterone receptor in NSCLCs. Progesterone receptor immunoreactivity was detected in 106 of 228 NSCLCs (46.5%). Progesterone receptor–positive NSCLC was frequently detected in female and adenocarcinoma, and was inversely associated with tumor-node-metastasis stage and histologic differentiation. Progesterone receptor status was also associated with better clinical outcome of the patients, and a multivariate analysis revealed progesterone receptor status as an independent prognostic factor. Progesterone-synthesizing enzymes were detected in NSCLCs, and tissue concentration of progesterone was higher in these cases (n = 42). Immunoblotting analyses showed the presence of progesterone receptor in three NSCLC cell lines (A549, LCSC#2, and 1-87), but not in RERF-LC-OK or PC3. Transcriptional activities of progesterone receptor were increased by progesterone in these three progesterone receptor–positive NSCLC cells by luciferase assays. Cell proliferation was inhibited by progesterone in these progesterone receptor–positive NSCLC cells in a dose-dependent manner, which was inhibited by progesterone receptor blocker. Proliferation of these tumor cells injected into nude mice was also dose-dependently inhibited by progesterone, with a concomitant increase of p21 and p27 and a decrease of cyclin A, cyclin E, and Ki67. Results of our present study suggested that progesterone receptor was a potent prognostic factor in NSCLCs and progesterone inhibited growth of progesterone receptor–positive NSCLC cells. Therefore, progesterone therapy may be clinically effective in suppressing development of progesterone receptor–positive NSCLC patients.
Characterization of a cis-diamminedichloroplatinum(II)-resistant human ovarian cancer cell line and its use in evaluation of platinum analogues. (1987)

Human ovarian cancer cell lines with stable cisplatin resistance have been developed by chronic exposure of the parent cisplatin-sensitive A2780 line to increasing concentrations of cisplatin. 2780CP8 (CP8 refers to this cell line's growth in medium containing 8 microM cisplatin) has several clonal cytogenetic abnormalities but lacks homogeneously staining regions or double-minute chromosomes. It has a significantly greater monolayer growth rate, cloning efficiency in agarose, and total glutathione content compared to the A2780 line, but similar activities of several glutathione-dependent enzymes. The 2780CP8 subline is 7.3-fold resistant to cisplatin compared to the A2780 line, as well as cross-resistant to irradiation and melphalan. It is not cross-resistant to Adriamycin, but this develops with increased cisplatin resistance (14-fold) obtained by further cisplatin exposure of 2780CP8. Of the cisplatin analogues tested which are of current clinical interest, carboplatin, iproplatin, and tetraplatin, only the latter is more cytotoxic than cisplatin in the A2780 and 2780CP8 lines. The 2780CP8 subline is also cross-resistant to these analogues in the relative order carboplatin greater than iproplatin greater than tetraplatin (most to least cross-resistant). Treatment of a highly cisplatin resistant cell line (2780CP70) with either melphalan or cisplatin was associated with a significant increase in [3H]thymidine incorporation into DNA in the presence of 10 mM hydroxyurea compared with the parent sensitive cell line which showed essentially no capacity to repair DNA damage by these drugs. A2780 and its cisplatin-resistant cell lines may thus be useful in studying drug resistance mechanisms, in screening new drugs for activity (especially against drug resistant tumors), and in formulating induction and salvage therapies for ovarian cancer.
RNAi in drug development: Practical considerations (2005)

The development of pharmaceuticals is a complex process that requires a tremendous investment of human and financial resources. In the post-genomic era, drug development has traditionally followed an established protocol that begins with the identification of a new target, proceeds with the identification, optimization and clinical evaluation of small molecule inhibitors of that target and culminates with the successful launch of a new pharmaceutical entity (Figure 27.1). The estimated cost of bringing a new drug to the market place is approximately $900 million over an 8+ year timeframe. RNAi technology can be applied at multiple steps in the drug development process and has the potential to change the pattern of drug development altogether. Indeed, RNAi has been widely employed as a powerful target discovery and validation tool in vitro and is currently being applied in vivo for target validation using whole organisms. In addition several companies are pursuing the clinical development RNAi compounds for the treatment of various diseases.
Deep RBFNet: Point Cloud Feature Learning using Radial Basis Functions (2018)

Three-dimensional object recognition has recently achieved great progress thanks to the development of effective point cloud-based learning frameworks, such as PointNet and its extensions. However, existing methods rely heavily on fully connected layers, which introduce a significant amount of parameters, making the network harder to train and prone to overfitting problems. In this paper, we propose a simple yet effective framework for point set feature learning by leveraging a nonlinear activation layer encoded by Radial Basis Function (RBF) kernels. Unlike PointNet variants, that fail to recognize local point patterns, our approach explicitly models the spatial distribution of point clouds by aggregating features from sparsely distributed RBF kernels. A typical RBF kernel, e.g. Gaussian function, naturally penalizes long-distance response and is only activated by neighboring points. Such localized response generates highly discriminative features given different point distributions. In addition, our framework allows the joint optimization of kernel distribution and its receptive field, automatically evolving kernel configurations in an end-to-end manner. We demonstrate that the proposed network with a single RBF layer can outperform the state-of-the-art Pointnet++ in terms of classification accuracy for 3D object recognition tasks. Moreover, the introduction of nonlinear mappings significantly reduces the number of network parameters and computational cost, enabling significantly faster training and a deployable point cloud recognition solution on portable devices with limited resources.
Evaluating the Efficacy and Safety of Two Doses of the Polyclonal Anti-Tumor Necrosis Factor-α Fragment Antibody AZD9773 in Adult Patients With Severe Sepsis and/or Septic Shock (2013)

AZD9773 rapidly and efficiently decreased plasma tumor necrosis factor-α concentration in patients with severe sepsis/septic shock, but this effect did not translate into clinical benefit.
Genetic engineering of a lysosomal enzyme fusion protein for targeted delivery across the human blood‐brain barrier (2007)

Mucopolysaccharidosis Type I, Hurler's Syndrome, is a lysosomal storage disorder that affects the brain. The missing enzyme, alpha-L-iduronidase (IDUA), does not cross the blood-brain barrier (BBB). To enable BBB transport of the enzyme, human IDUA was fused to the carboxyl terminus of the heavy chain of a chimeric monoclonal antibody (MAb) to the human insulin receptor (HIR). The HIRMAb crosses the BBB on the endogenous insulin receptor, and acts as a molecular Trojan horse to ferry into brain the IDUA. Transfection of COS cells resulted in high levels of IDUA enzyme activity both in the medium and in the intracellular space. The size of the fusion heavy chain, as measured with Western blotting and antibodies to either human IDUA or human IgG, was increased about 80 kDa, relative to the size of the heavy chain of the parent HIRMAb. The IDUA enzyme specific activity of the affinity purified HIRMAb-IDUA fusion protein was 363 +/- 37 U/microg protein, which is comparable to specific activity of recombinant IDUA. The accumulation of glycosoaminoglycans in Hurler fibroblasts was decreased 70% by treatment with the HIRMAb-IDUA fusion protein. Confocal microscopy showed targeting of the fusion protein to the lysosome. The HIRMAb-IDUA fusion protein bound with high affinity to the HIR, and was rapidly transported into the brain of the adult Rhesus monkey following intravenous administration. The HIRMAb-IDUA fusion protein is a new treatment for Hurler's syndrome, which has been specifically engineered to cross the human BBB.
A 533-MHz BiCMOS superscalar RISC microprocessor (1997)

This 533-MHz BiCMOS very large scale integration (VLSI) implementation of the PowerPC architecture contains three pipelines and a large on-chip secondary cache to achieve a peak performance of 1600 MIPS. The 15 mm/spl times/10 mm die contains 2.7 M transistors (2M CMOS and 0.7 M bipolar) and dissipates less than 85 W. The die is fabricated in a six-level metal, 0.5-/spl mu/m BiCMOS process and requires 3.6 and 2.1 V power supplies.
Exploring the Potential of Conditional Adversarial Networks for Optical and SAR Image Matching (2018)

Tasks such as the monitoring of natural disasters or the detection of change highly benefit from complementary information about an area or a specific object of interest. The required information is provided by fusing high accurate coregistered and georeferenced datasets. Aligned high-resolution optical and synthetic aperture radar (SAR) data additionally enable an absolute geolocation accuracy improvement of the optical images by extracting accurate and reliable ground control points (GCPs) from the SAR images. In this paper, we investigate the applicability of a deep learning based matching concept for the generation of precise and accurate GCPs from SAR satellite images by matching optical and SAR images. To this end, conditional generative adversarial networks (cGANs) are trained to generate SAR-like image patches from optical images. For training and testing, optical and SAR image patches are extracted from TerraSAR-X and PRISM image pairs covering greater urban areas spread over Europe. The artificially generated patches are then used to improve the conditions for three known matching approaches based on normalized cross-correlation (NCC), scale-invariant feature transform (SIFT), and binary robust invariant scalable key (BRISK), which are normally not usable for the matching of optical and SAR images. The results validate that a NCC-, SIFT-, and BRISK-based matching greatly benefit, in terms of matching accuracy and precision, from the use of the artificial templates. The comparison with two state-of-the-art optical and SAR matching approaches shows the potential of the proposed method but also revealed some challenges and the necessity for further developments.
Lysophosphatidic acid is detectable in human bronchoalveolar lavage fluids at baseline and increased after segmental allergen challenge (2006)

Lysophosphatidic acid is detectable in human BAL fluids at baseline and its expression increases during allergic inflammation. LPA does not appear to be a dominant chemoattractant for eosinophils or lymphocytes during allergic airway inflammation. In the absence of ongoing inflammation, LPA may promote epithelial barrier integrity.
Structure of the complex oligosaccharides of fetuin. (1979)

The complete structure of the complex oligosaccharides of fetuin has been established. The three fractions of complex oligosaccharide which were isolated by ion exchange chromatography following pronase digestion (F-I, F-II, and F-III) had identical molar ratios of sialic acid (Sia), galactose, mannose, and N-acetylglucosamine of 3:3:3:5. A combination of methylation analyses, Smith periodate degradations, and endoglycosidase and exoglycosidase digestions were utilized to establish the structure which is proposed to be: (see article of journal). Features of this structure not previously established include the presence of 2 residues of alpha2,3- and 1 residue of alpha2,6-linked sialic acid and their location relative to the mannose branch points. Also unusual is the presence of an alpha-linked branch mannose with substituents at positions 2 and 4 which is in turn linked to position 6 of the beta-linked, branch mannose. These features result in unexpected resistance to specific exoglycosidases.
Biomedical Program for the Converted 200-MeV Synchrocyclotron at the Gustaf Werner Institute (1985)

Biomedical Program for the Converted 200-MeV Synchrocyclotron at the Gustaf Werner Institute, Radiation Research Supplement, Vol. 8, Heavy Charged Particles in Research and Medicine. Proceedings of a Symposium Held at the Lawrence Berkeley Laboratory, University of California, Berkeley, California, May 1-3, 1985 (Nov., 1985), pp. S310-S318
Characterization of a cDNA coding for human protein C. (1984)

Protein C is a precursor to a serine protease that is present in mammalian plasma. In its activated form, it readily inactivates factor Va and factor VIIIa, two proteins that participate as cofactors in the blood coagulation cascade. In the present studies, a lambda gt11 library containing cDNA inserts prepared from human liver mRNA has been screened with an antibody to human protein C. Seven positive clones were isolated from 2 X 10(6) phage and were plaque-purified. The cDNA inserts of two of these phage were sequenced and shown to code for human protein C. Each cDNA insert coded for a portion of the light chain of the molecule, a connecting region, the heavy chain, a stop codon, a 3'-noncoding region, and a poly(A) tail. The length of the noncoding sequence on the 3' end differed in the two clones, but each contained a processing or polyadenylylation signal followed by a poly(A) tail. The amino acid sequence as determined from the cDNA indicates that protein C is synthesized as a single-chain polypeptide containing the light chain and the heavy chain connected by a dipeptide of Lys-Arg. The single-chain molecule is then converted to the light and heavy chains by cleavage of two or more internal peptide bonds. In plasma, the heavy and light chains of protein C are linked together by a disulfide bond. The amino acid sequence of human protein C shows a high degree of homology with that of the bovine molecule. The DNA sequence coding for the catalytic region near the active site serine in human protein C also showed a high degree of DNA and amino acid sequence identity with prothrombin, factor IX, and factor X, three of the other vitamin K-dependent serine proteases that are present in plasma.
Molecular Cloning and Expression of Chick Chondrocyte Chondroitin 6-Sulfotransferase (1995)

Chondroitin 6-sulfotransferase (C6ST) catalyzes the transfer of sulfate from 3'-phosphoadenosine 5'-phosphosulfate to position 6 of the N-acetylgalactosamine residue of chondroitin. The enzyme has been purified previously to apparent homogeneity from the serum-free culture medium of chick chondrocytes. The purified enzyme also catalyzed the sulfation of keratan sulfate. We have now cloned the cDNA of the enzyme. This cDNA contains a single open reading frame that predicts a protein composed of 458 amino acid residues. The protein predicts a Type II transmembrane topology similar to other glycosyltransferases and heparin/heparan sulfate N-sulfotransferase/N-deacetylases. Evidence that the predicted protein corresponds to the previously purified C6ST was the following: (a) the predicted sequence of the protein contains all of the known amino acid sequence, (b) when the cDNA was introduced in a eukaryotic expression vector and transfected in COS-7 cells, both the C6ST activity and the keratan sulfate sulfotransferase activity were overexpressed, (c) a polyclonal antibody raised against a fusion peptide, which was expressed from a cDNA containing the sequence coding for 150 amino acid residues of the predicted protein, cross-reacted to the purified C6ST, and (d) the predicted protein contained six potential sites for N-glycosylation, which corresponds to the observation that the purified C6ST is an N-linked glycoprotein. The amino-terminal amino acid sequence of the purified protein was found in the transmembrane domain, suggesting that the purified protein might be released from the chondrocytes after proteolytic cleavage in the transmembrane domain.
Universal architecture of bacterial chemoreceptor arrays (2009)

Chemoreceptors are key components of the high-performance signal transduction system that controls bacterial chemotaxis. Chemoreceptors are typically localized in a cluster at the cell pole, where interactions among the receptors in the cluster are thought to contribute to the high sensitivity, wide dynamic range, and precise adaptation of the signaling system. Previous structural and genomic studies have produced conflicting models, however, for the arrangement of the chemoreceptors in the clusters. Using whole-cell electron cryo-tomography, here we show that chemoreceptors of different classes and in many different species representing several major bacterial phyla are all arranged into a highly conserved, 12-nm hexagonal array consistent with the proposed "trimer of dimers" organization. The various observed lengths of the receptors confirm current models for the methylation, flexible bundle, signaling, and linker sub-domains in vivo. Our results suggest that the basic mechanism and function of receptor clustering is universal among bacterial species and was thus conserved during evolution.
Roles of DNA polymerase I in leading and lagging-strand replication defined by a high-resolution mutation footprint of ColE1 plasmid replication (2011)

DNA polymerase I (pol I) processes RNA primers during lagging-strand synthesis and fills small gaps during DNA repair reactions. However, it is unclear how pol I and pol III work together during replication and repair or how extensive pol I processing of Okazaki fragments is in vivo. Here, we address these questions by analyzing pol I mutations generated through error-prone replication of ColE1 plasmids. The data were obtained by direct sequencing, allowing an accurate determination of the mutation spectrum and distribution. Pol I's mutational footprint suggests: (i) during leading-strand replication pol I is gradually replaced by pol III over at least 1.3 kb; (ii) pol I processing of Okazaki fragments is limited to ∼20 nt and (iii) the size of Okazaki fragments is short (∼250 nt). While based on ColE1 plasmid replication, our findings are likely relevant to other pol I replicative processes such as chromosomal replication and DNA repair, which differ from ColE1 replication mostly at the recruitment steps. This mutation footprinting approach should help establish the role of other prokaryotic or eukaryotic polymerases in vivo, and provides a tool to investigate how sequence topology, DNA damage, or interactions with protein partners may affect the function of individual DNA polymerases.
New insights into amino acid metabolism, β-cell function and diabetes (2005)

Specific amino acids are now known to acutely and chronically regulate insulin secretion from pancreatic beta-cells in vivo and in vitro. Understanding the molecular mechanisms by which amino acids regulate insulin secretion may identify novel targets for future diabetes therapies. Mitochondrial metabolism is crucial for the coupling of amino acid and glucose recognition to the exocytosis of the insulin granules. This is illustrated by in vitro and in vivo observations discussed in the present review. Mitochondria generate ATP, which is the main coupling factor in insulin secretion; however, the subsequent Ca2+ signal in the cytosol is necessary, but not sufficient, for full development of sustained insulin secretion. Hence mitochondria generate ATP and other coupling factors serving as fuel sensors for the control of the exocytotic process. Numerous studies have sought to identify the factors that mediate the amplifying pathway over the Ca2+ signal in nutrient-stimulated insulin secretion. Predominantly, these factors are nucleotides (GTP, ATP, cAMP and NADPH), although metabolites have also been proposed, such as long-chain acyl-CoA derivatives and the key amino acid glutamate. This scenario highlights further the importance of the key enzymes or transporters, glutamate dehydrogenase, the aspartate and alanine aminotransferases and the malate/aspartate shuttle, in the control of insulin secretion. Therefore amino acids may play a direct or indirect (via generation of putative messengers of mitochondrial origin) role in insulin secretion.
A role for inflammation in irritable bowel syndrome? (2002)

Attention has been directed to the putative role of low grade mucosal inflammation in irritable bowel syndrome (IBS) on the basis of evidence showing that some patients with IBS have an increased number of inflammatory cells in the colonic and ileal mucosa. Previous episodes of infectious enteritis, genetic factors, undiagnosed food allergies, and changes in bacterial microflora may all play a role in promoting and perpetuating this low grade inflammatory process. Human and animal studies support the concept that inflammation may perturb gastrointestinal reflexes and activate the visceral sensory system even when the inflammatory response is minimal and confined to the mucosa. Thus abnormal neuroimmune interactions may contribute to the altered gastrointestinal physiology and hypersensitivity that underlies IBS. A brief review of the human and animal studies that have focused on the putative role of intestinal inflammation and infections in the pathogenesis of IBS is given.
Hematopoietic stem cell trafficking in liver injury (2005)

Bone marrow (BM) hematopoietic stem cells (HSCs) have been shown to facilitate regeneration in multiple nonhematopoietic tissues by either generating epithelial cells or altering the inflammatory response. Depending on injury type, the predominant mechanism of epithelial lineage regeneration occurs by spontaneous cell fusion or transdifferentiation. Irrespective of the mechanism, mobilization from the BM is a prerequisite. Mechanisms by which HSCs mobilize into damaged organs are currently under scrutiny. Murine and human studies have shown that the chemokine SDF-1 and its receptor CXCR4 participate in the mobilization of HSCs from BM and in the migration of HSCs to injured liver. SDF-1 is a potent HSC chemoattractant and is produced by the liver. Production is increased during liver injury leading to increased HSC migration to the liver, a finding diminished by neutralizing anti-CXCR4 antibodies. Additional factors have been implicated in the control of hepatic migration of HSCs such as IL-8, hepatocyte growth factor, and MMP-9. Matriceal remodeling is an essential component in HSC engraftment, and MMP-9 expression is increased in liver injury. This review focuses on the complex interaction of chemokines, adhesion molecules, and extracellular matrix factors required for successful migration and engraftment of HSCs into the liver.