gebhart/patrepeval huggingface dataset:
Developing combination strategies using PD-1 checkpoint inhibitors to treat cancer (2018)

More than 3000 clinical trials are evaluating the clinical activity of the PD-1 checkpoint inhibitors as monotherapies and in combinations with other cancer therapies [1]. The PD-1 checkpoint inhibitors are remarkable for their clinical activities in shrinking tumors across a wide range of tumor types, in causing durable responses, and in their tolerability. These attributes position them as favorable agents in clinical combinations. Historically, approaches to cancer therapy combinations focused on agents with orthogonal activities to avoid shared resistance mechanisms and shared toxicities. Although CTLA-4/PD-1 combinations have progressed based on possible immune interactions, additional approaches have used more orthogonal treatments such as standard of care chemotherapies and anti-angiogenesis inhibitors. Using the concept of independent activity pioneered by Bliss [2], examples of these approaches were compared. Both standard of care chemotherapy and anti-angiogenesis combinations show promising clinical activity above that predicted by the independent contributions of the agents tested on their own. In contrast, the combinations of CTLA4/PD-1 checkpoint inhibitors in renal cancer and melanoma show no more activity than that predicted by the independent contributions of the monotherapies. This update on approaches to the development of clinical combination therapies highlights the potential importance of combining PD-1 checkpoint inhibitors with a broad range of clinically active partners.
A 90nm CMOS SoC UWB pulse radar for respiratory rate monitoring (2011)

UWB technology (3.1 to 10.6GHz) allows new applications for both data communication and sensing. Due to their potential in terms of resolution and extremely low level of EIRP spectral density (<; -41.3dBm/MHz), UWB radars are very attractive for a large set of civil and military sensing applications, as ground penetrating, surveillance, localization, intra-wall and through-wall detections and biomedical imaging. Moreover, with respect to continuous-wave (CW) radars, UWB radar transceivers present a lower circuit complexity since no frequency conversions are required, leading to lower power consumption (Pc) for longer battery autonomy.
Antisense inhibition of connective tissue growth factor (CTGF/CCN2) mRNA limits hypertrophic scarring without affecting wound healing in vivo (2008)

Augmented expression of connective tissue growth factor (CTGF/CCN2) is observed in healing wounds and in a variety of fibrotic disorders. It appears to enhance many of the effects of transforming growth factor-beta and has been shown to have independent fibrogenic functions. Despite these observations, its importance to dermal wound healing and the transition from wound to scar remains poorly defined. In this study, we use established rabbit models to evaluate the roles of CTGF in dermal wound healing and hypertrophic scarring. We show that CTGF mRNA demonstrates persistent up-regulation in hypertrophic scars. Treatment of wounds with antisense oligonucleotides to CTGF has no measurable effect on early wound closure. However, antisense therapy significantly limits subsequent hypertrophic scarring. Inhibition of CTGF is associated with a marked reduction in the number of myofibroblasts in scars and decreased transcription of TIMP-1 and types I and III collagen. These findings confirm CTGF to be a key mediator of hypertrophic scarring in this model. Its effect on myofibroblasts in this setting suggests a mechanism whereby it plays this role. Its limited participation in early healing implies that it may be a useful and specific target for modulating hypertrophic scarring following injury.
A general approach to site-specific antibody drug conjugates (2014)

Using an expanded genetic code, antibodies with site-specifically incorporated nonnative amino acids were produced in stable cell lines derived from a CHO cell line with titers over 1 g/L. Using anti-5T4 and anti-Her2 antibodies as model systems, site-specific antibody drug conjugates (NDCs) were produced, via oxime bond formation between ketones on the side chain of the incorporated nonnative amino acid and hydroxylamine functionalized monomethyl auristatin D with either protease-cleavable or noncleavable linkers. When noncleavable linkers were used, these conjugates were highly stable and displayed improved in vitro efficacy as well as in vivo efficacy and pharmacokinetic stability in rodent models relative to conventional antibody drug conjugates conjugated through either engineered surface-exposed or reduced interchain disulfide bond cysteine residues. The advantages of the oxime-bonded, site-specific NDCs were even more apparent when low-antigen-expressing (2+) target cell lines were used in the comparative studies. NDCs generated with protease-cleavable linkers demonstrated that the site of conjugation had a significant impact on the stability of these rationally designed prodrug linkers. In a single-dose rat toxicology study, a site-specific anti-Her2 NDC was well tolerated at dose levels up to 90 mg/kg. These experiments support the notion that chemically defined antibody conjugates can be synthesized in commercially relevant yields and can lead to antibody drug conjugates with improved properties relative to the heterogeneous conjugates formed by nonspecific chemical modification.
Wear of polymeric bearing materials: The effects of in vivo implantation (1976)

The gross biocompatibility of the materials implanted was generally satisfactory. Weight gain during implantation due to net sorption of fluid was negligible for PPO and UHMWPE. Delrin AF specimens gained less than 0.5%, while SP-1 and SP-21 gained up to 2% in weight. Amoco-AI specimens gained up to 7% in weight. The friction coefficient of implanted samples of UHMWPE was lower by 20 to 40% than for the virgin material. The friction coefficient of the other implanted materials was usually somewhat higher than the friction coefficient of the corresponding virgin material. The largest increase in the friction coefficient was 38% for Delrin AF. Wear characteristics of UHMWPE were not significantly changed by implantation for periods of three years. UHMWPE was the only acceptable bearing material tested. Significantly higher wear rates were observed for implanted blocks of the SP-21, a Delrin AF, and an Amoco-AI material. Because of excellent creep resistance, virgin wear rates, and other favorable properties of the polyimides, further testings are in progress to indicate potential application of these polymers.
NKH477: A novel bronchodilator produces potentiation and tachyphylaxis reversal to salbutamol in isolated guinea pig trachea (1999)

The relaxant responses of the β2-adrenoceptor agonist salbutamol and NKH477, an activator of adenylate cyclase, were compared and the possible potentiating effect of NKH477 on salbutamol-induced bronchodilatation was measured together with the effectiveness of NKH477 in reversing tachyphylaxis development to salbutamol. The in vitro bronchodilator effect of salbutamol and NKH477 (10–9 – 10–5 M) was measured on isolated guinea pig tracheal ring segments precontracted with carbachol (10–6 M). Both salbutamol and NKH477 produced a concentration-dependent relaxation. EC50 values were determined from cumulative concentration–response curves. Salbutamol was more potent than NKH477 in relaxing the tracheal preparations (7.1 ± 0.1 compared to 6.1 ± 0.2, respectively). NKH477 produced a significant increase in the salbutamol-induced bronchodilator effect. The potency values recorded for salbutamol were 7.1 ± 0.1, 7.4 ± 0.2, 7.6 ± 0.1, and 8.6 ± 0.4 in the absence and presence of NKH477 (3 × 10–8 M, 10–7 M, and 3 × 10–7 M, respectively). Reproducible relaxant responses could be elicited to salbutamol and NKH477 after 24 h incubation in Krebs' solution. Tachyphylaxis to the relaxant effects of salbutamol was experimentally induced by 24-h incubation of the preparations in Krebs' solution containing salbutamol (10–6, 3 × 10–6 or 10–5 M). The potency of salbutamol was reduced to 6.9 ± 0.2, 6.8 ± 0.2, and 6.0 ± 0.2 after 24 h incubation with salbutamol 10–6 M, 3 × 10–6 M or 10–5 M, respectively. NKH477 (3 × 10–7 M) produced a complete reversal of tachyphylaxis to salbutamol-induced relaxation in salbutamol pretreated tissues. The potency of salbutamol was increased to 7.4 ± 0.2, 7.1 ± 0.1, and 7.3 ± 0.1 after the addition of NKH477 (3 × 10–7 M) to the preparations preincubated (24 h) with salbutamol 10–6, 3 × 10–6, or 10–5 M, respectively. NKH477 shares with salbutamol the ability to relax airway smooth muscle and produces an apparent increase of the bronchodilator effects of salbutamol and reverses tachyphylaxis. Drug Dev. Res. 48:154–159, 1999. © 1999 Wiley-Liss, Inc.
High expression of a cytokeratin-associated protein in many cancers (2006)

We have described previously a cDNA library made from membrane-bound polysomal mRNA prepared from breast and prostate cancer cell lines. The library is highly enriched for cDNAs encoding membrane proteins, secreted proteins, and cytokeratins. To characterize this library, 25,277 cDNA clones were sequenced and aligned with various databases; 1,439 clones did not align with known genes. From this set of clones we identified a previously uncharacterized gene encoding a 334-aa protein. Although protein structural motif prediction programs indicate that the gene encodes a membrane protein comprising a signal sequence, a series of leucine-rich repeats, and a single transmembrane domain with a cytoplasmic tail, confocal microscopy of MCF7 breast cancer cells demonstrates that the protein is not directly associated with the plasma membrane or intracellular membranes but instead colocalizes with intermediate filaments and cytokeratins within the cell. Immunofluorescence studies also show that protein expression is increased greatly in mitotic MCF7 cells, and immunohistochemistry demonstrates its expression in human breast cancer cells. Analysis of mRNA levels in 25 different normal tissues by RT-PCR shows that this gene is expressed highly in normal prostate and salivary gland, very weakly in colon, pancreas, and intestine, and not at all in other tissues. RT-PCR studies on human cancer samples show that the RNA is expressed highly in many cancer cell lines and cancer specimens, including 26 of 33 human breast cancers, 3 of 3 prostate cancers, 3 of 3 colon cancers, and 3 of 3 pancreatic cancers. We name the protein CAPC, cytokeratin-associated protein in cancer.
Structural Characterization of the UL25 DNA-Packaging Protein from Herpes Simplex Virus Type 1 (2006)

Herpesviruses replicate their double stranded DNA genomes as high-molecular-weight concatemers which are subsequently cleaved into unit-length genomes by a complex mechanism that is tightly coupled to DNA insertion into a preformed capsid structure, the procapsid. The herpes simplex virus type 1 UL25 protein is incorporated into the capsid during DNA packaging, and previous studies of a null mutant have demonstrated that its function is essential at the late stages of the head-filling process, either to allow packaging to proceed to completion or for retention of the viral genome within the capsid. We have expressed and purified an N-terminally truncated form of the 580-residue UL25 protein and have determined the crystallographic structure of the region corresponding to amino acids 134 to 580 at 2.1-Angstroms resolution. This structure, the first for any herpesvirus protein involved in processing and packaging of viral DNA, reveals a novel fold, a distinctive electrostatic distribution, and a unique "flexible" architecture in which numerous flexible loops emanate from a stable core. Evolutionary trace analysis of UL25 and its homologues in other herpesviruses was used to locate potentially important amino acids on the surface of the protein, leading to the identification of four putative docking regions for protein partners.
Protein tyrosine phosphatase containing SH2 domains: characterization, preferential expression in hematopoietic cells, and localization to human chromosome 12p12-p13. (1992)

Protein tyrosine phosphorylation has been implicated in the growth and functional responses of hematopoietic cells. Recently, approaches have been developed to characterize the protein tyrosine phosphatases that may contribute to regulation of protein tyrosine phosphorylation. One novel protein tyrosine phosphatase was expressed predominantly in hematopoietic cells. Hematopoietic cell phosphatase encodes a 68-kDa protein that contains a single phosphatase conserved domain. Unlike other known protein tyrosine phosphatases, hematopoietic cell phosphatase contains two src homology 2 domains. We also cloned the human homolog, which has 95% amino acid sequence identity. Both the murine and human gene products have tyrosine-specific phosphatase activity, and both are expressed predominantly in hematopoietic cells. Importantly, the human gene maps to chromosome 12 region p12-p13. This region is associated with rearrangements in approximately 10% of cases of acute lymphocytic leukemia in children.
The Use of Next Generation Sequencing and Junction Sequence Analysis Bioinformatics to Achieve Molecular Characterization of Crops Improved Through Modern Biotechnology (2012)

The assessment of genetically modified (GM) crops for regulatory approval currently requires a detailed molecular characterization of the DNA sequence and integrity of the transgene locus. In addition, molecular characterization is a critical component of event selection and advancement during product development. Typically, molecular characterization has relied on Southern blot analysis to establish locus and copy number along with targeted sequencing of polymerase chain reaction products spanning any inserted DNA to complete the characterization process. Here we describe the use of next generation (NexGen) sequencing and junction sequence analysis bioinformatics in a new method for achieving full molecular characterization of a GM event without the need for Southern blot analysis. In this study, we examine a typical GM soybean [ Glycine max (L.) Merr.] line and demonstrate that this new method provides molecular characterization equivalent to the current Southern blot‐based method. We also examine an event containing in vivo DNA rearrangement of multiple transfer DNA inserts to demonstrate that the new method is effective at identifying complex cases. Next generation sequencing and bioinformatics offers certain advantages over current approaches, most notably the simplicity, efficiency, and consistency of the method, and provides a viable alternative for efficiently and robustly achieving molecular characterization of GM crops.
LEGO‐NMR Spectroscopy: A Method to Visualize Individual Subunits in Large Heteromeric Complexes (2013)

Seeing the big picture: Asymmetric macromolecular complexes that are NMR active in only a subset of their subunits can be prepared, thus decreasing NMR spectral complexity. For the hetero heptameric LSm1-7 and LSm2-8 rings NMR spectra of the individual subunits of the complete complex are obtained, showing a conserved RNA binding site. This LEGO-NMR technique makes large asymmetric complexes accessible to detailed NMR spectroscopic studies.
Identification of a zinc finger protein whose subcellular distribution is regulated by serum and nerve growth factor (1999)

A subclass of zinc finger proteins containing a unique protein motif called the positive regulatory (PR) domain has been described. The members include the PRDI-BF1/Blimp-1 protein, the Caenorhabditis elegans egl-43 and EVI1 gene products, and the retinoblastoma interacting protein RIZ. Here we describe a member of this family, SC-1, that exhibits several distinctive features. First, SC-1 interacts with the p75 neurotrophin receptor and is redistributed from the cytoplasm to the nucleus after nerve growth factor (NGF) treatment of transfected COS cells. The translocation of SC-1 to the nucleus was specific for p75, as NGF binding to the TrkA receptor did not lead to nuclear localization of SC-1. Thus, SC-1 provides a downstream transducer for the effects of NGF through the p75 neurotrophin receptor. Under normal growth conditions, SC-1 was found predominantly in the cytoplasm. On serum-starvation, SC-1 also translocated into the nucleus. A direct correlation between nuclear expression of SC-1 with the loss of BrdUrd incorporation was observed. These results imply that SC-1 may be involved in events associated with growth arrest.
Occurrence, Classification, and Biological Function of Hydrogenases:  An Overview (2007)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOccurrence, Classification, and Biological Function of Hydrogenases: An OverviewPaulette M. Vignais and Bernard BilloudView Author Information CEA Grenoble, Laboratoire de Biochimie et Biophysique des Systèmes Intégrés, UMR CEA/CNRS/UJF 5092, Institut de Recherches en Technologies et Sciences pour le Vivant (iRTSV), 17 rue des Martyrs, 38054 Grenoble cedex 9, France, and Atelier de BioInformatique Université Pierre et Marie Curie (Paris 6), 12 rue Cuvier, 75005 Paris, France Cite this: Chem. Rev. 2007, 107, 10, 4206–4272Publication Date (Web):October 10, 2007Publication History Received26 February 2007Published online10 October 2007Published inissue 1 October 2007https://pubs.acs.org/doi/10.1021/cr050196rhttps://doi.org/10.1021/cr050196rresearch-articleACS PublicationsCopyright © 2007 American Chemical SocietyRequest reuse permissionsArticle Views13248Altmetric-Citations1283LEARN 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-Alertsclose SUBJECTS:Bacteria,Cluster chemistry,Iron-sulfur clusters,Monomers,Peptides and proteins Get e-Alerts
Transcription Factor Glis3, a Novel Critical Player in the Regulation of Pancreatic β-Cell Development and Insulin Gene Expression (2009)

In this study, we report that the Krüppel-like zinc finger transcription factor Gli-similar 3 (Glis3) is induced during the secondary transition of pancreatic development, a stage of cell lineage specification and extensive patterning, and that Glis3(zf/zf) mutant mice develop neonatal diabetes, evidenced by hyperglycemia and hypoinsulinemia. The Glis3(zf/zf) mutant mouse pancreas shows a dramatic loss of beta and delta cells, contrasting a smaller relative loss of alpha, PP, and epsilon cells. In addition, Glis3(zf/zf) mutant mice develop ductal cysts, while no significant changes were observed in acini. Gene expression profiling and immunofluorescent staining demonstrated that the expression of pancreatic hormones and several transcription factors important in endocrine cell development, including Ngn3, MafA, and Pdx1, were significantly decreased in the developing pancreata of Glis3(zf/zf) mutant mice. The population of pancreatic progenitors appears not to be greatly affected in Glis3(zf/zf) mutant mice; however, the number of neurogenin 3 (Ngn3)-positive endocrine cell progenitors is significantly reduced. Our study indicates that Glis3 plays a key role in cell lineage specification, particularly in the development of mature pancreatic beta cells. In addition, we provide evidence that Glis3 regulates insulin gene expression through two Glis-binding sites in its proximal promoter, indicating that Glis3 also regulates beta-cell function.
Virtual Biopsies in Barrett's Esophagus Using an Impedance Probe (1999)

Preliminary results of electrical impedance measurements in squamous and columnar epithelia in rat and human tissues are presented. The aim of this work is to show the possibility of differentiating these two types of epithelia in terms of their electrical characteristics. For the measurements, we employed a 1.95-m-long, 3.2-mm-diameter, four-electrode probe designed to be used transendoscopically in the diagnosis of Barrett's esophagus (BE). BE is a condition in which the normal squamous epithelium of the esophagus is replaced by columnar epithelium of the intestinal type. This metaplasia is considered as a premalignant condition that puts patients at a 30-125-fold risk of developing adenocarcinoma of the esophagus. The diagnosis and surveillance of BE involve taking multiple biopsies, an expensive and time-consuming procedure. This study constitutes the first stage in the replacement of tissue biopsy by "virtual biopsies".
The Natural History of Post-Traumatic Reflex Sympathetic Dystrophy (1998)

The paper presents the results of a prospective trial to examine the natural history of early reflex sympathetic dystrophy (RSD). Thirty patients with post-traumatic RSD of the hand were observed without treatment. They were reassessed 1, 2 and 6 months after diagnosis with a final assessment at 10 to 18 months (average 13 months). Twenty-seven patients completed the study. Three were withdrawn during the study because of persistence of signs and symptoms of RSD and were given further treatment. Of the 27 patients who completed the study, only one showed sufficient features of the condition to warrant the diagnosis of mild RSD. In the remaining 26, most features of RSD had resolved spontaneously. Pain and swelling disappeared more quickly than other features of RSD. Although the signs and symptoms of RSD had largely gone at 13 months, the hands were still functionally impaired because of weaker grip strength.
Cytoskeleton alteration in MCF7R cells, a multidrug resistant human breast cancer cell line. (1998)

Various cytoskeleton modifications are associated with malignant cell transformation and have been used as prognostic factors. A human breast cancer cell line (MCF7S) and its multidrug resistant (MDR) subline (MCF7R) were characterized here for their intermediate filaments (IFs) expression (cytokeratin 8, 18, 19 and vimentin) as a function of their resistance phenotype. Modifications of these cytoskeleton molecules were analyzed by flow cytometry, immunofluorescence, electrophoresis and immunoblotting techniques. Cytokeratins 8 and 18 were similarly expressed in the cell lines. Cytokeratin 19 was expressed in the MCF7S cell line and not in the MCF7R variant, while vimentin was highly expressed in MCF7R and slightly in MCF7S. Analysis of IFs after the addition of doxorubicin (Dox) in the culture medium of MCF7S, showed an increase in cytokeratin 8 filaments. Vimentin expression in MCF7R was not modified in the presence of these different MDR modulators. Acquisition of MDR was associated with an increase and a redistribution of vimentin filaments characterized by a perinuclear polarization. These drug resistance associated changes might derive from different biological processes triggered by chemotherapy. In conclusion, this suggests that this intermediate filament could be a marker associated with chemoresistance or a marker of malignancy in certain epithelial cancers.