gebhart/patrepeval huggingface dataset:
Characterization of the receptor binding determinants of granulocyte colony stimulating factor (1997)

We performed a series of experiments using alanine-scanning mutagenesis to locate side chains within human granulocyte colony-stimulating factor (G-CSF) that are involved in human G-CSF receptor binding. We constructed a panel of 28 alanine mutants that examined all surface exposed residues on helices A and D, as well as all charged residues on the surface of G-CSF. The G-CSF mutants were expressed in a transiently transfected mammalian cell line and quantitated by a sensitive biosensor method. We measured the activity of mutant proteins using an in vitro proliferation assay and an ELISA binding competition assay. These studies show that there is a region of five charged residues on helices A and C employed by G-CSF in binding its receptor, with the most important residue in this binding patch being Glu 19. Both wild-type G-CSF and the E19A mutant were expressed in E. coli. The re-folded proteins were found to have proliferative activities similar to the analogous proteins from mammalian cells: furthermore, biophysical analysis indicated that the E19A mutation does not cause gross structural perturbations in G-CSF. Although G-CSF is likely to signal through receptor homo-dimerization, we found no compelling evidence for a second receptor binding region. We also found no evidence of self-antagonism at high G-CSF concentrations, suggesting that, in contrast to human growth hormone (hGH) and erythropoietin (EPO), G-CSF probably does not signal via a pure 2:1 receptor ligand complex. Thus, G-CSF, while having a similar tertiary structure to hGH and EPO, uses different areas of the four helix bundle for high-affinity interaction with its receptor.
Monitoring deployed software using software tomography (2002)

Software products are often released with missing functionality or errors that result in failures in the field. In previous work, we presented the Gamma technology, which facilitates remote monitoring of deployed software and allows for a prompt reaction to failures. In this paper, we investigate one of the principal technologies on which Gamma is based: software tomography. Software tomography splits monitoring tasks across many instances of the software, so that partial information can be (1) collected from users by means of light-weight instrumentation and (2) merged to gather the overall monitoring information. After describing the technology, we illustrate an instance of software tomography for a specific monitoring task. We also present two case studies that we performed to evaluate the presented technique on a real program. The results of the studies show that software tomography can be successfully applied to collect accurate monitoring information using only minimal instrumentation on each deployed program instance.
The Promise of Molecular Profiling for Cancer Identification and Treatment (2004)

The completion of the human genome sequence, in conjunction with newer, cheaper, and more reliable methods of gene expression analysis has the potential to revolutionize cancer diagnosis and treatment. By providing a molecular portrait of an individual cancer, this technology will allow clinicians to determine the origin of the cancer, its potential for metastasis, its specific drug responsiveness, and the probability of its recurrence.
A Network Algorithm for Performing Fisher's Exact Test in r × c Contingency Tables (1983)

Abstract An exact test of significance of the hypothesis that the row and column effects are independent in an r × c contingency table can be executed in principle by generalizing Fisher's exact treatment of the 2 × 2 contingency table. Each table in a conditional reference set of r × c tables with fixed marginal sums is assigned a generalized hypergeometric probability. The significance level is then computed by summing the probabilities of all tables that are no larger (on the probability scale) than the observed table. However, the computational effort required to generate all r × c contingency tables with fixed marginal sums severely limits the use of Fisher's exact test. A novel technique that considerably extends the bounds of computational feasibility of the exact test is proposed here. The problem is transformed into one of identifying all paths through a directed acyclic network that equal or exceed a fixed length. Some interesting new optimization theorems are developed in the process. The numerical results reveal that for sparse contingency tables Fisher's exact test and Pearson's χ2 test frequently lead to contradictory inferences concerning row and column independence.
Clades of huge phages from across Earth’s ecosystems (2020)

Bacteriophages typically have small genomes<sup>1</sup> and depend on their bacterial hosts for replication<sup>2</sup>. Here we sequenced DNA from diverse ecosystems and found hundreds of phage genomes with lengths of more than 200 kilobases (kb), including a genome of 735 kb, which is-to our knowledge-the largest phage genome to be described to date. Thirty-five genomes were manually curated to completion (circular and no gaps). Expanded genetic repertoires include diverse and previously undescribed CRISPR-Cas systems, transfer RNAs (tRNAs), tRNA synthetases, tRNA-modification enzymes, translation-initiation and elongation factors, and ribosomal proteins. The CRISPR-Cas systems of phages have the capacity to silence host transcription factors and translational genes, potentially as part of a larger interaction network that intercepts translation to redirect biosynthesis to phage-encoded functions. In addition, some phages may repurpose bacterial CRISPR-Cas systems to eliminate competing phages. We phylogenetically define the major clades of huge phages from human and other animal microbiomes, as well as from oceans, lakes, sediments, soils and the built environment. We conclude that the large gene inventories of huge phages reflect a conserved biological strategy, and that the phages are distributed across a broad bacterial host range and across Earth's ecosystems.
Activation of mutated K‐ras in donor endometrial epithelium and stroma promotes lesion growth in an intact immunocompetent murine model of endometriosis (2011)

Endometriosis is a common chronic gynaecological condition, affecting 5-10% of women of child-bearing age. Its study has been hampered by lack of genetically tractable models. We transplanted steroid-manipulated, menstrual-like endometrium from K-ras(G12V/+) /Ah-Cre(+/+) /ROSA26R-LacZ(+/+) mice into gonad-intact immunocompetent wild-type mice. This led to endometriosis-like lesion development. Long-term lesion survival depended on the presence of the activated K-ras in the small proportion of the cells in the mature lesion that had undergone Cre-mediated K-ras activation. LacZ activity demonstrated Cre-mediated recombination in both endometrial epithelial cells and stromal cells, and transgenic K-ras expression was confirmed by RT-PCR. The endometriosis lesions developed without exogenous oestradiol supplementation and anti-oestrogen (fulvestrant, ICI 182780) treatment greatly suppressed their growth. Immunohistochemistry confirmed that as in human endometriosis, there was invasion and activation of fibroblasts, endothelial cells, and macrophages, with marked collagen deposition in the lesions. This model provides an opportunity to investigate endometriosis lesion establishment, growth, and regression in genetically tractable, immunocompetent, and hormonally intact mice. Furthermore, for the first time it provides a suitable model to test clinically validated driver genes in a faithful mouse model of the predisposing endometriotic lesion, thus providing the correct cellular context and microenvironment for ovarian clear cell carcinogenesis.
Stable transmission of targeted gene modification using single-stranded oligonucleotides with flanking LNAs (2005)

Targeted mutagenesis directed by oligonucleotides (ONs) is a promising method for manipulating the genome in higher eukaryotes. In this study, we have compared gene editing by different ONs on two new target sequences, the eBFP and the rd1 mutant photoreceptor betaPDE cDNAs, which were integrated as single copy transgenes at the same genomic site in 293T cells. Interestingly, antisense ONs were superior to sense ONs for one target only, showing that target sequence can by itself impart strand-bias in gene editing. The most efficient ONs were short 25 nt ONs with flanking locked nucleic acids (LNAs), a chemistry that had only been tested for targeted nucleotide mutagenesis in yeast, and 25 nt ONs with phosphorothioate linkages. We showed that LNA-modified ONs mediate dose-dependent target modification and analyzed the importance of LNA position and content. Importantly, when using ONs with flanking LNAs, targeted gene modification was stably transmitted during cell division, which allowed reliable cloning of modified cells, a feature essential for further applications in functional genomics and gene therapy. Finally, we showed that ONs with flanking LNAs aimed at correcting the rd1 stop mutation could promote survival of photoreceptors in retinas of rd1 mutant mice, suggesting that they are also active in vivo.
Cloned cDNA sequences of the hypoxanthine/guanine phosphoribosyltransferase gene from a mouse neuroblastoma cell line found to have amplified genomic sequences. (1982)

Cloned cDNA sequences of the murine hypoxanthine/guanine phosphoribosyltransferase (HPRT; EC 2.4.2.8) gene have been isolated by using a mouse neuroblastoma cell line containing increased levels of a variant HPRT protein. We have used these sequences as probes to demonstrate that protein overproduction in this cell line is a consequence of at least a 20-fold increase in HPRT mRNA levels resulting from approximately 50-fold amplification of HPRT genomic sequences. The largest cDNA insert so far characterized represents about 70% of the HPRT mRNA sequence. This cDNA is shown to possess regions of homology with mRNA and DNA from Chinese hamster, baboon, and human, thus facilitating detailed analysis of this locus in these four species.
A Reappraisal of the Application of the Trendelenburg Operation to Massive Fatal Embolism (1963)

ALTHOUGH Trendelenburg1 had proposed and attempted pulmonary-artery embolectomy for massive embolism sixteen years previously it remained for Kirschner,2 in 1924, to perform the first successful operative procedure. Thereafter, within a seven-year period, Meyer,3 Crafoord4 and Nyström5 recorded a total of 8 embolectomies with survival. Enthusiasm for the undertaking was dampened only by Churchill's6 report, in 1934, of 10 consecutive unsuccessful arteriotomies performed at the Massachusetts General Hospital. During the preceding five-year period at this institution embolectomy operative kits had been kept in readiness in the operating suite at all times. The patient suspected of harboring a massive embolus was closely . . .
Human papillomavirus and disease mechanisms: relevance to oral and cervical cancers* (2005)

Oral squamous cell carcinoma (OSCC) is the sixth most common malignancy and is a major cause of cancer morbidity and mortality worldwide. Carcinoma of the uterine cervix is the most common female malignancy in the world. While cervical cancer is a worldwide disease, oral cancer has the highest incidence in developing countries, especially among tobacco and alcohol users and betel quid chewers. A strong association of cervical and oral cancer with high‐risk human papillomavirus (HPV) 16 and 18 infections underlines the importance of the virus in the pathogenesis of these squamous cell carcinomas. Functionally high‐risk HPV infection contributes to carcinogenesis and tumor progression predominantly through the actions of two viral oncogenes, E6 and E7. The E6 and E7 genes have been studied in different patient populations and a number of variants have been described. More than 40 variants have been classified and may be related to differences in progression of squamous intraepithelial lesions. The transcription factor, NF κ B and its activation pathways are frequently targeted by viruses and aberrant constitutive activation of NF κ B is frequently found in human tumors of diverse tissue origin. Diet–gene interactions are also likely to contribute considerably to the observed inter‐individual variations in HPV associated cancer risk, in response to exposures to the nutritional factors that have the potential to promote or protect against cancer.
Photosensitive resins containing p‐dimethylaminobenzylidene derivatives and diphenyliodonium salt as photoinitiators (1987)

Abstract A series of p ‐dimethylaminobenzylidene derivatives was able to sensitize the photodecomposition of diphenyliodonium salt to afford highly photosensitive negative‐type resins. When a polymer‐bearing methacryloylated group in the side chain was sensitized with a combination of the p ‐dimethylaminobenzylidene compounds and the iodonium salt, the polymer demonstrated high sensitivity even to 488 nm light emitted from an Argon laser. The same photoinitiator systems were applicable to insolubilize poly(glycidyl methacrylate) through cationic photopolymerization. The storage stability of these types of photoinitiators depends on the structure of the benzylidene compounds; decreasing the basicity of the amino group enhanced the thermal stability.
Cloning of the human twist gene: Its expression is retained in adult mesodermally-derived tissues (1997)

We have previously reported on the isolation of several differentially expressed genes derived from young and senescent non growing WI-38 human fetal lung-derived fibroblasts. A 0.8-kb cDNA clone, isolate EPC-A2 (early population doubling cDNA-A2), encodes the 3' end of the human homolog of the Twist protein. Twist genes encode basic helix-loop-helix DNA-binding transcription factors that play crucial roles in mesoderm development. Here, we report the cloning and sequencing of the genomic human twist gene. It encodes a protein of 201 amino acids with 96% amino acid sequence identity to mouse Twist, and 100% sequence conservation in the DNA-binding region among all species in which it has been characterized. We further show that expression of human twist is retained in mesodermally-derived tissues and cell lines derived from adult donors.
Phage display selection of a peptide DNase II inhibitor that enhances gene delivery (2001)

A novel peptide DNase II inhibitor has been used to increase transfection. The level of enhancement was found to be significant in multiple cell types with multiple synthetic vectors.
Treatment of Visceral Leishmaniasis with Sterically Stabilized Liposomes Containing Camptothecin (2001)

The efficacy of 20(S)-camptothecin (CPT), free and incorporated into sterically stabilized liposomes, has been investigated in vitro against Leishmania donovani promastigotes and in vivo in a murine model of visceral leishmaniasis. Incubation of L. donovani promastigotes with free or liposomal CPT inhibited the growth of parasites in a dose-dependent manner. Tissue distribution studies revealed that the intraperitoneal administration of liposomal CPT was efficient for the delivery of high drug levels to the liver and spleen. Treatment of infected mice with intraperitoneal injections of free and liposomal CPT significantly reduced the parasite loads in the livers by 43 and 55%, respectively, compared with the loads for untreated controls. However, both treatments caused normochromic anemia and neutropenia.
The human osteoclast precursor circulates in the monocyte fraction. (1996)

The osteoclast is known to be formed by fusion of circulating mononuclear precursor cells of haematopoietic origin. The precise nature of these circulating cells and, in particular, their relation to monocytes is unknown. We have developed an in vitro system of human osteoclast formation whereby human monocytes [CD14, CD11a, CD11b and HLA-DR positive, and tartrate-resistant acid phosphatase (TRAP), calcitonin receptor (CTR), vitronectin receptor (VNR) negative] were isolated and cocultured for up to 21 days with UMR106 rat osteoblast-like cells or ST2 mouse preadipocytic bone marrow stromal cells in the presence of 1 alpha, 25 dihydroxyvitamin D3 (1,25(OH)2D3) and macrophage colony stimulating factor (M-CSF). Numerous TRAP, VNR and CTR positive multinucleated cells, capable of extensive lacunar bone resorption, formed in these cocultures; the absolute requirements for this to occur were contact with the above bone stromal cells, 1,25(OH)2D3, and M-CSF. These results show that the human mononuclear osteoclast precursor circulates in the monocyte fraction and exhibits a monocyte phenotype, acquiring osteoclast phenotypic features in the process of differentiation into mature functional osteoclasts.
The Male Factor in Fertility and Infertility. II. Spermatozoön Counts in 1000 Men of Known Fertility and in 1000 Cases of Infertile Marriage (1951)

No AccessJournal of Urology1 Sep 1951The Male Factor in Fertility and Infertility. II. Spermatozoön Counts in 1000 Men of Known Fertility and in 1000 Cases of Infertile Marriage John MacLeod, andPh.D. Ruth Z. GoldM.A. John MacLeodJohn MacLeod , and Ruth Z. GoldRuth Z. Gold View All Author Informationhttps://doi.org/10.1016/S0022-5347(17)74358-3AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail © 1951 by The American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited ByNiederberger C (2016) The Male Factor in Fertility and InfertilityJournal of Urology, VOL. 197, NO. 2S, (S92-S93), Online publication date: 1-Feb-2017.Lipshultz L, Ross C, Whorton D, Milby T, Smith R and Joyner R (2018) Dibromochloropropane and its Effect on Testicular Function in ManJournal of Urology, VOL. 124, NO. 4, (464-468), Online publication date: 1-Oct-1980.Cockett A, Netto I, Dougherty K and Urry R (2018) Semen Analysis: A Review of Samples from 225 Men Seen at an Infertility ClinicJournal of Urology, VOL. 114, NO. 4, (560-563), Online publication date: 1-Oct-1975.Mannion R and Cottrell T (2018) Correlation between Testicular Biopsy and Sperm CountJournal of Urology, VOL. 85, NO. 6, (953-955), Online publication date: 1-Jun-1961.Veenema R and Lattimer J (2018) Genital Tuberculosis in the Male: Clinical Pathology and Effect on FertilityJournal of Urology, VOL. 78, NO. 1, (65-77), Online publication date: 1-Jul-1957.Macleod J (2018) Certain Concepts in Human Male FertilityJournal of Urology, VOL. 67, NO. 1, (19-26), Online publication date: 1-Jan-1952. Volume 66Issue 3September 1951Page: 436-449 Advertisement Copyright & Permissions© 1951 by The American Urological Association Education and Research, Inc.MetricsAuthor Information John MacLeod More articles by this author Ruth Z. Gold More articles by this author Expand All Advertisement PDF DownloadLoading ...
Macrophage activation syndrome following initiation of etanercept in a child with systemic onset juvenile rheumatoid arthritis. (2003)

Systemic onset juvenile rheumatoid arthritis (JRA) accounts for 10-15% of all JRA. Macrophage activation syndrome (MAS), which can also be considered as secondary hemophagocytic lymphohistiocytosis, is a potentially life-threatening complication of systemic onset JRA. We describe a child with systemic onset JRA who developed MAS after initiation of etanercept therapy.
Transfection Using DEAE‐Dextran (1997)

Transfection of cultured mammalian cells using diethylaminoethyl (DEAE)-dextran/DNA can be an attractive alternative to other transfection methods in many circumstances. The major advantages of the technique are its relative simplicity and speed, limited expense, and remarkably reproducible interexperimental and intraexperimental transfection efficiency. Disadvantages include inhibition of cell growth and induction of heterogeneous morphological changes in cells. Furthermore, the concentration of serum in the culture medium must be transiently reduced during the transfection. In general, DEAE-dextran DNA transfection is ideal for transient transfections with promoter/reporter plasmids in analyses of promoter and enhancer functions, and is suitable for overexpression of recombinant protein in transient transfections or for generation of stable cell lines using vectors designed to exist in the cell as episomes. This unit presents a general description of DEAE-dextran transfection, as well as two more specific protocols for typical experimental applications. The basic protocol is suitable for transfection of anchorage-dependent (attached) cells. For cells that grow in suspension, electroporation or lipofection is usually preferred, although DEAE-dextran-mediated transfection can be used.
Diversity in the signalling and regulation of G-protein-coupled receptors (1999)

Conference Article| February 01 1999 Diversity in the signalling and regulation of G-protein-coupled receptors G. Milligan; G. Milligan 1 1To whom correspondence should be addressed Search for other works by this author on: This Site PubMed Google Scholar D. A. Groarke; D. A. Groarke 1Molecular Pharmacology Group, Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland, U.K. Search for other works by this author on: This Site PubMed Google Scholar A. McLean; A. McLean 1Molecular Pharmacology Group, Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland, U.K. Search for other works by this author on: This Site PubMed Google Scholar R. Ward; R. Ward 1Molecular Pharmacology Group, Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland, U.K. Search for other works by this author on: This Site PubMed Google Scholar C. W. Fong; C. W. Fong 1Molecular Pharmacology Group, Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland, U.K. Search for other works by this author on: This Site PubMed Google Scholar A. Cavalli; A. Cavalli 1Molecular Pharmacology Group, Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland, U.K. Search for other works by this author on: This Site PubMed Google Scholar T. Drmota T. Drmota 1Molecular Pharmacology Group, Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland, U.K. Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1999) 27 (2): 149–154. https://doi.org/10.1042/bst0270149 Article history Received: August 10 1998 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation G. Milligan, D. A. Groarke, A. McLean, R. Ward, C. W. Fong, A. Cavalli, T. Drmota; Diversity in the signalling and regulation of G-protein-coupled receptors. Biochem Soc Trans 1 February 1999; 27 (2): 149–154. doi: https://doi.org/10.1042/bst0270149 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search Keywords: GPCR, G-protein-coupled receptor, GTP[S], guanosine 5′-[γ-thio] triphosphate, GFP, green fluorescent protein, TRH, thyrotropin-releasing hormone, TRH-R, TRH receptor This content is only available as a PDF. © 1999 Biochemical Society1999 Article PDF first page preview Close Modal You do not currently have access to this content.