gebhart/patrepeval huggingface dataset:
Mutations in Human Breast Cancer: An Overview (1989)

Studies of mammary tumorigenesis in mice infected with the mouse mammary tumor virus and in certain strains of transgenic mice with an activated oncogene have provided strong evidence that multiple mutations contribute to the initiation and progression of malignancies in the breast. The increasing availability of recombinant DNA probes that detect various proto-oncogenes, growth factor genes, and growth factor receptor genes, as well as restriction fragment length polymorphisms in the human population, have made possible a molecular approach for the identification of frequently occurring mutations in primary human breast tumor DNA. The aim of studies using this molecular approach has been to investigate whether specific mutations are highly associated with various clinical parameters, including disease prognosis. Eight mutations have been identified, including amplification of c-myc, c-erbB2, and int-2, as well as loss of heterozygosity on five chromosomes (1q, 3p, 11p, 13q, and 17p). Loss of heterozygosity is thought to unmask recessive mutations of tumor-suppressor genes. In some studies, amplification of either c-myc, c-erbB2, or int-2 has been found to have a significant association with high risk of relapse or poor survival. The current status of these mutations as potentially useful prognostic indicators for the management of the disease is controversial and points to the need for further research in this area.
Murine tumor cells expressing the gene for the human interferon αβ receptor elicit antibodies in syngeneic mice to the active form of the receptor (1991)

The cellular receptor for the human alpha and beta interferons (IFN) was expressed, by gene transfer, in a murine hepatoma-derived cell line, BTG 9A. Injected subcutaneously into the syngeneic mouse (C57BL/6), the parental and the transfected cells grew and formed tumors which later regressed. More than half the mice bearing tumors derived from cells expressing the receptor, developed IgG antibodies capable of blocking the activity, on human cells, of human recombinant IFN-alpha B, -alpha A, -alpha D and of natural human IFN-beta, but not of recombinant IFN-gamma. Cross-reactivity of human IFN-alpha on murine and bovine cells was unaffected by these antibodies. The binding of human IFN-alpha to solubilized receptors from human lymphoid cell lines was also blocked and complexes of radiolabeled recombinant IFN-alpha A or IFN-alpha B, chemically cross-linked to their human receptor could be immunoprecipitated by the antisera. IFN alpha beta receptor protein, purified by electrophoresis in sodium dodecylsulfate, was not recognized. We conclude that the antibodies are directed against the forms of the IFN alpha beta receptor actually expressed on the membrane.
Mechanism of Inhibition of Bacillus subtilis DNA Polymerase III by the Arylhydrazinopyrimidine Antimicrobial Agents (1974)

Arylhydrazinopyrimidines inhibit DNA synthesis in Bacillus subtilis by promoting formation of a specific, long-lived ternary complex with DNA polymerase III and the template-primer DNA. DNA polymerase III contains an associated, single-strand-selective exonuclease which generates 5'-mononucleotides. Drug inhibition of the nuclease similarly proceeds through formation of the ternary complex. The ternary complex was isolated by agarose chromatography. Like inhibition of the nuclease, optimum formation of the complex requires duplex DNA with single-stranded regions such as bacteriophage lambda DNA (purely single- and double-stranded DNA are ineffective) and is antagonized by specific deoxyribonucleoside triphosphates. Formation of the ternary complex requires a di- or polyvalent cation and is inhibited by sulfhydryl reagents and high ionic strength. The complex dissociates with a half-life of the order of minutes at 4 degrees .
Temporally Graded Retrograde Amnesia of Contextual Fear after Hippocampal Damage in Rats: Within-Subjects Examination (1999)

We have shown previously that electrolytic lesions of the dorsal hippocampus (DH) produce a severe deficit in contextual fear if made 1 d, but not 28 d, after fear conditioning (). As such, the hippocampus seems to play a time-limited role in the consolidation of contextual fear conditioning. Here, we examine retrograde amnesia of contextual fear produced by DH lesions in a within-subjects design. Unlike our previous reports, rats had both a remote and recent memory at the time of the lesion. Rats were given 10 tone-shock pairings in one context (remote memory) and 10 tone-shock pairings in a distinct context (with a different tone) 50 d later (recent memory), followed by DH or sham lesions 1 d later. Relative to controls, DH-lesioned rats exhibited no deficit in remote contextual fear, but recent contextual fear memory was severely impaired. They also did not exhibit deficits in tone freezing. This highly specific deficit in recent contextual memory demonstrated in a within-subjects design favors mnemonic over performance accounts of hippocampal involvement in fear. These findings also provide further support for a time-limited role of the hippocampus in memory storage.
Â¿Doctor, quÃ© piensa usted sobre sus pacientes con EPOC? (2014)

La evaluación del trabajo que desarrollamos en atención primaria es una forma de detectar los puntos débiles, ayudándonos a mejorar. El objetivo del presente trabajo es conocer la opinión de los médicos de familia de un centro de salud (CS) sobre sus pacientes con EPOC. Como método se ha utilizado una encuesta a la que respondieron los médicos antes y después de presentar los resultados de la evaluación de esos pacientes. Se ha evaluado anualmente durante un periodo de tres años (junio 2008 - mayo 2011) una muestra aleatoria de 137 pacientes con diagnóstico activo de EPOC en su historia clínica electrónica (HCE). La prevalencia registrada de EPOC en el CS ha pasado de 3,07% en 2009 a 3,23% en 2011. El porcentaje de pacientes diagnosticados incorrectamente de EPOC en la HCE ha sido del 20,4%. La edad media era de 70,3 años (DE 12,4) y el 69,3% eran varones. En el tercer año evaluado, constaba un 31% de pacientes fumadores, un porcentaje similar de no fumadores y en el 38% restante no había registro de dicho hábito. Se registraron 89 espirometrías. En el 69,3% se realizó una radiografía de tórax. La vacuna antineumocócica sólo constaba en el 12,4% de los casos. A la vista de estos datos cuantitativos nos damos cuenta de que existen aspectos susceptibles de mejorar, pero esto sólo si conocemos la realidad objetiva que nos aporta la evaluación de nuestro trabajo y no sólo la sensación subjetiva de cómo creemos tener controlados a nuestros pacientes.
An AU-Rich Element in the 3′ Untranslated Region of the Spinach Chloroplast petD Gene Participates in Sequence-Specific RNA-Protein Complex Formation (1995)

In chloroplasts, the 3' untranslated regions of most mRNAs contain a stem-loop-forming inverted repeat (IR) sequence that is required for mRNA stability and correct 3'-end formation. The IR regions of several mRNAs are also known to bind chloroplast proteins, as judged from in vitro gel mobility shift and UV cross-linking assays, and these RNA-protein interactions may be involved in the regulation of chloroplast mRNA processing and/or stability. Here we describe in detail the RNA and protein components that are involved in 3' IR-containing RNA (3' IR-RNA)-protein complex formation for the spinach chloroplast petD gene, which encodes subunit IV of the cytochrome b6/f complex. We show that the complex contains 55-, 41-, and 29-kDa RNA-binding proteins (ribonucleoproteins [RNPs]). These proteins together protect a 90-nucleotide segment of RNA from RNase T1 digestion; this RNA contains the IR and downstream flanking sequences. Competition experiments using 3' IR-RNAs from the psbA or rbcL gene demonstrate that the RNPs have a strong specificity for the petD sequence. Site-directed mutagenesis was carried out to define the RNA sequence elements required for complex formation. These studies identified an 8-nucleotide AU-rich sequence downstream of the IR; mutations within this sequence had moderate to severe effects on RNA-protein complex formation. Although other similar sequences are present in the petD 3' untranslated region, only a single copy, which we have termed box II, appears to be essential for in vitro protein binding. In addition, the IR itself is necessary for optimal complex formation. These two sequence elements together with an RNP complex may direct correct 3'-end processing and/or influence the stability of petD mRNA in chloroplasts.
Assessment of tracheal temperature and humidity in laryngectomized individuals and the influence of a heat and moisture exchanger on tracheal climate (2008)

Assessment of intratracheal temperature and humidity, and evaluation of HME effectiveness is feasible with the ACE. The tested HME significantly increases the intratracheal humidity, but decreases the intratracheal temperature. Relative humidity calculations suggest that increasing the thermal capacity of this rehabilitation device can further increase the heat and moisture exchange efficiency.
Growing polymers from peptides and proteins: a biomedical perspective (2013)

This review covers the development of the in situ growth of polymers from biomolecules, also termed the “grafting from” conjugation methodology. We trace the evolution of this field of research, with an emphasis on recently developed methods to synthesize polymer conjugates of peptides and proteins with control over the site of conjugation, the stoichiometry of the conjugate, and the chain length and polydispersity of the polymer. We highlight the functional properties and potential biomedical applications of the peptide/protein–polymer conjugates, including conjugates with more advanced architecture and self-assembly behaviour.
Anti-tumor activity against multiple myeloma by combination of KW-2478, an Hsp90 inhibitor, with bortezomib (2012)

Heat shock protein 90 (Hsp90) is a promising target for anti-tumor therapy. We previously reported the anti-tumor activity of a novel Hsp90 inhibitor, KW-2478, in multiple myeloma (MM) as a single agent. In this study, we examined the combinational effect of KW-2478 and bortezomib, a proteasome inhibitor, in vitro and in vivo. In vitro, KW-2478 enhanced bortezomib-induced cell growth inhibition, both in MM cell lines and primary patient MM cells. The combination of KW-2478 and bortezomib also induced caspase activation in MM cell lines. Interestingly, the combination synergistically enhanced the expression of Hsp70B, a homolog of Hsp70, in human MM cells and peripheral blood mononuclear cells, indicating Hsp70B could be a surrogate biomarker for the combination of Hsp90 and proteasome inhibitors. In vivo, the combination of KW-2478 with bortezomib showed synergistic anti-tumor activity without significant body weight loss in a subcutaneously inoculated human myeloma model. Furthermore, the combination also showed synergistic reduction of tumor burden in bone marrow in an orthotopic myeloma model. Our results strongly suggest that combination of KW-2478 with bortezomib could exhibit enhanced anti-tumor activity against human myeloma.
Phosphate anion binding: enhanced transport of nucleotide monophosphates using a sapphyrin carrier (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhosphate anion binding: enhanced transport of nucleotide monophosphates using a sapphyrin carrierHiroyuki Furuta, Michael J. Cyr, and Jonathan L. SesslerCite this: J. Am. Chem. Soc. 1991, 113, 17, 6677–6678Publication Date (Print):August 1, 1991Publication History Published online1 May 2002Published inissue 1 August 1991https://pubs.acs.org/doi/10.1021/ja00017a051https://doi.org/10.1021/ja00017a051research-articleACS PublicationsRequest reuse permissionsArticle Views313Altmetric-Citations91LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Interaction of polypyridyl ruthenium(II) complexes containing non-planar ligands with DNA (1999)

2-(2-Chlorophenyl)imidazo[4,5-f]1,10-phenanthroline (CIP) or 2-(2-nitrophenyl)imidazo[4,5-f]1,10-phenanthroline (NIP) and their complexes [Ru(bpy)2(CIP)]2+ and [Ru(bpy)2(NIP)]2+ (bpy = 2,2′-bipyridine) have been synthesized and characterized. The binding of the two complexes to calf thymus DNA has been investigated with spectrophotometric methods and viscosity measurements. The experimental results indicate that the two complexes bind to DNA through a partial intercalative mode that is different from the bonding mode for their parent compound, [Ru(bpy)2(PIP)]2+ (PIP = 2-phenylimidazo[4,5-f]1,10-phenanthroline). The crystal structure of [Ru(bpy)2(CIP)][ClO4]2·2H2O was determined by X-ray diffraction analysis; the imidazo[4,5-f]1,10-phenanthroline moiety is not coplanar with the 2-chlorophenyl ring, having a dihedral angle of 44.5° in the CIP.
Fistulizing Crohn’s disease: Diagnosis and management (2013)

Fistulizing Crohn's disease represents an evolving, yet unresolved, issue for multidisciplinary management. Perianal fistulas are the most frequent findings in fistulizing Crohn's disease. While enterocutaneous fistulas are rare, they are associated with considerable morbidity and mortality. Detailed evaluation of the fistula tract by advanced imaging techniques is required to determine the most suitable management options. The fundamentals of perianal fistula management are to evaluate the complexity of the fistula tract, and exclude proctitis and associated abscess. The main goals of the treatment are abscess drainage, which is mandatory, before initiating immunosuppressive medical therapy, resolution of fistula discharge, preservation of continence and, in the long term, avoidance of proctectomy with permanent stoma. The management of enterocutaneous fistulas comprises of sepsis control, skin care, nutritional optimization and, if needed, delayed surgery.
Mutations in the Trp-Ser-X-Trp-Ser motif of the erythropoietin receptor abolish processing, ligand binding, and activation of the receptor. (1992)

The erythropoietin receptor (EPOR) is a member of the newly identified cytokine receptor superfamily. A common sequence motif, Trp-Ser-X-Trp-Ser (WSXWS), near the transmembrane domain is highly conserved in this family. To determine the function of this motif, we constructed deletion and insertion mutations in this part of the EPOR and introduced them into an interleukin-3 (IL-3)-dependent hematopoietic Ba/F3 cell line. Cells expressing the wild-type EPOR displayed 1,500 erythropoietin (EPO)-binding sites/cell with a single affinity of about 300 pM and proliferate in the presence of IL-3 or EPO. Ba/F3 cells expressing receptors mutated in the WSXWS motif displayed little EPO binding on the cell surface and did not grow in the presence of EPO. The mutant receptors were retained in the endoplasmic reticulum (ER) and, as such, were unable to bind EPO. A single Gly insertion between the two WS sequences caused defects in receptor structure and function similar to mutations lacking all or part of the WSXWS motif. The EPOR can be activated, resulting in proliferation independent of EPO either by an Arg129 to Cys point mutation or by association with the Friend spleen focus-forming virus (SFFV) envelope glycoprotein gp55. Introduction of the point mutation (Arg129 to Cys) did not activate any of the receptors mutated in the WSXWS motif. Moreover, gp55 did not activate the mutant receptors in Ba/F3 cells. Our study indicates that the WSXWS motif is critical for protein folding, ligand-binding, and signal transduction.
Segregating heap objects by reference behavior and lifetime (1998)

Dynamic storage allocation has become increasingly important in many applications, in part due to the use of the object-oriented paradigm. At the same time, processor speeds are increasing faster than memory speeds and programs are increasing in size faster than memories. In this paper, we investigate efforts to predict heap object reference and lifetime behavior at the time objects are allocated. Our approach uses profile-based optimization, and considers a variety of different information sources present at the time of object allocation to predict the object's reference frequency and lifetime. Our results, based on measurements of six allocation intensive programs, show that program references to heap objects are highly predictable and that our prediction methods can successfully predict the behavior of these heap objects. We show that our methods can decrease the page fault rate of the programs measured, sometimes dramatically, in cases where the physical memory available to the program is constrained.
The amidomethylation of some N,N-dialkylanilines (Tscherniac-Einhorn reaction) (1975)

The reaction of some representative N,N-dialkylanilines with N- hydroxymethylphthalimide in concentrated sulphuric acid solution (the Tscherniac-Einhorn reaction) has been studied and the structures of the resultant phthalimide derivatives elucidated (principally by means of p.m.r. spectroscopy). In some instances, when two equivalents of the reagent were used, the in corporation of two phthalimidomethyl groups into the N,N-dialkylaniline molecule was achieved. Similar results were obtained when the less reactive N-hydroxymethylchloroacetamide was used as the amidomethylating reagent.
Purification and subunit structure of hepatocyte growth factor from rat platelets (1987)

A hepatocyte growth factor (HGF) that stimulates DNA synthesis of adult rat hepatocytes in primary culture was purified as a homogeneous material from platelets of 1000 rats by a four-step procedure: stimulation of its release from platelets by thrombin, cation-exchanger fast protein liquid chromatography (FPLC) on a Mono S column, heparin-Sepharose CL-6B chromatography, and reverse-phase HPLC on a C4 column. The purified HGF stimulated DNA synthesis of adult rat hepatocytes in primary culture at 1 ng/ml and was maximally effective at 5 ng/ml, being about twice as potent as EGF at this concentration. HGF did not stimulate DNA synthesis of Swiss 3T3 cells. It was found to be a heat- and acid-labile protein that was inactivated by reduction with dithiothreitol. The purified HGF had a molecular mass of 82 kDa, as estimated by SDS-PAGE, and was found to be a heterodimer which dissociated into a large subunit of 69 kDa and a small one of 34 kDa by SDS-PAGE under reducing conditions. These biological and chemical properties showed that HGF was not identical with any known growth factors, including platelet-derived growth factor (PDGF).
Neurogenic detrusor overactivity: an update on management options. (2013)

Neurogenic detrusor overactivity (NDO) affects a variety of patients with storage and voiding dysfunction including those with multiple sclerosis, spinal cord injuries, Parkinson's disease, cerebral palsy, and myelomeningocele, and includes symptoms of urinary frequency, urgency, and incontinence. Primary treatment goals are 1) preventing renal injury, and 2) improving quality of life. First-line therapies include behavioral and anticholinergic agents, with onabotulinum toxin-A as the only FDA- approved second-line therapy, and non-FDA approved second-line therapies including neuromodulation, and intravesical vanilloids. Surgical intervention is reserved for those at risk for upper-tract deterioration and with persistent incontinence. In select individuals an indwelling catheter may be necessary.
Synthetic peptides non‐covalently bound to bacterial hsp 70 elicit peptide‐specific T‐cell responses in vivo (1996)

We have examined the immunogenicity of complexes formed by non-covalent association of a synthetic peptide corresponding to influenza A virus nucleoprotein, residues 206-229 (pNP) and Mycobacterium tuberculosis heat-shock protein 70 (hsp 70). One or two injections of these complexes given to BALB/c mice without any additional adjuvant, were capable of eliciting very strong peptide-specific proliferative T-cell responses in the spleen. These responses were dependent on the stability of the complex since immunogenicity was lost when dissociated with ATP prior to immunization. T-cell responses to hsp 70 were easily generated by immunization with the purified chaperone alone, either after primary or secondary immunization. Injection of pNP-hsp 70 complexes, however, although generating good primary responses, resulted in very much decreased proliferative responses to the hsp 70.
BRCA-Mutation–Associated Fallopian Tube Carcinoma (2005)

Fallopian tube cancer is part of the BRCA mutation phenotype and seems to share many clinical features with sporadic fallopian tube cancers, including no exclusively proximal disease. The presentation of BRCA-associated fallopian tube cancers may, however, occur at a younger age and have an improved survival.
MicroRNA let-7c Regulates Macrophage Polarization (2013)

Macrophages demonstrate a high level of plasticity, with the ability to undergo dynamic transition between M1 and M2 polarized phenotypes. The role of microRNAs (miRNAs) in regulating macrophage polarization has been largely undefined. In this study, we found that miRNA let-7c is expressed at a higher level in M-BMM (M2 macrophages) than in GM-BMM (M1 macrophages). let-7c levels are also greater in alveolar macrophages from fibrotic lungs as compared with those from normal lungs. let-7c expression was decreased when M-BMM converted to GM-BMM, whereas it increased when GM-BMM converted to M-BMM. LPS stimulation reduced let-7c expression in M-BMM. We found that overexpression of let-7c in GM-BMM diminished M1 phenotype expression while promoting polarization to the M2 phenotype. In contrast, knockdown of let-7c in M-BMM promoted M1 polarization and diminished M2 phenotype expression. We found that let-7c targets C/EBP-δ, a transcriptional factor that plays an important role in inflammatory response. Furthermore, we found that let-7c regulates bactericidal and phagocytic activities of macrophages, two functional phenotypes implicated in macrophage polarization. Our data suggest that the miRNA let-7c plays an important role in regulating macrophage polarization.
The nonlinear pathway of Y ganglion cells in the cat retina. (1979)

Retinal ganglion cells of the Y type in the cat retina produce two different types of response: linear and nonlinear. The nonlinear responses are generated by a separate and independent nonlinear pathway. The functional connectivity in this pathway is analyzed here by comparing the observed second-order frequency responses of Y cells with predictions of a "sandwich model" in which a static nonlinear stage is sandwiched between two linear filters. The model agrees well with the qualitative and quantitative features of the second-order responses. The prefilter in the model may well be the bipolar cells and the nonlinearity and postfilter in the model are probably associated with amacrine cells.