gebhart/patrepeval huggingface dataset:
Carcinoembryonic antigen in 228 patients with carcinoma of the lung (1975)

Two hundred and twenty-eight patients who were treated for carcinoma of the lung were followed and their plasma CEA levels assessed at intervals during the course of the disease. In addition, plasma samples were taken from 487 healthy blood donors for comparison as a control. CEA assay is not selective or specific enough, at this time, to be used for screening purposes even though 68% of the patients who have lung cancer will have an elevated concentration of CEA regardless of the histological cell type. In patients with plasma levels of CEA above 15 ng/ml the prognosis is uniformly poor. CEA in the author's view does have value as a prognostic marker capable of suggesting the successful resection of a tumor and to a lesser degree confirming the clinical objective response to the radiotherapy or chemotherapy. It was found that the presence of CEA was not necessarily related to the volume of the tumor or the site of organ metastasis, but reflects the metabolic properties and characteristics of the individual tumor as it occurs in the patient.
Formal Synthesis of (+)-Phorbol1 (2001)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTFormal Synthesis of (+)-Phorbol1Kwangho Lee and Jin Kun ChaView Author Information Department of Chemistry University of Alabama Tuscaloosa, Alabama 35487 Cite this: J. Am. Chem. Soc. 2001, 123, 23, 5590–5591Publication Date (Web):May 16, 2001Publication History Received12 March 2001Published online16 May 2001Published inissue 1 June 2001https://pubs.acs.org/doi/10.1021/ja010643uhttps://doi.org/10.1021/ja010643urapid-communicationACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views4146Altmetric-Citations102LEARN 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 SUBJECTS:Alkyls,Cyclization,Hydrocarbons,Organic synthesis,Redox reactions Get e-Alerts
Frequent Loss of Heterozygosity on Chromosomes 3p and 17p without VHL or p53 Mutations Suggests Involvement of Unidentified Tumor Suppressor Genes in Follicular Thyroid Carcinoma1 (1997)

Follicular thyroid carcinoma (FTC) exhibits frequent loss of heterozygosity (LOH) on chromosomes 10q and 3p, suggesting involvement of tumor suppressor genes. We screened 14 FTC (10 Hurthle cell carcinomas and 4 nonoxyphilic FTC), 14 papillary thyroid carcinomas, and 7 follicular adenomas for LOH on chromosome arms 1p, 3p, 3q, 10p, 10q, 11p, 11q, 13q, 17p, and 17q. LOH was more frequent in FTC than in follicular adenoma or papillary thyroid carcinoma. In FTC, rates of LOH on 3p (86%), 17p (72%), and 10q (57%) were higher than the average rate of LOH (33%; P < 0.05). Most frequently involved were 3p21-25 and 17p13.1-13.3, the sites for the VHL (3p25-26) and p53 (17p13.1) tumor suppressors. We, therefore, characterized these genes by dideoxy fingerprinting and DNA sequencing. Two FTC had mutations in p53, but only 1 of these exhibited LOH at 17p. No VHL gene mutations were found. Thus, neither p53 nor VHL genes play a significant role in the pathogenesis of differentiated thyroid cancer. LOH on 17p, but not on 3p or 10q, was correlated with mortality. Accordingly, 3p and 10q LOH may represent early, and 17p LOH late, events in FTC development. The data suggest the presence of novel tumor suppressor genes on chromosomes 3p and 17p that may be important in the pathogenesis of FTC.
Nitration and inactivation of manganese superoxide dismutase in chronic rejection of human renal allografts. (1996)

Inflammatory processes in chronic rejection remain a serious clinical problem in organ transplantation. Activated cellular infiltrate produces high levels of both superoxide and nitric oxide. These reactive oxygen species interact to form peroxynitrite, a potent oxidant that can modify proteins to form 3-nitrotyrosine. We identified enhanced immunostaining for nitrotyrosine localized to tubular epithelium of chronically rejected human renal allografts. Western blot analysis of rejected tissue demonstrated that tyrosine nitration was restricted to a few specific polypeptides. Immunoprecipitation and amino acid sequencing techniques identified manganese superoxide dismutase, the major antioxidant enzyme in mitochondria, as one of the targets of tyrosine nitration. Total manganese superoxide dismutase protein was increased in rejected kidney, particularly in the tubular epithelium; however, enzymatic activity was significantly decreased. Exposure of recombinant human manganese superoxide dismutase to peroxynitrite resulted in a dose-dependent (IC50 = 10 microM) decrease in enzymatic activity and concomitant increase in tyrosine nitration. Collectively, these observations suggest a role for peroxynitrite during development and progression of chronic rejection in human renal allografts. In addition, inactivation of manganese superoxide dismutase by peroxynitrite may represent a general mechanism that progressively increases the production of peroxynitrite, leading to irreversible oxidative injury to mitochondria.
Baculovirus-mediated expression and characterization of the full-length murine DNA methyltransferase (1997)

The original cDNA sequence reported for the murine DNA methyltransferase (MTase) was not full length. Recently, additional cDNA sequences have been reported that lie upstream of the original and contain an extended open reading frame with three additional ATGs in frame with the coding region [Tucker et al . (1996) Proc. Natl. Acad. Sci. USA , 93, 12920-12925; Yoder et al . (1996) J. Biol. Chem . 271, 31092-31097]. Genomic DNA upstream of this ATG contains two more ATGs in frame and no obvious splice site. We have constructed, and expressed in baculovirus, MTase clones that begin at each of these four ATGs and examined their properties. Constructs beginning with any of the first three ATGs as their initiator methionines give a predominant DNA MTase band of approximately 185 kDa on SDS-PAGE corresponding to translational initiation at the third ATG. The fourth ATG construct gives a much smaller protein band of 173 kDa. The 185 kDa protein was purified by HPLC, characterized by mass spectrometry and has a measured molecular mass of 184 +/- 0.5 kDa. All of these MTases were functional in vitro and steady state kinetic analysis showed that the recombinant proteins exhibit similar kinetic properties irrespective of their length. The homogeneous recombinant enzyme from the fourth ATG construct shows a 2.5-fold preference for a hemi-methylated DNA substrate as compared to an unmethylated substrate, whereas the 185 kDa protein is equally active on both substrates. The kinetic properties of the recombinant enzyme are similar to those reported for the native MTase derived from murine erythroleukemia cells. The new clones are capable of yielding large quantities of intact MTases for further structural and functional studies.
<title>Planar waveguides as efficient transducers for bioaffinity sensors</title> (1996)

Specific detection of extremely low amounts of antigens or disease markers allowing the diagnosis of diseases and infections at a very early stage has become a major driving force for the development of new generations of biochemical sensors. To match this goal, we propose the substitution of the widely used fiber-shaped evanescent field sensors by planar single-mode metal oxide waveguides. In combination with bioaffinity assays, this transducer geometry offers benefits such as enhanced sensitivity, ease of sensor handling and preparation, sample volume reduction, versatility, and low cost per test. Recently, planar waveguides have been used in sensor schemes exploiting the changes of the so-called effective refractive index (caused by changes in mass of surface-bound biomolecules): grating couplers, surface plasmon resonance, and interferometers. However, compared to luminescence-based sensor schemes, the sensitivities of these label-free methods are inferior. In this paper we report on a new generation of luminescence- based bioaffinity sensors for human diagnostics including optimization of the planar evanescent field transducers, the design of a compact sensor system, and a first study of the binding of fluorophore-labeled IgG to protein A immobilized on the transducer.
Characterization of α,α-trehalase released in the intestinal lumen by the probiotic Saccharomyces boulardii (2008)

Our data suggest that alpha,alpha-trehalase deficiency is more common than is believed and that oral administration of S. boulardii could be beneficial in patients with digestive symptoms caused by trehalose intolerance.
De novo assembly of human genomes with massively parallel short read sequencing (2009)

Next-generation massively parallel DNA sequencing technologies provide ultrahigh throughput at a substantially lower unit data cost; however, the data are very short read length sequences, making de novo assembly extremely challenging. Here, we describe a novel method for de novo assembly of large genomes from short read sequences. We successfully assembled both the Asian and African human genome sequences, achieving an N50 contig size of 7.4 and 5.9 kilobases (kb) and scaffold of 446.3 and 61.9 kb, respectively. The development of this de novo short read assembly method creates new opportunities for building reference sequences and carrying out accurate analyses of unexplored genomes in a cost-effective way.
Synthetic protein transduction domains: enhanced transduction potential in vitro and in vivo. (2001)

The protein transduction domain (PTD) embedded in the HIV TAT protein (amino acids 47-57) has been shown to successfully mediate the introduction of heterologous peptides and proteins in excess of Mr 100,000 into mammalian cells in vitro and in vivo. We report here that the modeled structure of the TAT PTD is a strong amphipathic helix. On the basis of this information, we synthesized a series of synthetic PTDs that strengthen the alpha-helical content and optimize the placement of arginine residues. Several PTD peptides possessed significantly enhanced protein transduction potential compared with TAT in vitro and in vivo. These optimized PTDs have the potential to deliver both existing and novel anticancer therapeutics.
Molecular Factors and Biochemical Pathways Induced by Febrile Temperature in Intraerythrocytic Plasmodium falciparum Parasites (2007)

Intermittent episodes of febrile illness are the most benign and recognized symptom of infection with malaria parasites, although the effects on parasite survival and virulence remain unclear. In this study, we identified the molecular factors altered in response to febrile temperature by measuring differential expression levels of individual genes using high-density oligonucleotide microarray technology and by performing biological assays in asexual-stage Plasmodium falciparum parasite cultures incubated at 37 degrees C and 41 degrees C (an elevated temperature that is equivalent to malaria-induced febrile illness in the host). Elevated temperature had a profound influence on expression of individual genes; 336 of approximately 5,300 genes (6.3% of the genome) had altered expression profiles. Of these, 163 genes (49%) were upregulated by twofold or greater, and 173 genes (51%) were downregulated by twofold or greater. In-depth sensitive sequence profile analysis revealed that febrile temperature-induced responses caused significant alterations in the major parasite biologic networks and pathways and that these changes are well coordinated and intricately linked. One of the most notable transcriptional changes occurs in genes encoding proteins containing the predicted Pexel motifs that are exported into the host cytoplasm or inserted into the host cell membrane and are likely to be associated with erythrocyte remodeling and parasite sequestration functions. Using our sensitive computational analysis, we were also able to assign biochemical or biologic functional predictions for at least 100 distinct genes previously annotated as "hypothetical." We find that cultivation of P. falciparum parasites at 41 degrees C leads to parasite death in a time-dependent manner. The presence of the "crisis forms" and the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling-positive parasites following heat treatment strongly support the notion that an apoptosis-like cell death mechanism might be induced in response to febrile temperatures. These studies enhance the possibility of designing vaccines and drugs on the basis of disruption in molecules and pathways of parasite survival and virulence activated in response to febrile temperatures.
Melanocortin Receptor Binding Determinants in the Agouti Protein (1998)

The agouti protein plays an important role in the development of diabetes and obesity in rodents and has been shown to be a potent antagonist of melanocortin receptors. For this reason alanine-scanning mutagenesis was performed on the agouti protein carboxyl terminus to locate residues important for melanocortin receptor binding inhibition. When agouti residues Arg116 and Phe118 are changed to alanine, very large decreases in agouti affinity for melanocortin receptor 1, 3, and 4 result. Mutation of Phe117 to alanine causes a similar increase in agouti KI app at melanocortin receptor 4. Substitution of agouti residue Asp108 with alanine results in large increases in KI app for all three melanocortin receptors examined. All of these residues are conserved in the agouti-related transcript, ART, whose expression is up-regulated in animal models of obesity. The three-dimensional structure of the agouti carboxyl terminus was modeled, and residues which decrease receptor binding by a factor of ≥15 when mutated to alanine localize to one side of the structure. These agouti variants with altered receptor selectivity may be useful in determining the role of melanocortin receptors in diabetes and obesity.
Melatonin increases survival and inhibits oxidative and amyloid pathology in a transgenic model of Alzheimer's disease (2003)

Increased levels of a 40-42 amino-acid peptide called the amyloid beta protein (A beta) and evidence of oxidative damage are early neuropathological markers of Alzheimer's disease (AD). Previous investigations have demonstrated that melatonin is decreased during the aging process and that patients with AD have more profound reductions of this hormone. It has also been recently shown that melatonin protects neuronal cells from A beta-mediated oxidative damage and inhibits the formation of amyloid fibrils in vitro. However, a direct relationship between melatonin and the biochemical pathology of AD had not been demonstrated. We used a transgenic mouse model of Alzheimer's amyloidosis and monitored over time the effects of administering melatonin on brain levels of A beta, abnormal protein nitration, and survival of the mice. We report here that administration of melatonin partially inhibited the expected time-dependent elevation of beta-amyloid, reduced abnormal nitration of proteins, and increased survival in the treated transgenic mice. These findings may bear relevance to the pathogenesis and therapy of AD.
Using web-based search data to predict macroeconomic statistics (2005)

Tracking common search terms used on the Web can produce accurate, useful statistics about the unemployment rate. We hope to extend this approach to other economic statistics.
Quantitative analysis of myocardial fibrosis in normals, hypertensive hearts, and hypertrophic cardiomyopathy. (1986)

The distribution of fibrosis was studied quantitatively in the entire left ventricular wall of a transverse slice of the heart from 10 necropsy cases of hypertrophic cardiomyopathy, 10 cases of hypertensive heart disease, and 20 normal adults. The percentage area (mean (SD)) of fibrosis in the left ventricular wall in hypertrophic cardiomyopathy (10.5 (4.3)%) was significantly greater than that in hypertensive heart disease (2.6 (1.5)%) or in normal hearts (1.1 (0.5)%). In hypertrophic cardiomyopathy the percentage area of fibrosis was greater (13.1 (4.8)%) in the ventricular septum than in the left ventricular free wall (7.7 (4.2)%) whereas in hypertensive heart disease and normal hearts values in these two areas were similar. The percentage area of fibrosis in the left ventricular free wall (where myocardial fibre disarray was not extensive even in hypertrophic cardiomyopathy) was greater in hypertrophic cardiomyopathy than in hypertensive heart disease. The percentage area of fibrosis correlated with heart weight in hypertensive heart disease, but not in hypertrophic cardiomyopathy. These results suggest that widespread fibrosis in hypertrophic cardiomyopathy cannot be explained by cardiac hypertrophy alone, and that disarray and other factors are also important in pathogenesis. The increase in the percentage area of fibrosis from the outer to the inner third of the left ventricular free wall in hypertrophic cardiomyopathy and in hypertension probably reflected transmural gradients of wall stress and myocardial fibre diameter. Although fibrosis is not specific to hypertrophic cardiomyopathy, its quantification and analysis of its regional distribution provide information that is useful in investigating the pathophysiology of the disorder.
Role of the Conserved Dipeptide Gly75 and Cys76 on HIV-1 Vpr Function (1995)

Vpr is one of the accessory proteins encoded by the HIV-1 genome. Several interesting features associated with Vpr include incorporation into virus particles, ability to oligomerize, localization in the nucleus, and positive effect on virus production and replication. In order to understand the structure-function relationship of Vpr, we have analyzed the role of the Gly75 and Cys76 (GC) residues which are highly conserved in HIV-1 Vpr and in Vpr and Vpx of HIV-2/SIV. We have generated several substitution mutants involving this dipeptide and have evaluated for expression, stability, nuclear localization, and virion incorporation of Vpr. Our data demonstrate that the GC residues are not essential for virion incorporation and nuclear localization of Vpr. Serine substitution for Cys, however, restricted the localization of Vpr in the cytoplasm without affecting the Gag-directed incorporation of Vpr into virus-like particles. Interestingly, the cysteine-substituted mutants showed altered stability in comparison to the wild type, and substitution mutants for glycine showed minimal effect on stability. These results indicate that the glycine and cysteine do not play a role in nuclear localization or virion incorporation properties of Vpr and further suggest that these two functions of Vpr may not be interdependent.
Intratumoral injection of adenoviral vectors encoding tumor-targeted immunoconjugates for cancer immunotherapy (2000)

The efficacy and safety of a new immunotherapy protocol for cancer were tested in a severe combined immunodeficient mouse model of human skin and metastatic lung melanoma. The protocol involves intratumoral injections of replication-incompetent adenoviral vectors encoding immunoconjugates composed of the Fc region of an IgG1 immunoglobulin conjugated to a tumor-targeting domain. One targeting domain is factor VII that binds to tissue factor expressed on endothelial cells lining the tumor neovasculature and on tumor cells; the active site of factor VII was mutated to inhibit the initiation of blood coagulation. Another targeting domain is a single-chain Fv antibody that binds to a cognate antigen expressed on human melanoma cells. The adenoviral vectors infect mainly the cells of the injected tumor, which synthesize and secrete the immunoconjugates. The bloodborne immunoconjugates induce a cytolytic immune response against the targeted neovasculature endothelial cells and tumor cells. The mouse model experiments showed that intratumoral delivery of the factor VII immunoconjugate, either alone or together with the single-chain Fv immunoconjugate, resulted in growth inhibition and regression of the injected tumor, and also of distant metastatic tumors, without evidence of damage to normal organs. There was extensive destruction of the tumor neovasculature, presumably mediated by the factor VII immunoconjugate bound to tissue factor on neovasculature endothelial cells. Because tissue factor is generally expressed on neovascular endothelial cells and tumor cells, a factor VII immunoconjugate could be used for immunotherapy against a broad range of human solid tumors.
Thermally stable ohmic contacts to p-type GaAs. IX. NiInW and NiIn(Mn)W contact metals (1991)

Thermally stable, low-resistance p-type ohmic contacts have been developed by depositing NiInW metals on GaAs substrates in which Be and F were coimplanted. The contacts provided resistances of about 1.4 Ω mm after annealing at temperatures in the range of 300–800 °C for short times. The electrical properties did not deteriorate after annealing at 400 °C for more than 100 h, which far exceeds the requirements for current GaAs device fabrication. The present study demonstrated for the first time that thermally stable, low-resistance ohmic contacts to both n- and p-type GaAs can be fabricated using the same metallurgy. In addition, NiInW ohmic contacts were prepared by simultaneous (one-step) annealing for ion-implant activation and contact formation, which simplifies significantly the device fabrication process. A factor-of-2 reduction of the contact resistances was achieved by slight etching of the GaAs surface prior to the contact metal deposition so that the metal/GaAs interface contacted the peak position of the Be concentration in the GaAs substrate. Another method used to reduce the contact resistance was to add a small amount of Mn to the NiInW metals: the resistance decreased with increasing amounts of Mn. The contacts had smooth morphology and shallow depth, less than 70 nm, which is desirable for very-large-scale integration device application.