gebhart/patrepeval huggingface dataset:
Quantitative real‐time RT‐PCR for detection of disseminated tumor cells in peripheral blood of patients with colorectal cancer using different mRNA markers (2003)

The detection of disseminated tumor cells in peripheral blood from colorectal cancer patients by RT-PCR could be an attractive method for selecting patients for adjuvant therapy. We here report on real-time RT-PCR assays (LightCycler) to quantitate potential mRNA markers. We investigated specimens from colon carcinoma and normal colon mucosa tissues, cell lines, blood samples from 129 patients with colorectal cancer (all stages) and 58 reference blood samples (healthy donors, persons suffering from inflammatory bowel or infectious diseases). The expression profile in tissues showed high values for CEA and CK20, whereas in cell lines ProtM was predominant. All markers were detected in reference and patient blood samples (ProtM, 22, 17%; CEA, 84, 86%; CK20, 85, 88%). After quantitative analysis, the definition of cutoff values for each marker and the combination of markers, 13% of patients were judged to have elevated marker concentrations in their blood, from which only 6 had values significantly differing from cutoff value. There were no differences between stages of disease. In the case of 19 patients, investigated prior to and 1 week after surgery, 2 samples revealed a significant postoperative increase in CEA or CK20 mRNA concentration. In spite of high expression levels in tissues and cell lines, we were not able to differentiate satisfyingly mRNA markers originating from tumor cells and those from illegitimate transcription in hematopoetic cells in blood. We conclude that either copy numbers of analyzed markers in circulating tumor cells are not sufficient for detection or, more probably, peripheral blood is not a suitable compartment for detection of tumor cells in colorectal cancer.
Quantitation of Human Immunodeficiency Virus Provirus and Circulating Virus: Relationship with Immunologic Parameters (1992)

Virologic and seroimmunologic parameters were determined in 56 persons infected with human immunodeficiency virus (HIV). The provirus level varied from 10 to 100,000/10(6) CD4+ lymphocytes, and genomic HIV RNA was detectable in 39 of 56 patients at a relative concentration varying from 10 to greater than 250 copies/mL of serum. Provirus expressed as copies per 10(6) CD4+ lymphocytes and as circulating virus per milliliter of serum increased with disease progression and decrease of CD4+ cell concentration. The mean provirus concentration expressed per milliliter of blood varied little among categories of patients with various levels of CD4+ cells, but there was a progressive increase of circulating HIV genomic RNA. These virologic data suggest that during the course of HIV infection, an increasing proportion of the remaining CD4+ lymphocytes harbor the HIV genome and produce infectious virus. Finally, there was a marked correlation between increased provirus and genomic RNA concentration and three seroimmunologic markers: decrease in CD4+ cell count, p24 antigenemia, and disappearance of antibodies to HIV core antigen.
Practical control of SERRS enhancement (2005)

The demonstration that quantitative and sensitive analysis can be carried out using surface enhanced resonance Raman scattering (SERRS) prompted a discussion and investigation of the main variables which are within the control of the analyst using colloidal silver as the substrate. Previous papers have dealt with the crucial need to obtain good chemisorption of the analyte to the surface and have reported the use of specially designed dyes for SERRS. One of the most variable processes is the aggregation of the colloid. Here, we investigate the addition of controlled amounts of an organic aggregating agent, poly-L-lysine, at concentrations which reduce the zeta potential in a controlled manner, thus aiding aggregation control. The relationship between the excitation frequency, the surface plasmon resonance frequency of the silver colloid and the frequency of the maximum absorbance of the molecular chromophore is studied using low concentrations of dye and no aggregating agent. Under these conditions, little to no aggregation is expected. The magnitude of the enhancement is strongly dependent on the frequency of the molecular chromophore as well as the plasmon resonance frequency. However, when sodium chloride is used to aggregate the colloid, a larger enhancement is obtained and the strong dependence on the molecular chromophore largely disappears. A much broader enhancement profile is obtained which appears to be related more to the specific enhancement processes caused by aggregation than the frequency of the chromophore. However, the total enhancement for SERRS is higher than for SERS thus indicating that the chromophore is still important to the process.
Total synthesis of nuclear analogues of 7-methylcephalosporin (1973)

A synthetic route which was developed for the preparation of nuclear analogues of the penicillins and cephalosporins has been used to synthesise 8-oxo-7α-phenylacetamido-6αH-1-aza-4-thiabicyclo[4.2.0]octane-2α-carboxylic acid (19),7α-methyl-8-oxo-7β-phenylacetamido-6αH-1-aza-4-thiabicyclo[4.2.0]octane-2α-carboxylic acid (27), and 7α-methyl-8-oxo-7β-phenylacetamido-6αH-1-aza-4-thiabicyclo[4.2.0]oct-2-ene-2-carboxylic acid (30).
Mechanism of carboxypeptidase‐Y‐catalysed peptide semisynthesis (1992)

The initial rate steady-state kinetics of carboxypeptidase-Y-catalyzed hydrolysis and aminolysis reactions with some alpha-N-benzoyl-L-tyrosinyl compounds has been investigated using L-valinamide as the nucleophile in aminolysis. Hydrolysis of alpha-N-benzoyl-L-tyrosinyl ethyl ester, 4-nitroanilide, and -amide has been studied in the pH range 4-9. The results are interpreted in terms of the classical serine proteinase mechanism, which involves enzyme-substrate complex formation, followed by acylation and deacylation of the enzyme. The three reactions share the same deacylation step. It is rate-determining with the ester substrate, but with the 4-nitroaniline acylation is and this is even more pronounced with the amide. From the pH dependencies, no change of rate-determining step is apparent in the range pH 4-9. For the 4-nitroanilide and the amide substrates, the kinetic parameter, Kc/Km, is influenced by an ionizing group with a pK value of 6. Probably this is the active-site histidine residue, which thus is active in acylation in its deprotonated form. That group affects the deacylation reaction similarly as seen from the kinetics of the ester substrate. Aminolysis occurs in parallel to hydrolysis in the presence of reactive nucleophiles. Here L-valinamide was used as model nucleophile. The analysis of the observed kinetic effects of L-valinamide on the initial rate behaviour of carboxypeptidase-Y-catalyzed hydrolysis reactions suggests a reaction mechanism which involves (a) the binding of the free nucleophile to the free enzyme and (b) reaction of the free nucleophile with the acyl-enzyme complex forming an enzyme-aminolysis product complex, which dissociates into the free enzyme and the aminolysis product. The reactions are characterized by a number of kinetic parameters, the values of which are determined. The results of aminolysis progress reactions indicate that the formation of the product in high yields is strongly dependent on the leaving group of the substrate. The initial production of aminolysis product, however, is the same for the three substrates. But the fact that their Kc/Km values differ by several orders of magnitude leads to significantly different progresses of the aminolysis. The ester substrate is the only one that efficiently competes with and hinders the hydrolysis of the aminolysis product.
The sequence of a type II keratin gene expressed in human skin: conservation of structure among all intermediate filament genes. (1985)

We report here the coding sequence of the gene for a 56-kDa type II keratin (designated K6b). Using a subclone specific for a unique 3' noncoding region of the encoded mRNA, we have shown that this gene is one of at least two 56-kDa keratin genes expressed in abundance in human epidermis. Segmenting the coding portion of this gene are eight introns, six of which are identically positioned with those of a distantly related type III intermediate filament gene (vimentin), and five of which are identically positioned with those of a distantly related type I gene (50-kDa keratin). These results indicate a common ancestral origin for all three classes of intermediate filament genes. All of the highly conserved intron positions are located within, but do not demarcate, the four central alpha-helical domains common to all intermediate filament polypeptides, suggesting that these genes were probably not created piecemeal by recombination-mediated linkage of separate structural domains as they presently are known.
Escherichia coli engineered to produce eicosapentaenoic acid becomes resistant against oxidative damages (2006)

The colony-forming ability of Escherichia coli genetically engineered to produce eicosapentaenoic acid (EPA) grown in 3mM hydrogen peroxide (H(2)O(2)) was similar to that of untreated cells. It was rapidly lost in the absence of EPA. H(2)O(2)-induced protein carbonylation was enhanced in cells lacking EPA. The fatty acid composition of the transformants was unaffected by H(2)O(2) treatment, but the amount of fatty acids decreased in cultures of cells lacking EPA and increased in cultures of cells producing EPA, suggesting that cellular EPA is stable in the presence of H(2)O(2) in vivo and may protect cells directly against oxidative damage. We discuss the possible role of EPA in partially blocking the penetration of H(2)O(2) into cells through membranes containing EPA.
The appendicitis scores may be useful in reducing the costs of treatment for right lower quadrant pain (2013)

The implementation of Alvarado and Lintula scores for the decision of hospital admission and appendectomy would have reduced overall treatment charges for acute RLQ pain.
Topical Therapy in Neonates (2008)

Topical therapy offers the potential to achieve higher concentrations of a drug in the skin with minimal exposure of other organs. This can greatly increase efficacy and safety relative to systemic administration 1 - 2 . Successful topical therapy depends not only on selection of the most appropriate pharmacologically active ingredient but also on the most optimal vehicle for delivery. Gels enhance penetration through the epidermis, while lotions offer the convenience of easy spreadability over large areas 3,4 . Creams are emulsions of oil and water and the ratio of these ingredients determines the texture, emollient and occlusive properties of the product. Ointments are water-insoluble occlusive mixtures of animal, vegetable or mineral lipids. Several antibiotics, antifungal, antiviral and antiparasitic agents are commercially available, but due consideration should be given to their efficacy and side effects before prescribing them in neonates 56 . Children are more susceptible to local and systemic effects of topical corticosteroids than are adults. Several types of adverse reactions are possible following the use of topical corticosteroids, so they should be used more cautiously and only when specifically indicated.
Effects of Cyclosporin A on Immune Activation Markers in Patients with Active Psoriasis (1999)

Although there is evidence for systemic immune activation in psoriasis, sIL-2R is the most consistently increased activation marker, related to the Th1 immune response, that may be used as a marker for monitoring disease activity and response to treatment with CsA in psoriatic patients.
Data structures and algorithms for nearest neighbor search in general metric spaces (1993)

We consider the computational problem of finding nearest neighbors in general metric spaces. Of particular interest are spaces that may not be conveniently embedded or approximated in Euclidian space, or where the dimensionality of a Euclidian representation 1s very high. Also relevant are high-dimensional Euclidian settings in which the distribution of data is in some sense of lower dimension and embedded in the space. The up-tree (vantage point tree) is introduced in several forms, together‘ with &&ciated algorithms, as an improved method for these difficult search nroblems. Tree construcI tion executes in O(nlog(n i ) time, and search is under certain circumstances and in the imit, O(log(n)) expected time. The theoretical basis for this approach is developed and the results of several experiments are reported. In Euclidian cases, kd-tree performance is compared.
Phosphatidylinositide 3-Kinase Priming Couples c-FLIP to T Cell Activation (2003)

Cellular FLICE (FADD-like interleukin-1-beta-converting enzyme)-inhibitory protein (c-FLIP) inhibits death receptor-induced apoptosis by binding to FADD (Fas-associated death domain protein) and pro-caspase-8. c-FLIP has also been shown to transmit activation signals and to enhance interleukin (IL)-2 production. However, c-FLIP-mediated T cell activation is difficult to detect in most cells. We found that in DO11.10 T cells, c-FLIP expression led to inhibition of IL-2 production, in contrast to the readily detectable c-FLIP-induced activation in Jurkat cells. A direct comparison revealed that distinct signal pathways were regulated by c-FLIP in Jurkat cells and DO11.10 cells. We investigated whether constitutively activated phosphatidylinositide 3-kinase (PI3K) in Jurkat cells stimulated c-FLIP. Inhibition of PI3K in Jurkat cells abrogated a c-FLIP-mediated increase in IL-2 production. In addition, c-FLIP coordinated with active PI3K for ERK activation. Furthermore, introduction of PTEN back into Jurkat cells eliminated the stimulatory effect of c-FLIP on IL-2 production and ERK activation. Our results suggest that priming with PI3K promotes the coupling of c-FLIP to T cell activation.
Isolation of a clone encoding a second dragline silk fibroin. Nephila clavipes dragline silk is a two-protein fiber. (1992)

Spider dragline silk is a unique protein fiber possessing both high tensile strength and high elasticity. A partial cDNA clone for one dragline silk protein (Spidroin 1) was previously isolated. However, the predicted amino acid sequence could not account for the amino acid composition of dragline silk. We have isolated a partial cDNA clone for another dragline silk protein (Spidroin 2), demonstrating that dragline silk is composed of multiple proteins. The amino acid sequence exhibits an entirely different repetitive motif than Spidroin 1. Spidroin 2 is predicted to consist of linked beta-turns in proline-rich regions which alternate with beta-sheet regions composed of polyalanine segments. This structure for Spidroin 2 provides a model for dragline silk structure and function.
Human papillomavirus DNA in genital tumours. (1984)

Human papillomaviruses (HPV) types 16 and 18 have been identified in two different human cervical carcinomas. The viral DNAs were molecularly cloned and used as probes to screen a large number of genital tumours by Southern blot analysis. HPV 16 or HPV 18 sequences were found in a high percentage of cervical carcinomas but only in a small number of condylomata acuminata or flat condylomas. The majority of the latter lesions, however, contained HPV 6 or HPV 11 sequences, respectively, which, in contrast, were detected only rarely in carcinoma in situ or invasive carcinomas. A similar distribution of the different papillomaviruses was observed when cell scrapings taken from the cervix were tested by in situ hybridization.
Hypermethylated Genes as Biomarkers of Cancer in Women with Pathologic Nipple Discharge (2009)

Abstract Purpose: In a pilot study of women with pathologic nipple discharge (PND) undergoing ductoscopy, we tested quantitative assessment of gene promoter hypermethylation using quantitative multiplex methylation–specific PCR (QM-MSP) to enhance detection of duct carcinoma in situ (DCIS). Experimental Design: Women with PND underwent ductoscopy; ducts with significant lesions were surgically resected (36 ducts in 33 women) and those with minimal findings were not (28 ducts in 16 women). QM-MSP was done on ductoscopy cell samples. Results were compared with cytology and tissue histology. Results: Cells from ducts with significant lesions on ductoscopy had significantly higher levels of methylation than those with minimal findings. Furthermore, cells from ducts with DCIS displayed higher levels of methylation than those with benign lesions such as papilloma (P = 0.006); or ducts with minimal findings on ductoscopy (P = 0.0001). Cumulative RASSF1A, TWIST1, and HIN1 gene methylation accurately distinguished ducts with cancerous versus benign lesions (100% sensitivity, 72% specificity, and area under the curve of 0.91 according to receiving operating characteristic analyses). QM-MSP analysis was more informative than cytology (100% versus 29% sensitivity, respectively), for detecting DCIS. In a validation set of paraffin-embedded DCIS and papilloma samples from women presenting with PND, QM-MSP was significantly higher in DNA from DCIS than papilloma sections (P = 0.002). Conclusion: The positive predictive value of ductoscopy was more than doubled (19% versus 47%) with the addition of QM-MSP, demonstrating the benefit of targeting ducts having both high methylation and significant abnormalities on ductoscopy for surgical excision. Future large-scale studies to validate this approach are needed.
CER4Encodes an Alcohol-Forming Fatty Acyl-Coenzyme A Reductase Involved in Cuticular Wax Production in Arabidopsis (2006)

A waxy cuticle that serves as a protective barrier against uncontrolled water loss and environmental damage coats the aerial surfaces of land plants. It is composed of a cutin polymer matrix and waxes. Cuticular waxes are complex mixtures of very-long-chain fatty acids and their derivatives. We report here the molecular cloning and characterization of CER4, a wax biosynthetic gene from Arabidopsis (Arabidopsis thaliana). Arabidopsis cer4 mutants exhibit major decreases in stem primary alcohols and wax esters, and slightly elevated levels of aldehydes, alkanes, secondary alcohols, and ketones. This phenotype suggested that CER4 encoded an alcohol-forming fatty acyl-coenzyme A reductase (FAR). We identified eight FAR-like genes in Arabidopsis that are highly related to an alcohol-forming FAR expressed in seeds of jojoba (Simmondsia chinensis). Molecular characterization of CER4 alleles and genomic complementation revealed that one of these eight genes, At4g33790, encoded the FAR required for cuticular wax production. Expression of CER4 cDNA in yeast (Saccharomyces cerevisiae) resulted in the accumulation of C24:0 and C26:0 primary alcohols. Fully functional green fluorescent protein-tagged CER4 protein was localized to the endoplasmic reticulum in yeast cells by confocal microscopy. Analysis of gene expression by reverse transcription-PCR indicated that CER4 was expressed in leaves, stems, flowers, siliques, and roots. Expression of a beta-glucuronidase reporter gene driven by the CER4 promoter in transgenic plants was detected in epidermal cells of leaves and stems, consistent with a dedicated role for CER4 in cuticular wax biosynthesis. CER4 was also expressed in all cell types in the elongation zone of young roots. These data indicate that CER4 is an alcohol-forming FAR that has specificity for very-long-chain fatty acids and is responsible for the synthesis of primary alcohols in the epidermal cells of aerial tissues and in roots.
A Biochemical Genomics Approach for Identifying Genes by the Activity of Their Products (1999)

For the identification of yeast genes specifying biochemical activities, a genomic strategy that is rapid, sensitive, and widely applicable was developed with an array of 6144 individual yeast strains, each containing a different yeast open reading frame (ORF) fused to glutathione S-transferase (GST). For the identification of ORF-associated activities, strains were grown in defined pools, and GST-ORFs were purified. Then, pools were assayed for activities, and active pools were deconvoluted to identify the source strains. Three previously unknown ORF-associated activities were identified with this strategy: a cyclic phosphodiesterase that acts on adenosine diphosphate-ribose 1"-2" cyclic phosphate (Appr>p), an Appr-1"-p-processing activity, and a cytochrome c methyltransferase.
An in vitro screening method to evaluate chemicals as potential chemotherapeutants to control Aeromonas hydrophila infection in channel catfish (2011)

An in vitro screening method using catfish gill cells to identify potential effective chemotherapeutants described here will cut cost in research compared with the method of using live fish to screen lead compounds for fish disease control.
Regulation of Gene Expression at the Beginning of Mammalian Development (1995)

The maternal to zygotic transition can be viewed as a cascade of events that begins when fertilization triggers the zygotic clock that delays early ZGA until formation of a 2-cell embryo. Early ZGA, in turn, appears to be required for expression of late ZGA, and late ZGA is required to form a 4-cell embryo. ZGA in mammals is a time-dependent mechanism rather than a cell cycle-dependent mechanism that delays both transcription and translation of nascent transcripts. Thus, zygotic gene transcripts appear to be handled differently than maternal mRNA, a phenomenon also observed in Xenopus (55). The length of this delay is species-dependent, occurring at the 2-cell stage in mice, the 4-8-cell stage in cows and humans, and the 8-16-cell stage in sheep and rabbits (4). However, concurrent with formation of a 2-cell embryo in the mouse and rabbit (47,56), perhaps in all mammals, a general chromatin-mediated repression of promoter activity appears. Repression factors are inherited by the maternal pronucleus from the oocyte but are absent in the paternal pronucleus and not available until sometime during the transition from a late 1-cell to a 2-cell embryo. This means that paternally inherited genes are exposed to a different environment in fertilized eggs than are maternally inherited genes, a situation that could contribute to genomic imprinting. Chromatin-mediated repression of promoter activity prior to ZGA is similar to what is observed during Xenopus embryogenesis (31,32) and ensures that genes are not expressed until the appropriate time in development when positive acting factors, such as enhancers, can relieve this repression. The ability to use enhancers appears to depend on the acquisition of specific co-activators at the 2-cell stage in mice and perhaps later in other mammals (47,56), concurrent with ZGA. Even then, the mechanism by which enhancers communicate with promoters changes during development (Fig. 2), providing an opportunity for enhancer-mediated stimulating of TATA-less promoters (e.g. housekeeping genes) early during development while eliminating this mechanism later during development.(ABSTRACT TRUNCATED AT 400 WORDS)