gebhart/patrepeval huggingface dataset:
Characterization of mitochondrial DNA using lowstringency single specific primer amplification analyzed by laser induced fluorescence – capillary electrophoresis (1996)

Polymerase chain reaction (PCR)-based DNA typing is routinely used in forensics for identity testing. Those assays that distinguish single nucleotide polymorphisms (SNPs) require other biochemical reactions in addition to PCR to identify the sequence polymorphisms. Low-stringency sequence-specific PCR (LSSP-PCR) is an example of a recent method that does not require additional biochemical treatments. The analysis of LSSP-PCR by capillary electrophoresis (CE) to discriminate the highly polymorphic mitochondrial DNA (mtDNA) D-loop region is described. The DNA from five individuals were amplified (first step) using sequence-specific primers to produce 1021 bp fragments containing the D-loop region. Each fragment was isolated by electroelution using CE and UV detection, and subjected to a second amplification (second step) using a single primer annealed under low stringency conditions. This generated a range or profile of PCR products for each sample, which were resolved and analyzed by CE with the intercalator TOTO-1 and laser-induced fluorescence (LIF) detection. The LSSP-PCR profiles were unique for each individual, indicating that this technique may be applicable for forensic identity testing.
Review--antibiotic treatment in inflammatory bowel disease: rifaximin, a new possible approach. (2000)

The etiology of inflammatory disease is still unknown, but a body of evidence from clinical and experimental observation indicates a role for intestinal microflora in the pathogenesis of this disease. Reduction of microflora using antibiotics, bowel rest and fecal diversion decreases activity in Crohn's disease and in ulcerative colitis. Several trials have been carried out on the use of antibiotic treatment in patients with active ulcerative colitis with contrasting results. A number of trials have been carried out using Rifaximin, a non-absorbable broad-spectrum antibiotic, confirming the absence of systemic bioavalaibility of the drug even when administered at very high doses and for prolonged periods. It may therefore be useful in treatment of ulcerative colitis and pouchitis, since its absorption through inflamed mucosa is negligible, it maintains a topical action without systemic effects and the lack of resistant bacterial strains may allow prolonged and repeated treatments.
Discriminative Frequent Pattern Analysis for Effective Classification (2007)

The application of frequent patterns in classification appeared in sporadic studies and achieved initial success in the classification of relational data, text documents and graphs. In this paper, we conduct a systematic exploration of frequent pattern-based classification, and provide solid reasons supporting this methodology. It was well known that feature combinations (patterns) could capture more underlying semantics than single features. However, inclusion of infrequent patterns may not significantly improve the accuracy due to their limited predictive power. By building a connection between pattern frequency and discriminative measures such as information gain and Fisher score, we develop a strategy to set minimum support in frequent pattern mining for generating useful patterns. Based on this strategy, coupled with a proposed feature selection algorithm, discriminative frequent patterns can be generated for building high quality classifiers. We demonstrate that the frequent pattern-based classification framework can achieve good scalability and high accuracy in classifying large datasets. Empirical studies indicate that significant improvement in classification accuracy is achieved (up to 12% in UCI datasets) using the so-selected discriminative frequent patterns.
Detection of human tumor cells by amplicon fusion site polymerase chain reaction (AFS-PCR) (2011)

Reliable diagnostic strategies for individuals with cancer demand practical methods for highly sensitive and specific detection of tumor cells. Amplification of genomic regions that include putative oncogenes is common in tumor cells of various types. Genomic array platforms offer the opportunity to identify and precisely map amplified genomic regions (ampGRs). The stable existence of these tumor cell–specific genomic aberrations during and after therapy, in theory, make ampGRs optimal targets for cancer diagnostics. In this study, we mapped ampGRs around the proto-oncogene MYCN of human neuroblastomas using a high-resolution tiling array (HR-TA). Based on the HR-TA data, we were able to precisely describe the telomeric and centromeric borders of the ampGRs and deduce virtual fusion sites of the joined ampGRs (amplicon fusion sites [AFSs]). These AFSs served as blueprints for the subsequent design of AFS bridging PCR assays (AFS-PCRs). Strikingly, these assays were absolutely tumor cell specific and capable of detecting 1 tumor cell in 1 × 10(6) to 8 × 10(6) control cells. We successfully proved the in vivo practicability of AFS-PCR by detecting and quantifying the specific AFS DNA of human MYCN-amplified neuroblastomas in the patients’ corresponding peripheral blood and bone marrow samples. Thus, we believe AFS-PCR could become a powerful and nevertheless feasible personalized diagnostic tool applicable to a large number of cancer patients, including children with MYCN-amplified neuroblastomas.
Observations Concerning the Sequence of Two Additional Specifically Encapsidated RNA Fragments Originating from the Tobacco‐Mosaic‐Virus Coat‐Protein Cistron (1975)

The incubation of 25‐S tobacco mosaic virus (TMV) protein with a mixture of RNA fragments produced by partial T 1 RNase digestion of TMV RNA results in the encapsidation of only a few species of RNA. In addition to the most predominant species, fragment 1, whose sequence has been described in the preceding paper, two other species, fragment 41 and fragment 21, are coated by the protein. These two RNA fragments were purified by polyacrylamide gel electrophoresis and subjected to total digestion with pancreatic and T 1 RNase. The oligonucleotides were separated by paper electrophoresis and characterized insofar as possible by digestion with the complementary ribonuclease. From the amino acid coding capacity of the oligonucleotides liberated from fragments 41 and 21 by T 1 RNase digestion, it appears that these two fragments, like fragment 1, are derived from the coat protein cistron. They are situated immediately prior to fragment 1 and, together with this fragment, constitute a continuous stretch of 232 nucleotides of the cistron which codes for amino acids 53 to 130 of the coat protein. The order of the fragments in the sequence is 21 – 41 – 1. A possible model for the secondary structure of this portion of the sequence is proposed.
2-Nitroimidazole (EF5) binding predicts radiation resistance in individual 9L s.c. tumors. (1996)

The presence of hypoxic tumor cells is known to be an important cause of radiation treatment resistance in vivo. The ability to predict the presence and extent of hypoxic cells in individual tumors would allow the addition of specific "antihypoxia"-based treatment regimes. Hypoxia can be monitored by measuring the binding of 2-nitroimidazoles. We have tested the hypothesis that binding of EF5, a fluorinated derivative of the 2-nitroimidazole, Etanidazole, can predict radioresistance in individual tumors. Fischer rats bearing 9L s.c. tumors were given injections i.v. with EF5 3 h before irradiation and tumor harvest. Tumor cells were dissociated for flow cytometric analysis and plating efficiency studies. EF5 binding was detected via monoclonal antibodies conjugated to the orange emitting dye, Cy3. In air breathing rats, for a given radiation dose, a large amount of variation in plating efficiency was seen. However, there was minimal variability of the plating efficiency for tumors irradiated in euthanized animals (hypoxic tumors; correlation coefficient for the fitted curve = 0.93) and in cells dissociated from tumors and irradiated in suspension (correlation coefficient for the fitted curve = 0.99), suggesting that varying sensitivity to the cell disaggregation technique was not responsible. In contrast, a good correlation between the relative radiation resistance or hypoxic survival and EF5 binding of "moderately" hypoxic cells in air breathing rats was identified using these techniques. In these 9L s.c. tumors, intertumor variation in oxygenation accounted for most of the range in individual tumor radiation response, and this was found to be independent of tumor size. This study provides evidence for the application of EF5 binding with monoclonal antibody detection as an in vivo predictive assay of individual tumor hypoxia and resultant therapy resistance.
Vision in the Brain (2026)

An illustrated guide to the fields of neuroscience. It begins by establishing a basic background of knowledge about brain anatomy and organization, with a particular emphasis on neurons and how they communicate. Later chapters discuss the organization of the visual system in detail.
A new paclitaxel prodrug for use in ADEPT strategy (2003)

A new paclitaxel prodrug intended for use in Antibody-Directed Prodrug Therapy (ADEPT) or Prodrug Monotherapy (PMT) has been prepared. This prodrug was originally designed to be activated into the drug by human beta-glucuronidase. In order to enhance the liberation rate of paclitaxel, an elongated spacer system including a nitro-aromatic derivative and a N,N'-methylethylenediamine was incorporated between the sugar moiety and the drug. Indeed, this new prodrug proved to be activated significantly faster than a former paclitaxel prodrug containing a conventional spacer.
An algorithm for adaptive predistortion of certain time-varying nonlinear high-power amplifiers (2003)

An extended Kalman filter (EKF) is proposed for adaptive precompensation of time-varying nonlinear distortion caused by high-power amplifiers (HPA) such as traveling wave tube (TWT) amplifiers frequently used in for instance, radar transmitters. In many applications, a means for adaptive predistortion is essential in order to reduce out-of band transmission. The proposed scheme is based on a nonlinear Wiener model for identification of the HPA characteristics and a predistorter with a Hammerstein-type structure. The usefulness of the proposed scheme is illustrated by means of a numerical example. In particular, it is shown that suppression of nonlinear distortion, introduced by a typical Ku-band TWT amplifier, in the order of 25-30 dB can be achieved. Furthermore, the performance of the EKF is compared to that of the recursive prediction error method (RPEM) and the stochastic gradient algorithm (LMS).
microphthalmia, a critical factor in melanocyte development, defines a discrete transcription factor family. (1994)

The microphthalmia (mi) gene appears essential for pigment cell development and/or survival, based on its mutation in mi mice. It has also been linked to the human disorder Waardenburg Syndrome. The mi gene was recently cloned and predicts a basic/helix-loop-helix/leucine zipper (b-HLH-ZIP) factor with tissue-restricted expression. Here, we show that Mi protein binds DNA as a homo- or heterodimer with TFEB, TFE3, or TFEC, together constituting a new MiT family. Mi can also activate transcription through recognition of the M box, a highly conserved pigmentation gene promoter element, and may thereby determine tissue-specific expression of pigmentation enzymes. Six mi mutations shown recently to cluster in the b-HLH-ZIP region produce surprising and instructive effects on DNA recognition and oligomerization. An alternatively spliced exon located outside of the b-HLH-ZIP region is shown to significantly modulate DNA recognition by the basic domain. These findings suggest that Mi's critical roles in melanocyte survival and pigmentation are mediated by MiT family interactions and transcriptional activities.
Cooperative Role for Activated α4β1 Integrin and Chondroitin Sulfate Proteoglycans in Cell Adhesion to the Heparin III Domain of Fibronectin (1999)

We recently reported that the heparin (Hep) III domain of fibronectin contains the H2 cell adhesion site in repeat III5 which binds activated alpha4 integrins. We have now further characterized the heparin and cell binding activities of this domain. A recombinant fragment containing repeats III4-III5 (FN-III4-5) induced Jurkat cell adhesion upon integrin activation with Mn2+ or TS2/16 monoclonal antibody (anti-beta1). Adhesion of Mn2+-treated cells to FN-III4-5 or FN-III5 fragments was inhibited by chondroitinase ABC and ACII but not by the anti-alpha4 monoclonal antibody HP2/1. In contrast, HP2/1 completely blocked adhesion of TS2/16-treated cells while chondroitinase had a partial (FN-III4-5) or minor (FN-III5) effect. Thus, the role of each receptor depended on the stimulus used to activate alpha4 beta1. The combination of HP2/1 and chondroitinase at dilutions which did not inhibit when used individually abolished adhesion of Mn2+ or TS2/16-treated cells to both fragments, indicating a cooperative effect between alpha4beta1 and chondroitin sulfate proteoglycans (CSPG). Furthermore, we have identified a 20-amino acid sequence in III5 (HBP/III5) which binds heparin and induces cell adhesion via CSPG exclusively. Although soluble HBP/III5 was a poor inhibitor, when combined with H2, it abolished adhesion to FN-III4-5 and FN-III5 fragments. These results establish that adhesion to the Hep III domain involves the cooperation of activated alpha4 beta1 and CSPG and show that HBP/III5 is a novel heparin and CSPG-binding site contributing to cell adhesion to this domain.
p63/p73 expression mediates cisplatin sensitivity in a subset of triple-negative primary breast cancer: Implications for a new clinical trial (2007)

10522 Background: Triple-negative breast cancer (ER-, PgR- and HER2-negative) has a poor prognosis relative to other subtypes, even with the best available chemotherapy. We recently reported that in squamous cell cancers, p63 promotes survival by direct interaction with and inhibition of p73-dependent apoptosis. We now report on the role of p63/p73 in triple-negative breast cancer. Methods: We performed quantitative RT-PCR on primary breast cancer specimens to determine the expression of specific p63 and p73 isoforms. Cell culture experiments used MCF7, HCC-1937, MDA-MB-468, T47D, and MCF10A cell lines. Lentiviral p63 and p73 shRNA were used for knockdown experiments. Chemotherapy dose-response curves were generated using MTT assay. Results: In primary tumors, ΔNp63 and TAp73 isoforms are expressed exclusively within a subset of triple-negative tumors in which p53 mutations are commonly found. Knockdown of p63 in triple-negative cell lines, but not the ER-positive MCF7 line, induced apoptosis which was specifically dependent on p73 expression. Breast cancer cell lines expressing p63/p73 exhibited p73-dependent sensitivity to cisplatin. Knockdown of p73 resulted in a 10–100 fold increase in the IC50 of cisplatin, but no change in doxorubicin or paclitaxel sensitivity. Exogenous p73 expression in MCF10A cells, which have high levels of p63 but no p73, confers increased sensitivity to cisplatin. Conclusion: These results show that p63/p73expression promotes survival in a subset of breast cancers, and they provide a mechanism for cisplatin sensitivity. These findings suggest that p63/p73 expression may serve as a biomarker to predict cisplatin sensitivity in triple-negative breast cancer. Based on these results, we are conducting a phase II study of 39 patients evaluating cisplatin as first line therapy for metastatic triple-negative breast cancer. The primary endpoints are overall objective response rate and response rate in low versus high p63/p73 expressing subgroups. No significant financial relationships to disclose.
Cancer cell adaptation to chemotherapy (2005)

This study suggests that up-regulation of resistance genes or down-regulation in target genes may occur rapidly in human solid tumors, within days of the start of treatment, and that similar changes are present in pre- and post-chemotherapy biopsy material. The molecular processes used by each tumor appear to be linked to the drug used, but there is also heterogeneity between individual tumors, even those with the same histological type, in the pattern and magnitude of response to the same drugs. Adaptation to chemotherapy may explain why prediction of resistance mechanisms is difficult on the basis of tumor type alone or individual markers, and suggests that more complex predictive methods are required to improve the response rates to chemotherapy.
Inhibition of telomerase by linear-chain fatty acids: a structural analysis (2002)

In the present study, we have found that mono-unsaturated linear-chain fatty acids in the cis configuration with C(18) hydrocarbon chains (i.e. oleic acid) strongly inhibited the activity of human telomerase in a cell-free enzymic assay, with an IC(50) value of 8.6 microM. Interestingly, fatty acids with hydrocarbon chain lengths below 16 or above 20 carbons substantially decreased the potency of inhibition of telomerase. Moreover, the cis-mono-unsaturated C(18) linear-chain fatty acid oleic acid was the strongest inhibitor of all the fatty acids tested. A kinetic study revealed that oleic acid competitively inhibited the activity of telomerase ( K (i)=3.06 microM) with respect to the telomerase substrate primer. The energy-minimized three-dimensional structure of the linear-chain fatty acid was calculated and modelled. A molecule width of 11.53-14.26 A (where 1 A=0.1 nm) in the C(16) to C(20) fatty acid structure was suggested to be important for telomerase inhibition. The three-dimensional structure of the telomerase active site (i.e. the substrate primer-binding site) appears to have a pocket that could bind oleic acid, with the pocket being 8.50 A long and 12.80 A wide.
A uniform convergence bound for the area under the ROC curve (2005)

The area under the ROC curve (AUC) has been advocated as an evaluation criterion for the bipartite ranking problem. We study uniform convergence properties of the AUC; in particular, we derive a distribution-free uniform convergence bound for the AUC which serves to bound the expected accuracy of a learned ranking function in terms of its empirical AUC on the training sequence from which it is learned. Our bound is expressed in terms of a new set of combinatorial parameters that we term the bipartite rank-shatter coefficients; these play the same role in our result as do the standard VC-dimension related shatter coefficients (also known as the growth function) in uniform convergence results for the classification error rate. A comparison of our result with a recent uniform convergence result derived by Freund et al. [FISS03] for a quantity closely related to the AUC shows that the bound provided by our result can be considerably tighter. 1
Stemming algorithms: A case study for detailed evaluation (1996)

The majority of information retrieval experiments are evaluated by measures such as average precision and average recall. Fundamental decisions about the superiority of one retrieval technique over another are made solely on the basis of these measures. We claim that average performance figures need to be validated with a careful statistical analysis and that there is a great deal of additional information that can be uncovered by looking closely at the results of individual queries. This article is a case study of stemming algorithms which describes a number of novel approaches to evaluation and demonstrates their value. © 1996 John Wiley & Sons, Inc.
Palladium(II)-Catalyzed Oxidation of Aldehydes and Ketones. 1. Carbonylation of Ketones with Carbon Monoxide Catalyzed by Palladium(II) Chloride in Methanol (2000)

Unsubstituted or alkyl-substituted cyclic ketones react with PdCl2 in methanol under a CO atmosphere to give mainly acyclic diesters along with some acyclic chloro-substituted monoesters. The monosubstituted cyclic ketones, 2-hydroxy- and 2-methoxycyclohexanone, do not give ring cleavage but rather produce 2-(carbomethoxy)cyclohex-2-en-1-one. 13CO labeling experiments indicate one CO is inserted in forming the diester product so the second ester group must arise from the original ketone group. Two mechanisms are possible for the diester reaction. One involves initial Pd(II)-CO2CH3 insertion across the double bond of the enol form of the ketone while the second involves initial addition of Pd(II)-OCH3 followed by CO insertion into the new Pd(II)-carbon bond formed. Pd(II) elimination and acid-catalyzed ring cleavage produce the second methyl ester group in both routes. The chloro-substituted monoester is formed by initial Pd(II)-Cl insertion across the double bond followed by the acid-catalyzed ring cleavage. The 2-(carbomethoxy)cyclohex-2-en-1-one must result from elimination of water or methanol from the alpha-ketoester product formed by the initial methoxycarbonylation of the enol form of the ketone. As expected, the acyclic ketone, 2-decanone, formed methyl acetate and a mixture of methyl nonanoate and 1-chlorooctane as products.
The Granulocyte-Macrophage Colony-Stimulating Factors (1985)

The granulocyte-macrophage colony-stimulating factors are well-characterized specific glycoproteins that interact to control the production, differentiation, and function of two related white cell populations of the blood, the granulocytes and monocyte-macrophages. Widely produced in the body, these regulators probably play an important role in resistance to infections. The proliferation of myeloid leukemia cells remains dependent on stimulation by colony-stimulating factors, although one of them also has the ability to suppress leukemic populations by inducing terminal differentiation.
Globin switches in yolk sac–like primitive and fetal-like definitive red blood cells produced from human embryonic stem cells (2007)

We have previously shown that coculture of human embryonic stem cells (hESCs) for 14 days with immortalized fetal hepatocytes yields CD34(+) cells that can be expanded in serum-free liquid culture into large numbers of megaloblastic nucleated erythroblasts resembling yolk sac-derived cells. We show here that these primitive erythroblasts undergo a switch in hemoglobin (Hb) composition during late terminal erythroid maturation with the basophilic erythroblasts expressing predominantly Hb Gower I (zeta(2)epsilon(2)) and the orthochromatic erythroblasts hemoglobin Gower II (alpha(2)epsilon(2)). This suggests that the switch from Hb Gower I to Hb Gower II, the first hemoglobin switch in humans is a maturation switch not a lineage switch. We also show that extending the coculture of the hESCs with immortalized fetal hepatocytes to 35 days yields CD34(+) cells that differentiate into more developmentally mature, fetal liver-like erythroblasts, that are smaller, express mostly fetal hemoglobin, and can enucleate. We conclude that hESC-derived erythropoiesis closely mimics early human development because the first 2 human hemoglobin switches are recapitulated, and because yolk sac-like and fetal liver-like cells are sequentially produced. Development of a method that yields erythroid cells with an adult phenotype remains necessary, because the most mature cells that can be produced with current systems express less than 2% adult beta-globin mRNA.