gebhart/patrepeval huggingface dataset:
Search for New and Improved Radiolabeling Methods for Monoclonal Antibodies: A Review of Different Methods (1993)

The radiolabeling of monoclonal antibodies for routine clinical applications have been intensively researched during the past decade. The traditional radiolabeling methods are direct radioiodination using oxidative reagents, such as chloramine T, and coupling metals by use of bifunctional chelates like diethylenetriamine-pentaacetic acid (DTPA). More recently technetium labeling has also been used. In this review the selection of different radioisotopes is discussed as well as the various traditional or newer methods to introduce the radiolabel into the antibody structure. Labeling methods for radiohalogens, for technetium and rhenium isotopes, and for 3-valent cation radiometals are reviewed. Some of the newer methods offer simplified labeling procedures, but usually the new methods are more complicated than the earlier ones. However, new labeling methods are available for almost any radioelement group and they may result in better preserved original nature of the antibody and lead to better clinical results.
Strain improvement of Aspergillus niger for enhanced lipase production. (2001)

The enhancement of lipase production from Aspergillus niger was attempted by ultraviolet (UV) and nitrous acid mutagenesis, and the mutants were selected on media containing bile salts. Nitrous acid mutants exhibited increased efficiency for lipase production when compared with UV mutants in submerged fermentation. The hyperproducing UV and nitrous acid mutants were further subjected to a second step of mutagenesis to devise an economical and ecofriendly technique for lipase production by the effective use of hydrocarbons. One percent kerosene was found to be optimal for lipase production, and one of the mutant strains NAII exhibited 2.53 times more increased lipase activity than the parental strain did. This investigation indicates a possible role for the A. niger mutant strains in the biodegradation of oil-polluted environments for the development of ecofriendly technologies.
Phylogenetic analysis of the phytochrome superfamily reveals distinct microbial subfamilies of photoreceptors (2005)

Phys (phytochromes) are a superfamily of photochromic photoreceptors that employ a bilin-type chromophore to sense red and far-red light. Although originally thought to be restricted to plants, accumulating genetic and genomic analyses now indicate that they are also prevalent among micro-organisms. By a combination of phylogenetic and biochemical studies, we have expanded the Phy superfamily and organized its members into distinct functional clades which include the phys (plant Phys), BphPs (bacteriophytochromes), Cphs (cyanobacterial Phys), Fphs (fungal Phys) and a collection of Phy-like sequences. All contain a signature GAF (cGMP phosphodiesterase/adenylate cyclase/FhlA) domain, which houses the bilin lyase activity. A PHY domain (uppercase letters are used to denote the PHY domain specifically), which helps stabilize the Pfr form (far-red-light-absorbing form of Phy), is downstream of the GAF region in all but the Phy-like sequences. The phy, Cph, BphP and Fph families also include a PLD [N-terminal PAS (Per/Arnt/Sim)-like domain] upstream of the GAF domain. Site-directed mutagenesis of conserved residues within the GAF and PLD motifs supports their importance in chromophore binding and/or spectral activity. In agreement with Lamparter, Carrascal, Michael, Martinez, Rottwinkel and Abian [(2004) Biochemistry 43, 3659-3669], a conserved cysteine within the PLD of several BphPs was found to be necessary for binding the chromophore via the C-3 vinyl side chain on the bilin A ring. Phy-type sequences were also discovered in the actinobacterium Kineococcus radiotolerans and collections of microorganisms obtained from marine and extremely acidic environments, thus expanding further the range of these photoreceptors. Based on their organization and distribution, the evolution of the Phy superfamily into distinct photoreceptor types is proposed.
Wnt signaling promotes oncogenic transformation by inhibiting c-Myc–induced apoptosis (2002)

Aberrant activation of the Wnt/beta-catenin signaling pathway is associated with numerous human cancers and often correlates with the overexpression or amplification of the c-myc oncogene. Paradoxical to the cellular transformation potential of c-Myc is its ability to also induce apoptosis. Using an inducible c-MycER expression system, we found that Wnt/beta-catenin signaling suppressed apoptosis by inhibiting c-Myc-induced release of cytochrome c and caspase activation. Both cyclooxygenase 2 and WISP-1 were identified as effectors of the Wnt-mediated antiapoptotic signal. Soft agar assays showed that neither c-Myc nor Wnt-1 alone was sufficient to induce cellular transformation, but that Wnt and c-Myc coordinated in inducing transformation. Furthermore, coexpression of Wnt-1 and c-Myc induced high-frequency and rapid tumor growth in nude mice. Extensive apoptotic bodies were characteristic of c-Myc-induced tumors, but not tumors induced by coactivation of c-Myc and Wnt-1, indicating that the antiapoptotic function of Wnt-1 plays a critical role in the synergetic action between c-Myc and Wnt-1. These results elucidate the molecular mechanisms by which Wnt/beta-catenin inhibits apoptosis and provide new insight into Wnt signaling-mediated oncogenesis.
Adaptive control of waveguide modes in a two-mode-fiber (2014)

We experimentally demonstrate an adaptive-optics-based approach that allows selective excitation of waveguide modes and their mixtures in a two-mode fiber (TMF). A phase-only spatial light modulator is used for wavefront control, using feedback signals provided by the correlation between the experimentally measured field distribution and the desired mode profiles. Experimental results show the optical field within the TMF can be shaped to be pure linearly polarized (LP) modes or their combinations. Analysis shows selective mode excitation can be achieved using only 5 × 5 independent phase blocks. With proper feedback signals, this method should enable one to precisely control the optical field within any multimode fiber or other types of waveguides in real time.
Cloning of a rat brain succinic semialdehyde reductase involved in the synthesis of the neuromodulator γ-hydroxybutyrate (1998)

The gamma-hydroxybutyrate biosynthetic enzyme succinic semialdehyde reductase (SSR) was purified to homogeneity from rat brain. Peptides were generated by tryptic cleavage and sequenced. PCR primers were designed from the amino acid sequences of two of the peptides showing a similarity (75-85%) to a mitochondrial aldehyde dehydrogenase. A PCR-amplified DNA fragment was generated from recombinant plasmids prepared by a mass excision procedure from a rat hippocampal cDNA library and used as a probe to screen this cDNA library. One cDNA of 1341 bp had an open reading frame encoding a protein of 447 residues with a deduced molecular mass of 47967 Da. The enzyme was expressed in Escherichia coli. Immunoblotting analysis revealed the existence of a protein with the same electrophoretic mobility as the SSR purified from rat brain and with an estimated molecular mass of 45 kDa. Northern blot experiments showed that this enzyme was not expressed in the kidney or in the liver. In the brain tissue, a single but rather broad band was labelled under high stringency conditions, suggesting the presence of more than one messenger species coding for SSR. Hybridization in situ performed on brain tissue slices showed specific labelling of the hippocampus, the upper cortex layer, the thalamus, the substantia nigra, the cerebellum, the pons medulla and the olfactory tract. The recombinant enzyme showed catalytic properties similar to those of the SSR purified from rat brain, particularly in regard to its substrate affinities and Ki for inhibition by phthalaldehydic acid. Valproic acid did not inhibit the cloned SSR. This enzyme had 20-35% identity in highly conserved regions involved in NADPH binding with four other proteins belonging to the aldo-oxo reductase family.
Beyond microRNA – Novel RNAs derived from small non-coding RNA and their implication in cancer (2013)

Over the recent years, Next Generation Sequencing (NGS) technologies targeting the microRNA transcriptome revealed the existence of many different RNA fragments derived from small RNA species other than microRNA. Although initially discarded as RNA turnover artifacts, accumulating evidence suggests that RNA fragments derived from small nucleolar RNA (snoRNA) and transfer RNA (tRNA) are not just random degradation products but rather stable entities, which may have functional activity in the normal and malignant cell. This review summarizes new findings describing the detection and alterations in expression of snoRNA-derived (sdRNA) and tRNA-derived (tRF) RNAs. We focus on the possible interactions of sdRNAs and tRFs with the canonical microRNA pathways in the cell and present current hypotheses on the function of these RNAs.
Metronomic Chemotherapy Enhances the Efficacy of Antivascular Therapy in Ovarian Cancer (2007)

Metronomic chemotherapy is the frequent administration of low doses of chemotherapeutic agents targeting tumor-associated endothelial cells. We examined the efficacy of metronomic taxanes alone and in combination with AEE788-a dual epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) inhibitor-in an orthotopic mouse model of ovarian cancer. Growth-modulating effects of metronomic and maximum tolerated dose (MTD) regimens on overall survival were tested in vivo using both chemotherapy-sensitive (HeyA8 and SKOV3ip1) and chemotherapy-resistant (HeyA8-MDR) models. Treated tumors were stained for microvessel density (CD31), proliferation index (proliferating cell nuclear antigen), and apoptosis (terminal deoxyribonucleotide transferase-mediated nick-end labeling). The cytotoxic effects of MTD and metronomic dosing were tested with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Effects of metronomic regimens on circulating endothelial precursors (CEP) and tumor-specific cell-free DNA levels were assessed. In vivo, metronomic docetaxel resulted in significant reduction of tumor growth in the taxane-sensitive cell lines, whereas metronomic docetaxel plus AEE788 had an additive effect resulting in significant prolongation in survival. Combination therapy was effective even in the taxane-resistant model. Metronomic chemotherapy alone and combined with AEE788 resulted in a decrease in the proliferative index and microvessel density of treated tumors, whereas combination therapy increased the apoptotic index (P < 0.001). In vitro, metronomic taxanes caused endothelial cell toxicity at 10- to 100-fold lower concentrations compared with MTD dosing. Metronomic regimens inhibited mobilization of CEPs (P < 0.05) and led to a decrease in cell-free DNA levels (P < 0.05). Our results suggest that metronomic taxane chemotherapy with dual EGFR and VEGFR inhibition is highly efficacious and should be considered for future clinical trials.
THE SYNTHESIS OF 5-FLUOROPYRIMIDINES (1957)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTHE SYNTHESIS OF 5-FLUOROPYRIMIDINESRobert Duschinsky, Edward Pleven, and Charles HeidelbergerCite this: J. Am. Chem. Soc. 1957, 79, 16, 4559–4560Publication Date (Print):August 1, 1957Publication History Published online1 May 2002Published inissue 1 August 1957https://pubs.acs.org/doi/10.1021/ja01573a087https://doi.org/10.1021/ja01573a087research-articleACS PublicationsRequest reuse permissionsArticle Views2477Altmetric-Citations384LEARN 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-Alertsclose Get e-Alerts
Viral protein R of human immunodeficiency virus types 1 and 2 is dispensable for replication and cytopathogenicity in lymphoid cells (1989)

Viral protein R (VPR) is conserved in human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2). To assess its function, we have constructed mutations within the vpr coding regions of HIV-1 and HIV-2 predicted to express truncated VPR products. Infectious virus was produced by each proviral clone and showed similar replication kinetics and cytopathogenicity when compared with the corresponding parental proviral clone.
IFN-γ and Its Receptor Subunit IFNGR1 Are Recruited to the IFN-γ-Activated Sequence Element at the Promoter Site of IFN-γ-Activated Genes: Evidence of Transactivational Activity in IFNGR1 (2006)

We have shown previously that IFN-gamma and one of its receptor subunits, IFNGR1, are translocated to the nucleus, together with STAT1alpha as one macromolecular complex, via the classical importin-dependent pathway. In this study, we have identified the nuclear targets of IFN-gamma and IFNGR1. By chromatin immunoprecipitation followed by PCR, IFN-gamma, its receptor subunit IFNGR1, and STAT1alpha were found to be associated with the IFN-gamma-activated sequence (GAS) in the promoter of two of the genes stimulated by IFN-gamma. Immunoprecipitated chromatin also showed the association of the IFN-gamma, IFNGR1, and STAT1alpha on the same DNA sequence. Examination of nuclear extracts from WISH cells treated with IFN-gamma revealed the specific binding of IFN-gamma, IFNGR1, and STAT1alpha to biotinylated GAS nucleotide sequence. Association of IFN-gamma, IFNGR1, and STAT1alpha with the GAS promoter was also demonstrated by EMSA. Transfection with a GAS-luciferase gene together with the IFNGR1 and nonsecreted IFN-gamma resulted in enhanced reporter activity. In addition, IFNGR1 fused to the yeast GAL4 DNA binding domain resulted in enhanced transcription from a GAL4 response element, suggesting the presence of a trans activation domain in IFNGR1. Our observations put IFN-gamma and its receptor subunit, IFNGR1, in direct contact with the promoter region of IFN-gamma-activated genes with associated increased activity, thus suggesting a transcriptional/cotranscriptional role for IFN-gamma/IFNGR1 as well as a possible role in determining the specificity of IFN-gamma action.
Light Weight Background Blurring for Video Conferencing Applications (2006)

Background blurring is an effective way to both preserving privacy and keeping communication effective during video conferencing. This paper proposes a light weight real-time algorithm to perform background blurring using a fast background modeling algorithm combined with a face detector/tracker. A soft decision is made at each pixel whether it belongs to the foreground or the background based on multiple vision features. The classification results are mapped to a per-pixel blurring radius image to blur the background. The algorithm produces satisfactory results under a wide range of conditions, and occupies less than 30% of the CPU cycles on a 3 GHz Pentium 4 machine without further optimization.
A Critical Comparison of Methods to Quantify Stratum corneum Removed by Tape Stripping (1996)

Skin surface stripping with adhesive tape has been used to study the barrier function of the stratum corneum. Usually, the amount of stratum corneum removed by stripping is not linearly proportional to the number of strips removed. The generally accepted quantitative method to determine the amount of stratum corneum material on a tape strip is weighing. This method however has certain drawbacks, it is time consuming and laborious because tape strips have to be weighed twice and sometimes it cannot be used to determine concentration profiles in the skin of active substances in topically applied vehicles. In this paper, the accuracy and reliability of an alternative method to determine the amount of stratum corneum removed by tape stripping of the skin was investigated and compared to weighing. It is based on the spectrophotometric examination of the tape. The light absorption by the proteins on the tape is correlated to the weight of the stratum corneum material. This method was found to be easier and faster than weighing, but it was less reliable because the light scattering of the stratum corneum on the tape largely overshadowed the absorption of the proteins. The light scattering showed a linear increase with an increasing amount of material on the tape, but with a large variability, resulting in calibration curves with correlations of 0.8400. However, direct spectroscopic analysis of stratum corneum tape strips has some distinct advantages even if it cannot be used for the exact quantification of stratum corneum proteins. With direct spectroscopic measurements, a tape strip can be laterally examined to inspect its homogeneity. Direct spectroscopic measurements on tape strips might also be employed to investigate the lateral and in-depth distribution of strongly light-absorbing substances in the stratum corneum.
A new fault location algorithm for radial transmission lines with loads (1989)

Conventional fault location schemes do not take loads and their variable impedance behavior into account. This leads to unacceptable errors in the case of radial transmission lines with loads, commonly found at the 120 kV and lower levels. A novel method for such lines is proposed. The fault distance is obtained by solving an implicit equation. Single-phase-to-ground, phase-to-phase, and three-phase-to-ground faults are treated. The effect of the scheme is illustrated by simulated faults.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Distant metastases in ovarian cancer: association with p53 mutations. (1999)

Distant metastases are unusual occurrences at presentation and during the progression of epithelial ovarian cancer. There are no good clinical predictors of this phenomenon. Because p53 dysfunction is common in ovarian cancer, we chose to investigate whether specific types of mutations predicted a predisposition to distant metastasis. We hypothesized that the complete absence of intact p53 protein as seen with p53 null mutations may be associated with an enhanced tendency to develop distant metastatic disease. The complete coding sequence of 130 tumor DNA samples was screened for p53 mutations by single-strand conformational polymorphism analysis. Abnormal single-strand conformational polymorphism findings were correlated with the specific DNA sequence abnormalities and outcome. Ninety-four (72%) tumors carried p53 mutations. Sixty-two were missense mutations, and 32 were null mutations (6 nonsense mutations, 23 frameshift mutations, and 3 splice-site mutations). Twenty-eight patients were found to have distant metastases (pericardium, brain, parenchymal liver, spleen, or lung) either at presentation or during the course of their treatment. Distant metastases were nearly 8-fold more common in patients whose tumors carried a null mutation (66%) than in those with either missense mutations (8%) or wild-type p53 (8%; P<0.001). When a null mutation was present, 25% of the tumors were associated with distant metastases at initial diagnosis. No individual with wild-type p53 or a missense mutation in the tumor presented with distant metastasis. Tumors with null mutations were more likely to be associated with lymph node metastasis (P = 0.003), advanced stage (stage III/IV; P<0.001) and high grade (grade II/III; P<0.001), at presentation. These tumors progressed with distant metastases more swiftly than did tumors with either missense mutations (mean, 1.18 versus 2.71 years; P = 0.04) or wild-type p53 (3.57 years; P = 0.015). In contrast to the popular dogma, distant metastases in ovarian cancer do not necessarily result from prolonged treatment of disease. They may be predicted to occur early in the disease course due to a specific molecular genetic abnormality: null mutation of the p53 tumor suppressor gene. These findings need to be carefully considered when choosing between regional versus systemic treatment modalities.
Phase I clinical evaluation of 9,10-anthracenedicarboxyaldehyde[bis(4,5-dihydro-1H-imidazol-2-yl)hydrazone]dihydrochloride (bisantrene). (1982)

9,10-Anthracenedicarboxyaldehyde[bis(4,5-dihydro-1H-imidazol-2-y1)-hydrazone ]dihydrochloride (bisantrene) is one of a series of anthracenedicarboxyaldehyde compounds that has significant antitumor activity similar to that of doxorubicin in experimental mouse tumor systems. A phase I clinical study was conducted using a weekly x 3 schedule. Twenty-six patients with a wide variety of advanced malignant solid tumors received a total of 39 courses of the drug at doses ranging from 40 to 180 mg/m2/week x 3. Leukopenia was the dose-limiting toxic effect. Other toxic effects included malaise, which was observed in 49% of the courses, nausea and vomiting in 36%, fever in 21%, and phlebitis in 21%. No responses were observed in this study. For phase II studies, using this schedule, a starting dose of 150 mg/m2/week x 3 repeated every 4-5 weeks is recommended. In patients who have received minimal or no therapy, the starting dose should be 180 mg/m2.
Modeling of Hydraulic-Fracture-Network Propagation in a Naturally Fractured Formation (2011)

Summary Hydraulic fracturing in shale-gas reservoirs has often resulted in complex-fracture-network growth, as evidenced by microseismic monitoring. The nature and degree of fracture complexity must be understood clearly to optimize stimulation design and completion strategy. Unfortunately, the existing single-planar-fracture models used in the industry today are not able to simulate complex fracture networks. A new hydraulic-fracture model is developed to simulate complex-fracture-network propagation in a formation with pre-existing natural fractures. The model solves a system of equations governing fracture deformation, height growth, fluid flow, and proppant transport in a complex fracture network with multiple propagating fracture tips. The interaction between a hydraulic fracture and pre-existing natural fractures is taken into account by using an analytical crossing model and is validated against experimental data. The model is able to predict whether a hydraulic-fracture front crosses or is arrested by a natural fracture it encounters, which leads to complexity. It also considers the mechanical interaction among the adjacent fractures (i.e., the "stress shadow" effect). An efficient numerical scheme is used in the model so it can simulate the complex problem in a relatively short computation time to allow for day-to-day engineering design use. Simulation results from the new complex-fracture model show that stress anisotropy, natural fractures, and interfacial friction play critical roles in creating fracture-network complexity. Decreasing stress anisotropy or interfacial friction can change the induced-fracture geometry from a biwing fracture to a complex fracture network for the same initial natural fractures. The results presented illustrate the importance of rock fabrics and stresses on fracture complexity in unconventional reservoirs. These results have major implications for matching microseismic observations and improving fracture stimulation design.