gebhart/patrepeval huggingface dataset:
Synthesis and restriction enzyme analysis of oligodeoxyribonucleotides containing the anti-cancer drug 2', 2'-difluoro-2'-deoxycytidine (1992)

The anti-cancer drug 2',2'-difluoro-2'-deoxycytidine (dFdC) is internally incorporated into DNA in vitro. To determine the effects of this incorporation on DNA structure and function, the beta-cyanoethyl phosphoramidite of dFdC was synthesized and oligodeoxyribonucleotides containing dFdC were made using automated solid phase DNA synthesis techniques. Extension of the coupling time was required to achieve high coupling efficiency, suggesting a significant reduction in the rate of phosphotriester formation. Insertion of dFdC 5' into the recognition sequence of restriction enzymes HpaII and KpnI reduced the rate of cutting by 4% and 14% over 60 minutes. This reduction is similar to the effects seen with arabinofuranosylcytidine (ara-C) but small compared to the reductions caused by base analogues and phosphothioates. Insertion of dFdC into the BamHI recognition sequence, but not 5' to the cut site, did not alter the rate of cutting/recognition. The presence of a single dFdC reduced the Tm's of oligomers by 2-4 degrees C, depending on sequence and location. These results demonstrate that, once incorporated into DNA, dFdC does not greatly alter recognition between DNA and restriction enzymes; however, it does significantly alter duplex stability.
Atomic and Macroscopic Reaction Rates of a Surface-Catalyzed Reaction (1997)

The catalytic oxidation of carbon monoxide (CO) on a platinum (111) surface was studied by scanning tunneling microscopy. The adsorbed oxygen atoms and CO molecules were imaged with atomic resolution, and their reactions to carbon dioxide (CO2) were monitored as functions of time. The results allowed the formulation of a rate law that takes the distribution of the reactants in separate domains into account. From temperature-dependent measurements, the kinetic parameters were obtained. Their values agree well with data from macroscopic measurements. In this way, a kinetic description of a chemical reaction was achieved that is based solely on the statistics of the underlying atomic processes.
Affinity‐matured anti‐glycoprotein NMB recombinant immunotoxins targeting malignant gliomas and melanomas (2010)

Glycoprotein NMB (GPNMB), a transmembrane glycoprotein highly expressed in high-grade gliomas (HGGs), is an attractive target in cancer immunotherapy. We isolated a GPNMB-specific scFv clone, G49, from a human synthetic phage-display library. To obtain mutant single-chain variable-fragment antibodies (scFvs) with improved affinity and immunotoxins with increased activity, we subjected G49 to in vitro affinity maturation by a complementarity-determining-region (CDR) random-mutagenesis technique. Using light-chain CDR3 mutagenesis, cell-based panning by phage display, subsequent heavy-chain CDR1 mutagenesis, and flow-cytometric selection by yeast-surface display, we generated the mutant scFv clone 902V, with an overall 11-fold increase in affinity for GPNMB. Clone 902V was further randomized throughout the whole scFv by error-prone PCR, and one mutant, F6V, was selected by yeast-surface display. F6V scFv, differing from 902V by one amino-acid change in the light-chain CDR2, exhibited an affinity for GPNMB of 0.30 nM. The F6V mutant scFv clone was fused with a truncated form of Pseudomonas exotoxin A to form the immunotoxin F6V-PE38. F6V-PE38 demonstrated significant protein-synthesis-inhibition activity on GPNMB-expressing glioma and malignant melanoma cells (IC(50) = 0.5 ng/ml [8 pM]), a 60-fold improvement over G49 activity, but no cytotoxicity on GPNMB-negative cells. Furthermore, F6V-PE38 exhibited significant antitumor activity against subcutaneous malignant glioma xenografts in two nude-mouse models and a melanoma neoplastic meningitis model in athymic rats. These GPNMB-specific scFv antibodies and immunotoxins hold promise as reagents in targeted therapy for HGGs and other GPNMB-expressing malignancies.
Increased labeling of human melanoma cells in vitro using combinations of monoclonal antibodies recognizing separate cell surface antigenic determinants. (1985)

A panel of mouse anti-melanoma monoclonal antibodies (MoAb) were analyzed for reactivity with human melanoma cells singly and in combination. Five MoAb, ZME-018, 96.5, P94, 4.2, and 5.1, reactive with individual cell surface melanoma-associated antigens were tested with seven melanoma cell lines and seven fresh tumor biopsies. Cells were incubated with the MoAb, indirectly stained with fluorescein-conjugated goat anti-mouse immunoglobulin, and analyzed by flow cytometry. Percentage of labeled cells and relative fluorescence intensity (FI) with individual MoAb varied with different cell lines and biopsy samples. The most reactive MoAb, ZME-018, 96.5, and P94, labeled 29-93% of the cells from cell lines with relative FI of 2-59 units, thereby demonstrating phenotypic diversity of these cells. Similar results were obtained with cells derived from tumor biopsies, where 1-73% of cells were labeled and relative FI ranged from 0-27. These variations were reduced by using a "cocktail" of MoAb which recognized different melanoma-associated antigens. In cell lines both the percentage of labeled cells (range, 82-95%) and relative FI (range, 36-115) increased substantially (P less than 0.025 and P less than 0.005, respectively) when a "cocktail" prepared from all five MoAb rather than individual MoAb was used. A cocktail of MoAb increased the percentage of labeled tumor biopsy cells (range, 53-78; P less than 0.01) and relative FI (range, 11-69; P less than 0.025). The mean FI obtained by incubating cells with a cocktail of suboptimal concentrations of three MoAb (ZME-018, 96.5, P94) was 48 +/- 12 (SD), which was significantly increased compared to the mean FI seen with suboptimal concentrations of MoAb alone (ZME-018, 7 +/- 10; 96.5, 8 +/- 7; P94, 2 +/- 2; P less than 0.005). These findings were confirmed by radioimmunoassay using a combination of two MoAb, ZME-018 and 96.5. The data suggest that cocktails of MoAb were more effective than single MoAb alone for melanoma tumor cell labeling in vitro and might be more effective for tumor imaging and therapy.
Nucleotide Sequence of the Capsid Protein Gene and 3' Non-coding Region of Papaya Mosaic Virus RNA (1988)

The nucleotide sequences of cDNA clones corresponding to the 3' OH end of papaya mosaic virus RNA have been determined. The 3'-terminal sequence obtained was 900 nucleotides in length, excluding the poly(A) tail, and contained an open reading frame capable of giving rise to a protein of 214 amino acid residues with an Mr of 22930. This protein was identified as the viral capsid protein. The 3' non-coding region of PMV genome RNA was about 121 nucleotides long [excluding the poly(A) tail] and homologous to the complementary sequence of the non-coding region at the 5' end of PMV RNA. A long open reading frame was also found in the predicted 5' end region of the negative strand.
Clinical Significance of Skin Reactions to Mite Extracts in Children with Asthma (1969)

The mite Dermatophagoides pteronyssinus has been identified in dust from the houses of children in Birmingham suffering from asthma. Skin tests were carried out on 150 asthmatic children with extracts of D. pteronyssinus, of the related species D. farinae, of other mites found in house dust, and of crude house dust. Though positive reactions to D. pteronyssinus were obtained more frequently and were of greater size than those to the other extracts, it was considered that D. farinae is a suitable substitute for D. pteronyssinus for skin testing.In further tests on 302 asthmatic children with mite extracts and with extracts of allergens obtained commercially reactions to the former extracts were much more common than reactions to the latter.Major skin reactions (weals with diameter of 5 mm. or more) were present in 77% of children with a history of perennial asthma and house-dust sensitivity. Hence allergy to house-dust mites, particularly D. pteronyssinus, is of considerable importance in childhood asthma, and further study of the ecology and control of the mites in dust is desirable.
Synthesis of (+-)-hexahydropronuciferine and related compounds (1971)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of (+-)-hexahydropronuciferine and related compoundsJohn W. Huffman and C. E. OpligerCite this: J. Org. Chem. 1971, 36, 1, 111–117Publication Date (Print):January 1, 1971Publication History Published online1 May 2002Published inissue 1 January 1971https://pubs.acs.org/doi/10.1021/jo00800a024https://doi.org/10.1021/jo00800a024research-articleACS PublicationsRequest reuse permissionsArticle Views160Altmetric-Citations10LEARN 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
Forensic expertise at Congress (2013)

Abstract Melinda Merck is a leading American expert in veterinary forensics, particularly animal cruelty cases.
Micro-Fabricated 130–180 GHz Frequency Scanning Waveguide Arrays (2012)

This paper describes frequency scanning slot arrays operating from 130 to 180 GHz. The arrays are micro-fabricated using the PolyStrata sequential copper deposition process. Measured reflection coefficient and radiation patterns agree with HFSS full-wave simulations. The voltage standing wave ratio is less than 1.75:1 over the entire frequency range, and the measured scanning is 1.04 <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$^{\circ }/$</tex> </formula> GHz from 130 to 150 GHz and 32.5 <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$^{\circ }$</tex></formula> over the full frequency range. The measured gain is 15.5 dBi for a 10-element array at 150 GHz and 18.9 dBi for a 20-element array at 150 GHz with about 3 dB of variation over the scan range.
Free Vascularized Fibular Grafts for Reconstruction of Skeletal Defects (2004)

Nourished by the peroneal vessels, the versatile free vascularized fibular graft can be transferred to reconstruct skeletal defects of the extremities. It may be combined with skin, fascia, muscle, and growth-plate tissue to address the needs of the recipient site. It may be cut transversely and folded to reconstruct the length and width of tibial or femoral defects. The main indications for this graft are defects larger than 5 to 6 cm or with poor vascularity of the surrounding soft tissues. Detailed preoperative planning, experience in microvascular techniques, and careful postoperative follow-up are necessary to minimize complications and improve outcome. The free vascularized fibular graft has been successfully applied as a reconstruction option in patients with traumatic or septic skeletal defect, after tumor resection, and has shown promise in patients with congenital pseudarthrosis.
Re-figuring Bradshaw: Art, Place and Landscape in the Victoria River District (2002)

The emergence of legislation dealing with Aboriginal land rights, native title and cultural heritage protection has provided a range of prospective avenues for the recognition and protection of minority Indigenous land interests in Australia. This historic accommodation within state legislative structures has, in turn, fostered a renewed interest and desire among Aboriginal communities to reassert their links to ancestral country. Focusing on one area of the Northern Territory, this article explores aspects of cultural attachment and affiliation to land through the medium of the painted image and artistic representation of mythologised place.
Chemical stabilization of tetrahydrobiopterin by L-ascorbic acid: contribution to placental endothelial nitric oxide synthase activity (2002)

The aim of this study was to characterize the mechanism of the chemical interaction between L-ascorbic acid (ASC) and tetrahydrobiopterin (BH(4)) in vitro and to examine its effect on the activity of endothelial nitric oxide synthase (eNOS) in first trimester human placentae. At room temperature, in Tris-HCl buffer (pH 7.4), both ASC and BH(4) were readily oxidized by dissolved O(2) or H(2)O(2). BH(4) was more sensitive to auto-oxidation, while ASC was more susceptible to oxidation by H(2)O(2). Addition of 36 micromol/l BH(4) to 143 micromol/l ASC increased the initial rate of ASC oxidation 3.2-fold in a catalase-sensitive manner, indicating that enhanced ASC oxidation is partly due to the formation of H(2)O(2). In the presence of catalase, BH(4) still stimulated 1.9-fold the initial rate of ASC oxidation, suggesting that another auto-oxidation product of BH(4), most probably quininoid-BH(2) (qBH(2)), could also stimulate ASC oxidation while itself being reduced back to BH(4). ASC prevented the auto-oxidation of BH(4) in a concentration-dependent fashion, with 3 mmol/l ASC providing an almost complete stabilization of 25 micromol/l BH(4). Importantly, basal eNOS activity in placental microsomes was stimulated 2.5-fold by 0.5 micromol/l BH(4), and 0.5 mmol/l ASC enhanced the BH(4)-stimulation 1.4-fold, with a smaller effect on basal eNOS activity. Taken together, the findings support the notion that the stabilizing action of ASC on BH(4) is related to the ASC-mediated reductive reversal of the auto-oxidation process of BH(4). Moreover, we demonstrated that concentrations of ASC present in the placenta as a common vitamin C supply are sufficient to protect cellular free BH(4) and may contribute to the stimulation of placental eNOS activity.
Principles of docking: An overview of search algorithms and a guide to scoring functions (2002)

The docking field has come of age. The time is ripe to present the principles of docking, reviewing the current state of the field. Two reasons are largely responsible for the maturity of the computational docking area. First, the early optimism that the very presence of the "correct" native conformation within the list of predicted docked conformations signals a near solution to the docking problem, has been replaced by the stark realization of the extreme difficulty of the next scoring/ranking step. Second, in the last couple of years more realistic approaches to handling molecular flexibility in docking schemes have emerged. As in folding, these derive from concepts abstracted from statistical mechanics, namely, populations. Docking and folding are interrelated. From the purely physical standpoint, binding and folding are analogous processes, with similar underlying principles. Computationally, the tools developed for docking will be tremendously useful for folding. For large, multidomain proteins, domain docking is probably the only rational way, mimicking the hierarchical nature of protein folding. The complexity of the problem is huge. Here we divide the computational docking problem into its two separate components. As in folding, solving the docking problem involves efficient search (and matching) algorithms, which cover the relevant conformational space, and selective scoring functions, which are both efficient and effectively discriminate between native and non-native solutions. It is universally recognized that docking of drugs is immensely important. However, protein-protein docking is equally so, relating to recognition, cellular pathways, and macromolecular assemblies. Proteins function when they are bound to other molecules. Consequently, we present the review from both the computational and the biological points of view. Although large, it covers only partially the extensive body of literature, relating to small (drug) and to large protein-protein molecule docking, to rigid and to flexible. Unfortunately, when reviewing these, a major difficulty in assessing the results is the non-uniformity in the formats in which they are presented in the literature. Consequently, we further propose a way to rectify it here.
Premature chain termination is a unifying mechanism for COL1A1 null alleles in osteogenesis imperfecta type I cell strains. (1996)

Nonsense and frameshift mutations, which predict premature termination of translation, often cause a dramatic reduction in the amount of transcript from the mutant allele (nonsense-mediated mRNA decay). In some genes, these mutations also influence RNA splicing and induce skipping of the exon that contains the nonsense codon. To begin to dissect how premature termination alters the metabolism of RNA from the COL1A1 gene, we studied nonsense and frameshift mutations distributed over exons 11-49 of the gene. These mutations were originally identified in 10 unrelated families with osteogenesis imperfecta (OI) type 1. We observed marked reduction in steady-state amounts of mRNA from the mutant allele in both total cellular and nuclear RNA extracts of cells from affected individuals, suggesting that nonsense-mediated decay of COL1A1 RNA is a nuclear phenomenon. Position of the mutation within the gene did not influence this observation. None of the mutations induced skipping of either the exon containing the mutation or, for the frameshifts, the downstream exons with the new termination sites. Our data suggest that nonsense and frameshift mutations throughout most of the COL1A1 gene result in a null allele, which is associated with the predictable mild clinical phenotype, OI type 1.
The essential 26S proteasome subunit Rpn11 confers multidrug resistance to mammalian cells. (2003)

Rpn11-overexpression in mammalian cells affects cell proliferation and the response to cytotoxic drugs, both of which may promote tumor cell escape from chemotherapeutic agents, and may serve as a marker for MDR-cells.
The state-of-the-art of silicon-on-sapphire CMOS RF switches (2005)

Silicon-on-Sapphire (SOS) CMOS FETs have many properties which are desirable for RF switch applications. By being manufactured on an insulating sapphire substrate, the bulk parasitic capacitances typical of CMOS FETs are eliminated. The SOS FET has a very low Ron-Coff product, allowing for low insertion loss and high isolation in high frequency applications. Despite the low breakdown voltage intrinsic to Si, SOS FETs can be stacked in series to withstand high voltages when biased in subthreshold. This work studies the tradeoffs of SOS RF switch design and compares SOS against other technologies such as GaAs and Si-based SOI. Also presented is a high power SP6T switch with insertion loss of 0.6 dB at 2 GHz and isolation of 40 dB at 2 GHz. The presented switch has the highest linearity reported to date of any SP6T switch with a P1dB of 20 W and OIP3 of <+70 dBm.
R&M Management of a Vehicle Reliability Growth Programme (2008)

Military vehicles are required to have high leveis of reliability in order to be fully effective, rapidly deployable, and affordable. Reliability growth programmes are typically used to achieve the desired levels of reliability. A Reliability Growth Test (RGT) is a well-structured process of finding reliability problems by testing, incorporating corrective actions resulting in the elimination of systematic failure modes leading to reliability growth.A review of Ministry of Defence (MoD) vehicle reliability growth programmes [1] concluded that only one of the five vehicle programmes examined, achieved their reliability targets as planned. This paper investigates the reasons for the failings and presents an approach which aims to mitigate the Reliability and Maintainability (R&M) programme risks, which was developed as part of an MSc dissertation entitled “Risk Management of a Reliability Growth Programme” [2].
Pharmacokinetics of an Antisense Phosphorothioate Oligodeoxynucleotide against rev from Human Immunodeficiency Virus Type 1 in the Adult Male Rat Following Single Injections and Continuous Infusion (1994)

An antisense phosphorothioate oligodeoxynucleotide 27-mer complementary to the rev gene mRNA of the human immunodeficiency virus (HIV-1) was administered to rats through intravenous injections and subcutaneous infusions in order to investigate the disposition of this compound. In addition, nonlethal toxic responses of the rat were evaluated. A biphasic plasma clearance with t1/2 alpha of 20-25 min and t1/2 beta of 27-41 hr was observed. Single doses ranging from 35 to 3257 micrograms were examined, and the plasma concentration and area under the plasma concentration-time curve (AUC) were found to be directly proportional to the dose. Continuous subcutaneous infusion of 50 mg over 28 days was also examined. The oligonucleotide is completely eliminated in the urine over 3 days. Electrophoretic analysis demonstrated that the excreted compound has the same mobility and UV-absorbance profile as the administered compound. Measurement of accumulation and distribution into tissues revealed unique tissue-specific rates and extent of oligonucleotide movement into and out of tissues. Results of the chronic infusion study suggest that uptake into tissue is not saturated, even after 28 days of infusion. Analysis of blood plasma from oligonucleotide-treated animals shows a possible transient elevation in levels of lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), but not alkaline phosphatase (AP), gamma-glutamyltransferase (GT), and bilirubin. The data collectively support the potential utility of phosphorothioate oligonucleotides as therapeutic agents in vivo.
Genetics of scoliosis in chickens (1981)

The genetics of an inherited form of scoliosis in chickens was studied to estimate the number of genes involved, whether they are autosomal or sex-linked, their degree of dominance and penetrance, and the heritability of this trait in this population. Expression of scoliosis and in the progeny was analyzed by radiographs of birds 12 weeks of age or older. Crosses between an inbred line selected for scoliosis expression (incidence of scoliosis - 89 percent) and a highly inbred line displaying normal spinal development provided data for genetic analyses. The incidence of expression of scoliotic parent line implicates three major autosomal, recessive genes. The significantly higher incidence of severe scoliosis found in the homogametic male sex is ascribed to a sex-influenced, on the scoliosis trait rather than to sex-linkage. Variation of expression observed in the scoliotic line is attributed to incomplete penetrance of the major genes, additive effects of minor modifying genes, and primarily to environmental effects. Because of the similarities in the expression of this disease in chickens and humans, the inheritance pattern determined for chickens may provide useful insights into that operating for so-called adolescent idiopathic scoliosis in humans.