gebhart/patrepeval huggingface dataset:
Lung cancer in lifelong non-smokers. Edinburgh Lung Cancer Group. (1991)

The Edinburgh Lung Cancer Group registered 3070 new patients with lung cancer in the five years 1981-5 from a catchment population of 950,000. After review only 74 (2%) were classified as lifelong non-smokers. They differed significantly from the 2996 smokers with lung cancer in that far more were female (77% v 26%) and their mean age was higher (75.4 v 68.0 years). More were in the worst Karnofsky performance categories and fewer patients underwent surgery. The stages of disease were similarly distributed in the two groups and the five year survival was equally poor (5%). Histological cell type was determined in 59 of the 74 patients. All histological cell types were present. More non-smokers had adenocarcinoma than smokers (42% v 13%) and fewer had squamous cell carcinoma (32% v 49%) or small cell carcinoma (15% v 24%). Lung cancer in lifelong non-smokers is uncommon and the diagnosis should therefore always be questioned.
Tumor Characteristics of Carriers and Noncarriers of the deCODE 8q24 Prostate Cancer Susceptibility Alleles (2008)

In our predominantly surgically treated population there was a significant association between 8q24 prostate cancer susceptibility alleles, particularly the -8 allele, and high grade disease. In men with a family history of prostate cancer the presence of 1 or more of these alleles also conferred a greater risk of some adverse pathological features.
Efficacy of cytotoxic agents against human tumor xenografts is markedly enhanced by coadministration of ZD1839 (Iressa), an inhibitor of EGFR tyrosine kinase. (2000)

The blockade of epidermal growth factor receptor (EGFR) function with monoclonal antibodies has major antiproliferative effects against human tumors in vivo. Similar antiproliferative effects against some of these same tumors have also been observed with specific inhibitors of the EGFR-associated tyrosine kinase. One such inhibitor, the p.o. active ZD1839 (Iressa), has pronounced antiproliferative activity against human tumor xenografts. We now show that coadministration of ZD1839, as with anti-EGFR, will enhance the efficacy of cytotoxic agents against human vulvar (A431), lung (A549 and SK-LC-16 NSCL and LX-1), and prostate (PC-3 and TSU-PR1) tumors. Oral ZD1839 (five times daily x 2) and cytotoxic agents (i.p. every 3-4 days x 4) were given for a period of 2 weeks to mice with well-established tumors. On this schedule, the maximum tolerated dose (150 mg/kg) of ZD1839 induced partial regression of A431, a tumor that expresses high levels of EGFR, 70-80% inhibition among tumors with low but highly variable levels of EGFR expression (A549, SKLC-16, TSU-PR1, and PC-3), and 50-55% inhibition against the LX-1 tumor, which expresses very low levels of EGFR. ZD1839 was very effective in potentiating most cytotoxic agents in combination treatment against all of these tumors, irrespective of EGFR status, but dose reduction of ZD1839 below its single-agent maximum tolerated dose was required for optimum tolerance. The pronounced growth inhibitory action of the platinums, cisplatin and carboplatinum, as single agents against A431 vulvar, A549 and LX-1 lung, and TSU-PR1 and PC-3 prostate tumors was increased several-fold when ZD1839 was added, with some regression of A431 and PC-3 tumors. Although the taxanes, paclitaxel or docetaxel, as single agents markedly inhibited the growth of A431, LX-1, SK-LC-16, TSU-PR1, and PC-3, when combined with ZD1839, partial or complete regression was usually seen. Against A549, the growth inhibition of doxorubicin was increased 10-fold (>99%) with ZD1839. The folate analogue, edatrexate, was highly growth inhibitory against A549, LX-1, and TSU-PR1, whereas edatrexate combined with ZD1839 resulted in partial or complete regression in these tumors. Against the A431 tumor, paclitaxel alone either was highly growth inhibitory or induced some regression, but when combined with ZD1839, pronounced regression was obtained. Combination with gemcitabine neither added nor detracted from baseline cytotoxic efficacy, whereas ZD1839 combined with vinorelbine was poorly tolerated. Overall, these results suggest that potentiation of cytotoxic treatment with ZD1839 does not require high levels of EGFR expression in the target tumors. They also suggest significant clinical benefit from ZD1839 in combination with a variety of widely used cytotoxic agents.
Stimuli-Responsive Surfaces Using Polyampholyte Polymer Brushes Prepared via Atom Transfer Radical Polymerization (2007)

The synthesis of AB diblock copolymer polyampholyte polymer brushes of the type Si/SiO2//poly(acrylic acid-b-vinyl pyridine) prepared using atom transfer radical polymerization is reported. Both 2- and 4-vinyl pyridine have been used. The diblock polyampholyte polymer brushes demonstrate stimuli-responsive behavior with respect to pH, showing both polyelectrolyte and polyampholyte effects. Furthermore, we have quaternized the 4-vinyl pyridine segments to form a mixed weak/strong, or annealed/quenched, polyelectrolyte system. The quaternized polymer brush exhibits different pH-responsive behavior, with decreasing film thickness being observed with increasing pH.
Oxidized LDL induces the expression of ALBP/aP2 mRNA and protein in human THP-1 macrophages (2000)

The adipocyte lipid-binding protein (ALBP/aP2) belongs to a multigene family of fatty acid and retinoid transport proteins. This protein is abundantly expressed in the cytoplasm and nuclear region of adipocytes and is postulated to serve as a lipid shuttle, solubilizing hydrophobic fatty acids and delivering them to the appropriate metabolic system for utilization. This report demonstrates that human cholesterol-loaded THP-1 macrophages express ALBP/aP2 and that its expression can be stimulated by oxidized low density lipoprotein (oxLDL). The increase in mRNA expression was paralleled by a similar increase in ALBP/aP2 protein. The increase in ALBP/aP2 mRNA and protein in oxLDL-stimulated THP-1 macrophages is concentration and time dependent and is inhibited by treatment of the cells with an antioxidant inhibitor of nuclear factor-kappaB (NF-kappaB), pyrrolidine dithiocarbamate (PDTC), and with protein kinase C (PKC) inhibitors bisindolylmaleimide I and Ro-31-8220. These results suggest that activation of both NF-kappaB and PKC signaling pathways is necessary for oxLDL-induced ALBP/aP2 gene expression in THP-1 macrophages and that the upregulation of the fatty acid carrier may be a necessary event in foam cell formation.
The study on vascular endothelial growth factor renature condition (1999)

Recombinant VEGF_(165) was expressed in E. coli. It exists as inclusion body. In order to obtain biologically active human VEGF_(165), se studied following conditions: the proportion of GSSG/GSH, the pH of solution, the time, the concentration of arginine and the initial VEGF_(165) protein.
Pheromone binding proteins in the European and Asian corn borers: no protein change associated with pheromone differences (1999)

Pheromone binding proteins (PBPs) are thought to play a role in the recognition of sex pheromone in male moth antennae. By binding selectively to different components of pheromone blends, these PBPs could play a role in differentiating between structurally related compounds. In this study we have characterized the pheromone binding proteins of two pheromone strains of the European corn borer (Ostrinia nubilalis) and also the closely related Asian corn borer (O. furnacalis). We have been able to detect only one PBP gene, which encodes a mature protein that is identical in amino acid sequence in individuals from different pheromone strains and different species. This result suggests that the PBP is not detecting differences between the two isomeric compounds of the European corn borer pheromone or the difference in double bond position between the pheromone molecules of the European and Asian corn borers.
Silicon nanoparticles synthesised through reactive high-energy ball milling: enhancement of optical properties from the removal of iron impurities (2014)

Alkyl-terminated silicon nanoparticles (SiNPs) were prepared through reactive high-energy ball milling with contamination of iron from the steel milling materials. Iron impurities in the form of iron nanoparticles cause a decrease of photoluminescence intensity and an increase of the UV absorption. The iron impurities were removed either by gel permeation chromatography separation or by treatment with an aqueous HCl solution. The photoluminescence properties of the SiNPs were enhanced after the removal of iron. Transmission electron microscopy, energy-dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy and proton nuclear magnetic resonance were used to determine morphology, elemental composition and surface passivation of SiNPs.
Framework selection can influence pharmacokinetics of a humanized therapeutic antibody through differences in molecule charge (2014)

Pharmacokinetic (PK) testing of a humanized (κI, VH3 framework) and affinity matured anti-hepatitis C virus E2-glycoprotein (HCV-E2) antibody (hu5B3.κ1VH3.v3) in rats revealed unexpected fast clearance (34.9 mL/day/kg). This antibody binds to the rat recycling receptor FcRn as expected for a human IgG1 antibody and does not display non-specific binding to baculovirus particles in an assay that is correlated with fast clearance in cynomolgus monkey. The antigen is not expressed in rat so target-dependent clearance does not contribute to PK. Removal of the affinity maturation changes (hu5B3.κ1VH3.v1) did not restore normal clearance. The antibody was re-humanized on a κ4, VH1 framework and the non-affinity matured version (hu5B3.κ4VH1.v1) was shown to have normal clearance (8.5 mL/day/kg). Since the change in framework results in a lower pI, primarily due to more negative charge on the κ4 template, the effect of additional charge variation on antibody PK was tested by incorporating substitutions obtained through phage display affinity maturation of hu5B3.κ1VH3.v1. A variant having a pI of 8.61 gave very fast clearance (140 mL/day/kg) whereas a molecule with pI of 6.10 gave slow clearance (5.8 mL/kg/day). Both antibodies exhibited comparable binding to rat FcRn, but biodistribution experiments showed that the high pI variant was catabolized in liver and spleen. These results suggest antibody charge can have an effect on PK through alterations in antibody catabolism independent of FcRn-mediated recycling. Furthermore, introduction of affinity maturation changes into the lower pI framework yielded a candidate with PK and virus neutralization properties suitable for clinical development.
Building Disease-Specific Drug-Protein Connectivity Maps from Molecular Interaction Networks and PubMed Abstracts (2009)

The recently proposed concept of molecular connectivity maps enables researchers to integrate experimental measurements of genes, proteins, metabolites, and drug compounds under similar biological conditions. The study of these maps provides opportunities for future toxicogenomics and drug discovery applications. We developed a computational framework to build disease-specific drug-protein connectivity maps. We integrated gene/protein and drug connectivity information based on protein interaction networks and literature mining, without requiring gene expression profile information derived from drug perturbation experiments on disease samples. We described the development and application of this computational framework using Alzheimer's Disease (AD) as a primary example in three steps. First, molecular interaction networks were incorporated to reduce bias and improve relevance of AD seed proteins. Second, PubMed abstracts were used to retrieve enriched drug terms that are indirectly associated with AD through molecular mechanistic studies. Third and lastly, a comprehensive AD connectivity map was created by relating enriched drugs and related proteins in literature. We showed that this molecular connectivity map development approach outperformed both curated drug target databases and conventional information retrieval systems. Our initial explorations of the AD connectivity map yielded a new hypothesis that diltiazem and quinidine may be investigated as candidate drugs for AD treatment. Molecular connectivity maps derived computationally can help study molecular signature differences between different classes of drugs in specific disease contexts. To achieve overall good data coverage and quality, a series of statistical methods have been developed to overcome high levels of data noise in biological networks and literature mining results. Further development of computational molecular connectivity maps to cover major disease areas will likely set up a new model for drug development, in which therapeutic/toxicological profiles of candidate drugs can be checked computationally before costly clinical trials begin.
Antisera to the variable region of ras oncogene proteins, and specific detection of H-ras expression in an experimental model of chemical carcinogenesis. (1987)

Antisera were prepared in mice, rats and rabbits by immunization with peptides corresponding to regions of highest variability, located near the C-termini of four ras proteins. Two of these, H-ras (171-189) and K-rasB (171-186), react uniquely with H-ras and K-rasB gene products in immunoblots and immunoprecipitation reactions. Affinity-purified rabbit H-ras (171-189) antibody detects H-ras p21 in tissue culture cells and in tissue sections. Epithelial cells in normal mouse skin and cells in papillomas and carcinomas, in a mouse model system of chemical carcinogenesis in which mutational activation of H-ras occurs with high frequency, express high levels of H-ras p21 protein. These results suggest an hypothesis to explain the mechanism and preferential activation of particular ras loci in certain neoplasia.
Polymerization of an activated ester monomer based on 4-vinylsulfonic acid and its polymer analogous reaction (2010)

Homopolymers containing sulfonic ester side groups were synthesized by reversible addition–fragmentation chain transfer (RAFT) polymerization utilizing benzyl dithiobenzoate, cumyl dithiobenzoate, and 4-cyano-4-((thiobenzoyl)sulfanyl)pentanoic acid as chain transfer agents. Likewise diblock copolymers containing poly(styrene), poly(octylstyrene) and poly(pentafluorostyrene) as the second block were synthesized. Additionally, nitroxide mediated polymerization (NMP) was investigated for the synthesis of a homopolymer as well as for a diblock copolymer. Furthermore, the post-polymerization functionalization with various amines to yield the respective sulfonamides was conducted. The conversion was analyzed by 1H NMR spectroscopy, 19F NMR spectroscopy and FT-IR spectroscopy and in many cases a very high conversion (>96%) was observed. In addition the reaction kinetics of the post-polymerization functionalization of poly(pentafluorophenyl 4-vinylbenzene sulfonate) and the corresponding carboxyl ester poly(pentafluorophenyl 4-vinylbenzoate) were compared by analysis of the reactions by time-resolved 19F NMR spectroscopy. It was found that poly(pentafluorophenyl 4-vinylbenzoate) showed a higher stability towards hydrolysis and a significantly higher reactivity, resulting in complete conversions with different amines.
Gene Targeting Protocols (1999)

The cover depicts the presence of active Green Fluorescent Protein being expressed in Chinese Hamster Ovary (CHO) cells. The phenotypic change is a result of the activity of the chimeric oligonucleotide on CHO cells that have integrated copies of mutated (inactive) GFP genes. Cells that have not been targeted or corrected to wild-type appear in the background. The technique known as gene repair or chimeraplasty was pioneered by the editor who supplied this picture.
Very low level laser therapy attenuates edema and pain in experimental models. (2004)

In this study, we tested a new square wave microprocessor-controlled red laser with an extremely low peak power output (<3 mW; very low level laser therapy [vLLLT]) in experimental pain in the rat. Acute inflammation was induced by intraplantar injection of carrageenan, chronic inflammation was induced by complete Freund's adjuvant (CFA) and neuropathic pain was produced by sciatic nerve chronic constriction injury (CCI). In our study vLLLT was effective in reducing edema and hyperalgesia in acute and chronic inflammation if administered at the points usually selected for acupuncture. Moreover, spontaneous pain and thermal hyperalgesia were reduced in CCI rats treated with vLLLT In conclusion, vLLLT reduced edema and induced analgesia in experimental plantar pain in rats. We interpret this to mean that enkephalin mRNA level was strongly upregulated in the external layers of the dorsal horn of the spinal cord in CFA and CCI animals, and that vLLLT further increased the mRNA level in single neurons.
Breathing through an inspiratory threshold device improves stroke volume during central hypovolemia in humans (2008)

Inspiratory resistance induced by breathing through an impedance threshold device (ITD) reduces intrathoracic pressure and increases stroke volume (SV) in supine normovolemic humans. We hypothesized that breathing through an ITD would also be associated with a protection of SV and a subsequent increase in the tolerance to progressive central hypovolemia. Eight volunteers (5 men, 3 women) were instrumented to record ECG and beat-by-beat arterial pressure and SV (Finometer). Tolerance to progressive lower body negative pressure (LBNP) was assessed while subjects breathed against either 0 (sham ITD) or -7 cmH(2)O inspiratory resistance (active ITD); experiments were performed on separate days. Because the active ITD increased LBNP tolerance time from 2,014 +/- 106 to 2,259 +/- 138 s (P = 0.006), data were analyzed (time and frequency domains) under both conditions at the time at which cardiovascular collapse occurred during the sham experiment to determine the mechanisms underlying this protective effect. At this time point, arterial blood pressure, SV, and cardiac output were higher (P < or = 0.005) when breathing on the active ITD rather than the sham ITD, whereas indirect indicators of autonomic activity (low- and high-frequency oscillations of the R-to-R interval) were not altered. ITD breathing did not alter the transfer function between systolic arterial pressure and R-to-R interval, indicating that integrated baroreflex sensitivity was similar between the two conditions. These data show that breathing against inspiratory resistance increases tolerance to progressive central hypovolemia by better maintaining SV, cardiac output, and arterial blood pressures via primarily mechanical rather than neural mechanisms.
Crown ether catalysis of decarboxylation and decarbalkoxylation of β-keto acids and malonates: a synthetic application (1980)

The effect of 18-crown-6 ether on the decarboxylation rates of the sodium and potassium salts of 3-camphorcarboxylic acid 1 and of 1-carbomethoxy-1-carboxycyclohexane 2 was studied. For 2 the K-18C6 salt reacted ca. 10 4 times faster than the parent acid. This remarkable difference in reactivity was used in developing a one-pot, two-step procedure for decarbalkoxylation of malonic esters. This procedure was then applied to a range of malonates, β-keto esters, and an α-cyano ester. The effect of 15C5, other cations, and good nucleophiles was also studied.
Design of ion-implanted MOSFET's with very small physical dimensions (1974)

This paper considers the design, fabrication, and characterization of very small Mosfet switching devices suitable for digital integrated circuits, using dimensions of the order of 1 /spl mu/. Scaling relationships are presented which show how a conventional MOSFET can be reduced in size. An improved small device structure is presented that uses ion implantation, to provide shallow source and drain regions and a nonuniform substrate doping profile. One-dimensional models are used to predict the substrate doping profile and the corresponding threshold voltage versus source voltage characteristic. A two-dimensional current transport model is used to predict the relative degree of short-channel effects for different device parameter combinations. Polysilicon-gate MOSFET's with channel lengths as short as 0.5 /spl mu/ were fabricated, and the device characteristics measured and compared with predicted values. The performance improvement expected from using these very small devices in highly miniaturized integrated circuits is projected.
Effects of Cyclosporine and Cortisone on the Pathogenesis of Primary Infection with Cytomegalovirus in the Guinea Pig (1986)

Effects of the immunosuppressive agents cyclosporine (CsA) and cortisone on the pathogenesis of primary infections with cytomegalovirus (CMV) were investigated in the guinea pig model. All animals received 10(4) 50% tissue culture infectious doses of virulent salivary gland-passaged guinea pig CMV (GPCMV) subcutaneously on day 0. Oral CsA (20 mg/kg per day) and/or subcutaneous cortisone (10 mg/kg per day) were administered until the animals were killed on day 14. Untreated controls developed lymphocytosis, and GPCMV was isolated from 19.4% of cocultivated tissues. Animals treated with CsA alone developed lymphopenia, and GPCMV was isolated from 53% of their tissues, including 16 of 16 lungs. Histopathology showed widespread viral inclusions and minimal inflammatory response to GPCMV in CsA-treated animals. Guinea pigs treated with either cortisone or CsA/cortisone did not develop lymphopenia, and their rates of isolation of GPCMV were significantly lower than those of CsA-treated animals.
A sea urchin genome project: Sequence scan, virtual map, and additional resources (2000)

Results of a first-stage Sea Urchin Genome Project are summarized here. The species chosen was Strongylocentrotus purpuratus, a research model of major importance in developmental and molecular biology. A virtual map of the genome was constructed by sequencing the ends of 76,020 bacterial artificial chromosome (BAC) recombinants (average length, 125 kb). The BAC-end sequence tag connectors (STCs) occur an average of 10 kb apart, and, together with restriction digest patterns recorded for the same BAC clones, they provide immediate access to contigs of several hundred kilobases surrounding any gene of interest. The STCs survey >5% of the genome and provide the estimate that this genome contains approximately 27,350 protein-coding genes. The frequency distribution and canonical sequences of all middle and highly repetitive sequence families in the genome were obtained from the STCs as well. The 500-kb Hox gene complex of this species is being sequenced in its entirety. In addition, arrayed cDNA libraries of >10(5) clones each were constructed from every major stage of embryogenesis, several individual cell types, and adult tissues and are available to the community. The accumulated STC data and an expanding expressed sequence tag database (at present including >12, 000 sequences) have been reported to GenBank and are accessible on public web sites.
The Behavior in Successive Nuclear Divisions of a Chromosome Broken at Meiosis (1939)

After reporting her observations of ring chromosomes, McClintock followed broken chromatids through successive cycles of cell
 division, in which she could observe the behavior of the monstrous chromosome 9 through meiosis and crossing-over.
 McClintock reported in a long series of articles that the chromatid breakage-fusion-bridge (BFB) cycle occurred only in the
 germ cells and endosperm, while the chromosome BFB continued in the sporophyte, which meant that she could selectively produce
 persistent variegation in plant tissues.