gebhart/patrepeval huggingface dataset:
Gefitinib-Sensitive EGFR Lacking Residues 746–750 Exhibits Hypophosphorylation at Tyrosine Residue 1045, Hypoubiquitination, And Impaired Endocytosis (2007)

Gefitinib-sensitive nonsmall cell lung cancers (NSCLC) are characterized by somatic mutations in the kinase domain of epidermal growth factor receptor (EGFR). The mutant EGFR forms are reported to mediate characteristic signal transduction pathways that are different from those mediated by the wild-type EGFR and are involved in transformation in vivo. We have examined signal transduction pathways initiated from a frequently identified gefitinib-sensitizing mutant EGFR lacking residues 746-750 by employing a mouse fibroblast cell line that is free of endogenous EGFR and transiently transfected COS-7 cells. Upon EGF stimulation, the deletion-mutant EGFR mediated prolonged downstream signals. The analysis of the phosphotyrosine patterns of the receptor revealed that the deletion-mutant EGFR lacked phosphorylation at tyrosine residue 1045, which is the major binding site of Cbl. The EGF-induced endocytosis of the deletion-mutant EGFR was impaired. The ubiquitination and downregulation of the deletion-mutant EGFR were also reduced. On the other hand, another mutant, EGFR, possessing a L858R substitution, exhibited phosphorylation at 1045 and its downstream signalings were not prolonged. These data suggest that the signal transduction pathways initiated from these mutant forms are different, and that impaired endocytosis might be responsible for the prolonged signals mediated by the deletion-mutant EGFR.
Aging of Solvent-Casting PLA-Mg Hydrophobic Films: Impact on Bacterial Adhesion and Viability (2019)

Biomaterials used for the manufacture of biomedical devices must have suitable surface properties avoiding bacterial colonization and/or proliferation. Most biomaterial-related infections start during the surgery. Bacteria can begin colonization of the surface of a device right after implantation or in the next few hours. This time may also be sufficient to begin the deterioration of a biodegradable implant. This work explores the surface changes that hydrophobic films of poly(lactic) acid reinforced with Mg particles, prepared by solving-casting, undergone after in vitro degradation at different times. Hydrophobicity, surface tension, zeta potential, topography, and elemental composition were obtained from new and aged films. The initial degradation for 4 h was combined with unspecific bacterial adhesion and viability tests to check if degraded films are more or less susceptible to be contaminated. The degradation of the films decreases their hydrophobicity and causes the appearance of a biocompatible layer, composed mainly of magnesium phosphate. The release of Mg2+ is very acute at the beginning of the degradation process, and such positive charges may favor the electrostatic approach and attachment of Staphylococci. However, all bacteria attached on the films containing Mg particles appeared damaged, ensuring the bacteriostatic effect of these films, even after the first hours of their degradation.
Poly(3-Hydroxybutyrate) Production with High Productivity and High Polymer Content by a Fed-Batch Culture of Alcaligenes latus under Nitrogen Limitation (1997)

Alcaligenes latus has been known to produce poly(3-hydroxybutyrate) (PHB) in a growth-associated manner even under nutrient-sufficient conditions. However, the PHB content obtained by fed-batch culture was always low, at ca. 50%, which makes the recovery process inefficient. In this study, the effect of applying nitrogen limitation on the production of PHB by A. latus was examined. In flask and batch cultures, the PHB synthesis rate could be increased considerably by applying nitrogen limitation. The PHB content could be increased to 87% by applying nitrogen limitation in batch culture, which was considerably higher than that typically obtainable (50%) under nitrogen-sufficient conditions. In fed-batch culture, cells were first cultured by the DO-stat feeding strategy without applying nitrogen limitation. Nitrogen limitation was applied at a cell concentration of 76 g (dry cell weight)/liter, and the sucrose concentration was maintained within 5 to 20 g/liter. After 8 h of nitrogen limitation, the cell concentration, PHB concentration, and PHB content reached 111.7 g (dry cell weight)/liter, 98.7 g/liter, and 88%, respectively, resulting in a productivity of 4.94 g of PHB/liter/h. The highest PHB productivity, 5.13 g/liter/h, was obtained after 16 h.
Phenylalanine Biosynthesis in Escherichia coli K-12: Mutants Derepressed for Chorismate Mutase P-Prephenate Dehydratase (1971)

Mutants were isolated which are derepressed for the synthesis of chorismate mutase P-prephenate dehydratase. No other enzymes involved in the synthesis of phenylalanine are derepressed in these strains. These mutants are able to grow in concentrations of o- and p-fluorophenylalanine that inhibit the growth of AB3259, the strain from which they were derived. They also excrete phenylalanine. Genetic analysis shows that the mutations causing this derepression are closely linked to the structural gene for this enzyme (cotransduction frequency of 95% or more with pheA). The gene in which they occur has been designated pheO since this gene has all of the properties predicted for an operator gene controlling the pheA structural gene. Finally, the pheO mutant alleles have been shown to be dominant in diploids.
Mechanical strength of repairs of the rotator cuff (1994)

We have studied the mechanical properties of several current techniques of tendon-to-bone suture employed in rotator-cuff repair. Non-absorbable braided polyester and absorbable polyglactin and polyglycolic acid sutures best combined ultimate tensile strength and stiffness. Polyglyconate and polydioxanone sutures failed only at high loads, but elongated considerably under moderate loads. We then compared the mechanical properties of nine different techniques of tendon grasping, using 159 normal infraspinatus tendons from sheep. The most commonly used simple stitch was mechanically poor: repairs with two or four such stitches failed at 184 N and 208 N respectively. A new modification of the Mason-Allen suture technique improved the ultimate tensile strength to 359 N for two stitches. Finally, we studied the mechanical properties of several methods of anchorage to bone using typically osteoporotic specimens. Single and even double transosseous sutures and suture anchor fixation both failed at low tensile loads (about 140 N). The use of a 2 mm thick, plate-like augmentation device improved the failure strength to 329 N. The mechanical properties of many current repair techniques are poor and can be greatly improved by using good materials, an improved tendon-grasping suture, and augmentation at the bone attachment.
In situ deposition of superconducting YBa2Cu3O7−x and DyBa2Cu3O7−x thin films by organometallic molecular-beam epitaxy (1991)

Smooth, c-axis oriented, superconducting thin films of YBa2Cu3O7−x and DyBa2Cu3O7−x have been grown on (100) MgO by organometallic molecular-beam epitaxy. To our knowledge this is the first report of this technique for the fabrication of this class of high Tc superconductors. Y (or Dy) β-diketonate organometallic sources are utilized with Ba and Cu metallic sources. Films are grown in situ by codepositing from these sources in an ozone ambient with a substrate temperature of 700 °C. The use of an active oxygen source (ozone) is required for decomposition of the organometallic sources as well as for the attainment of superconducting films in situ. The films are characterized by Tc’s as high as 85 K and Jc’s of 1.2×106 A/cm2 at 12 K and 2.4×103 A/cm2 at 77 K. In addition to the four point Tc and Jc results, alternating-current susceptibility measurements are also reported. The composition of the films has been determined by Rutherford backscattering spectroscopy, Auger and secondary ion mass spectroscopy analysis, with the smoothness of the films characterized by scanning tunneling microscopy.
The Global Non-determinism and the Theory of Interpretive Effects (2012)

This paper proposes a new theory of merge within the global nondeterminism (Yang 2011b) in terms of the theory of interpretive effects. The major claims are as follows. First, the notion of derivational null hypothesis is proposed in place of the notion of edge feature (EF) (Chomsky 2008). Various problems with the notion of EF within Chomsky’s (2008) own theory are pointed out. It is shown that the theory of minimalism is significantly improved by adopting the derivational null hypothesis in place of the notion of EF. At the same time, adopting the derivational null hypothesis is shown to make significant theoretical progress in grammatical theory. Second, the notion of EPP is shown to be replaced by the notion of ‘null effect’ within the global non?determinism. The notion of EPP has been treated as a residual element in the theory of minimalism. It will be shown that the notion of ‘null effect’ is motivated as a formal element within the theory of non?determinism. Third, the notion of obligatory movement should be systematically re?defined as the ‘marked merge’ within the nondeterminism, so that the notion of obligatory movement can be eliminated from the grammatical theory. Accordingly, the notion of optional movement should be systematically re?defined as the ‘unmarked merge’ within the non?determinism.
Molecular cloning, tissue distribution and chromosomal localization of a novel member of the opioid receptor gene family (1994)

A cDNA was isolated from rat brain by low stringency hybridization with the rat mu opioid receptor cDNA. Sequence analysis of this clone indicated that it contains an open reading frame capable of encoding a 367 amino acid protein. The deduced amino acid sequence of this protein shows high degrees of homology to all three opioid receptors, mu, kappa, and delta, suggesting that it is a member of the opioid receptor gene family. RNA blot analysis detected high level expression of the receptor mRNA in the brain. Southern blot analysis suggests that it is a single-copy gene, and mapping studies localized the gene on mouse chromosome 2. Despite the high sequence homologies between this protein and the other opioid receptors, expression studies of this clone in COS-7 cells did not show binding to [3H]diprenorphine, a ligand that binds to the other three opioid receptors. Furthermore, co-expression of this receptor with a G protein-activated potassium channel in Xenopus oocytes did not show functional coupling upon stimulation with mu, kappa and delta agonists. Given the similar degrees of high homology to the mu, kappa and delta opioid receptors and the lack of apparent affinity for their ligands, this receptor does not appear to belong to any of the three known classes of opioid receptors. Rather, it represents a novel member of the opioid receptor gene family, not identified from previous pharmacological studies.
Chlamydia trachomatis: Genome sequence analysis of lymphogranuloma venereum isolates (2007)

Chlamydia trachomatis is the most common cause of sexually transmitted infections in the UK, a statistic that is also reflected globally. There are three biovariants of C. trachomatis: trachoma (serotypes A-C) and two sexually transmitted pathovars; serotypes D-K and lymphogranuloma venereum (LGV). Trachoma isolates and the sexually transmitted serotypes D-K are noninvasive, whereas the LGV strains are invasive, causing a disseminating infection of the local draining lymph nodes. Genome sequences are available for single isolates from the trachoma (serotype A) and sexually transmitted (serotype D) biotypes. We sequenced two isolates from the remaining biotype, LGV, a long-term laboratory passaged strain and the recent "epidemic" LGV isolate-causing proctitis. Although the genome of the LGV strain shows no additional genes that could account for the differences in disease outcome, we found evidence of functional gene loss and identified regions of heightened sequence variation that have previously been shown to be important sites for interstrain recombination. We have used new sequencing technologies to show that the recent clinical LGV isolate causing proctitis is unlikely to be a newly emerged strain but is most probably an old strain with relatively new clinical manifestations.
Pharmacological and biochemical demonstration of the role of cyclooxygenase 2 in inflammation and pain. (1994)

Nonsteroidal antiinflammatory drugs (NSAIDs) are widely used for the treatment of inflammatory diseases, but significant side effects such as gastrointestinal erosion and renal damage limit their use. NSAIDs inhibit the enzyme cyclooxygenase (COX), which catalyzes the conversion of arachidonic acid to prostaglandins (PGs) and thromboxane. Two forms of COX have been identified--COX-1, which is constitutively expressed in most tissues and organs, and the inducible enzyme, COX-2, which has been localized primarily to inflammatory cells and tissues. In an animal model of acute inflammation (injection of carrageenan into the footpad), edema was produced that was associated with marked accumulation of COX-2 mRNA and thromboxane. A selective inhibitor of COX-2 (SC-58125) inhibited edema at the inflammatory site and was analgesic but had no effect on PG production in the stomach and did not cause gastric toxicity. These data suggest that selective inhibition of COX-2 may produce superior antiinflammatory drugs with substantial safety advantages over existing NSAIDs.
Cloning and Functional Expression of a Human Uridine Nucleotide Receptor (1995)

In order to isolate new subtypes of P2 purinoceptors, sets of degenerate oligonucleotide primers were synthesized on the basis of the best conserved segments in the published sequences of the chick brain P2Y/P2Y1 and murine neuroblastoma P2U/P2Y2 receptors. Their use in polymerase chain reaction (PCR) experiments on human genomic DNA amplified, among other things, a 712-base pair sequence, that was used as a probe to screen a human genomic DNA library. Several clones corresponding to a single locus were isolated, and the sequence analysis revealed an intronless 1095-base pair open reading frame. The deduced amino acid sequence is consistent with a G protein-coupled receptor and exhibits 51% identity with the human P2Y2 receptor and 35% with the chick P2Y1 receptor. A close comparison with the human P2Y2 sequence reveals the conservation of histidine 262, arginine 265, lysine 289, and arginine 292, which were reported to be involved in nucleotide binding (Erb, L., Garrad, R., Wang, Y., Quinn, T., Turner, J. T., and Weisman, G. A. (1995) J. Biol. Chem. 270, 4185-4188). Northern blot analysis detected a 1.8-kilobase messenger RNA in human placenta. The coding sequence was inserted in the pcDNA3 vector in order to transfect 1321N1 human astrocytoma cells. In cells stably expressing the receptor, UTP and UDP stimulated the formation of inositol phosphates with equivalent potency and maximal effect, ATP behaved as a partial agonist, and ADP was almost inactive. We have thus cloned a new member of the G protein-coupled P2 purinergic receptor family, which functionally behaves as a pyrimidinergic receptor.
PEA3 sites within the progression elevated gene-3 (PEG-3) promoter and mitogen-activated protein kinase contribute to differential PEG-3 expression in Ha-ras and v-raf oncogene transformed rat embryo cells (2001)

Transformation of normal cloned rat embryo fibroblast (CREF) cells with cellular oncogenes results in acquisition of anchorage-independent growth and oncogenic potential in nude mice. These cellular changes correlate with an induction in the expression of a cancer progression-promoting gene, progression elevated gene-3 (PEG-3). To define the mechanism of activation of PEG-3 as a function of transformation by the Ha-ras and v-raf oncogenes, evaluations of the signaling and transcriptional regulation of the approximately 2.0 kb promoter region of the PEG-3 gene, PEG-Prom, was undertaken. The full-length and various mutated regions of the PEG-Prom were linked to a luciferase reporter construct and tested for promoter activity in CREF and oncogene-transformed CREF cells. An analysis was also performed using CREF cells doubly transformed with Ha-ras and the Ha-ras specific suppressor gene Krev-1, which inhibits the transformed phenotype in vitro. These assays document an association between expression of the transcription regulator PEA3 and PEG-3. The levels of PEA3 and PEG-3 RNA and proteins are elevated in the oncogenically transformed CREF cells, and reduced in transformation and tumorigenic suppressed Ha-ras/Krev-1 doubly transformed CREF cells. Enhanced tumorigenic behavior, PEG-3 promoter function and PEG-3 expression in Ha-ras transformed cells were all dependent upon increased activity within the mitogen-activated protein kinase (MAPK) pathway. Electrophoretic mobility shift assays and DNase I footprinting experiments indicate that PEA3 binds to sites within the PEG-Prom in transformed rodent cells in an area adjacent to the TATA box in a MAPK-dependent fashion. These findings demonstrate an association between Ha-ras and v-raf transformation of CREF cells with elevated PEA3 and PEG-3 expression, and they implicate MAPK signaling via PEA3 as a signaling cascade involved in activation of the PEG-Prom.
Hydrogels by Stereocomplex Formation and Their Use as Drug Delivery Matrices (2003)

Block and graft copolymer hydrogels, physically crosslinked through stereocomplex formation of poly- or oligo(lactic acid) chains of opposite chirality, are described. Protein-loaded hydrogels of dextran-g-oligo(L/D-lactic acid) are obtained from aqueous solutions of the two polymers (containing L- and D-grafts, respectively). These hydrogels degraded in a period of 1-7 days, depending on polymer composition. Lysozyme was quantitatively released with full preservation of its activity.
A General Model for the Genetic Analysis of Pedigree Data (1971)

Assuming random mating and random sampling of pedigrees, the likelihood of a set of pedigree data is developed in terms of: (1) the population distribution of the different genotypes; (2) the phenotypic distributions for the different genotypes, and (3) the genotypic distribution of offspring given the parents’ genotypes. This last is given for any number of unlinked autosomal loci, two linked autosomal loci, an X-linked locus, and combinations of these possibilities. Methods are given for using this likelihood to test specific genetic hypotheses and for genetic counselling.
Model‐based screening by risk with application to down's syndrome (1992)

Screening for a disorder may be carried out by assessing the risk that an individual is affected given the values of variables whose distributions alter when the disorder is present. An optimal screening policy is obtained by identifying those individuals whose risk is greater than some cut-off value. This paper summarizes the way in which risk is derived from the likelihood ratio of being affected by the disorder, and compares three different methods of estimating the likelihood ratio, namely direct estimation, logistic regression and distribution modelling. For continuous variables that have a multivariate normal distribution, screening by risk is equivalent to the use of quadratic discrimination. The paper shows how estimates of the risk and associated detection and false positive rates can be derived for a screening policy which uses specified risk cut-offs. Screening by risk has the counter-intuitive property that as the separation in the distribution of screening variables between affected and unaffected individuals increases, the detection and false positive rates may both increase. The approach is explored using data on antenatal screening for Down's syndrome. The method of choice is model-based; the model is described and tested for goodness of fit. Complications arising from outliers and non-normality must be overcome before an appropriate assessment of risk can be made. The concept of shrinkage is used to estimate the detection of false positive rates that may be expected in a new data set.
Blood-brain barrier penetration abolished by N-methyl quaternization of nicotine. (1993)

The present study determined the effect of organically quaternizing either of the two tertiary nitrogen sites of nicotine to assess the in vivo effects of the permanently ionized states of the synthesized N-[14C]methylnicotines on brain uptake in rat after intracarotid injection. Male Sprague-Dawley rats were used to measure the brain uptake index (BUI) by single-pass clearance in brain after rapid injection at pH 7.4 into the left common carotid artery (expressed as a percentage) relative to simultaneously injected 3HOH. The BUI of [14C]mannitol, a control for the method background, was measured to be 2.6 +/- 0.6. At physiological pH, in striking contrast to the [pyrrolidine-2-14C]nicotine BUI of 120 +/- 3, the N-[14C]-methylnicotines had a BUI of 3.0 +/- 0.6, which was not significantly different from the method background and which indicated abolition of blood-brain barrier penetration of nicotine with the sensitivity of the BUI method.
The Tablet Formulation of Lopinavir/Ritonavir Provides Similar Bioavailability to the Soft-Gelatin Capsule Formulation With Less Pharmacokinetic Variability and Diminished Food Effect (2007)

Lopinavir, an HIV protease inhibitor, is coformulated with ritonavir to enhance the bioavailability and pharmacokinetics of lopinavir. The original solid oral formulation of lopinavir/ritonavir, a soft-gelatin capsule (SGC), requires refrigerated storage, is taken as 6 capsules daily at the recommended adult dose, and is administered with food to maximize the bioavailability of lopinavir. Melt extrusion technology was used to produce a tablet formulation reducing the number of dosage units administered per day and simplifying storage requirements. Three studies assessed the bioavailability of tablet doses of lopinavir/ritonavir at 800/200 mg or 400/100 mg under different meal conditions compared with equal doses of the SGC after a moderate-fat meal. The tablet was bioequivalent to the SGC after a moderate-fat meal with respect to lopinavir and ritonavir areas under the concentration-time curve. Compared with the SGC formulation, the tablet formulation resulted in more consistent lopinavir and ritonavir exposures within and across studies and across meal conditions. The diminished food effect and decreased variability of the tablet are likely to result in more consistent lopinavir and ritonavir exposures, minimizing the likelihood of extreme high or low values compared with the SGC.
Influence of Surface Modifiers on the Structure of Precipitated Calcium Carbonate (1999)

A calcium carbonate (CaCO3) sorbent synthesized in the presence of surface modifiers has recently been developed in this laboratory for the purpose of enhancing the reactivity toward SO2 at high temperatures (800−1150 °C). The calcium carbonate particles are produced by precipitation from an aqueous suspension of calcium hydroxide by bubbling pure CO2. The operating parameters such as suspension concentration, gas flow rate, and concentration of surface modifiers are varied to study their influence on the particle size, surface area, and pore volume. The synthesized CaCO3 particles exhibit dramatically high SO2 reactivity and sorbent utilization. The increased reactivity is primarily due to the development of an open initial pore structure of the sorbent brought about by the action of surface-active agents, compared to the conventional calcium-based sorbents. ζ-potential measurements indicate that addition and subsequent adsorption of anionic surfactants neutralize the high positive surface charge (30 mV) on the precipitated calcium carbonate and facilitate particle agglomeration and pore structure development. High surface area (>55 m2/g) and pore volume (>0.175 cm3/g) are obtained for particles with neutral or near-neutral surface changes.