gebhart/patrepeval huggingface dataset:
Antisense-mediated reduction in insulin-like growth factor-I receptor expression suppresses the malignant phenotype of a human alveolar rhabdomyosarcoma. (1994)

The expression of the insulin-like growth factors (IGFs) and their receptors has been linked to cellular proliferation and tumorigenicity in a number of model systems. Since rhabdomyosarcoma cells express IGF-I receptors, an autocrine or paracrine loop involving this receptor and its ligands could be responsible in part for the growth characteristics of this tumor. To assess directly the role of the IGF-I receptor in rhabdomyosarcoma cell growth and tumorigenicity, a human alveolar rhabdomyosarcoma cell line with high IGF-I receptor expression was transfected with an amplifiable IGF-I receptor antisense expression vector. Four unique, transfected clones were analyzed and found to have reduced IGF-I receptor expression relative to the parental line. Integration of the antisense sequence was demonstrated by Southern blot analysis, and expression of antisense message in these clones was shown by S1 nuclease protection assay. Reduced IGF-I receptor surface expression in the transfectants was shown by decreased immunofluorescence with an IGF-I receptor monoclonal antibody and by decreased IGF-I binding as measured by Scatchard analysis. These clones had markedly reduced growth rates in vitro, impaired colony formation in soft agar, and failed to form tumors in immunodeficient mice when compared with vector-transfected clones. These results demonstrate that reduction of IGF-I receptor expression can inhibit both the in vitro and in vivo growth of a human rhabdomyosarcoma cell line and suggest a role for the IGF-I receptor in mediating neoplastic growth in this mesenchymally derived tumor.
Target dependence of antisense oligodeoxynucleotide inhibition of c-Ha-ras p21 expression and focus formation in T24-transformed NIH3T3 cells. (1990)

The relationship of antisense oligodeoxynucleotide inhibition to the predicted secondary structure of human c-Ha-ras oncogene mRNA was examined. Three antisense pentadecade-oxynucleotides complementary to the 5' cap region, a predicted loop in the 5' untranslated region, and the initiation codon region of c-Ha-ras mRNA were synthesized. T24-transformed NIH3T3 cells were treated for 24 hr with each anti-ras oligomer or control sequence. The levels of c-Ha-ras p21 antigen were then analyzed by radioimmunoprecipitation. Inhibition of p21 expression was sequence-specific and dose-dependent. The efficacy of the cap sequence in reducing p21 expression was greater than that of the initiation codon target, which in turn was more effective than the target upstream of the initiation codon. Antisense inhibition of p21 expression correlated with inhibition of focus formation.
Synthesis and polymerization of a styryl terminated oligovinylpyrrolidone macromonomer (1985)

Abstract The esterification of a carboxy group terminated vinylpyrrolidone oligomer with chloromethylstyrene under mild conditions resulted in a styryl terminated oligovinylpyrrolidone macromonomer. The purity of the obtained macromonomer was greater than 95%. Copolymerization of the macromonomer with styrene in ethanol using BPO as catalyst yielded a graft copolymer having a hydrophobic backbone and amphiphilic branches, which was found to have a spherical form and was dispersable in water and ethanol.
Developmental expression and biochemical analysis of the Arabidopsis atao1 gene encoding an H2O2‐generating diamine oxidase (1998)

A copper amine oxidase encoding gene, atao1, has been isolated and characterized from Arabidopsis thaliana. Sequence analysis reveals that atao1 encodes a 668 amino acid polypeptide (ATAO1) with 48% identity to copper amine oxidases from pea and lentil. The promoter region of atao1 was transcriptionally fused with the reporter genes encoding beta-glucuronidase and modified green fluorescent protein. Analysis of transgenic Arabidopsis together with in situ hybridization of wild-type plants reveals temporally and spatially discrete patterns of gene expression in lateral root cap cells, vascular tissue of roots, developing leaves, the hypocotyl, and in the style/stigmatal tissue. Enzyme activity assays show that ATAO1 preferentially oxidizes the aliphatic diamine putrescine with production of the corresponding aldehyde, ammonia and hydrogen peroxide, a recognized plant signal molecule and substrate for peroxidases. Histochemical analysis reveals that atao1 expression in developing tracheary elements precedes and overlaps with lignification and therefore is a good marker for vascular development. In both vascular tissue and the root cap, atao1 expression occurs in cells destined to undergo programmed cell death.
Combinatorial peptidomics: a generic approach for protein expression profiling (2003)

Traditional approaches to protein profiling were built around the concept of investigating one protein at a time and have long since reached their limits of throughput. Here we present a completely new approach for comprehensive compositional analysis of complex protein mixtures, capable of overcoming the deficiencies of current proteomics techniques. The Combinatorial methodology utilises the peptidomics approach, in which protein samples are proteolytically digested using one or a combination of proteases prior to any assay being carried out. The second fundamental principle is the combinatorial depletion of the crude protein digest (i.e. of the peptide pool) by chemical crosslinking through amino acid side chains. Our approach relies on the chemical reactivities of the amino acids and therefore the amino acid content of the peptides (i.e. their information content) rather than their physical properties. Combinatorial peptidomics does not use affinity reagents and relies on neither chromatography nor electrophoretic separation techniques. It is the first generic methodology applicable to protein expression profiling, that is independent of the physical properties of proteins and does not require any prior knowledge of the proteins. Alternatively, a specific combinatorial strategy may be designed to analyse a particular known protein on the basis of that protein sequence alone or, in the absence of reliable protein sequence, even the predicted amino acid translation of an EST sequence. Combinatorial peptidomics is especially suitable for use with high throughput micro- and nano-fluidic platforms capable of running multiple depletion reactions in a single disposable chip.
Solid-phase synthesis and biological properties of .psi.[CH2NH] pseudopeptide analogs of a highly potent somatostatin octapeptide (1987)

A series of psi [CH2NH] pseudopeptide analogues of a potent somatostatin octapeptide analogue, H-D-Phe-Cys-Try-D-Trp-Lys-Val-Cys-Thr-NH2, were synthesized by using a newly developed solid-phase method for direct introduction of the CH2NH peptide bond isostere. Analogues were obtained in normal yields via a combination of sodium cyanoborohydride mediated reductive alkylation of resin-bound peptide amine with a tert-butoxycarbonyl amino acid aldehyde for introduction of a CH2NH bond and normal solid-phase peptide chemistry. A racemization test on a model pseudodipeptide indicated that no more than 6% racemization took place during the aldehyde preparation and alkylation steps. Analogues were examined for their ability to inhibit growth hormone release in vivo in sodium pentobarbital anesthetized rats and in vitro from cultured rat anterior pituitary cells. Analogues modified at the amide carbonyl of Cys2 and Lys5 showed the highest in vivo activity (20 and 8 times more potent than SRIF, respectively) and in vitro activity (0.17 and 0.67 times as active as SRIF). This compared to in vivo and in vitro potencies of 8000% and 100%, respectively, for the parent analogue. Modification of the other cyclic ring amide carbonyls of Tyr3, D-Trp4, and Val6 or the N- or C-terminal amide carbonyl of D-Phe1 or Cys7 gave analogues with considerably lower in vitro or in vivo potencies. The results appear to offer support for a proposed type II beta-turn solution conformation centered on the D-Trp-Lys portion of SRIF octapeptide analogues, resulting in possible hydrogen-bonding interactions between Tyr3 and Val6 and D-Phe1 and Thr8 residues in the parent peptide. These would then be disrupted by methylene replacement of the carbonyl groups with concomitant loss of biological activity as was observed.
B cell-targeted therapy in autoimmune disease: rationale, mechanisms, and clinical application. (2008)

B cells play a critical role in the pathogenesis of rheumatoid arthritis (RA) and other autoimmune diseases. Recently, a number of biologic agents that target B cells have been tested as therapies for these conditions. These agents either deplete B cells, by targeting cell-surface antigens such as CD20, or block B cell function, for example by inhibiting the activity of B cell survival factors such as BLyS. Of this group of agents, the first in clinical use has been rituximab, a chimeric monoclonal antibody that depletes B cells by binding to the CD20 cell-surface antigen. Initially introduced as a treatment for non-Hodgkin's lymphoma, rituximab is now approved for the treatment of RA. In this review we explore the rationale behind B cell-targeted therapy, highlight the results of clinical trials with rituximab in RA and other autoimmune diseases, and describe other emerging therapies directed at B cells.
Impact energy absorption of three mouthguard materials in three environments (2010)

The objective of this study was to compare the impact energy absorption of three mouthguard materials in three environments. Thirty specimens with 12.7 cm x 12.7 cm x 4 mm dimensions were prepared for each material: ethylene vinyl acetate (EVA, T&S Dental and Plastics), Pro-form (Dental Resources Inc), and PolyShok (Sportsguard Laboratories). Ten specimens of each material were conditioned for 1 h at 37 degrees C in three environments: dry (ambient) condition, deionized water and artificial saliva. Specimens were impacted at 20 mph by a 0.5-inch diameter indenter containing a force transducer (Dynatup Model 9250 HV, Instron Corp), based upon ASTM Standard D3763. Energy absorption was determined from the area under the force-time curve during impact (approximately 5 or 7 ms depending on the material). Groups were compared using anova and the Tukey test. Energy absorption values, normalized to specimen thickness (mean +/- SD in J mm(-1)), were: (i) Dry: EVA 4.73 +/- 0.27, Pro-form 3.55 +/- 0.25, PolyShok 6.32 +/- 0.24; (ii) DI water: EVA 4.82 +/- 0.40, Pro-form 3.78 +/- 0.33, PolyShok 5.87 +/- 0.38; (iii) Artificial saliva: EVA 5.63 +/- 0.49, Pro-form 4.01 +/- 0.54, PolyShok 6.37 +/- 0.55. PolyShok was the most energy-absorbent material in all three environments. EVA was significantly more impact resistant than Pro-form in all three environments. EVA and Pro-form performed significantly better after saliva conditioning than dry or water conditioned, but PolyShok did not show any difference in energy absorption when conditioned in any of the three environments. Characteristic deformation patterns from impact loading were observed with an SEM for each material. The superior energy absorption for PolyShok is attributed to the polyurethane additive.
Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer (2021)

Progression-free and overall survival were significantly longer with sacituzumab govitecan than with single-agent chemotherapy among patients with metastatic triple-negative breast cancer. Myelosuppression and diarrhea were more frequent with sacituzumab govitecan. (Funded by Immunomedics; ASCENT ClinicalTrials.gov number, NCT02574455; EudraCT number, 2017-003019-21.).
Clinical trial of an inhibitor of RAGE-Aβ interactions in Alzheimer disease (2014)

This study provides Class I evidence that in patients with AD high-dose PF-04494700 increased cognitive decline at 6 months and Class IV evidence that low-dose PF-04494700 slowed cognitive decline at 18 months.
Fabrication of Storage Capacitance-Enhanced Capacitors with a Rough Electrode (1990)

In order to produce high-performance capacitors with a rough surface polysilicon film as a storage electrode, we investigate various fabrication conditions for polysilicon films. We fabricated such capacitors that attained 1.55 times as much capacitance as those with a conventional polysilicon electrode. Capacitors with the rough electrode show almost identical leakage current characteristics to those of conventional ones. In the evaluation of their reliability, we found that they have lifetimes of more than 1×10 10 seconds, which is sufficient for next-generation DRAM applications.
Enhanced Symbiotic Performance by Rhizobium tropici Glycogen Synthase Mutants (2001)

We isolated a Tn5-induced Rhizobium tropici mutant that has enhanced capacity to oxidize N,N-dimethyl-p-phenylendiamine (DMPD) and therefore has enhanced respiration via cytochrome oxidase. The mutant had increased levels of the cytochromes c(1) and CycM and a small increase in the amount of cytochrome aa(3). In plant tests, the mutant increased the dry weight of Phaseolus vulgaris plants by 20 to 38% compared with the control strain, thus showing significantly enhanced symbiotic performance. The predicted product of the mutated gene is homologous to glycogen synthases from several bacteria, and the mutant lacked glycogen. The DNA sequence of the adjacent gene region revealed six genes predicted to encode products homologous to the following gene products from Escherichia coli: glycogen phosphorylase (glgP), glycogen branching enzyme (glgB), ADP glucose pyrophosphorylase (glgC), glycogen synthase (glgA), phosphoglucomutase (pgm), and glycogen debranching enzyme (glgX). All six genes are transcribed in the same direction, and analysis with lacZ gene fusions suggests that the first five genes are organized in one operon, although pgm appears to have an additional promoter; glgX is transcribed independently. Surprisingly, the glgA mutant had decreased levels of high-molecular-weight exopolysaccharide after growth on glucose, but levels were normal after growth on galactose. A deletion mutant was constructed in order to generate a nonpolar mutation in glgA. This mutant had a phenotype similar to that of the Tn5 mutant, indicating that the enhanced respiration and symbiotic nitrogen fixation and decreased exopolysaccharide were due to mutation of glgA and not to a polar effect on a downstream gene.
The contribution of Na channel block to the negative inotropic effect of antiarrhythmic drugs (1986)

The specific Na channel blocker tetrodotoxin (TTX) produces a direct negative inotropic effect on the isolated guinea-pig papillary muscle stimulated at 1 Hz. The toxin is significantly more potent in reducing maximal upstroke velocity of the transmembrane action potential (Vmax, an index of the available Na conductance) than in reducing force of contraction (Fc), the IC50 for Vmax divided by the IC50 for Fc being 0.23 (95% confidence interval, 0.16-0.43). This IC50 ratio defines the negative inotropic influence of Na channel blockade per se, because TTX has no known action other than blocking Na channels. Vmax-reducing to negative inotropic concentration ratios were also obtained for 5 widely used and 2 experimental antiarrhythmic agents belonging to the Na channel-blocking class (class 1). Five of these drugs (aprindine, CCI 22277, disopyramide, mexiletine, and quinidine) differed significantly from TTX in that the Na channel block was associated with a stronger negative inotropic effect. It is concluded that one or more mechanisms in addition to Na channel blockade are involved in the negative inotropic effect of these antiarrhythmic drugs. If the antiarrhythmic activity of class 1 agents depended solely on Na channel block, more selective agents with less negative inotropic action could conceivably be developed.
Isolation of Nervous Necrosis Virus from Hybrid Grouper (<i>Epinephelus fuscoguttatus</i>♀ × <i>Epinephelus lanceolatus</i>♂) Cultured in Guangxi, China (2019)

Outbreaks of suspected viral nervous necrosis emerged in cultured groupers in Guangxi, China in August 2018. ​Histopathology showed severe vacuolation in the brain tissue of the diseased juvenile hybrid grouper (Epinephelus fuscoguttatus♀ × Epinephelus lanceolatus♂). ​A nervous necrosis virus (NNV) was isolated from pooled sample of the brain and eyes using a grouper cell line EAGB. ​Cytopathic effect with multiple cytoplasmic vacuolation cells developed in EAGB cells. ​The coat protein gene sequence of the isolate (GNNV-Gx) showed that it belonged to RGNNV genotype and was most closely related to that of a tiger grouper NNV registered in GenBank. ​The infectivity of the isolate decreased remarkably at pH 3 and pH 10 and was susceptible to 60°C.
The Synthesis of Peptides by Means of Proteolytic Enzymes (1977)

Abstract Nagarse, papain, pepsin and thermolysin were found to catalyze the peptide bond formation between two amino acids or peptides, one protected with a suitable group at the amino group and the other at the carboxyl group. Experiments with various combinations of amino acids and dipeptides show specificity in the catalytic action in varying degree which depending on the nature of the enzyme. Since the condensation takes place efficiently under mild conditions, this method opens up a useful way for the synthesis of peptides.
Increasing Polypropylene High Temperature Stability by Blending Polypropylene-Bonded Hindered Phenol Antioxidant (2018)

Currently, hindered phenol (HP) antioxidants mixed in PP products provide thermal-oxidative protection during PP melt processing (homogeneous mixing). However, there are concerns about their effectiveness during applications. This paper presents computer simulation and experimental results to demonstrate a facile phase separation of HP molecules in the PP matrix and investigates a new approach that can dramatically improve PP thermal-oxidative stability under elevated temperatures. This technology is centered on a new PP–HP copolymer containing a few comonomer units with HP moieties, homogeneously distributed along the polymer chain. Because of the cocrystallization between the PP and PP–HP copolymer, all HP antioxidant groups are homogeneously distributed in the PP matrix (amorphous domains). The resulting PP/PP–HP blends demonstrate a thermal-oxidative stability nearly proportional to the HP content. While commercial PP products (containing regular antioxidants and stabilizers) degrade within a few minutes at 210 °C in air, the PP/PP–HP blend, with the same concentration of HP groups, demonstrates nearly no detectable weight loss after 1000 h. In an ASTM endurance test under a targeted application temperature (140 °C in air), the commercial PP shows 1% weight loss within 10 days. On the other hand, the new PP/PP–HP (5/1) blend with the same HP content lasts for about 2 years under the same constant heating condition. Overall, the experiment results of the PP–HP antioxidant present the potential of expanding PP applications into a far higher temperature range (>140 °C) under thermal-oxidative environments.
Incidence of Invasive Breast Cancer by Hormone Receptor Status From 1992 to 1998 (2002)

From 1992 to 1998, the proportion of tumors that are hormone receptor-positive rose as the proportion of hormone receptor-negative tumors declined. Because the incidence rates of hormone receptor-negative tumors remained fairly constant over these years, the overall rise in breast cancer incidence rates in the United States seems to be primarily a result of the increase in the incidence of hormone receptor-positive tumors. Hormonal factors may account for this trend.
Decision Analysis of Discordant Thyroid Nodule Biopsy Guideline Criteria (2008)

As a general approach to 10- to 14-mm thyroid nodules, routine FNAB appears to be the least desirable. This analysis offers additional data that physicians can use when choosing diagnostic approaches to small thyroid nodules based on perceived risks of delayed cancer diagnosis and unnecessary thyroid surgery.
Inversion modeling of gravity with prismatic mass bodies (1991)

Abstract A combined method for forward and inverse modeling of gravity data is presented. Based on the Fourier transform of Poisson's equation, the forward modeling is suitable for observation points above, within, and below causative masses with any prescribed density distribution. The inversion is linearized in the spatial domain by superimposing numerous prismatic bodies, each having constant but different density, and fixed geometry. Our inversion algorithm adopts a sampling window to reduce memory storage and computations. Testing, with synthetic and field data, demonstrates that a successful inversion can be obtained from crudely estimated a priori density distributions and uncertainties. Lateral variations in density are well resolved but depth resolution often requires better constrained a priori information. Under various a priori conditions, our modeling indicates that sediment density tends to vary exponentially with depth in the San Jacinto basin, southern California.
In vitro display technologies reveal novel biopharmaceutics (2006)

Display technologies are fundamental to the isolation of specific high-affinity binding proteins for diagnostic and therapeutic applications in cancer, neurodegenerative, and infectious diseases as well as autoimmune and inflammatory disorders. Applications extend into the broad field of antibody (Ab) engineering, synthetic enzymes, proteomics, and cell-free protein synthesis. Recently, in vitro display technologies have come to prominence due to the isolation of high-affinity human antibodies by phage display, the development of novel scaffolds for ribosome display, and the discovery of novel protein-protein interactions. In vitro display represents an emerging and innovative technology for the rapid isolation and evolution of high-affinity peptides and proteins. So far, only one clinical drug candidate produced by in vitro display technology has been approved by the FDA for use in humans, but several are in clinical or preclinical testing. This review highlights recent advances in various engineered biopharmaceutical products isolated by in vitro display with a focus on the commercial developments.
Tyrphostins. 5. Potent Inhibitors of Platelet-Derived Growth Factor Receptor Tyrosine Kinase:  Structure−Activity Relationships in Quinoxalines, Quinolines, and Indole Tyrphostins (1996)

A series of 3-indoleacrylonitrile tyrphostins, 2-chloro-3-phenylquinolines, and 3-arylquinoxalines were prepared and tested for inhibition of platelet-derived growth factor receptor tyrosine kinase (PDGF-RTK) activity. The potency of the inhibitors was found to be quinoxalines > quinolines > indoles. Lipophilic groups (methyl, methoxy) in the 6 and 7 positions and phenyl at the 3 position of quinoxalines and quinolines were essential for potency, in contrast to the hydrophilic catechol group in tyrphostins active against EGFR kinase inhibition at different sites. The inhibitors showed selectivity for PDGF and were not active against EGF receptor and HER-2/c-ErbB-2 receptor.
Cone connudrum (1991)

Physics is fun, particularly when the simplest experiment yields astonishing effects. The following phenomenon was observed while setting up an experiment with a high-power laser beam which was directed through two lenses. The first lens served to expand the beam so that it would fill the second lens, beyond which the beam was brought to a focus. Dust particles could be seen swirling in the cones of bright light. After a short period, one dust particle was seen to become lodged at the focus, remaining there for several seconds before vanishing. Why? On the face of it, confinement in the transverse direction seemed fairly easy to explain: confinement along the beam axis was not so obvious.