gebhart/patrepeval huggingface dataset:
Dual mechanisms of inhibition of DNA synthesis by triciribine. (1990)

The inhibition of DNA synthesis in triciribine (TCN)-treated L1210 cells was shown to involve two mechanisms, with different concentration dependence. (a) Initiation of new replicons and possibly of Okazaki fragments was inhibited when the cells were treated with 0.1 microM TCN. The inhibition of replicon initiation was shown by the rate of alkaline elution of [3H]DNA from 15-min-[3H]thymidine-labeled cells being slower if the cells had been pretreated with TCN, indicating that the average size of actively replicating DNA strands was increased. (b) At 1 microM TCN elongation of previously initiated DNA chains was also inhibited. This conclusion was suggested by the decrease in the rate of alkaline elution of [3H]DNA, during postlabeling incubation, being less if TCN was included in the medium. The mechanism of inhibition of DNA synthesis by TCN was shown not to involve DNA strand breakage or cross-linking, inhibition of polyamine biosynthesis, inhibition of purine de novo biosynthesis, inhibition of DNA polymerase alpha or DNA primase, or inhibition of ligation of Okazaki fragments. The effects of TCN on the incorporation of [3H]thymidine into Okazaki fragments and higher molecular weight DNA suggested the possibilities of inhibition of Okazaki fragment initiation and/or DNA polymerase delta.
Preparation and Properties of Thin Film Boron Nitride (1968)

Clear, vitreous films of boron nitride up to 6000Aå thick have been deposited on a variety of substrates at 600 °–1000 °C by a reaction between diborane and ammonia in hydrogen or inert carrier gas. Deposition rate may be readily adjusted to 50–1000 Aå/min. Most samples were made at either 600° or 800°, with some attendant variation in film properties. The 600° material contains some residual B‐H bonding. The film is essentially amorphous to electron diffraction. The refractive index is 1.7–1.8, the 1 MHz dielectric constant ∼ 3 1/2, the dielectric strength , and the The band gap is 3.8 ev and the phonon temperature in the neighborhood of 2000°K. For semiconductor junction protection boron nitride has no advantage over silicon nitride. 600° deposition directly on Si has produced surface charges as low as , but there are room‐temperature drifts, and high‐field conduction also. BN deposited at 800° on Si is electrically similar to silicon nitride. Etching of BN film also presents the same problems as does silicon nitride. BN is not as good a barrier against sodium ion permeation. Attack by atmospheric moisture over a long period has varied from insignificant to extensive conversion to orthoboric acid.
A Brain Penetrant Mutant IDH1 Inhibitor Provides In Vivo Survival Benefit (2017)

Mutations in IDH1 are highly prevalent in human glioma. First line treatment is radiotherapy, which many patients often forego to avoid treatment-associated morbidities. The high prevalence of IDH1 mutations in glioma highlights the need for brain-penetrant IDH1 mutant-selective inhibitors as an alternative therapeutic option. Here, we have explored the utility of such an inhibitor in IDH1 mutant patient-derived models to assess the potential therapeutic benefits associated with intracranial 2-HG inhibition. Treatment of mutant IDH1 cell line models led to a decrease in intracellular 2-HG levels both in vitro and in vivo. Interestingly, inhibition of 2-HG production had no effect on in vitro IDH1 mutant glioma cell proliferation. In contrast, IDH1 mutant-selective inhibitors provided considerable survival benefit in vivo. However, even with near complete inhibition of intratumoral 2-HG production, not all mutant glioma models responded to treatment. The results suggest that disruption of 2-HG production with brain-penetrant inhibitors in IDH1 mutant gliomas may have substantial patient benefit.
The BSD Syslog Protocol (2001)

This document describes the observed behavior of the syslog protocol. This protocol has been used for the transmission of event notification messages across networks for many years. While this protocol was originally developed on the University of California Berkeley Software Distribution (BSD) TCP/IP system implementations, its value to operations and management has led it to be ported to many other operating systems as well as being embedded into many other networked devices.
Heterogeneity of the mutation rates of influenza A viruses: isolation of mutator mutants (1992)

The rates of mutation to the mar (monoclonal antibody-resistant) genotype of individual influenza virus plaque isolates, obtained from a stock generated after two successive cloning steps, have been determined by the fluctuation test. When a random sample of 60 clones was analyzed, 7 contained a proportion of mar mutants significantly higher than the average, and among them, 2 showed a mutation rate two to three times higher than the average value obtained for the virus population when the hemagglutinin-specific monoclonal antibody 2G10 was used. In order to look for mutants with higher mutation rates, a systematic search was carried out with a nonmutagenized virus stock, and several clones with increased mutation rates were isolated. One of them (mut43) was characterized further and was shown to have a mutation rate three to four times higher than that of the virus population at the sites defined by two nonoverlapping, hemagglutinin-specific monoclonal antibodies as well as at the site defined by a neuraminidase-specific monoclonal antibody. These results indicate that the mutation rate of an influenza virus is a weighted average of the contributions of a heterogeneous population. The consequences of this fact for the adaptive evolution of influenza viruses are discussed.
Ein rationelles Herstellungsverfahren für 2H-Isoindole (1984)

2H-Isoindole 2 mit spezifischem Substitutionsmuster sind durch Retro-En-Reaktion der N-Propinylverbindungen 1 zu erhalten. Die Edukte sind gut zugänglich, und bei der Thermolyse entstehen flüchtige Begleitprodukte.
Optimization of long-baseline optical interferometers for gravitational-wave detection (1988)

The goal of this paper is to analyze and to evaluate the different configurations currently considered for the interferometric detectors of gravitational waves. We first study the properties of elementary gravito-optic transducers (i.e., delay lines or Fabry-Perot resonators) using an original formalism which allows one to understand and to compare easily the properties of complex interferometers involving these elements, such as recycling or synchronous recycling interferometers. We also describe the new idea of using detuned Fabry-Perot resonators, and we show that, in some cases, it may represent the best compromise between bandwidth and peak sensitivity.
TP53 copy number expansion is associated with the evolution of increased body size and an enhanced DNA damage response in elephants (2016)

A major constraint on the evolution of large body sizes in animals is an increased risk of developing cancer. There is no correlation, however, between body size and cancer risk. This lack of correlation is often referred to as 'Peto's Paradox'. Here, we show that the elephant genome encodes 20 copies of the tumor suppressor gene <i>TP53</i> and that the increase in <i>TP53</i> copy number occurred coincident with the evolution of large body sizes, the evolution of extreme sensitivity to genotoxic stress, and a hyperactive TP53 signaling pathway in the elephant (Proboscidean) lineage. Furthermore, we show that several of the <i>TP53</i> retrogenes (<i>TP53RTGs</i>) are transcribed and likely translated. While <i>TP53RTGs</i> do not appear to directly function as transcription factors, they do contribute to the enhanced sensitivity of elephant cells to DNA damage and the induction of apoptosis by regulating activity of the TP53 signaling pathway. These results suggest that an increase in the copy number of <i>TP53</i> may have played a direct role in the evolution of very large body sizes and the resolution of Peto's paradox in Proboscideans.
Selection of Metal Oxide Charge Transport Layers for Colloidal Quantum Dot LEDs (2009)

We investigate the effect of the electronic energy level positioning, conductivity, and morphology of metal oxide charge transport layers on the performance of light emitting devices (LEDs) that consist of a colloidally synthesized quantum dot (QD) luminescent film embedded between electron and hole injecting ceramic layers. We demonstrate that understanding of these material properties and their effect on charging processes in QDs enables the systematic design of higher efficiency QD-LEDs and excitation of QDs with different emission colors using the same device structure.
Induction of pigmentation in mouse fibroblasts by expression of human tyrosinase cDNA. (1989)

A distinguishing characteristic of cells of the melanocyte lineage is the expression of the melanosomal enzyme tyrosinase that catalyzes the synthesis of the pigment melanin. A tyrosinase cDNA clone, designated BBTY-1, was isolated from a library constructed from the pigmented TA99+/CF21+ melanoma cell line SK-MEL-19. Expression of BBTY-1 in mouse L929 fibroblasts led to synthesis and expression of active tyrosinase, and, unexpectedly, to stable production of melanin. Melanin was synthesized and stored within membrane-bound vesicles in the cytoplasm of transfected fibroblasts. BBTY-1 detected a 2.4-kb mRNA transcript in nine of nine pigmented, tyrosinase-positive melanoma cell lines. Tyrosinase transcripts of the same size and abundance were detected in a subset (three of eight) of nonpigmented, tyrosinase-negative melanoma cell lines, suggesting that post-transcriptional events are important in regulating tyrosinase activity. Two melanocyte antigens, recognized by mAbs TA99 and CF21, that are specifically located within melanosomes and are coexpressed with tyrosinase activity, did not react with transfected mouse fibroblasts expressing human tyrosinase, supporting the conclusion that these antigenic determinants are distinct from the tyrosinase molecule coded for by BBTY-1.
Concurrent infections by two dengue virus serotypes among dengue patients in Taiwan. (2003)

The co-circulation of multiple dengue virus serotypes in the same region has been reported in several countries in Southeast Asia as well as in Central and South America for decades. Although outbreaks involving more than one serotype of dengue virus have been reported in Taiwan since 1987, concurrent infection in the same individual by multiple serotypes of dengue virus have never been identified. Using a modified multiplex reverse transcription-polymerase chain reaction assay, we detected and determined the serotypes of 21 dengue patients during an outbreak in southern Taiwan in 2000. While either dengue type 2 or type 3 virus was found in most cases, 2 of the 21 cases were concurrent infections by both dengue type 2 and dengue type 3 viruses. This was further confirmed by sequence analysis of the amplified products. This study reports for the first time that concurrent infections occur in Taiwan, and suggests that future virologic surveillance of dengue outbreak in Taiwan should take this into consideration.
Studies on the Toxicity and Antiviral Activity of Various Polynucleotides (1973)

Various polynucleotides were examined for antiviral activity and toxicity in mice. Although the antiviral potency of the various interferon inducers varied, there was a concomitant variation in toxicity. This was reflected by a fivefold range in therapeutic ratio for the various compounds. In addition, no polynucleotide proved to be a more potent interferon inducer than polyinosinic.polycytidylic acid [(poly rI).(poly rC)]. Our results suggest that there may be intrinsic limitations to the development of polynucleotide interferon inducers having improved therapeutic ratios.
Synthesis and potential antipsychotic activity of 1H-imidazo[1,2-c]pyrazolo[3,4-e]pyrimidines (1988)

The synthesis of a series of 1H-imidazo[1,2-c]pyrazolo[3,4-e]pyrimidines is reported along with the effects of these compounds in preclinical tests for antipsychotic activity. Certain of these compounds displayed antipsychotic-like effects in conditioned avoidance tests, but unlike currently used antipsychotic drugs, they did not have affinity for brain dopamine receptors. These compounds also did not cause dystonias predictive of extrapyramidal side effects in monkeys at doses that produced behavioral effects. On the basis of this unique biological profile, a member of this series 7,8-dihydro-8-ethyl-1,3,5-trimethyl-1H-imidao[1,2-c]pyrazol[3,4-e] pyrimidine (19, CI-943), has been selected for clinical evaluation as an antipsychotic agent.
Effect of Magnesium on Calcium and Oxalate Ion Binding (2013)

The presence of magnesium ions tends to destabilize calcium oxalate ion pairs and reduce the size of their aggregates. Mg(2+) inhibitory effect is synergistic with citrate and remains effective in acidic environments. Further studies are needed to see if this can be applied to in vivo models as well as extending this to other stone inhibitors and promoters.
Carbon−Nitrogen-Bond-Forming Reductive Elimination of Arylamines from Palladium(II) Phosphine Complexes (1997)

A series of monomeric palladium amido complexes of the form trans-(PPh3)2Pd(Ar)(NAr‘2) and (DPPF)Pd(Ar)(NAr‘2) (DPPF = 1,1‘-bis(diphenylphosphino)ferrocene) and dimeric palladium amido complexes of the form {(PPh3)Pd(Ar)(μ-NHR)}2 (R = Ph, t-Bu) have been prepared by the reaction of lithium and potassium amides with palladium aryl halide complexes. An X-ray crystal structure of (DPPF)Pd(p-NMe2C6H4)[N(p-CH3C6H4)2] was obtained. Upon thermolysis in the presence of PPh3, serving as a trapping agent, both the monomeric and dimeric palladium amido complexes underwent C−N-bond-forming reductive elimination to form arylamines in high yields along with a Pd(0) species. Reductive elimination was also observed from azametallacycle (PPh3)Pd(η2-C6H4C6H4NH), to form carbazole and Pd(PPh3)4 at room temperature. Mechanistic studies on the reductive elimination reactions of the monomeric PPh3-ligated amido complexes indicated the presence of two competing pathways for the formation of amine. At low [PPh3], reductive elimination occurs via phosphine dissociation to form a three-coordinate intermediate; however, as [PPh3] is increased, a pathway of reductive elimination from a four-coordinate complex becomes dominant. The DPPF-ligated palladium amido complexes directly eliminated amine from the four-coordinate complex. The mechanism of the reductive elimination from dimeric palladium amido complexes was also studied. These complexes undergo reductive elimination of amine via dimer dissociation to generate a three-coordinate intermediate analogous to those formed by the PPh3-ligated monomeric amido complexes. The C−N-bond forming reductive elimination reactions were accelerated by electron-withdrawing groups on the Pd bound aryl group and by electron-donating groups on the amido ligand, suggesting that the aryl group acts as an electrophile and the amido ligand acts as a nucleophile.
Method to Detect Substitutions in the Interferon–Sensitivity—Determining Region of Hepatitis C Virus 1B for Prediction of Response to Interferon Therapy (2001)

Substitutions deduced by direct sequencing in the interferon–sensitivity—determining region (ISDR) of hepatitis C virus (HCV) are related to patients' responses to interferon (IFN), but sequencing is time consuming and results are only for the dominant virus. We developed a rapid method to detect such changes. With serum from 50 patients with chronic hepatitis C (genotype 1b) given IFN–α, a way to detect changes in ISDR by hybridization with oligonucleotide probes that had a prototype nucleotide sequence of HCV–J was established. Hybridization intensity was expressed as optical density (OD NS5A ). The method was checked with serum from 100 more patients. In the study of 50 patients, all 21 with the prototype sequences had a high OD NS5A (≥0.4), and all 8 patients with a mutant–type sequence had low values (≤0.2). Twelve (95% confidence interval, 36–81%) of 20 patients with OD NS5A of &lt;0.4 and 2 (1%–22%) of 30 patients with OD NS5A ≥0.4 had complete responses (CR). All nine (66%–100%) patients with OD NS5A &lt;0.4 and little HCV RNA (&lt;100 kIU/mL) had CR, but none (0%–14%) of the 24 patients with high values from both predictors had CR. In the study of 100 patients, OD NS5A and the HCV RNA level were independent predictors of the effects of IFN. By multivariate analysis, the odds ratio for a CR in patients with OD NS5A of ≥0.4 was 0.015 (0.001–0.190) compared with the other patients ( P = .001). In conclusion, our method should be useful in identification of prototype strains, which generally resist IFN therapy.
Metabolic Engineering of ω3-Very Long Chain Polyunsaturated Fatty Acid Production by an Exclusively Acyl-CoA-dependent Pathway (2008)

omega3-Very long chain polyunsaturated fatty acids (VLCPUFA) are essential for human development and brain function and, thus, are indispensable components of the human diet. The current main source of VLCPUFAs is represented by ocean fish stocks, which are in severe decline, and the development of alternative, sustainable sources of VLCPUFAs is urgently required. Our research aims at exploiting the powerful infrastructure available for the large scale culture of oilseed crops, such as rapeseed, to produce VLCPUFAs such as eicosapentaenoic acid in transgenic plants. VLCPUFA biosynthesis requires repeated desaturation and repeated elongation of long chain fatty acid substrates. In previous experiments the production of eicosapentaenoic acid in transgenic plants was found to be limited by an unexpected bottleneck represented by the acyl exchange between the site of desaturation, endoplasmic reticulum-associated phospholipids, and the site of elongation, the cytosolic acyl-CoA pool. Here we report on the establishment of a coordinated, exclusively acyl-CoA-dependent pathway, which avoids the rate-limiting transesterification steps between the acyl lipids and the acyl-CoA pool during VLCPUFA biosynthesis. The pathway is defined by previously uncharacterized enzymes, encoded by cDNAs isolated from the microalga Mantoniella squamata. The conceptual enzymatic pathway was established and characterized first in yeast to provide proof-of-concept data for its feasibility and subsequently in seeds of Arabidopsis thaliana. The comparison of the acyl-CoA-dependent pathway with the known lipid-linked pathway for VLCPUFA biosynthesis showed that the acyl-CoA-dependent pathway circumvents the bottleneck of switching the Delta6-desaturated fatty acids between lipids and acyl-CoA in Arabidopsis seeds.
Comparative molecular field analysis-based predictive model of structure-function relationships of polyamine transport inhibitors in L1210 cells. (1997)

Maintenance of intracellular polyamine concentrations necessary for cell growth and proliferation is regulated in part by an energy-dependent polyamine uptake system. To obtain information on the characteristics of the polyamine uptake system in L1210 leukemia cells, we have applied computational chemistry techniques to the study of relationships between structure and function of 57 polyamine analogues. Ki values of polyamine analogues, derived from competitive inhibition of [3H]spermidine transport into L1210 cells, were chosen as the measure of biological activity. Using comparative molecular field analysis (CoMFA), a model was constructed to relate molecular structure with biological activity. The model was based on 4 monocationic, 8 dicationic, 14 tricationic, and 20 tetracationic polyamine analogues with a range of Ki values for the inhibition of [3H]spermidine uptake of 0.97-521 microM. The CoMFA model successfully predicted the inhibitory potency of 11 polyamines that had not previously been tested for polyamine uptake inhibitory activity. The 11 values predicted were within 33 +/- 62% of the actual Ki values. The test group included aziridinyl diamines, acetylated spermidines, two new oxazolidinonyl spermidines, monoaziridinyl spermidines, and a diaziridinyl spermine. Several of the compounds from this test group have been shown to have anticancer activity in mice. Consistent with the CoMFA model, certain basic functional groups, such as aziridines that have pKa values in the range of 6-7, seem to interact with the polyamine transporter in a cationic form. The results suggest that the CoMFA model is useful in drug design strategies as a predictive tool for the discovery of new anticancer agents that utilize a polyamine transporter for cellular uptake.
High molecular weight hyaluronan decreases UVB-induced apoptosis and inflammation in human epithelial corneal cells. (2009)

To our knowledge, we report for the first time the ability of HMW-HA to protect cells against UV irradiation. According to our results, HMW-HA provides anti-inflammatory and anti-apoptotic signals to cells exposed to UVB.
Pseudomonas aeruginosa Displays Multiple Phenotypes during Development as a Biofilm (2002)

Complementary approaches were employed to characterize transitional episodes in Pseudomonas aeruginosa biofilm development using direct observation and whole-cell protein analysis. Microscopy and in situ reporter gene analysis were used to directly observe changes in biofilm physiology and to act as signposts to standardize protein collection for two-dimensional electrophoretic analysis and protein identification in chemostat and continuous-culture biofilm-grown populations. Using these approaches, we characterized five stages of biofilm development: (i) reversible attachment, (ii) irreversible attachment, (iii) maturation-1, (iv) maturation-2, and (v) dispersion. Biofilm cells were shown to change regulation of motility, alginate production, and quorum sensing during the process of development. The average difference in detectable protein regulation between each of the five stages of development was 35% (approximately 525 proteins). When planktonic cells were compared with maturation-2 stage biofilm cells, more than 800 proteins were shown to have a sixfold or greater change in expression level (over 50% of the proteome). This difference was higher than when planktonic P. aeruginosa were compared with planktonic cultures of Pseudomonas putida. Las quorum sensing was shown to play no role in early biofilm development but was important in later stages. Biofilm cells in the dispersion stage were more similar to planktonic bacteria than to maturation-2 stage bacteria. These results demonstrate that P. aeruginosa displays multiple phenotypes during biofilm development and that knowledge of stage-specific physiology may be important in detecting and controlling biofilm growth.