gebhart/patrepeval huggingface dataset:
PCR Bias Toward the Wild-Type k- ras and p53 Sequences: Implications for PCR Detection of Mutations and Cancer Diagnosis (1998)

PCR-based cancer diagnosis requires detection of rare mutations in k-ras, p53 or other genes. The assumption has been that mutant and wild-type sequences amplify with near equal efficiency, so that they are eventually present in proportions representative of the starting material. Work on factor IX suggests that this assumption is invalid for one case of near-sequence identity. To test the generality of this phenomenon and its relevance to cancer diagnosis, primers distant from point mutations in p53 and k-ras were used to amplify wild-type and mutant sequences from these genes. A substantial bias against PCR amplification of mutants was observed for two regions of the p53 gene and one region of k-ras. For k-ras and p53, bias was observed when the wild-type and mutant sequences were amplified separately or when mixed in equal proportions before PCR. Bias was present with proofreading and non-proofreading polymerases. Mutant and wild-type segments of the factor V, cystic fibrosis transmembrane conductance regulator and prothrombin genes were amplified and did not exhibit PCR bias. Therefore, the assumption of equal PCR efficiency for point mutant and wild-type sequences is invalid in several systems. Quantitative or diagnostic PCR will require validation for each locus, and enrichment strategies may be needed to optimize detection of mutants.
Modeling nanoscale temperature gradients and conductivity evolution in pulsed light sintering of silver nanowire networks (2018)

Sintering of metal nanowire (NW) networks on transparent polymers is an emerging approach for fabricating transparent conductive electrodes used in multiple devices. Pulsed light sintering is a scalable sintering process in which large-area, broad-spectrum xenon lamp light causes rapid NW fusion to increase network conductivity, while embedding the NWs in the polymer to increase mechanical robustness. This paper develops a multiphysical approach for predicting evolution of conductivity, NW fusion and nanoscale temperature gradients on the substrate during pulsed light sintering of silver NWs on polycarbonate. Model predictions are successfully validated against experimentally measured temperature and electrical resistance evolution. New insight is obtained into the diameter-dependent kinetics of NW fusion and nanoscale temperature gradients on the substrate, which are difficult to obtain experimentally. These observations also lead to the understanding that NW embedding in intense pulsed light sintering (IPL) can occur below the glass transition temperature of the polymer, and to a new differential thermal expansion-based mechanism of NW embedding during IPL. These insights, and the developed model, create a framework for physics-guided choice of NWs, substrate and process parameters to control conductivity and prevent substrate damage during the process.
The protein encoded by a growth arrest-specific gene (gas6) is a new member of the vitamin K-dependent proteins related to protein S, a negative coregulator in the blood coagulation cascade. (1993)

A set of growth arrest-specific genes (gas) whose expression is negatively regulated after serum induction has previously been described (C. Schneider, R. M. King, and L. Philipson, Cell 54:787-793, 1988). The detailed analysis of one of them, gas6, is reported here, gas6 mRNA (2.6 kb) is abundantly expressed in serum-starved (48 h in 0.5% fetal calf serum) NIH 3T3 cells but decreases dramatically after fetal calf serum or basic fibroblast growth factor stimulation. The human homolog of gas6 was also cloned and sequenced, revealing a high degree of homology and a similar pattern of expression in IMR90 human fibroblasts. Computer analysis of the protein encoded by murine and human gas6 cDNAs showed significant homology (43 and 44% amino acid identity, respectively) to human protein S, a negative coregulator in the blood coagulation pathway. By using an anti-human Gas6 monospecific affinity-purified antibody, we show that the biosynthetic level of human Gas6 fully reflects mRNA expression in IMR90 human fibroblasts. This finding thus defines a new member of vitamin K-dependent proteins that is expressed in many human and mouse tissues and may be involved in the regulation of a protease cascade relevant in growth regulation.
Object-oriented spreadsheets: the analytic spreadsheet package (1986)

The ASP package, a spreadsheet implemented in Smalltalk-80, is discussed. A description of the unique data manipulation features of ASP is given. A discussion of how these features arise from the Smalltalk-80 environment is included, with emphasis on features not common to all object oriented languages.
Large-Plaque Mutants of Sindbis Virus Show Reduced Binding to Heparan Sulfate, Heightened Viremia, and Slower Clearance from the Circulation (2000)

Laboratory strains of Sindbis virus must bind to the negatively charged glycosaminoglycan heparan sulfate in order to efficiently infect cultured cells. During infection of mice, however, we have frequently observed the development of large-plaque viral mutants with a reduced ability to bind to heparan sulfate. Sequencing of these mutants revealed changes of positively charged amino acids in putative heparin-binding domains of the E2 glycoprotein. Recombinant viruses were constructed with these changes as single amino acid substitutions in a strain Toto 1101 background. All exhibited decreased binding to heparan sulfate and had larger plaques than Toto 1101. When injected subcutaneously into neonatal mice, large-plaque viruses produced higher-titer viremia and often caused higher mortality. Because circulating heparin-binding proteins are known to be rapidly sequestered by tissue heparan sulfate, we measured the kinetics of viral clearance following intravenous injection. Much of the parental small-plaque Toto 1101 strain of Sindbis virus was cleared from the circulation by the liver within minutes, in contrast to recombinant large-plaque viruses, which had longer circulating half-lives. These findings indicate that a decreased ability to bind to heparan sulfate allows more efficient viral production in vivo, which may in turn lead to increased mortality. Because Sindbis virus is only one of a growing number of viruses from many families which have been shown to bind to heparan sulfate, these results may be generally applicable to the pathogenesis of such viruses.
일반논문 : 시간의 비결정성과 주체의 구성과정 연구 -강은교의 중기시를 중심으로- (2012)

This study aims to uncover the text of internal strategies and social implications as examined in relation to Kang`s poems of the 1980s. This was carried out by focusing on the two poems, Sound collection and Wind song . First, this paper pays attention to the `sounds` and ``songs`` that the poet focuses on, as well as the way in which they are connected to amorphous historical figures as a means of examining the worldview awareness of reality. Second, the fragmentation of subjectivity as a result of the concept of time being overthrown is also considered. The undecidability of time is a resistance against the laws of the country based on a military mentality to control the people. In questioning standardized time, the absurdity of reality is dealt with. On the other hand, through the configuration aspects of the subject, the ``fixed`` subject required by the times is constantly in a hybrid and overlapping relationship with the other. This can be seen as a rejection of the fixed and transparent subject that contemporary reality needs. Finally, over the course of the series, this study attempts to understand the meaning of the (Kang`s) realism literary theory of this period. It is a reaction to contemporary reality through literature and a means of reconciliation through bonding with reality. Nevertheless, it is demonstrated that Kang`s poems of the 1980s, which have been less studied compared to her early poems, were consistent with the poetics of realism, forming a major branch in South Korean poetry.
Strong fiber Bragg grating fabrication by hybrid 157- and 248-nm laser exposure (2002)

A permanent 248-nm photosensitivity response was locked into hydrogen-loaded standard telecommunication fiber by uniform 157-nm F <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> -laser pre-exposure. Strong (>30 dB) fiber Bragg gratings were efficiently generated after hydrogen out-diffusion, improving the thermal stability. The 157-mn radiation produced weakly absorbing Si-OH and Ge-OH absorption bands at 1.39-μm.
Determination of Oil Saturation Distributions in Field Cores By Microwave Spectroscopy (1981)

ABSTRACT Two microwave absorption spectrometers have been developed for routine monitoring of So distributions during laboratory flooding experiments in field core material. Operating frequencies are 10.525 and 24.125 GHz. Based upon low-power, mass-produced microwave components, these instruments are inexpensive, safe, very compact and rugged and require no special expertise for operation. A core sample cell has been designed which permits So distributions to be determined in narrow rectangular and cylindrical cores. An indirect calibration technique has been developed using the injection of aqueous solutions of 2-propanol to compensate for the porosity variations and irregular Soi and Sorw distributions inherent to segmented field cores. Details of the instrumentation are presented with a theoretical description of instrumental response. The practical utility of this instrumentation for the a priori detection of core defects and quantitative determination of porosity distributions is demonstrated.
ALK: a tyrosine kinase target for cancer therapy (2017)

The anaplastic lymphoma kinase (<i>ALK</i>) gene plays an important physiologic role in the development of the brain and can be oncogenically altered in several malignancies, including non-small-cell lung cancer (NSCLC) and anaplastic large cell lymphomas (ALCL). Most prevalent <i>ALK</i> alterations are chromosomal rearrangements resulting in fusion genes, as seen in ALCL and NSCLC. In other tumors, <i>ALK</i> copy-number gains and activating <i>ALK</i> mutations have been described. Dramatic and often prolonged responses are seen in patients with <i>ALK</i> alterations when treated with ALK inhibitors. Three of these-crizotinib, ceritinib, and alectinib-are now FDA approved for the treatment of metastatic NSCLC positive for <i>ALK</i> fusions. However, the emergence of resistance is universal. Newer ALK inhibitors and other targeting strategies are being developed to counteract the newly emergent mechanism(s) of ALK inhibitor resistance. This review outlines the recent developments in our understanding and treatment of tumors with <i>ALK</i> alterations.
Orientation of Culex mosquitoes to carbon dioxide‐baited traps: flight manoeuvres and trapping efficiency (2006)

Females of Culex quinquefasciatus Say and Culex tarsalis Coquillet (Diptera: Culicidae) in the host-seeking stage were released and video recorded in three dimensions in a large field wind tunnel as they flew to four kinds of CO2-baited mosquito traps. The trapping efficiency (number of mosquitoes approaching compared to the number caught) was determined for each trap type. The Encephalitis Virus Surveillance (EVS), Mosquito Magnet Freedom (MMF) and Mosquito Magnet Liberty (MML) traps captured only 13-16% of approaching Cx. quinquefasciatus females, whereas the Mosquito Magnet-X (MMX) trap captured 58%. Similar results were obtained for Cx. tarsalis. Orientation behaviour and flight parameters of mosquitoes approaching the four traps were compared. Mosquitoes spent the most time orienting to the EVS trap. Flight speed decreased as mosquitoes entered the vicinity of each trap and a large portion of their time was spent within 30 cm downwind of the traps. Flights became highly tortuous downwind of the poorly performing traps and just upwind of the MMX trap. Differences between traps and possible explanations for the superior performance of the MMX trap are considered.
ChemInform Abstract: Synthesis of Insecticidally Active Halofenozide‐[(acyloxy)alkoxy]carbonyl and (Acyloxy)alkyl Derivatives. (2002)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Differences between mammalian ventral and dorsal spinal roots in response to blockade of potassium channels during maturation (1985)

Differences in potassium channel organization between motor and sensory fibres have been described in amphibians but have not previously been examined in mammals. In the present investigation, we studied whole nerve and single axon responses following pharmacological blockade of potassium conductance in rat ventral and dorsal spinal roots during maturation. Our results indicate a differential sensitivity in maturing mammalian motor and sensory fibres which is most apparent in younger roots. Specifically, application of 4-aminopyridine (4-AP) results in a broadening of the compound action potential in ventral roots which is associated with a delayed repolarization of the individual action potential of single fibres. In contrast, blockade of potassium channels in young dorsal roots results in a late negativity in the compound response which is correlated with multispike bursting activity recorded from single sensory fibres. The effects of 4-AP on ventral root fibres diminish earlier in the course of maturation than do the effects of 4-AP in dorsal root fibres. These results demonstrate developmental differences in the functional organization of potassium channels in mammalian motor and sensory axons which may have implications for differences in coding properties between these two classes of axons.
Otoferlin is a calcium sensor that directly regulates SNARE-mediated membrane fusion (2010)

Otoferlin is a large multi-C2 domain protein proposed to act as a calcium sensor that regulates synaptic vesicle exocytosis in cochlear hair cells. Although mutations in otoferlin have been associated with deafness, its contribution to neurotransmitter release is unresolved. Using recombinant proteins, we demonstrate that five of the six C2 domains of otoferlin sense calcium with apparent dissociation constants that ranged from 13-25 µM; in the presence of membranes, these apparent affinities increase by up to sevenfold. Using a reconstituted membrane fusion assay, we found that five of the six C2 domains of otoferlin stimulate membrane fusion in a calcium-dependent manner. We also demonstrate that a calcium binding-deficient form of the C2C domain is incapable of stimulating membrane fusion, further underscoring the importance of calcium for the protein's function. These results demonstrate for the first time that otoferlin is a calcium sensor that can directly regulate soluble N-ethyl-maleimide sensitive fusion protein attachment protein receptor-mediated membrane fusion reactions.
Analysis of Protein–Protein Interactions Utilizing Dual Bait Yeast Two-Hybrid System (2004)

To characterize a protein's function, it is often advantageous to identify other proteins with which it interacts. The yeast two-hybrid system is one of the most versatile methods available for detection and characterization of protein-protein interactions, and in the recent years it has become a mature and robust technology. A further improvement to this technique is the ability to examine and distinguish more than one interaction simultaneously. This is achieved in the Dual Bait, which has successfully been used to detect proteins and peptides that target specific motifs in larger proteins, to facilitate rapid identification of specific interactors from a pool of putative interacting proteins obtained in a library screen, and to score specific drug-mediated disruption of protein-protein interaction.
Activation and Inhibition of Cellular Calcium and Tyrosine Kinase Signaling Pathways Identify Targets of the HBx Protein Involved in Hepatitis B Virus Replication (2003)

Human hepatitis B virus (HBV) HBx protein is a multifunctional protein that activates cellular signaling pathways and is thought to be essential for viral infection. Woodchuck HBV mutants that lack HBx are unable to replicate in vivo or are severely impaired. HBV replication in HepG2 cells, a human hepatoblastoma cell line, is stimulated 5- to 10-fold by HBx protein. We have utilized the HepG2, HBx-dependent HBV replication system to study the effects of activators and inhibitors of cytosolic calcium and tyrosine kinase signaling pathways on viral replication. By transfecting either a wild-type HBV genome or an HBV genome that does not express HBx and then treating transfected cells with activators or inhibitors of signaling pathways, we identified compounds that either impair wild-type HBV replication or rescue HBx-deficient HBV replication. Geldanamycin or herbimycin A, tyrosine kinase inhibitors, blocked HBV replication. Derivatives of cyclosporine, i.e., cyclosporine A, cyclosporine H, and SDZ NIM811, which block cytosolic calcium signaling and specifically the mitochondrial permeability transition pore (SDZ NIM811), also impaired HBV replication. Treatment of cells with compounds that increase cytosolic calcium levels by a variety of mechanisms rescued replication of an HBx-deficient HBV mutant. Transcription of viral RNA and production of viral capsids were only minimally affected by these treatments. These results define a functional signaling circuit for HBV replication that includes calcium signaling and activation of cytosolic signaling pathways involving Src kinases, and they suggest that these pathways are stimulated by HBx acting on the mitochondrial transition pore.
Molecular defect (Gla+14----Lys) and its functional consequences in a hereditary factor X deficiency (factor X "Vorarlberg"). (1990)

Factor X (FX) "Vorarlberg" is a congenital FX deficiency characterized clinically by a mild bleeding tendency. Homozygous individuals have a FX activity of less than 10% in the extrinsic system and 25% in the intrinsic system. FX antigen is 20%. Using molecular techniques, two point mutations were detected in the coding sequence of the FX Vorarlberg gene: a G----A at base pair 160 in exon II resulting in a change of Gla14 (GAA) to Lys (AAA); a G----A at base pair 424 in exon V resulting in a change from Glu102 (GAG) to Lys (AAG). The mutations abolished a TaqI restriction site in exon II and an MnlI site in exon V. To determine whether these mutations are present on one or on both alleles, restriction analyses of amplified exon II and exon V fragments were performed. Analysis of the pedigree showed that the genotype for the mutation on exon II (homozygous versus heterozygous) correlates with the severity of the phenotypic coagulation defect. We therefore conclude that the mutation in exon II is responsible for the functional defect in FX Vorarlberg. We have also purified the mutant FX protein from patient plasma. Purified FX Vorarlberg is indistinguishable from normal FX on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Its activity is 15% of normal FX upon activation with factor VIIa/tissue factor, 75% upon activation with factor IXa/factor VIIIa, and 100% upon activation with RVV. Activation at varying Ca2+ concentrations shows that the affinity of FX Vorarlberg for Ca2+ is decreased. Factor Xa Vorarlberg is able to convert prothrombin at a normal rate but also shows decreased affinity for Ca2+ in this interaction. Upon addition of Ca2+, FX Vorarlberg does not undergo the same conformational change as normal FX. Our data show that FX Vorarlberg has a decreased affinity for Ca2+ which impedes a normal conformational change. This leads to a decreased rate of activation by factor VIIa/tissue factor and by factor IXa. The decrease is much more marked for the extrinsic than for the intrinsic pathway.
Accurate interferometric retardance measurements (1997)

A two-polarization Michelson interferometer with a low-retardance beam splitter and digital signal processing is used to measure the retardance of optical devices. Error analysis of the improved optical system and data processing shows that the measurement has an uncertainty of 0.039 degrees for measurements of nominally 90 degrees retarders. Retardance variations arising from coherent reflections in the retarder used for intercomparison add an uncertainty of from 0.005 degrees to 0.03 degrees , increasing the combined measurement uncertainty to as much as 0.049 degrees .
Isolation and expression of the gene encoding yeast mitochondrial malate dehydrogenase (1987)

The mitochondrial tricarboxylic acid cycle enzyme malate dehydrogenase was purified from Saccharomyces cerevisiae, and an antibody to the purified enzyme was obtained in rabbits. Immunoscreening of a yeast genomic DNA library cloned into a lambda gt11 expression vector with anti-malate dehydrogenase immunoglobulin G resulted in identification of a lambda recombinant encoding an immunoreactive beta-galactosidase fusion protein. The yeast DNA portion of the coding region for the fusion protein translates into an amino acid sequence which is very similar to carboxy-terminal sequences of malate dehydrogenases from other organisms. In s. cerevisiae transformed with a multicopy plasmid carrying the complete malate dehydrogenase gene, the specific activity and immunoreactivity of the mitochondrial isozyme are increased by eightfold. Expression of both the chromosomal and plasmid-borne genes is repressed by growth on glucose. Disruption of the chromosomal malate dehydrogenase gene in haploid S. cerevisiae produces mutants unable to grow on acetate and impaired in growth on glycerol plus lactate as carbon sources.
Sensory Habituation of Auditory Receptor Neurons: Implications for Sound Localization (2000)

Auditory receptor neurons exhibit sensory habituation; their responses decline with repeated stimulation. We studied the effects of sensory habituation on the neural encoding of sound localization cues using crickets as a model system. In crickets, Teleogryllus oceanicus, sound localization is based on binaural comparison of stimulus intensity. There are two potential codes at the receptor-neuron level for interaural intensity difference: interaural difference in response strength, i.e. spike rate and/or count, and interaural difference in response latency. These are affected differently by sensory habituation. When crickets are stimulated with cricket-song-like trains of sound pulses, response strength declines for successive pulses in the train, and the decrease becomes more pronounced as the stimulus intensity increases. Response decrement is thus greater for receptors serving the ear ipsilateral to the sound source, where intensity is higher, resulting in a decrease in the interaural difference in response strength. Sensory habituation also affects response latency, which increases for responses to successive sound pulses in the stimulus train. The change in latency is independent of intensity, and thus is similar for receptors serving both ears. As a result, interaural latency difference is unaffected by sensory habituation and may be a more reliable cue for sound localization.