gebhart/patrepeval huggingface dataset:
NTRK1 gene fusions as a novel oncogene target in lung cancer. (2013)

8023 Background: The identification and therapeutic targeting of oncogenic drivers in lung adenocarcinoma has led to significant clinical improvements for patients with EGFR mutations or ALK fusions. However, many lung cancer patients do not yet have an identified oncogenic driver and the discovery of new actionable oncogenic drivers is thus an active area of investigation. Methods: Tumor samples from 36 ‘pan-negative’ (EGFR, KRAS, ALK, and ROS1) lung adenocarcinoma patients were analyzed using a next generation sequencing (NGS) test performed in a CLIA-certified lab (Foundation Medicine, Cambridge, MA). Fluorescence in situ hybridization (FISH) screening using a novel NTRK1 break-apart assay was performed on an additional 61 pan-negative samples. Cells expressing the novel NTRK1 fusions were assayed for transformation and pharmacologic inhibition. Results: Two tumor samples were identified with gene fusions containing the kinase domain of TrkA, encoded by NTRK1, including one each with an MPRIP-NTRK1 (M21;N14) and CD74-NTRK1 (C8;N12) fusion. RT-PCR confirmed mRNA expression and identity of the fusion partner and FISH analysis detected split 5’/3’ signals corresponding to the NTRK1 gene. A third sample was identified by FISH analysis. Cloning and expression of MPRIP- and CD74-NTRK1 into NIH3T3 and Ba/F3 cells show constitutive activation of the TrkA kinase domain and transformation. Treatment of cells expressing NTRK1 fusions with several candidate pan-Trk inhibitors (ARRY-772, -523, and -470) as well as CEP-701 and crizotinib demonstrate decreased phosphorylation of the fusion oncoprotein and inhibition of cell proliferation. Treatment of the index patient harboring the MPRIP-NTRK1fusion with crizotinib led to minor transient tumor shrinkage. Conclusions: We identified a novel class of oncogenes, NTRK1 fusions, in lung adenocarcinomas that can be detected by NGS or FISH. Additional studies to determine the frequency and characteristics of NTRK1 fusions in lung cancer are ongoing. Our findings suggest prospective clinical trials of Trk inhibitors in NTRK1 fusion positive patients may be warranted. Support: CO Bioscience Discovery and Evaluation Grant and CO Clinical and Translational Sciences Institute Grant.
Captopril induces correction of postrenal transplant erythremia (1990)

Abstract. Kidney transplant patients may develop post-transplant erythremia (PTE), and in order to avoid thromboembolism venesection, anticoagulation and native kidney removal have been suggested. We propose captopril as an alternative therapy for PTE. Seven hypertensive PTE patients, aged 42 10 years with stable renal function, were investigated to exclude primary or secondary polycythemia. All patients manifested true erythrocytosis [red blood cells (RBC) mass > 20% of predicted level] with concomitant increases in hematocrit and hemoglobin levels. Captopril was introduced in gradually increasing doses up to 75 mg/day under careful monitoring of blood pressure and renal function. Weekly follow-up was arranged to evaluate drug efficacy. After captopril, a significant reduction with normalization of the RBC mass (42 4 vs 31 5 ml/kg; P < 0. 005) was observed. The RBC counts and hematocrit and hemoglobin levels also decreased. One patient had recurrent erythrocytosis after captopril withdrawal. Captopril may be a simple, effective, and non aggressive treatment for postrenal transplant erythremia.
The effect of trimethoprim on CYP2C8 mediated rosiglitazone metabolism in human liver microsomes and healthy subjects (2004)

These results indicate that trimethoprim is a competitive inhibitor of CYP2C8-mediated rosiglitazone metabolism in vitro and that trimethoprim administration increases plasma rosiglitazone concentrations in healthy subjects.
SQUIDs for nondestructive evaluation (1997)

We attempt a comprehensive review of all published research in nondestructive evaluation (NDE) performed with the superconducting quantum interference device (SQUID) magnetometer since the first work was reported in the mid-1980s. The SQUID is the most sensitive detector of magnetic flux known. The energy sensitivity of the SQUID may make it the most sensitive detector of any kind. The research on SQUIDs for NDE is based on the promise of that sensitivity and on the various other desirable properties developed for SQUID instrumentation in biomagnetism and other fields. The sensitivity of SQUID instruments down to very low frequencies allows them to function as eddy-current sensors with unparalleled depth resolution, and to image the static magnetization of paramagnetic materials and the flow of near-dc corrosion currents. The wide dynamic range of the SQUID makes it possible to image defects in steel structures and to measure the magnetomechanical behaviour of ferromagnetic materials with high sensitivity. In the last decade SQUID instrumentation designed specifically for NDE has appeared and improved the spatial resolution of most work to roughly 1 mm, with promise of another order of magnitude improvement within the next five years. Algorithms for flaw detection and image deconvolution have begun to flourish. With many talented, industrious people in the field, the future of SQUID NDE looks bright, provided the crucial first niche can be found.
Structural Organization of A Multifunctional Polyketide Synthase Involved in the Biosynthesis of the Macrolide Immunosuppressant FK506 (1997)

The immunosuppressant FK506 is a 23-membered macrocyclic polyketide produced by several Streptomyces species. Sequencing of a 19.5-kb contiguous segment of DNA from the FK506 gene cluster of Streptomyces sp. MA6548 revealed the presence of a single 19.3-kb open reading frame designated fkbA. fkbA encodes a component of the FK506 polyketide synthase, a complex enzyme system which catalyzes synthesis of the polyketide portion of FK506. The predicted product of gene fkbA is a 630,660-Da protein (6420 amino acids) that contains 19 independent domains with a high degree of amino acid sequence similarity to the catalytic activities of known fatty acid synthases. The identified domains are arranged into four repeated modules with a linear organization precisely as that of animal fatty acid synthase and type I polyketide synthase. Each module participates in one round of chain extension and subsequent processing and thus FkbA polypeptide catalyzes four of the ten condensation steps required for synthesis of the FK506 macrolactone ring. Disruption of fkbA results in the generation of an FK506 non-producing mutant demonstrating direct involvement of fkbA in the biosynthesis of FK506.
Optical Design of Waveguide Holographic Binocular Display for Machine Vision (2013)

A binocular display can satisfy competition mechanism of biological vision system and improve display precision. A binocular optical system is designed with waveguide holography (WGH) for small size and light weight. A superimposed holographic volume grating can split the image bearing lights into two equal intensity light beams. The out-coupling waveguide holographic gratings for the left and right eyes can implement image extension and imaging display. The simulation and experimental results reveal that excellent optical performances can be achieved for little distortion of less than 0.05%(nearly zero), light weight of about only 32g, and compact size. The display information can also be overlaid the outside scenes in eyeglass augmented reality and Machine Vision Display applications.
Advanced driver assistance systems information management and presentation (2004)

With the development of advanced driving assistance systems, in-vehicle&#13;\ncommunication and information systems, there are situations where the driver&#13;\nbecomes overloaded by information, creating potentially dangerous conditions.&#13;\nIn this Thesis a novel strategy is proposed, to prioritise and present&#13;\ninformation.&#13;\nFirstly two main criteria are extracted, that allow the ability to rank&#13;\nmessages: the risk associated with the non-presentation of the message, and&#13;\nits relevance to the environment. Fuzzy cognitive maps enable to represent&#13;\nexpert knowledge and model these relationships.&#13;\nSecondly, a strategy to present information is proposed. Using an importance&#13;\nindex, calculated from the previous risk and relevance indices, but&#13;\nalso information nature, time constraints and access frequency, a set of best&#13;\ninterfaces is selected. Furthermore design a model of driver workload is designed,&#13;\nbased on the multiple resources theory. By estimating in real time&#13;\nthe workload of the driver, the system enables to choose an optimal interface,&#13;\nthat should prevent overload.&#13;\nThis Thesis presents then the tools developed for the implementation and&#13;\ntesting of the model. A video capture and data transfer program, based on&#13;\nthe IEEE-1394 bus, enable in-vehicle real-time data capture and collection.&#13;\nMoreover, a software package for replay of the acquired data, analysis and&#13;\nsimulation is developed. Finally, the implementation of the prioritisation and&#13;\npresentation strategy is outlined.&#13;\nThe last part of this work is dedicated to the experiments and results.&#13;\nUsing an experimental vehicle, data in different driving conditions are collected.&#13;\nthe experiment is completed by creating data to simulate potentially&#13;\ndangerous situations, where driver is overloaded with information. The results show that the information management and presentation system is able&#13;\nto prevent overload in most conditions. Its structure and design allow to&#13;\nincorporate expert knowledge to refine the classification.
Copper-free click chemistry in living animals (2010)

Chemical reactions that enable selective biomolecule labeling in living organisms offer a means to probe biological processes in vivo. Very few reactions possess the requisite bioorthogonality, and, among these, only the Staudinger ligation between azides and triarylphosphines has been employed for direct covalent modification of biomolecules with probes in the mouse, an important model organism for studies of human disease. Here we explore an alternative bioorthogonal reaction, the 1,3-dipolar cycloaddition of azides and cyclooctynes, also known as "Cu-free click chemistry," for labeling biomolecules in live mice. Mice were administered peracetylated N-azidoacetylmannosamine (Ac(4)ManNAz) to metabolically label cell-surface sialic acids with azides. After subsequent injection with cyclooctyne reagents, glycoconjugate labeling was observed on isolated splenocytes and in a variety of tissues including the intestines, heart, and liver, with no apparent toxicity. The cyclooctynes tested displayed various labeling efficiencies that likely reflect the combined influence of intrinsic reactivity and bioavailability. These studies establish Cu-free click chemistry as a bioorthogonal reaction that can be executed in the physiologically relevant context of a mouse.
Stable single-wavelength operation of two-section coupled-cavity lasers under modulation using feedback control (1984)

Coupled-cavity lasers have been operated in a single longitudinal mode under high-speed modulation,1 and recently cleaved versions have been used in long-distance optical fiber experiments at 1.55 μm.2 Although relatively easy to fabricate, these devices generally require carefully adjusted bias currents and an adjustable controlled temperature. To operate in a more practical environment, it is generally believed that some sort of feedback control which can adapt to environmental changes as well as to device aging will be necessary. Some initial demonstrations have been performed.3
A New Packing for Separation of DNA Restriction Fragments by High Performance Liquid Chromatography (1984)

TSK-GEL SW was found to be useful as a packing in high performance liquid chromatography for the separation of double-stranded DNA restriction fragments. DNA fragments smaller than 300 base pairs were separated as discrete peaks depending solely upon difference in chain length. The recovery of DNA fragments was higher than 90%.
IL-27 Induces Th1 Differentiation via p38 MAPK/T-bet- and Intercellular Adhesion Molecule-1/LFA-1/ERK1/2-Dependent Pathways (2006)

IL-27, a novel member of the IL-6/IL-12 family, activates both STAT1 and STAT3 through its receptor, which consists of WSX-1 and gp130 subunits, resulting in positive and negative regulations of immune responses. We recently demonstrated that IL-27 induces Th1 differentiation through ICAM-1/LFA-1 interaction in a STAT1-dependent, but T-bet-independent mechanism. In this study, we further investigated the molecular mechanisms by focusing on p38 MAPK and ERK1/2. IL-27-induced Th1 differentiation was partially inhibited by lack of T-bet expression or by blocking ICAM-1/LFA-1 interaction with anti-ICAM-1 and/or anti-LFA-1, and further inhibited by both. Similarly, the p38 MAPK inhibitor, SB203580, or the inhibitor of ERK1/2 phosphorylation, PD98059, partially suppressed IL-27-induced Th1 differentiation and the combined treatment completely suppressed it. p38 MAPK was then revealed to be located upstream of T-bet, and SB203580, but not PD98059, inhibited T-bet-dependent Th1 differentiation. In contrast, ERK1/2 was shown to be located downstream of ICAM-1/LFA-1, and PD98059, but not SB203580, inhibited ICAM-1/LFA-1-dependent Th1 differentiation. Furthermore, it was demonstrated that STAT1 is important for IL-27-induced activation of ERK1/2, but not p38 MAPK, and that IL-27 directly induces mRNA expression of growth arrest and DNA damage-inducible 45gamma, which is known to mediate activation of p38 MAPK. Finally, IL-12Rbeta2 expression was shown to be up-regulated by IL-27 in both T-bet- and ICAM-1/LFA-1-dependent mechanisms. Taken together, these results suggest that IL-27 induces Th1 differentiation via two distinct pathways, p38 MAPK/T-bet- and ICAM-1/LFA-1/ERK1/2-dependent pathways. This is in contrast to IL-12, which induces it via only p38 MAPK/T-bet-dependent pathway.
Calibration and de-embedding of microwave measurements using any combination of one- or two-port standards (1987)

The study is made of the determination of the error two-ports in microwave and millimeter-wave measurements using known calibration standards. New explicit equations (CCC) have been derived which allow the use of any combination of standards described with their S-parameters. For singularity reasons different equations are needed depending on the type of the standards. The question of how many standards are really needed is also studied. According to the results, three are needed, no matter if they are one- or two-ports and reciprocal or not. There is, however, a description of a new method (TC) that uses only two standards as far as the symmetrical measurement fixture is concerned. A method is shown to use redundant equations to reduce the errors in over-determined problems. For convenience the de-embedding of the device under test is also shown. Except the last case, no general purpose equations have been found in the existing literature. The methods have been tested with...
Distinct B-Cell and T-Cell Lymphoproliferative Disease Prevalence among Dog Breeds Indicates Heritable Risk (2005)

Immunophenotypes in lymphoproliferative diseases (LPD) are prognostically significant, yet causative factors for these conditions, and specifically those associated with heritable risk, remain elusive. The full spectrum of LPD seen in humans occurs in dogs, but the incidence and lifetime risk of naturally occurring LPD differs among dog breeds. Taking advantage of the limited genetic heterogeneity that exists within dog breeds, we tested the hypothesis that the prevalence of LPD immunophenotypes would differ among different breeds. The sample population included 1,263 dogs representing 87 breeds. Immunophenotype was determined by the presence of clonal rearrangements of immunoglobulin heavy chain or T-cell receptor gamma chain. The probability of observing the number of B-cell or T-cell tumors in a particular breed or breed group was compared with three reference populations. Significance was computed using chi2 test, and logistic regression was used to confirm binomial predictions. The data show that, among 87 breeds tested, 15 showed significant differences from the prevalence of LPD immunophenotypes seen across the dog population as a whole. More significantly, elevated risk for T-cell LPD seems to have arisen ancestrally and is retained in related breed groups, whereas increased risk for B-cell disease may stem from different risk factors, or combinations of risk factors, arising during the process of breed derivation and selection. The data show that domestic dogs provide a unique and valuable resource to define factors that mediate risk as well as genes involved in the initiation of B-cell and T-cell LPD.
Nickel and Iron Pincer Complexes as Catalysts for the Reduction of Carbonyl Compounds (2015)

The reductions of aldehydes, ketones, and esters to alcohols are important processes for the synthesis of chemicals that are vital to our daily life, and the reduction of CO2 to methanol is expected to provide key technology for carbon management and energy storage in our future. Catalysts that affect the reduction of carbonyl compounds often contain ruthenium, osmium, or other precious metals. The high and fluctuating price, and the limited availability of these metals, calls for efforts to develop catalysts based on more abundant and less expensive first-row transition metals, such as nickel and iron. The challenge, however, is to identify ligand systems that can increase the thermal stability of the catalysts, enhance their reactivity, and bypass the one-electron pathways that are commonly observed for first-row transition metal complexes. Although many other strategies exist, this Account describes how we have utilized pincer ligands along with other ancillary ligands to accomplish these goals. The bis(phosphinite)-based pincer ligands (also known as POCOP-pincer ligands) create well-defined nickel hydride complexes as efficient catalysts for the hydrosilylation of aldehydes and ketones and the hydroboration of CO2 to methanol derivatives. The hydride ligands in these complexes are substantially nucleophilic, largely due to the enhancement by the strongly trans-influencing aryl groups. Under the same principle, the pincer-ligated nickel cyanomethyl complexes exhibit remarkably high activity (turnover numbers up to 82,000) for catalytically activating acetonitrile and the addition of H-CH2CN across the C═O bonds of aldehydes without requiring a base additive. Cyclometalation of bis(phosphinite)-based pincer ligands with low-valent iron species "Fe(PR3)4" results in diamagnetic Fe(II) hydride complexes, which are active catalysts for the hydrosilylation of aldehydes and ketones. Mechanistic investigation suggests that the hydride ligand is not delivered to the carbonyl substrates but is important to facilitate ligand dissociation prior to substrate activation. In the presence of CO, the amine-bis(phosphine)-based pincer ligands are also able to stabilize low-spin Fe(II) species. Iron dihydride complexes supported by these ligands are bifunctional as both the FeH and NH moieties participate in the reduction of C═O bonds. These iron pincer complexes are among the first iron-based catalysts for the hydrogenation of esters, including fatty acid methyl esters, which find broad applications in industry. Our studies demonstrate that pincer ligands are promising candidates for promoting the first-row transition metal-catalyzed reduction of carbonyl compounds with high efficiency. Further efforts in this research area are likely to lead to more efficient and practical catalysts.
DCDT2980S, an Anti-CD22-Monomethyl Auristatin E Antibody–Drug Conjugate, Is a Potential Treatment for Non-Hodgkin Lymphoma (2013)

Antibody-drug conjugates (ADC), potent cytotoxic drugs linked to antibodies via chemical linkers, allow specific targeting of drugs to neoplastic cells. We have used this technology to develop the ADC DCDT2980S that targets CD22, an antigen with expression limited to B cells and the vast majority of non-Hodgkin lymphomas (NHL). DCDT2980S consists of a humanized anti-CD22 monoclonal IgG1 antibody with a potent microtubule-disrupting agent, monomethyl auristatin E (MMAE), linked to the reduced cysteines of the antibody via a protease cleavable linker, maleimidocaproyl-valine-citrulline-p-aminobenzoyloxycarbonyl (MC-vc-PAB). We describe the efficacy, safety, and pharmacokinetics of DCDT2980S in animal models to assess its potential as a therapeutic for the treatment of B-cell malignancies. We did not find a strong correlation between in vitro or in vivo efficacy and CD22 surface expression, nor a correlation of sensitivity to free drug and in vitro potency. We show that DCDT2980S was capable of inducing complete tumor regression in xenograft mouse models of NHL and can be more effective than rituximab plus combination chemotherapy at drug exposures that were well tolerated in cynomolgus monkeys. These results suggest that DCDT2980S has an efficacy, safety, and pharmacokinetics profile that support potential treatment of NHL.
Induction by RNA of inositol independence in Neurospora crassa. (1975)

The effect of purified wild-type RNA (allo-RNA) on genetic reversion of inositol-requiring mutant 89601 of Neurospora crassa is described. The mutant (inos minus) strain, on treatment with the wild-type RNA preparation, was found to revert to wild type (inos+) in significant numbers. RNA from the mutant (iso-RNA) and allo-RNA digested by RNase were ineffective in causing genetic reversion at the inositol locus. The allo-RNA-induced revertants were stable and showed a Mendelian transmission of the inos+ character.
Modeling SRAM start-up behavior for Physical Unclonable Functions (2012)

One of the emerging technologies for cryptographic key storage is hardware intrinsic security based on Physical Unclonable Functions (PUFs); a PUF is a physical structure of a device that is hard to clone due to its inherent, device-unique and deep-submicron process variations. SRAM PUF is an example of such technology that is becoming popular. So far, only a little is published about modeling and analysis of their start-up values (SUVs). Reproducing the same start-up behavior every time the chip is powered-on is crucial to produce the same cryptographic key. This paper presents an analytical model for SUVs of an SRAM PUF based on Static Noise Margin (SNM), and reports some industrial measurements to validate the model. Simulation of the impact of different sensitivity parameters (such as variation in power supply, temperature, transistor geometry) has been performed. The results show that out of all sensitivity parameters, variation in threshold voltage is the one with the highest impact. Industrial measurements on real memory devices validate the simulation results.