gebhart/patrepeval huggingface dataset:
Genetics of eukaryotic RNA polymerases I, II, and III (1993)

The transcription of nucleus-encoded genes in eukaryotes is performed by three distinct RNA polymerases termed I, II, and III, each of which is a complex enzyme composed of more than 10 subunits. The isolation of genes encoding subunits of eukaryotic RNA polymerases from a wide spectrum of organisms has confirmed previous biochemical and immunological data indicating that all three enzymes are closely related in structures that have been conserved in evolution. Each RNA polymerase is an enzyme complex composed of two large subunits that are homologous to the two largest subunits of prokaryotic RNA polymerases and are associated with smaller polypeptides, some of which are common to two or to all three eukaryotic enzymes. This remarkable conservation of structure most probably underlies a conservation of function and emphasizes the likelihood that information gained from the study of RNA polymerases from one organism will be applicable to others. The recent isolation of many mutations affecting the structure and/or function of eukaryotic and prokaryotic RNA polymerases now makes it feasible to begin integrating genetic and biochemical information from various species in order to develop a picture of these enzymes. The picture of eukaryotic RNA polymerases depicted in this article emphasizes the role(s) of different polypeptide regions in interaction with other subunits, cofactors, substrates, inhibitors, or accessory transcription factors, as well as the requirement for these interactions in transcription initiation, elongation, pausing, termination, and/or enzyme assembly. Most mutations described here have been isolated in eukaryotic organisms that have well-developed experimental genetic systems as well as amenable biochemistry, such as Saccharomyces cerevisiae, Drosophila melanogaster, and Caenorhabditis elegans. When relevant, mutations affecting regions of Escherichia coli RNA polymerase that are conserved among eukaryotes and prokaryotes are also presented. In addition to providing information about the structure and function of eukaryotic RNA polymerases, the study of mutations and of the pleiotropic phenotypes they imposed has underscored the central role played by these enzymes in many fundamental processes such as development and cellular differentiation.
Multifunctional biohybrid magnetite microrobots for imaging-guided therapy (2017)

Magnetic microrobots and nanorobots can be remotely controlled to propel in complex biological fluids with high precision by using magnetic fields. Their potential for controlled navigation in hard-to-reach cavities of the human body makes them promising miniaturized robotic tools to diagnose and treat diseases in a minimally invasive manner. However, critical issues, such as motion tracking, biocompatibility, biodegradation, and diagnostic/therapeutic effects, need to be resolved to allow preclinical in vivo development and clinical trials. We report biohybrid magnetic robots endowed with multifunctional capabilities by integrating desired structural and functional attributes from a biological matrix and an engineered coating. Helical microswimmers were fabricated from <i>Spirulina</i> microalgae via a facile dip-coating process in magnetite (Fe<sub>3</sub>O<sub>4</sub>) suspensions, superparamagnetic, and equipped with robust navigation capability in various biofluids. The innate properties of the microalgae allowed in vivo fluorescence imaging and remote diagnostic sensing without the need for any surface modification. Furthermore, in vivo magnetic resonance imaging tracked a swarm of microswimmers inside rodent stomachs, a deep organ where fluorescence-based imaging ceased to work because of its penetration limitation. Meanwhile, the microswimmers were able to degrade and exhibited selective cytotoxicity to cancer cell lines, subject to the thickness of the Fe<sub>3</sub>O<sub>4</sub> coating, which could be tailored via the dip-coating process. The biohybrid microrobots reported herein represent a microrobotic platform that could be further developed for in vivo imaging-guided therapy and a proof of concept for the engineering of multifunctional microrobotic and nanorobotic devices.
Modification of the pitch of chiral nematic liquid crystals by means of photoisomerization of chiral dopants (1998)

New photoisomerizable chiral dopants have been studied. The dopants used were menthone derivatives, a chiral stilbene derivative and a nematic copolymer of a menthone derivative and a benzoyloxybenzonitrile derivative. NMR, HPLC and UV results showed that the E-Z-isomerization of all the compounds indicated proceeded rapidly upon UV exposure, without the formation of undesired by-products. Isomerization of the menthone derivatives, including the copolymer, induced a substantial decrease in the helical twisting power. The changes in helical twisting power induced by the isomerization of the chiral stilbene derivative were limited to a factor of 2. In mixtures of the photoisomerizable dopants with commercial dopants of opposite twisting senses and a nematic host mixture, the sign of the twisting sense could be reversed by illuminating the mixture with UV light. The viewing angle dependence of irradiated regions of a 90 -twisted nematic cell was rotated 90 with respect to the viewing angle dependence of the non-irradiated regions. It is expected that this approach may be useful in the preparation of dual domain TN cells with a reduced viewing angle dependence.
ChemInform Abstract: CYCLIC ANALOGS OF ETHAMBUTOL HAVING ANTIMYCOBACTERIAL ACTIVITY (1983)

Abstract Cyclopenta‐ ‐ non‐carbonsäureester (I) reagiert über sein Kaliumsalz (II) mit Methyliodid zum Keton (III), aus dem man über das Oxim (IV) den Amino‐ester (V) erhält.
A Phase I Study of Adenovirus-Mediated Transfer of the Human Cystic Fibrosis Transmembrane Conductance Regulator Gene to a Lung Segment of Individuals with Cystic Fibrosis (1999)

A third-generation adenoviral vector containing recombinant human cystic fibrosis transmembrane conductance regulator (CFTR) gene was delivered by bronchoscope in escalating doses to the conducting airway of 11 volunteers with cystic fibrosis. Assessments of dose-limiting toxicity (DLT), efficiency of gene transfer, and cell-mediated and humoral immune responses to vector administration were performed. DLT, manifest by flulike symptoms and transient radiographic infiltrates, was seen at 2.1 x 10(11) total viral particles. A highly specific assay for gene transfer was developed using in situ hybridization with an oligoprobe against unique vector sequence. Detectable gene transfer was observed in harvested bronchial epithelial cells (<1%) 4 days after vector instillation, which diminished to undetectable levels by day 43. Adenovirus-specific cell-mediated T cells were induced in most subjects, although only mild increases in systemic humoral immune response were observed. These results demonstrate that gene transfer to epithelium of the lower respiratory tract can be achieved in humans with adenoviral vectors but that efficiency is low and of short duration in the native CF airway.
Fluorogenic Peptide‐Based Substrates for Monitoring Thrombin Activity (2012)

The synthesis of a series of peptides containing C-terminal 7-amino-4-methylcoumarin (AMC) for use in the thrombin generation test (TGT) is described. The lead structure in this project was H-Gly-Gly-Arg-AMC, of which the water solubility and kinetic parameters (K(M) and k(cat)) are greatly improved over those of the substrate in current use in the TGT: Cbz-Gly-Gly-Arg-AMC. A series of N-terminally substituted Gly-Gly-Arg-AMC derivatives were synthesized, as well as implementation of structural changes at either the P(2) or P(3) position of the peptide backbone. Furthermore, two substrates were synthesized that have structural similarities to the chromogenic thrombin substrate SQ68 or that contain a 1,2,3-triazole moiety in the peptide chain, mimicking an amide bond. To determine the applicability of newly synthesized fluorogenic substrates for monitoring continuous thrombin generation, the K(M) and k(cat) values of the conversion of these fluorogenic substrates by thrombin (FIIa) and factor Xa (FXa) were quantified. An initial selection was made on basis of these data, and suitable substrates were further evaluated as substrates in the thrombin generation assay. Assessment of the acquired data showed that several substrates, including the SQ68 derivative Et-malonate-Gly-Arg-AMC and N-functionalized Gly-Gly-Arg-AMC derivatives, are suitable candidates for replacement of the substrate currently in use.
Epigenetic silencing of neurofilament genes promotes an aggressive phenotype in breast cancer (2015)

Neurofilament heavy polypeptide (NEFH) has recently been identified as a candidate DNA hypermethylated gene within the functional breast cancer hypermethylome. NEFH exists in a complex with neurofilament medium polypeptide (NEFM) and neurofilament light polypeptide (NEFL) to form neurofilaments, which are structural components of the cytoskeleton in mature neurons. Recent studies reported the deregulation of these proteins in several malignancies, suggesting that neurofilaments may have a role in other cell types as well. Using a comprehensive approach, we studied the epigenetic inactivation of neurofilament genes in breast cancer and the functional significance of this event. We report that DNA methylation-associated silencing of NEFH, NEFL, and NEFM in breast cancer is frequent, cancer-specific, and correlates with clinical features of disease progression. DNA methylation-mediated inactivation of these genes occurs also in multiple other cancer histologies including pancreas, gastric, and colon. Restoration of NEFH function, the major subunit of the neurofilament complex, reduces proliferation and growth of breast cancer cells and arrests them in Go/G1 phase of the cell cycle along with a reduction in migration and invasion. These findings suggest that DNA methylation-mediated silencing of the neurofilament genes NEFH, NEFM, and NEFL are frequent events that may contribute to the progression of breast cancer and possibly other malignancies.
Adoptive immunotherapy of ovarian carcinoma with bs-MAb-targeted lymphocytes: a multicenter study. (1992)

A bispecific monoclonal antibody (bs-MAb) (OC/TR) was produced in large quantities for the intraperitoneal (i.p.) treatment of ovarian cancer. The bs-MAb recognizes the folate-binding protein on ovarian cancer cells on the one hand and the CD3 activation site on T lymphocytes on the other. T lymphocytes were expanded ex vivo, targeted with OC/TR in vitro and administered to the i.p. cavity in the presence of soluble OC/TR. All patients developed human anti-mouse-antibodies (HAMA). In the Dutch study, 2 complete remissions (CR) were seen, 2 partial regressions (PR), I stable disease (SD) and I progressive disease (PD). In the Italian study 3 CR, I PR, I SD and 2 PD were seen.
Synthesis of benzoxazoles, benzothiazoles and benzimidazoles and evaluation of their antifungal, insecticidal and herbicidal activities. (1982)

Benzoxazoles, benzothiazoles and benzimidazoles having substituents on the azole and benzene nuclei were synthesized evaluated for antifungal, insecticidal and herbicidal activities. It was found that benzimidazoles tended to exhibit antifungal activity while benzothiazoles tended to show herbicidal activity. Chloro, trifluoromethyl, methoxy and ethoxy groups at the 5 position were potent substituents, and the 2-pyridyl group at the 2 position is a common structural unit. Among several active derivatives, 7-chloro-2-(2-pyridyl) benzimidazole and 2-(2-pyridyl)-5-trifluoromethylbenzothiazole exhibited significant activity against Panonycus citri.
CSF-1-induced resistance to viral infection in murine macrophages. (1987)

Murine peritoneal thioglycollate-elicited macrophages were cultured for 3 days in the presence or absence of highly purified human macrophage colony stimulating factor (CSF-1). The cells were then challenged with vesicular stomatitis virus (VSV) for 24 hr. Ability to resist viral infection was measured in two ways. First, macrophage viability after infection with VSV was measured by washing to remove dead cells, staining the remaining cells with crystal violet, and reading absorbance. Second, a yield reduction assay was used to measure viral replication in the macrophage cultures. Cells treated with CSF-1 (500 to 2000 U/ml) and infected with VSV looked similar microscopically to uninfected cells and had absorbance values twofold to threefold higher than those of infected cultures not treated with CSF-1. The CSF-1-treated cultures also had a virus titer one log lower than that of the untreated cultures. Treatment with partially purified murine CSF-1 induced a similar reduction in virus titer, whereas other murine CSF tested (purified murine GM-CSF, lung-conditioned medium that contains GM-CSF and G-CSF, and WEHI-3B-conditioned medium as a source of IL 3) had little to no effect on virus titer. Antibody to murine IFN-alpha/beta added to the macrophage cultures inhibited the protective effect of CSF-1, indicating that the CSF-1 effect was due to induction of endogenous IFN. Treatment with lipopolysaccharide (1 ng/ml) had some protective effect, which was blocked with polymyxin B. Polymyxin B did not inhibit the effect of CSF-1.
Effect of Active Immunization against LHRH or LH in Boars: Reproductive Consequences and Performance Traits (1986)

Forty crossbred boars were equally divided into eight groups at birth. Four groups were immunized (200 micrograms/boar) at 12 wk of age against either luteinizing hormone-releasing hormone (LHRH) conjugated to human serum globulin (LHRH-hSG) in complete Freund's adjuvant (CFA), LHRH-hSG in muramyldipeptide adjuvant (PEP), procine luteinizing hormone (LH) conjugated to hSG (pLH-hSG) in CFA or ovine LH (oLH) in CFA. Equal doses of boosters were given in either PEP or incomplete Freund's adjuvant (IFA) at 16 and 18 wk of age. Two groups of boars were immunized with either hSG + CFA or hSG + PEP (adjuvant controls). Two groups were castrated either at the time of weaning (castrate weaning) or at 16 wk when immunized boars were given their first booster injections (castrate booster). All pigs were slaughtered at 24 wk of age. Serum levels of LH and testosterone (T), LHRH or LH antibody titers, as well as testicular and accessory sex gland weights and histology were determined. By wk 16, LHRH antibody titers began to rise in those boars immunized against LHRH-hSG. Luteinizing hormone-releasing hormone antibody titers on wk 18, 20 and 22 were greater than those at wk 16. By 22 wk of age, LHRH-hSG boars had non-detectable plasma LH and T and reduced weights of testes and acessory sex glands. Boars immunized against oLH did not respond to treatment, whereas pLH-hSG boars showed a reduction in serum T levels and accessory sex gland weights. Immunization had no effect on average daily gain, hot carcass weights or loin eye area.(ABSTRACT TRUNCATED AT 250 WORDS)
Cervical magnetic stimulation: a new painless method for bilateral phrenic nerve stimulation in conscious humans (1989)

Assessing diaphragmatic contractility is a common goal in various situations. This assessment is mainly based on static or dynamic maximal voluntary maneuvers and twitch transdiaphragmatic pressures (Pdi) obtained by stimulation of the phrenic nerves (PS). PS eliminates the central components of diaphragmatic activation, but the available techniques of PS remain subject to some limitations. Transcutaneous PS is painful, and needle PS is potentially dangerous. Time-varying magnetic fields can stimulate nervous structures without pain and without adverse effects. In six subjects, we have studied cervical magnetic stimulation (CMS) as a method of PS. We have compared the stimulated Pdi (Pdistim) with the maximal Pdi obtained during static combined expulsive-Mueller maneuver (Pdimax) and with the Pdi generated during a sniff test (Pdisniff). CMS produced twitch Pdi averaging 33.4 +/- 9.7 cmH2O. Pdistim/Pdimax and Pdistim/Pdisniff were 24 +/- 6 and 41 +/- 14%, respectively. These values are comparable to those obtained in other studies with transcutaneous PS. They were highly reproducible in all the subjects. Electromyographic data provided evidence of bilateral maximal stimulation. CMS is a nonspecific method and may stimulate various nervous structures. However, diaphragmatic contraction was elicited by stimulation of the phrenic trunk, since the phrenicodiaphragmatic latencies (less than 7 ms) were in the range of values reported with direct stimulation of the trunk. Cocontraction of neck muscles, including the sternomastoid, was present, but its influence in the CMS-induced Pdi seems minimal. We conclude that magnetic stimulation is an easy, well-tolerated, reproducible safe, and valuable method to assess phrenic conduction and diaphragmatic twitch response.
Isothermal Amplification and Multimerization of DNA by Bst DNA Polymerase (2001)

We have demonstrated the isothermal in vitro amplification and multimerization of several different linear DNA targets using only two primers and the strongly strand-displacing exonuclease-negative Bst DNA polymerase. This reaction has been termed linear target isothermal multimerization and amplification (LIMA). LIMA has been compared with cascade rolling-circle amplification and has been found to be less sensitive but to yield similar variable-length multimeric dsDNA molecules. Products from several different LIMA reactions were characterized by restriction analysis and partial sequence determination. They were found to be multimers of subsets of the target sequence and were not purely primer derived. The sensitivities with respect to target concentration of several different LIMA reactions were determined, and they varied from 0.01 amol to 1 fmol. The sensitivity and specificity of LIMA were further tested using E. coli genomic DNA, and the selective amplification of a transposon fragment was demonstrated. A successful strategy for reducing LIMA-dependent background DNA synthesis in rolling-circle amplification embodiments was devised. This entailed the affinity purification of circular DNA templates before amplification.
The Polyomavirus BK Large T-Antigen-Derived Peptide Elicits an HLA-DR Promiscuous and Polyfunctional CD4+T-Cell Response (2011)

BK virus (BKV) nephropathy and hemorrhagic cystitis are increasingly recognized causes of disease in renal and hematopoietic stem cell transplant recipients, respectively. Functional characterization of the immune response to BKV is important for clinical diagnosis, prognosis, and vaccine design. A peptide mix (PepMix) and overlapping (OPP) or random (RPP) peptide pools derived from BKV large T antigen (LTA) were used to restimulate 14-day-expanded peripheral blood mononuclear cells (PBMC) from 27 healthy control subjects in gamma interferon (IFN-γ)-specific enzyme-linked immunospot (ELISPOT) assays. A T-cell response to LTA PepMix was detected in 15/27 subjects. A response was frequently observed with peptides derived from the helicase domain (9/15 subjects), while the DNA binding and host range domains were immunologically inert (0/15 subjects). For all nine subjects who responded to LTA peptide pools, the immune response could be explained largely by a 15-mer peptide designated P313. P313-specific CD4(+) T-cell clones demonstrated (i) stringent LTA peptide specificity; (ii) promiscuous recognition in the context of HLA-DR alleles; (iii) cross recognition of homologous peptides from the polyomavirus simian virus 40 (SV40); (iv) an effector memory phenotype, CD107a expression, and intracellular production of IFN-γ and tumor necrosis factor alpha (TNF-α); (v) cytotoxic activity in a chromium release assay; and (vi) the ability to directly present cognate antigen to autologous T cells. In conclusion, T-cell-mediated immunity to BKV in healthy subjects is associated with a polyfunctional population of CD4(+) T cells with dual T-helper and T-cytotoxic properties. HLA class II promiscuity in antigen presentation makes the targeted LTA peptide sequence a suitable candidate for inclusion in immunotherapy protocols.
Evolution and demands of SoC in ITS and mobile communication systems (2002)

As a center of mobile multimedia of the 21st century, we are very much looking forward to the explosion of RandD and business of the next generation of mobile communication systems and the ITS (intelligent transport systems) because ITS will enable information oriented in the field of the road, traffic and vehicles, by using the most advanced technologies of mobile communications and devices, for various purposes such as decrease of traffic accidents, reduction of traffic jams, increase in efficiency of logistics and harmony with the Earth's environment This paper first briefly introduces evolution of mobile communications and ITS in ministries, industries and academia in Japan. Then core communication technologies for ITS are overviewed, such as spread spectrum CDMA, adaptive antenna array, and software radio or software defined radio. The demands on SoC (system on a chip) to carry out the core technologies are addressed.
Novel Epitaxial Nickel Aluminide-Silicide with Low Schottky-Barrier and Series Resistance for Enhanced Performance of Dopant-Segregated Source/Drain N-channel MuGFETs (2007)

We have developed a novel epitaxial nickel-aluminide silicide (NiSi <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2-x</sub> Al <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">x</sub> ) to reduce the Schottky-Barrier height (SBH) and series resistance in n-channel MuGFETs with dopant-segregated Schottky-Barrier source/drain (DSS). 10% substitutional incorporation of Al in the Si matrix at the silicide-Si interface leads to a 37% reduction in the intrinsic SBH of nickel silicide. A further 42% effective reduction in the DSS SBH was attained with the combination of NiSi <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2-x</sub> Al <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">x</sub> and DSS technology. Saturation drive current enhancement of 94% for NiSi <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2-x</sub> Al <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">x</sub> DSS MuGFETs over NiSi DSS MuGFETs was achieved, attributed to SBH lowering, series resistance reduction and possibly silicide strain effects. As a result, an excellent drive current of 882 μA/μm at V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">GS</sub> -V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">T</sub> =V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">DS</sub> = 1.2 V was achieved for NiSi <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2-x</sub> Al <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">x</sub> DSS MuGFETs with 55 nm gate length.