gebhart/patrepeval huggingface dataset:
Design of two etoposide-amsacrine conjugates: topoisomerase II and tubuline polymerization inhibition and relation to cytotoxicity. (2000)

Topoisomerase II represents the main target for the antitumour drugs etoposide and amsacrine, which are both used clinically. Previous studies have shown that the glycoside moiety of etoposide is not necessary for cytotoxicity or DNA topoisomerase II inhibition. For this reason, we designed two epipodophyllotoxin derivatives for which the dispensable sugar moiety of etoposide has been replaced by a m-methoxy-methane-sulfonamide-anilino group analogous to the topoisomerase II-targeted domain of amsacrine. We report the synthesis of the hybrid molecules that have the epipodophyllotoxin and anilino groups directly linked (ICP-114) or connected by an ethylene spacer (ICP-147). Plasmid DNA relaxation and kinetoplast DNA decatenation assays were used to evaluate the effects of the drug on the catalytic activity of human topoisomerase II. We found that the hybrid ICP-147 was significantly more potent than both etoposide and amsacrine at stimulating DNA cleavage by the enzyme, whereas the hybrid ICP-114 lacking the linker chain was less potent. ICP-147 produces approximately 3 times more double-stranded breaks than ICP-114, suggesting that an ethylene spacer between the epipodophyllotoxin and amsacrine moieties is highly effective at inhibiting topoisomerase II. Sequencing data also supported the idea that the two moieties of ICP-147 participate to the interaction with topoisomerase II-DNA covalent complexes. Both hybrid compounds are more cytotoxic than etoposide but much less toxic than amsacrine toward L1210 leukemia cells. In addition to its effect on topoisomerase II, ICP-114 can inhibit tubulin polymerization, whereas ICP-147 is almost totally inactive in this assay. The unexpected capacity of ICP-114 to interfere with the polymerization of tubulin suggests that this compound can target tubulin dimers, as it is the case with certain antitumor sulfonamides. The design of etoposide-amsacrine hybrids may thus represent an opportunity for the discovery of dual inhibitors that target both topoisomerase II and tubulin.
The enzymatic detoxification of the mycotoxin deoxynivalenol: identification of DepA from the DON epimerization pathway (2017)

The biological detoxification of mycotoxins, including deoxynivalenol (DON), represents a very promising approach to address the challenging problem of cereal grain contamination. The recent discovery of Devosia mutans 17-2-E-8 (Devosia spp. 17-2-E-8), a bacterial isolate capable of transforming DON to the non-toxic stereoisomer 3-epi-deoxynivalenol, along with earlier reports of bacterial species capable of oxidizing DON to 3-keto-DON, has generated interest in the possible mechanism and enzyme(s) involved. An understanding of these details could pave the way for novel strategies to manage this widely present toxin. It was previously shown that DON epimerization proceeds through a two-step biocatalysis. Significantly, this report describes the identification of the first enzymatic step in this pathway. The enzyme, a dehydrogenase responsible for the selective oxidation of DON at the C3 position, was shown to readily convert DON to 3-keto-DON, a less toxic intermediate in the DON epimerization pathway. Furthermore, this study provides insights into the PQQ dependence of the enzyme. This enzyme may be part of a feasible strategy for DON mitigation within the near future.
Enzymatic oxidations in the biosynthesis of complex alkaloids (1998)

The biosynthesis of complex alkaloids in plants involves enzymes that, due to high substrate specificity, appear to have evolved solely for a role in secondary metabolism. At least one class of these enzymes, the oxidoreductases, catalyze transformations that are in some cases difficult to chemically mimick with an equivalent stereo- or regiospecificity and yield. Oxidoreductases are frequently catalyzing reactions that result in the formation of parent ring systems, thereby determining the class of alkaloid that a plant will produce. The oxidoreductases of alkaloid formation are a potential target for the biotechnological exploitation of medicinal plants in that they could be used for biomimetic syntheses of alkaloids. Analyzing the molecular genetics of alkaloid biosynthetic oxidations is requisite to eventual commercial application of these enzymes. To this end, a wealth of knowledge has been gained on the biochemistry of select monoterpenoid indole and isoquinoline biosynthetic pathways, and in recent years this has been complemented by molecular genetic analyses. As the nucleotide sequences of the oxidases of alkaloid synthesis become known, consensus sequences specific to select classes of enzymes can be identified. These consensus sequences will potentially facilitate the direct cloning of alkaloid biosynthetic genes without the need to purify the native enzyme for partial amino acid sequence determination or for antibody production prior to cDNA isolation. The current state of our knowledge of the biochemistry and molecular genetics of oxidases involved in alkaloid biosynthesis is reviewed herein.
Alcohol, Cannabis, Nicotine, and Caffeine Use and Symptom Distress in Schizophrenia (1995)

The high prevalence of substance use, e.g., alcohol and illegal and nonprescribed drugs, in schizophrenia is widely recognized. One explanation for this high prevalence is that substance use may be a self-initiated method for managing symptoms. To test whether the intake of four substances--alcohol, cannabis, nicotine, and caffeine--would increase with increases in symptom distress, daily self-reports of symptom distress and substance intake over 12 weeks were analyzed with pooled time series analyses. Compliance with neuroleptic medication was added to the analyses to control for any changes in prescribed medication compliance while using nonprescribed drugs or alcohol. Of the four substances studied, only nicotine was significantly related to symptom distress. Higher distress with prodromal symptoms was related to decreases in nicotine use. Analysis of caffeine did not meet the criteria for significance but does provide direction for further research. Higher distress, with neurotic symptoms, was related to increases in caffeine use. Further research is needed to clarify the relationship between nicotine and symptoms.
Ta1, a novel 105 KD human T cell activation antigen defined by a monoclonal antibody. (1984)

By using a murine monoclonal antibody produced against an IL 2-dependent human T cell line, we defined a T lineage-specific molecule, termed Ta1, that is expressed strongly on activated T lymphocytes of both the T4 and T8 subsets, as well as on T cell lines and clones, but only weakly on a fraction of resting T cells. SDS-PAGE analysis of immunoprecipitates from 125I-labeled, activated T cells demonstrates a single major band of apparent m.w. 105 KD under both reducing and nonreducing conditions. Unlike anti-IL 2 receptor antibodies, anti-Ta1 does not inhibit T cell proliferative responses to mitogen, antigen, or IL 2-containing medium. Moreover, anti-Ta1 has no effect on T cell-mediated cytotoxicity. Ta1 appears to be a novel human T cell-specific activation antigen that may serve as a useful marker of T cell activation in human disease.
Three-Dimensional Compositional Analysis of Drug Eluting Stent Coatings Using Cluster Secondary Ion Mass Spectrometry (2008)

Cluster secondary ion mass spectrometry (cluster SIMS) employing an SF5+ polyatomic primary ion sputter source in conjunction with a Bi3+ analysis source was used to obtain three-dimensional molecular information in polymeric-based drug-eluting stent coatings. The formulations of the coatings varied from 0% to 50% (w/w) sirolimus drug in poly(lactic-co-glycolic acid) and were prepared on both MP35N metal alloy coupons and bare metal stents. All cluster SIMS depth profiles obtained indicated a drug-enriched surface region, followed by a drug-depletion region, and finally a constant bulk composition region, similar to previous data obtained in polymeric blend systems. The drug overlayer thickness was determined to increase with increasing sirolimus content. Sample temperature was determined to play an important role in the resulting depth profiles, where it was shown that the best profiles were obtained at low temperatures (-100 degrees C). At these temperatures, molecular signals typically remained constant through the entire depth of the film (approximately 6.5 microm) in some cases, as opposed to the typical 1 microm-2 microm depth limit, which is achievable at room temperature. The 3-D imaging capabilities of cluster SIMS were successfully demonstrated and indicated a significant amount of subsurface domain formation in the 25% and 50% sirolimus samples, but not in the 5% sample, which was homogeneous. These results clearly illustrate the utility of cluster SIMS for probing the 3-D structure in polymeric-based drug delivery devices.
A novel dual-band antenna for hand-held portable telephone (2002)

A novel planar dual-band antenna mounted on the side of the hand-held telephone case has been realised to operate in the 0.9 GHz and 1.76 GHz bands using two separate antennas, one for each frequency. The size of the dual-band antenna is almost same as the planar inverted F-antenna operating at 0.9 GHz.
High-performance time-resolved fluorescence by direct waveform recording (2010)

We describe a high-performance time-resolved fluorescence (HPTRF) spectrometer that dramatically increases the rate at which precise and accurate subnanosecond-resolved fluorescence emission waveforms can be acquired in response to pulsed excitation. The key features of this instrument are an intense (1 μJ/pulse), high-repetition rate (10 kHz), and short (1 ns full width at half maximum) laser excitation source and a transient digitizer (0.125 ns per time point) that records a complete and accurate fluorescence decay curve for every laser pulse. For a typical fluorescent sample containing a few nanomoles of dye, a waveform with a signal/noise of about 100 can be acquired in response to a single laser pulse every 0.1 ms, at least 10(5) times faster than the conventional method of time-correlated single photon counting, with equal accuracy and precision in lifetime determination for lifetimes as short as 100 ps. Using standard single-lifetime samples, the detected signals are extremely reproducible, with waveform precision and linearity to within 1% error for single-pulse experiments. Waveforms acquired in 0.1 s (1000 pulses) with the HPTRF instrument were of sufficient precision to analyze two samples having different lifetimes, resolving minor components with high accuracy with respect to both lifetime and mole fraction. The instrument makes possible a new class of high-throughput time-resolved fluorescence experiments that should be especially powerful for biological applications, including transient kinetics, multidimensional fluorescence, and microplate formats.
Comparison of digital focus criteria for a TV microscope system (1984)

Existing focusing methods, such as standard deviation of gray values, gradients, information content of the image and the lateral inhibition function, were compared, and a new combination criterion was developed. This combined method consists of using the standard deviation of the image for coarse focusing followed by a modified form of the lateral inhibition for the fine focus. The lateral inhibitor model of the eye is a recursive filter that can be simplified to a nonrecursive filtering algorithm, as postulated by Rechenberg. The reported focus method operates over a focusing range (z-axis) of +/- 300 micron and is accurate within +/- 0.1 micron in the transmission, dark-field, and phase contrast microscope.
Clinical Efficacy of Three Assays for Cardiac Troponin I for Risk Stratification in Acute Coronary Syndromes: A Thrombolysis In Myocardial Infarction (TIMI) 11B Substudy (2000)

This study demonstrates the prognostic efficacy of three independently developed cTnI assays at a threshold of 0.1 microg/L for the prediction of adverse clinical outcomes among patients with non-ST-elevation acute coronary syndromes.
Nuclear Factor YY1 Inhibits Transforming Growth Factor β- and Bone Morphogenetic Protein-Induced Cell Differentiation (2003)

Smad proteins transduce transforming growth factor beta (TGF-beta) and bone morphogenetic protein (BMP) signals that regulate cell growth and differentiation. We have identified YY1, a transcription factor that positively or negatively regulates transcription of many genes, as a novel Smad-interacting protein. YY1 represses the induction of immediate-early genes to TGF-beta and BMP, such as the plasminogen activator inhibitor 1 gene (PAI-1) and the inhibitor of differentiation/inhibitor of DNA binding 1 gene (Id-1). YY1 inhibits binding of Smads to their cognate DNA elements in vitro and blocks Smad recruitment to the Smad-binding element-rich region of the PAI-1 promoter in vivo. YY1 interacts with the conserved N-terminal Mad homology 1 domain of Smad4 and to a lesser extent with Smad1, Smad2, and Smad3. The YY1 zinc finger domain mediates the association with Smads and is necessary for the repressive effect of YY1 on Smad transcriptional activity. Moreover, downregulation of endogenous YY1 by antisense and small interfering RNA strategies results in enhanced transcriptional responses to TGF-beta or BMP. Ectopic expression of YY1 inhibits, while knockdown of endogenous YY1 enhances, TGF-beta- and BMP-induced cell differentiation. In contrast, overexpression or knockdown of YY1 does not affect growth inhibition induced by TGF-beta or BMP. Accordingly, YY1 does not interfere with the regulation of immediate-early genes involved in the TGF-beta growth-inhibitory response, the cell cycle inhibitors p15 and p21, and the proto-oncogene c-myc. In conclusion, YY1 represses Smad transcriptional activities in a gene-specific manner and thus regulates cell differentiation induced by TGF-beta superfamily pathways.
Effect of Continuous Administration of Interferon- in Experimental Visceral Leishmaniasis (1990)

In experimental visceral leishmaniasis, intermittently administered interferon-gamma (IFN-gamma) induces antileishmanial activity, which is primarily microbistatic. To determine if the efficacy of IFN-gamma immunotherapy could be enhanced by continuous delivery, Leishmania donovani-infected mice were treated using a subcutaneous osmotic pump. Once-daily intraperitoneal injections of 10(5) or 10(6) units of IFN-gamma inhibited the replication of L. donovani within liver macrophages but overall did not reduce liver parasite burdens. In contrast, a comparable dose of IFN-gamma (2.4 x 10(5) units/day) administered continuously induced an enhanced effect and reduced liver burdens by almost 50%. Although pump delivery did not similarly increase the efficacy of antimony chemotherapy in infected mice, continuous treatment with IFN-gamma plus antimony produced an additive antileishmanial effect. These results suggest that continuous infusions of macrophage-activating lymphokines such as IFN-gamma (used alone or in combination with chemotherapy) may be required to optimize in vivo antimicrobial effects.
Electrical conductivity of silica gel in the presence of adsorbed water (1968)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTElectrical conductivity of silica gel in the presence of adsorbed waterJames Hunter Anderson Jr. and George A. ParksCite this: J. Phys. Chem. 1968, 72, 10, 3662–3668Publication Date (Print):October 1, 1968Publication History Published online1 May 2002Published inissue 1 October 1968https://pubs.acs.org/doi/10.1021/j100856a051https://doi.org/10.1021/j100856a051research-articleACS PublicationsRequest reuse permissionsArticle Views2581Altmetric-Citations390LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access options Get e-Alerts
The role of interferon‐gamma in the pathogenesis of experimental autoimmune disease of the peripheral nervous system (1990)

The role of interferon-gamma in the pathogenesis of experimental autoimmune disease of the peripheral nervous system was investigated. Administration of rat recombinant interferon-gamma markedly augmented both myelin-induced and T-cell line-mediated experimental autoimmune neuritis. Conversely, in vivo application of a monoclonal antibody to interferon-gamma suppressed the disease. Clinical and electrophysiological findings were corroborated by semiquantitative morphometric analysis. Mechanisms responsible for the enhancing effects of interferon-gamma include upregulation of major histocompatibility complex class II antigen expression in the nerve lesion, increased cellular influx of T cells and macrophages, and heightened macrophage activity with enhanced release of toxic oxygen species. These observations establish a pivotal role of the cytokine interferon-gamma in the pathogenesis of experimental autoimmune disease of the peripheral nervous system.
Synthesis, Characterization, and Properties of Metallic Copper Nanoparticles (1998)

Nanoscale particles of metallic copper clusters have been prepared by two methods, namely the thermal reduction and sonochemical reduction of copper(II) hydrazine carboxylate Cu(N2H3COO)2·2H2O complex in an aqueous medium. Both reduction processes take place under an argon atmosphere over a period of 2−3 h. The FT-IR, powder X-ray diffraction, and UV−visible studies support the reduction products of Cu2+ ions as metallic copper nanocrystallites. The powder X-ray analysis of the thermally derived products show the formation of pure metallic copper, while the sonochemical method yields a mixture of metallic copper and copper oxide (Cu2O). The formation of Cu2O along with the copper nanoparticles in the sonochemical process can be attributed to the partial oxidation of copper by in situ generated H2O2 under the sonochemical conditions. However, the presence of a mixture of an argon/hydrogen (95:5) atmosphere yields pure copper metallic nanoparticles, which could be due to the scavenging action of the hydrogen towards the OH• radicals that are produced in solution during ultrasonic irradiation. The synthesized copper nanoparticles exhibit a distinct absorption peak in the region of 550−650 nm. The transmission electron microscopy studies of the thermally derived copper show the presence of irregularly shaped particles (200−250 nm) having sharp edges and facets. On the other hand, the sonochemically derived copper powder shows the presence of porous aggregates (50−70 nm) that contain an irregular network of small nanoparticles. The copper nanoparticles are catalytically active toward an “Ullmann reaction”that is, the condensation of aryl halides to an extent of 80−90% conversion. The time course of catalysis was studied for condensation of iodobenzene at 200 °C for a period of 1−5 h. The catalytic ability of copper nanoparticles produced by the thermal and sonochemical methods was compared with that of commercial copper powders.
Synthesis of carboxylated poly(NIPAAm) oligomers and their application to form thermo-reversible polymer-enzyme conjugates (1994)

A thermo-reversible poly(N-isopropylacrylamide) poly(NIPAAm) oligomer with a carboxyl functional end group has been synthesized by radical polymerization using beta-mercaptopropionic acid as a chain transfer reagent. This polymer has been conjugated to an enzyme, beta-D-glucosidase, to form a thermo-reversible water soluble-insoluble polymer-enzyme conjugate. This conjugate can be used for separation, recovery and recycle of an enzyme simply by applying small temperature changes to the reaction medium. In contrast to the random polymer-enzyme conjugates reported in the literature, in this study the enzyme is coupled to each polymer chain by a single end attachment. These preliminary studies show that the conjugated enzyme exhibits very high retention of activity (> 90%) compared to the native enzyme and shows improved thermal stability.
Long-livedMn2+emission in nanocrystallineZnS:Mn2+ (1998)

Recently, it has been reported that doped semiconductor nanoparticles can yield both high luminescence efficiencies and a spectacular lifetime shortening, which suggests that doped semiconductor nanoparticles form a new class of luminescent materials for various applications. From lifetime measurements and time-resolved spectroscopy we conclude that the ${\mathrm{Mn}}^{2+}$ emission does not show a spectacular shortening of the decay time upon decreasing particle size as reported earlier. The luminescence of nanocrystalline ${\mathrm{Z}\mathrm{n}\mathrm{S}:\mathrm{M}\mathrm{n}}^{2+}$ indeed has a short decay time (\ensuremath{\sim}100 ns), but also shows a long ms range decay time. The short decay time is ascribed to a defect-related emission of ZnS, and is not from the decay of the ${}^{4}{\mathrm{T}}_{1}{\ensuremath{-}}^{6}{\mathrm{A}}_{1}$ transition of the ${\mathrm{Mn}}^{2+}$ impurity as suggested by other authors. The ${}^{4}{\mathrm{T}}_{1}{\ensuremath{-}}^{6}{\mathrm{A}}_{1}$ transition of the ${\mathrm{Mn}}^{2+}$ has a ``normal'' decay of about 1.9 ms. Based on our observations, we conclude that doped semiconductor nanoparticles do not form a new class of luminescent materials, combining a high efficiency with a short (ns) decay time.
CWR22: the first human prostate cancer xenograft with strongly androgen-dependent and relapsed strains both in vivo and in soft agar. (1996)

Most patients' prostate cancers respond to androgen deprivation but relapse after periods of several months to years. Only two prostate cancer xenografts, LNCaP and PC-346, have been reported to be responsive to androgen deprivation and to relapse subsequently. Both of these tumors shrink slightly, if at all, and relapse less than 5 weeks after androgen withdrawal. After androgen withdrawal, the human primary prostate cancer xenograft CWR22 regresses markedly, and prostate-specific antigen (PSA) falls up to 3000-fold in the blood of mice. PSA usually returns to normal. In some animals, the tumor relapses and is then designated CWR22R. In these animals, PSA starts to rise approximately 2-7 months, and tumor begins to grow 3-10 months after castration. Animals with CWR22 need to be euthanized because of large tumors 6-12 weeks after the transplantation of CWR22. Androgen withdrawal prolongs life approximately 3-4-fold.