gebhart/patrepeval huggingface dataset:
Broad-spectrum antiviral that interferes with de novo pyrimidine biosynthesis (2011)

Compound A3 was identified in a high-throughput screen for inhibitors of influenza virus replication. It displays broad-spectrum antiviral activity, and at noncytotoxic concentrations it is shown to inhibit the replication of negative-sense RNA viruses (influenza viruses A and B, Newcastle disease virus, and vesicular stomatitis virus), positive-sense RNA viruses (Sindbis virus, hepatitis C virus, West Nile virus, and dengue virus), DNA viruses (vaccinia virus and human adenovirus), and retroviruses (HIV). In contrast to mammalian cells, inhibition of viral replication by A3 is absent in chicken cells, which suggests species-specific activity of A3. Correspondingly, the antiviral activity of A3 can be linked to a cellular protein, dihydroorotate dehydrogenase (DHODH), which is an enzyme in the de novo pyrimidine biosynthesis pathway. Viral replication of both RNA and DNA viruses can be restored in the presence of excess uracil, which promotes pyrimidine salvage, or excess orotic acid, which is the product of DHODH in the de novo pyrimidine biosynthesis pathway. Based on these findings, it is proposed that A3 acts by depleting pyrimidine pools, which are crucial for efficient virus replication.
1.70 Å X‐ray structure of human apo kallikrein 1: Structural changes upon peptide inhibitor/substrate binding (2005)

Human kallikreins are serine proteases that comprise a recently identified large and closely related 15-member family. The kallikreins include both regulatory- and degradative-type proteases, impacting a variety of physiological processes including regulation of blood pressure, neuronal health, and the inflammatory response. While the function of the majority of the kallikreins remains to be elucidated, two members are useful biomarkers for prostate cancer and several others are potentially useful biomarkers for breast cancer, Alzheimer's, and Parkinson's disease. Human tissue kallikrein (human K1) is the best functionally characterized member of this family, and is known to play an important role in blood pressure regulation. As part of this function, human K1 exhibits unique dual-substrate specificity in hydrolyzing low molecular weight kininogen between both Arg-Ser and Met-Lys sequences. We report the X-ray crystal structure of mature, active recombinant human apo K1 at 1.70 A resolution. The active site exhibits structural features intermediate between that of apo and pro forms of known kallikrein structures. The S2 to S2' pockets demonstrate a variety of conformational changes in comparison to the porcine homolog of K1 in complex with peptide inhibitors, including the displacement of an extensive solvent network. These results indicate that the binding of a peptide substrate contributes to a structural rearrangement of the active-site Ser 195 resulting in a catalytically competent juxtaposition with the active-site His 57. The solvent networks within the S1 and S1' pockets suggest how the Arg-Ser and Met-Lys dual substrate specificity of human K1 is accommodated.
Measurement of Wet Antenna Effects on Millimetre Wave Propagation (2006)

The experiment "wet antenna effects on millimetre wave propagation" is carried out at the Robert Bosch GmbH, to analyse the partial and total signal degradation of automotive radar sensors. It reveals that, the existence of water film on the surface of antenna lens or its radome is the main cause for weak performance of radar sensors, operating at high frequencies in rainy and snowy weather conditions. However, it is possible to repress the formation of water film with proper antenna lens or radome design to a certain extent, to reduce its effect on the radar performance. The results, which are discussed in this paper, show that such performance limitation has to be generally taken into account by the automotive long range radar designers. Bosch has successfully implemented appropriate technology in its new generation automotive long range radar sensor.
Dissolution behavior of iron cyanide (Prussian blue) in contaminated soils (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDissolution behavior of iron cyanide (Prussian blue) in contaminated soilsJohannes C. L. Meeussen, Meindert G. Keizer, Willem H. Van Riemsdijk, and Frans A. M. De HaanCite this: Environ. Sci. Technol. 1992, 26, 9, 1832–1838Publication Date (Print):September 1, 1992Publication History Published online1 May 2002Published inissue 1 September 1992https://pubs.acs.org/doi/10.1021/es00033a019https://doi.org/10.1021/es00033a019research-articleACS PublicationsRequest reuse permissionsArticle Views1181Altmetric-Citations74LEARN 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 optionsGet e-Alertsclose Get e-Alerts
Age-Dependent Effect on the Level of Factor IX (1993)

Levels of factor IX:C and factor IX:Ag were measured in 120 healthy subjects with an age range of 1 to 67 years. Levels of factor IX:C were lowest in prepubertal subjects, then reached a plateau in early adult life with a secondary increase in later adult life (> 45 years). Changes in factor IX:Ag showed a similar trend. Factor IX:Ag disproportionately increased in early adult life, however, with a less pronounced increase in later life, resulting in peaking of the ratio in early adult life. It is suggested that caution be exercised in interpreting low normal factor IX:C levels in prepubertal children, and that interpretation of ratios of antigenic to coagulant activity may need to take subject age into consideration.
Olefin Rearrangements Assisted by a Molecular Metal−Oxo Surface:  The Chemistry of Calix[4]arene Tungsten(IV) (1999)

This report deals with the olefin rearrangements achieved on a W-calix[4]arene oxo fragment that mimicks a heterogeneous metal−oxo surface both in the results and the chemical pathways. The olefin complexation by the W(IV)-calix[4]arene fragment has been achieved, generating the [{p-But-calix[4]-(O)4}W]-d2 from the reduction of [cis-(Cl)2W{p-But-calix[4]-(O)4}], 1, in the presence of the appropriate olefin. With this method, [{p-But-calix[4]-(O)4}W(η2-C2H4)], 2, [{p-But-calix[4]-(O)4}W(η2-MeC2H3)], 3, and [{p-But-calix[4]-(O)4}W(C6H10)], 4, have been obtained. In the latter complex the very labile cyclohexene can be replaced by another olefin, such as trans-stilbene in [{p-But-calix[4]-(O)4}W(η2-Ph2C2H2)], 5. The ethylene complex, 2, undergoes deprotonation with LiBu, leading to the corresponding anionic alkylidyne [{p-But-calix[4]-(O)4}W⋮CMe]Li, 6, which can be protonated, not back to the starting olefin complex, but rather to the corresponding alkylidene [{p-But-calix[4]-(O)4}WC(H)Me], 7. Complexes 6 and 7 are interrelated by a reversible protonation−deprotonation reaction. The overall transformation of 2 into 7 is the isomerization of ethylene to alkylidene. The intermediacy of a metallacyclopropene in the deprotonation of 2 to give 6 has been proved by the isolation of [{p-But-calix[4]-(O)4}W(PhCHCPh)]Li, 8, from the deprotonation of 5. Compounds 5 and 8 are interrelated by a reversible protonation−deprotonation reaction, while the reaction of 8 with MeOTf led, rather, to the alkylation of one of the calix[4]arene oxygen atoms in [{p-But-calix[4]-(O)3(OMe)}W(PhCHCPh)], 9. The ethylene, 2, and propylene, 3, complexes undergo an electron-transfer-catalyzed reaction with ethylene and propylene to the corresponding metallacyclopentanes [{p-But-calix[4]-(O)4}W{CH2CH(R‘)CH(R)CH2}], [R = R‘ = H, 11; R = Me, R‘ = H, 12; R = R‘ = Me, 13]. Complexes 2, 3, 11, and 13 undergo a reversible one-electron reduction by Na to [{p-But-calix[4]-(O)4}W(η2-C2H3R)]Na, [R = H, 14; R = Me, 15] and to [{p-But-calix[4]-(O)4}W{CH2CH(R‘)CH(R)CH2}]Na, [R = R‘ = H, 16; R = R‘ = Me, 17]. Complexes 16 and 17 can be reoxidized by Cp2FeBPh4 back to 11 and 13, which do not undergo reversible decoupling of the olefins. The metallacyclopentane complex 11 undergoes deprotonation to [{p-But-calix[4]-(O)4}W{CH(CH2)2CH2}]Li, 18. Both 11 and 18 photochemically rearrange to the corresponding alkylidene [{p-But-calix[4]-(O)4}WC(H)Prn], 19, and alkylidyne [{p-But-calix[4]-(O)4}W⋮CPrn]Li, 20.
Application of CRISPR/Cas9-Based Gene Editing in HIV-1/AIDS Therapy (2019)

Despite the fact that great efforts have been made in the prevention and therapy of HIV-1 infection, HIV-1/AIDS remains a major threat to global human health. Highly active antiretroviral therapy (HAART) can suppress virus replication, but it cannot eradicate latent viral reservoirs in HIV-1/AIDS patients. Recently, the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated nuclease 9 (Cas9) system has been engineered as an effective gene-editing technology with the potential to treat HIV-1/AIDS. It can be used to target cellular co-factors or HIV-1 genome to reduce HIV-1 infection and clear the provirus, as well as to induce transcriptional activation of latent virus in latent viral reservoirs for elimination. This versatile gene editing technology has been successfully applied to HIV-1/AIDS prevention and reduction in human cells and animal models. Here, we update the rapid progress of CRISPR/Cas9-based HIV-1/AIDS therapy research in recent years and discuss the limitations and future perspectives of its application.
Use of tetrameric antibody complexes to stain cells for flow cytometry (1987)

Bifunctional tetrameric complexes of monoclonal antibodies were used to stain cells for flow cytometry. These complexes consist of two different mouse monoclonal IgG1 antibodies (one with specificity for a cell surface antigen, the other with specificity for a fluorochrome) cross-linked by two molecules of a monoclonal rat anti-mouse IgG1. The use of this immunological approach to cross-link fluorochromes to cell surface antigens was studied with tetrameric complexes containing Leu-3a or Leu-2a antibodies and monoclonal antibodies specific for the fluorochromes B- and R-phycoerythrin. The ability of such cyclic immune complexes to stain T-cell subset antigens on human peripheral blood lymphocytes was demonstrated in single and double-staining experiments. The results demonstrate that tetrameric antibody complexes provide a simple and efficient alternative to covalently labeled antibodies for the flow cytofluorimetric analysis of cell-surface antigens.
Thrombus formation and platelet-vessel wall interaction in the nephrotic syndrome under flow conditions. (1994)

Increased in vitro platelet aggregability and hypercoagulability are generally held to be main determinants in the prethrombotic state in nephrosis. In vivo, however, thrombotic events depend on the dynamic interaction of flowing blood with the vessel wall. The present study confirms that aggregability of platelets of nephrotic patients is significantly increased by mere stirring or by exogenous stimuli as adenosine diphosphate and arachidonic acid. Moreover, the nephrotic patients have high von Willebrand factor and decreased red blood cell deformability, which normally increase platelet-vessel wall interaction. However, perfusion studies under well-defined flow conditions, in which anticoagulated nephrotic blood was exposed to deendothelialized human umbilical artery segments and sprayed collagen, showed normal platelet adhesion and only a modest increase in the deposition of platelet aggregates. This suggests that some factor counteracts platelet-vessel wall interaction under flow conditions in the nephrotic syndrome. When tissue factor associated with endothelial extracellular matrix (ECM) was allowed to generate thrombin, perfusions with nephrotic blood over this ECM resulted in a strong increase in fibrin generation. The capacity of patient blood to form increased amounts of fibrin appeared strongly correlated with the level of hyperfibrinogenemia. Platelet adhesion as well as aggregation in these experiments was even decreased below control values. This suggests that fibrin coverage may block the direct contact between blood platelets and matrix. We therefore also studied the isolated effect of high fibrinogen on platelet-vessel wall interaction by increasing fibrinogen concentrations in normal blood. Modulation of fibrinogen concentrations in normal blood could mimic all the observations in nephrotic blood: platelet aggregation in suspension increased with increasing concentrations of fibrinogen, while platelet adhesion and aggregate formation under flow conditions decreased. In perfusions over tissue factor-rich matrix, fibrin deposition increased. Therefore, our observations indicate that nephrotic hyperaggregability in suspension is not associated with increased platelet vessel wall-interaction under flow conditions. The latter is probably counteracted by high levels of fibrinogen. Our observations further suggest that hyperfibrinogenemia may be a major thrombotic risk factor in nephrosis by inducing more fibrin depositions.
Adenoviral-mediated gene transfer to rabbit synovium in vivo. (1993)

Currently, treatment for rheumatoid arthritis and other inflammatory arthropathies is often ineffective in ameliorating the progression of the disease, particularly the invasive destruction of cartilage and bone by rheumatoid synovium. Multiple aspects of this inflammatory process are mediated by the synovial lining cells (synoviocytes). Genetic modification of these cells in vivo represents a potential method for the treatment of these conditions. In this report, we describe a novel technique for the genetic transduction of synovial lining cells in vivo using recombinant adenoviral vectors and intraarticular injection techniques. Purified high titer suspensions of a recombinant adenoviral vector containing the gene for Escherichia coli beta-galactosidase (AdCMVlacZ) were directly injected into the hind knees of New Zealand white rabbits. Synovial tissues were then examined for transgenic lacZ expression using a combination of in situ staining for beta-galactosidase activity, immunohistochemical staining, and transmission electron microscopy. High efficiency gene transfer and lacZ expression was observed in both type A and type B synoviocytes throughout the articular and periarticular synovium of the rabbit knee, with continued expression of transgenic lacZ detected for > or = 8 wk after infection.
Evaluation of substrate noise in CMOS and low-noise logic cells (2002)

The substrate noise generated by conventional CMOS and by different low-noise logic families is investigated by computer simulation of the circuits extracted from the layouts including the resistive substrate model. A widely used 0.8 /spl mu/m CMOS technology is considered. It is found that, in small cells, the noise reduction with respect to CMOS is only significant in cells with complementary outputs. In large driver cells, considerable noise reduction can be obtained (without complementary outputs). One of the low-noise families, however, exhibits large noise for high supply wire inductance (in the examples here, with 2 V supply voltage, the noise is even higher than for CMOS cells, for inductance above 10 nH).
A Dataflow-Based Scientific Workflow Composition Framework (2010)

Scientific workflow has recently become an enabling technology to automate and speed up the scientific discovery process. Although several scientific workflow management systems (SWFMSs) have been developed, a formal scientific workflow composition model in which workflow constructs are fully compositional one with another is still missing. In this paper, we propose a dataflow-based scientific workflow composition framework consisting of (1) a dataflow-based scientific workflow model that separates the declaration of the workflow interface from the definition of its functional body; (2) a set of workflow constructs, including Map, Reduce, Tree, Loop, Conditional, and Curry, which are fully compositional one with another; (3) a dataflow-based exception handling approach to support hierarchical exception propagation and user-defined exception handling. Our workflow composition framework is unique in that workflows are the only operands for composition; in this way, our approach elegantly solves the two-world problem in existing composition frameworks, in which composition needs to deal with both the world of tasks and the world of workflows. The proposed framework is implemented and several case studies are conducted to validate our techniques.
Reductions (2008)

The Barton deoxygenation (or Barton–McCombie deoxygenation) is a two-step reaction sequence for the reduction of an alcohol to an alkane. The alcohol is first converted to a methyl xanthate or thioimidazoyl carbamate. Then, the xanthate or thioimidazoyl carbamate is reduced with a tin hydride reagent under radical conditions to afford the alkane. Trialkylsilanes have also been used as the hydride source. Reviews: (a) McCombie, S. W. In Comprehensive Organic Synthesis; Trost, B. M.; Fleming, I., Eds.; Pergamon Press: Oxford, U. K., 1991; Vol. 8, Chapter 4.2: Reduction of Saturated Alcohols and Amines to Alkanes, pp. 818–824. (b) Crich, D.; Quintero, L. Chem. Rev. 1989, 89, 1413–1432. To a solution of the â-hydroxy-N-methyl-O-methylamide (0.272 g, 1.55 mol) in tetrahydrofuran (THF) (30 mL) were added carbon disulfide (6.75 mL, 112 mmol) and iodomethane (6.70 mL, 108 mmol) at 0 °C. The mixture was stirred at this temperature for 0.25 h, and then sodium hydride (60% suspension in mineral, 136.3 mg, 3.4 mmol) was added. After 20 min at 0 °C, the reaction was quenched by slow addition to 60 g of crushed ice. (Caution: hydrogen gas evolution!). The mixture was raised to room temperature and separated, and the aqueous layer was extracted with CH2Cl2 (4 × 15 mL). The combined organic extracts were dried (Na2SO4&lt;/aub&gt;), concentrated in vacuo, and purified (SiO2, 5% EtOAc in hexanes) to afford 0.354 g (86%) of the xanthate. To a solution of the xanthate (2.95 g, 11.1 mmol) in toluene (100 mL) was added tributyltin hydride (15.2 mL, 56.6 mmol) and 2,2´-azobisisobutyronitrile (AIBN, 0.109 g, 0.664 mmol). The reaction mixture was then heated to reflux for 1 h. The mixture was cooled, concentrated in vacuo, and purified (SiO2, 100% hexanes to remove tin byproducts, followed by 10% EtOAc in hexanes to elute product) to afford 1.69 g (96%) of the N-methyl-O-methylamide.
Infliximab for the Treatment of Fistulas in Patients with Crohn's Disease (1999)

Infliximab is an efficacious treatment for fistulas in patients with Crohn's disease.
Effects of Individual Ion Energies on Charge Measurements in Fourier Transform Charge Detection Mass Spectrometry (FT-CDMS) (2018)

A method to correct for the effect of ion energy on charge measurements of individual ions trapped and weighed with charge detection mass spectrometry (CDMS) is demonstrated. Ions with different energies induce different signal patterns inside an electrostatic ion trap. The sum of the amplitudes of the fundamental and second harmonic frequencies in the Fourier transform of the induced signal, which has been used to obtain the ion charge, depends on both ion energy and charge. The amplitudes of the fundamental frequencies of ions increase over time as ions lose energy by collisions with background gas and solvent loss from larger ions. Model ion signals are simulated with the same time-domain amplitude at different energies and frequencies and the resulting fundamental frequency amplitudes are used to normalize real ion signals for energy and frequency effects. The fundamental frequency amplitude decreases dramatically below 20 kHz and increases by ~ 17% from the highest energy to lowest energy that is stable with a given trap potential at all frequencies. Normalizing the fundamental frequency amplitude with the modeled amplitudes removes the systematic changes in the charge measurement of polyethylene glycol (PEG) and other ions and makes it possible to signal average the amplitude over long times, which reduces the charge uncertainty to 0.04% for a PEG ion for a 500-ms measurement. This method improves charge measurement accuracy and uncertainty, which are important for high-accuracy mass measurement with CDMS. Graphical abstract ᅟ.
Loss of brain tau defines novel sporadic and familial tauopathies with frontotemporal dementia (2001)

Dementia lacking distinctive histopathology (DLDH) or frontotemporal lobe degeneration (FTLD) is the most common neuropathological diagnosis for sporadic frontotemporal dementias (FTDs). The hallmarks of DLDH are neuron loss and gliosis in the absence of any disease-specific brain lesion. Similar brain pathology is also seen in a familial FTD pedigree known as hereditary dysphasic disinhibition dementia 2 (HDDD2). Abnormality in the function or isoform composition of the microtubule binding protein tau is a prominent feature in the brains of many patients with sporadic and hereditary FTDs. Therefore, we studied the tau protein in different brain regions from DLDH and HDDD2 patients. Our results indicate that a selective loss of all six tau isoforms, but not tau mRNA, occurs in these brains compared to normal control and Alzheimer's disease brains. Loss of tau protein was identified by Western blot analysis of protein extracts from DLDH and HDDD2 brains in regions both with and without neuronal degeneration. Functionally, this loss of tau protein may be equivalent to pathogenic mutations in the tau gene identified in familial FTD with parkinsonism linked to chromosome 17 (FTDP-17). Thus, DLDH and HDDD2 are novel tauopathies with a unique mechanism of pathogenesis. The presence of tau mRNA in these brains suggests that the level of tau protein may be controlled posttranscriptionally, at the level of either translation or mRNA stability.
CD30-mediated signaling promotes the development of human T helper type 2-like T cells. (1995)

We have recently shown that CD30, a member of the tumor necrosis factor/nerve growth factor receptor superfamily, is preferentially expressed by human T cell clones producing T helper (Th) type 2 cytokines. We report here that costimulation with an agonistic anti-CD30 monoclonal antibody enhanced antigen (Ag)-induced proliferation and cytokine secretion by established human Th2 and Th0 clones. Moreover, costimulation of peripheral blood mononuclear cells with the same anti-CD30 monoclonal antibody resulted in the preferential development of Ag-specific T cell lines and clones showing a Th2-like profile of cytokine secretion. In contrast, early blockade in bulk culture of CD30 ligand-CD30 interaction shifted the development of Ag-specific T cells towards the opposite (Th1-like) phenotype. Taken together, these data suggest that CD30 triggering of activated Th cells by CD30 ligand-expressing Ag-presenting cells may represent an important costimulatory signaling for the development of Th2-type responses.