gebhart/patrepeval huggingface dataset:
Functional Selectivity, Ligand-Directed Trafficking, Conformation-Specific Agonism: What's In A Name? (2005)

Research on the design of compounds to selectively affect specific subsets of signals downstream of receptors has burgeoned lately, and several reports discussed at Experimental Biology 2005 indicate progress is being made in the understanding of what makes a drug functionally selective. Different conformations adopted by receptors after associating with specific ligands can determine which intracellular signaling pathways get activated and which do not. The appeal of such specific compounds is enormous when one considers that many disease states might require the subtle manipulation of some (or even one) but not all downstream events stemming from specific receptor activation. Additionally, a better understanding of functional selectivity would likely improve the drug delivery process: if compounds are screened through several functional assays appropriately designed to look for compounds exhibiting a high degree of selectivity, then many potential lead compounds might not be as frequently overlooked.
Role of Solvent on the Silanization of Glass with Octadecyltrichlorosilane (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRole of Solvent on the Silanization of Glass with OctadecyltrichlorosilaneMark E. McGovern, Krishna M. R. Kallury, and Michael ThompsonCite this: Langmuir 1994, 10, 10, 3607–3614Publication Date (Print):October 1, 1994Publication History Published online1 May 2002Published inissue 1 October 1994https://pubs.acs.org/doi/10.1021/la00022a038https://doi.org/10.1021/la00022a038research-articleACS PublicationsRequest reuse permissionsArticle Views6302Altmetric-Citations293LEARN 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
Interferon Activates Macrophages to Produce Plasminogen Activator (1982)

Macrophages and monocytes become activated, by a variety of mechanisms, to exhibit cytotoxicity. Associated with this activation for cytotoxicity is the production of certain neutral proteases, especially plasminogen activator (PA), which may be involved in the mechanism of cytolysis. Supernatants from concanavalin A (Con A) or antigen-stimulated spleen cells contain factor(s) which render macrophages and monocytes activated in vitro (MAF/MIF). We have found that in addition to such spleen cell supernatants murine interferon was able to activate peptone-induced C57BL/6 peritoneal macrophages to produce PA but had no effect on human monocytes. Similarly, human recombinant interferon activated human monocytes but not murine macrophages to produce PA. In addition to displaying this species specificity, interferon was able to function as a monocyte/macrophage activator in this system just as in cytotoxicity and may be a regulator of monocyte/macrophage function in vivo by modulation of proteolytic enzymes.
A convenient synthesis of heterocyclic compounds containing 11-oxo-6,11,12,13-tetrahydrodibenzo[b,g][1,5]oxazonine fragment (2009)

A convenient synthesis of rare diaryl-fused nine-membered heterocyclic scaffold using a novel modification of four-component Ugi condensation based on the usage of aromatic aldehyde-acid as bifunctional component is described.
Compiling distributed C++ (2002)

Distributed C++ (DC++) is a language for writing parallel applications on loosely coupled distributed systems in C++. Its key idea is to extend the C++ class into 3 categories: gateway classes which act as communication and synchronization entry points between abstract processors, classes whose instances may be passed by value between abstract processors via gateways, and vanilla C++ classes. DC++ code is compiled to C++ code with calls to the DC++ runtime system. The DC++ compiler wraps gateway classes with handle classes so that remote procedure calls are transparent. It adds static variables to value classes and produces code which is used to marshal and unmarshal arguments when these value classes are used in remote procedure calls. Value classes are deep copied and preserve structure sharing. This paper shows DC++ compilation and performance.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The molecular signature of mantle cell lymphoma reveals multiple signals favoring cell survival. (2003)

Mantle cell lymphoma (MCL) is a prototypical neoplastic disease in which a common cytogenetic alteration, t11;14, leading to cyclin D1 overexpression, is associated with other changes that need to be considered in an explanation of the clinical, morphological, and molecular variability of this disease. Using a cDNA microarray (Oncochip-CNIO) containing clones for 6386 cancer-related genes, we have analyzed the expression profiles of a series of 38 cases. After normalization with the expression profiling of sorted mantle zone lymphocytes, we have related the findings to conventional clinical and molecular variables, including immunoglobulin variable heavy chain somatic mutation, blastoid cytology, increased proliferation, and long-term survival. MCL signature (446 genes) includes genes involved in apoptosis, cell cycle, signal transduction, and cell structure. Especially striking was the presence of multiple concurrent alterations in the tumor necrosis factor and nuclear factor kappaB pathway, and the overexpression of IL10R and SPARC genes. We also identified a molecular signature for the presence of immunoglobulin variable heavy chain somatic mutation, which includes a number of genes potentially relevant in cancer (CDC14A, ras, and others). Signatures for proliferation and blastoid cytology were also found. An integrated analysis of these data yields a gene-expression based survival predictor (26 genes grouped into two clusters), which distinguishes half of the patients with a survival probability of 52% at 5 years. The predictive model has been confirmed by cross-validation. In conclusion, MCL seems to combine a disease-specific signature and different sets of genes of which the expression is associated with key clinical, molecular, and immunophenotypical events.
ANTI-GLOBULIN RESPONSES TO RAT AND HUMANIZED CAMPATH-1 MONOCLONAL ANTIBODY USED TO TREAT TRANSPLANT REJECTION1 (1999)

Although anti-idiotype responses are theoretically possible against humanized therapeutic antibodies and are especially likely to be provoked by cell-binding antibodies, these data show that humanization offers a significant reduction in immunogenicity, potentially allowing repeat courses of treatment.
Self-cleavage of plus and minus RNA transcripts of avocado sunblotch viroid (1986)

Self-cleavage of both plus and minus RNA transcripts of the 247-residue avocado sunblotch viroid (ASBV), prepared from tandem dimeric cDNA clones, occurs specifically at two sites in each transcript to give monomeric plus and minus species. The cleavage reaction occurs both during transcription and on incubation of purified transcripts at pH 8 and 37 degrees C in the presence of magnesium ions to give a 3'-terminal 2',3'-cyclic phosphate and a 5'-terminal hydroxyl group. Although the self-cleavage occurs at different sites in the ASBV molecule for the plus and minus species, very similar secondary structures with high sequence homology can be drawn at each site. The results are considered to provide further evidence that ASBV is replicated in vivo by a rolling circle mechanism involving non-enzymic cleavage of high molecular weight RNA precursors of ASBV.
ABBA regulates plasma-membrane and actin dynamics to promote radial glia extension (2008)

Radial glia play key roles in neuronal migration, axon guidance, and neurogenesis during development of the central nervous system. However, the molecular mechanisms regulating growth and morphology of these extended cells are unknown. We show that ABBA, a novel member of the IRSp53-MIM protein family, is enriched in different types of radial glia. ABBA binds ATP-actin monomers with high affinity and deforms PtdIns(4,5)P(2)-rich membranes in vitro through its WH2 and IM domains, respectively. In radial-glia-like C6-R cells, ABBA localises to the interface between the actin cytoskeleton and plasma membrane, and its depletion by RNAi led to defects in lamellipodial dynamics and process extension. Together, this study identifies ABBA as a novel regulator of actin and plasma membrane dynamics in radial glial cells, and provides evidence that membrane binding and deformation activity is critical for the cellular functions of IRSp53-MIM-ABBA family proteins.
Clinical studies of tracheal gas insufflation. (2001)

Tracheal gas insufflation (TGI) is an adjunct to mechanical ventilation that allows ventilation with small tidal volumes while carbon dioxide (CO2) is satisfactorily cleared. Pioneering studies in healthy animals and in humans suffering respiratory failure showed that the expiratory flushing of proximal dead space decreased minute ventilation with no change in arterial partial pressure of carbon dioxide (PaCO2). Recent work indicates that conventional mechanical ventilation aided by TGI may represent a novel ventilatory strategy that succeeds in limiting both the distending forces acting on the lungs and the PaCO2 elevation of permissive hypercapnia. Furthermore, some studies suggest that weaning aided by TGI may allow a reduction in minute ventilation, PaCO2, physiologic dead space, and the patient's respiratory demands. Clinical use of TGI requires careful monitoring of delivered volumes and pressures to ensure safe clinical application and to evaluate the effect on lung function. Finally, routine use of TGI in intensive care warrants further investigation to solve some technical problems and randomized clinical trials to confirm the beneficial effects in the absence of complications.
Mining sequential patterns (2002)

We are given a large database of customer transactions, where each transaction consists of customer-id, transaction time, and the items bought in the transaction. We introduce the problem of mining sequential patterns over such databases. We present three algorithms to solve this problem, and empirically evaluate their performance using synthetic data. Two of the proposed algorithms, AprioriSome and AprioriAll, have comparable performance, albeit AprioriSome performs a little better when the minimum number of customers that must support a sequential pattern is low. Scale-up experiments show that both AprioriSome and AprioriAll scale linearly with the number of customer transactions. They also have excellent scale-up properties with respect to the number of transactions per customer and the number of items in a transaction.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Synthesis, characterisation and antitumour activity of platinum(II) complexes of novel functionalised poly(amido amine)s (1999)

Polyamidoamine polymers were prepared by hydrogen-transfer polyaddition of 2-methylpiperazine to 2,2′-bis(acrylamido)acetic acid sodium salt to yield PAA-1, polyaddition of amino-β-cyclodextrin and 2-methylpiperazine to 2,2′-bis(acrylamido)acetic acid to give PAA-2 and polyaddition of the same amino-β-cyclodextrin and 2-methylpiperazine to 1,4-bis(acryloyl)piperazine to produce PAA-3. These polymers were reacted with cisplatin to give products containing between 8–70 wt.-% platinum. The amount of platinum released from the conjugates during incubation at pH 5.5 and pH 7.4 varied between 0–20%/72 h. PAA-3-Pt showed pH-dependent platinum release. The PAA-platinates were generally less toxic towards lung tumour cell lines in vitro. The IC50 for cisplatin being 2–5 μg/mL and for the PAA-platinates 1–130 μg/mL, this was only to be expected due to their very different cellular pharmacokinetics. In vivo experiments showed that the PAA-1-Pt and PAA-2-Pt were equi-active compared with cisplatin against an i.p. L1210 leukaemia model, confirming their ability to liberate biologically active platinum species. Whereas PAA-1-Pt was significantly less toxic than cisplatin, PAA-2-Pt did show toxicity on repeated dosing, suggesting further investigations are needed to establish the biocompatibility of PAAs containing pendant β-cyclodextrin. PAA-1-Pt is suitable for further in vivo preclinical study in a range of solid tumour models.
DARTS-a dynamically adaptable transport service suitable for high speed networks (2002)

It has been shown that protocol processing represents a severe bottle-neck for high speed computer networks. The disadvantage of proposed solutions are their incompatibility with existing standardised protocol implementations and/or their complexity. One method of alleviating this limitation is to have an adaptable protocol stack, as proposed in this paper. Preliminary results are presented which show that significant gains in throughput can be achieved while still maintaining compatibility with existing standard protocol stacks.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Noninvasive Raman Spectroscopy of Human Tissue in vivo (2006)

We report the first transcutaneous Raman spectrum of human bone in vivo obtained at skin-safe laser illumination levels. The spectrum of thumb distal phalanx was obtained using spatially offset Raman spectroscopy (SORS), which provides chemically specific information on deep layers of human tissue, well beyond the reach of existing comparative approaches. The spectroscopy is based on collecting Raman spectra away from the point of laser illumination using concentric rings of optical fibers. As a generic analytical tool this approach paves the way for a range of uses including disease diagnosis, noninvasive probing of pharmaceutical products, biofilms, catalysts, paints, and in dermatological applications.
Immobilized lipase‐catalyzed production of structured lipids with eicosapentaenoic acid at specific positions (1996)

Abstract Structured lipids (SL) were synthesized by the interesterification reaction between medium‐chain triacylglycerols and eicosapentaenoic acid (EPA) ethyl ester. The products were partially purified, and the fatty acid at the sn ‐2 position was determined after pancreatic lipase‐catalyzed hydrolysis. The effect of additives (water and glycerol) on the rate of reaction was also investigated. Mol% EPA incorporated into the triacylglycerols was increased by adding water when trilaurin and tricaprylin were the substrates and IM 60 was the biocatalyst. With SP 435, EPA incorporation was always less with additional water than without water. The addition of glycerol (0.005 g or 0.01 g) improved interesterification catalyzed by IM 60 to some degree, but an excess amount (0.02 g) inhibited the reaction. The reaction with glycerol showed no significant difference with SP 435. After scale‐up and fractionation by column chromatography, we could recover approximately 0.3–0.4 g of product/g of reaction products. After hydrolysis by pancreatic lipase, we can conclude that IM 60 has a high specificity for sn ‐1,3 positions. With SP 435 lipase, 34.8–39.3 mol% of EPA was found at the sn ‐2 position of the recovered SL.
[Amantadine for the treatment of levodopa dyskinesias in Parkinson's disease]. (2000)

The development of dyskinesias is a common side effect during chronic levodopa therapy in parkinsonian patients. Recent reports suggest that amantadine, a drug with well known antiparkinsonian activity, is effective in the treatment of this complication. In order to evaluate its usefulness we conducted an open label, prospective and longitudinal study in 26 patients with Parkinson's disease (PD) on chronic levodopa therapy who presented peaks of dose dyskinesias. After 3 weeks' treatment dyskinesia severity was reduced by 70% (p < 0.0001) on the I SAPD scale and by 68.8% (p < 0.0002) on the UPDRS IV subscale. Patients were later evaluated every 45 days showing persistent drug benefit during follow-up ranging from 2 to 11 months (mean 6.5 months). One third of our series presented unwanted effects which were only severe enough in 2 cases to discontinue treatment. In the others, side effects were transient or readily abated with amantadine dose reduction. Our findings support amantadine as a safe and useful drug to treat levodopa-induced dyskinesias which on occasion prove as disabling as PD itself. Treatment with amantadine should routinely be considered before indicating pallidotomy for levodopa-induced dyskinesias.
Expressions and Roles of Periostin in Otolaryngological Diseases (2014)

Periostin is a 90-kDa member of the fasciclin-containing family; it functions as part of matricellular proteins, and its production by airway epithelial cells is induced by IL-4 and IL-13. Periostin is secreted by fibroblasts and upregulated in the airway epithelia of patients with bronchial asthma; it is considered to contribute to remodeling under this pathological condition. However, despite many studies in diverse research areas, our overall understanding of this intriguing molecule is still inadequate. Here, we integrate the available evidence on periostin expression and its roles in otolaryngological diseases, including allergic rhinitis, chronic rhinosinusitis with nasal polyps, aspirin-induced asthma, organized hematoma, eosinophilic otitis media, and IgG4-related disease. Periostin might be involved as an important structural mediator in pathological processes such as insult and injury, Th2-driven inflammation, extracellular matrix restructuring, fibrosclerosis, tumor angiogenesis, and tissue remodeling.
The ami locus of the Gram‐positive bacterium Streptococcus pneumoniae is similar to binding protein‐dependent transport operons of Gram‐negative bacteria (1990)

The complete nucleotide sequence of the ami locus of Streptococcus pneumoniae revealed the presence of six open reading frames, amiABCDEF. The predicted Ami proteins are probably involved in a transport system. The AmiA, C, D, E, and F proteins exhibit homology with components of the oligopeptide permeases (opp) of Salmonella typhimurium and Escherichia coli. Intriguingly, the AmiB protein is homologous to ArsC, a cytosolic modifier subunit of the anion pump encoded by the arsenical resistance operon of the R-factor R773 from E. coli. Data are presented which indicate that Ami is indeed a transport system.
Three Isostructural Furosemide Prodrugs (1998)

The structures of three furosemide prodrugs, pivaloyloxymethyl 4-chloro-N-furfuryl-5-sulfamoylanthranilate, C18H21ClN2O7S, butyryloxymethyl 4-chloro-N-furfuryl-5-sulfamoylanthranilate, C17H19ClN2O7S, and isobutyryloxymethyl 4-chloro-N-furfuryl-5-sulfamoylanthranilate, C17H19ClN2O7S, have been determined; the crystals have been shown to be isostructural. The crystal structures are described and compared with that of a related prodrug. The dihedral angle between the two planar rings of each prodrug is close to 70°. The space group is P\overline{1} in each case, and the molecules pack as dimers in infinite chains along one of the crystallographic axes.
Irreversible Nek2 Kinase Inhibitors with Cellular Activity (2011)

A structure-based approach was used to design irreversible, cysteine-targeted inhibitors of the human centrosomal kinase, Nek2. Potent inhibition of Nek2 kinase activity in biochemical and cell-based assays required a noncatalytic cysteine residue (Cys22), located near the glycine-rich loop in a subset of human kinases. Elaboration of an oxindole scaffold led to our most selective compound, oxindole propynamide 16 (JH295). Propynamide 16 irreversibly inhibited cellular Nek2 without affecting the mitotic kinases, Cdk1, Aurora B, or Plk1. Moreover, 16 did not perturb bipolar spindle assembly or the spindle assembly checkpoint. To our knowledge, 16 is the first small molecule shown to inactivate Nek2 kinase activity in cells.
Small molecules targeting severe acute respiratory syndrome human coronavirus (2004)

Severe acute respiratory syndrome (SARS) is an infectious disease caused by a novel human coronavirus. Currently, no effective antiviral agents exist against this type of virus. A cell-based assay, with SARS virus and Vero E6 cells, was developed to screen existing drugs, natural products, and synthetic compounds to identify effective anti-SARS agents. Of >10,000 agents tested, approximately 50 compounds were found active at 10 microM; among these compounds, two are existing drugs (Reserpine 13 and Aescin 5) and several are in clinical development. These 50 active compounds were tested again, and compounds 2-6, 10, and 13 showed active at 3 microM. The 50% inhibitory concentrations for the inhibition of viral replication (EC(50)) and host growth (CC(50)) were then measured and the selectivity index (SI = CC(50)/EC(50)) was determined. The EC(50), based on ELISA, and SI for Reserpine, Aescim, and Valinomycin are 3.4 microM (SI = 7.3), 6.0 microM (SI = 2.5), and 0.85 microM (SI = 80), respectively. Additional studies were carried out to further understand the mode of action of some active compounds, including ELISA, Western blot analysis, immunofluorescence and flow cytometry assays, and inhibition against the 3CL protease and viral entry. Of particular interest are the two anti-HIV agents, one as an entry blocker and the other as a 3CL protease inhibitor (K(i) = 0.6 microM).
TAK1‐mediated stress signaling pathways are essential for TNF‐α‐promoted pulmonary metastasis of murine colon cancer cells (2005)

We have recently established a TNF-alpha-promoted metastasis model, in which the ability to metastasize to the lung was enhanced by stimulation of cultured colon 26 cells with TNF-alpha before intravenous inoculation. To investigate intracellular events in metastatic cascades of TNF-alpha-treated cancer cells, we have focused on the stress signaling pathways to c-Jun N-terminal kinase (JNK) and p38. Treatment with a specific inhibitor, SP600125 or SB203580, in vitro suppressed TNF-alpha-induced migration and pulmonary metastasis. Activation of endogenous TAK1, a mitogen-activated protein kinase (MAP3K) regulating the JNK and p38 MAPK pathways, was induced rapidly by TNF-alpha, and co-transfection of TAK1 with its activator protein TAB1 stimulated activation of JNK and p38 MAPKs, which led to activation of the transcription factor AP-1. The activation of stress signaling pathways by TAK1 resulted in enhanced migration to fibronectin in vitro and metastasis to the lung in vivo without affecting cell proliferation in vitro and tumor growth in vivo. Moreover, knockdown of endogenous TAK1 using small interfering RNA (siRNA) suppressed the TNF-alpha-induced JNK/p38 activation, migration and pulmonary metastasis. These results indicate that TAK1-mediated stress signaling pathways in cancer cells are essential for TNF-alpha-promoted metastasis to the lung.