gebhart/patrepeval huggingface dataset:
Nuclear factor B as a target for new drug development in myeloid malignancies (2007)

The transcription nuclear factor k B (NF-kB) can intervene in oncogenesis through to its capacity to regulate the expression of a large number of genes that regulate apoptosis, cell proliferation and differentiation as well as inflammation, angiogenesis and tumor migration. Impaired NF-kB activity has been demonstrated not only in solid cancers but also in various types of hematologic malignancies including acute myeloid leukemia, chronic myelogenous leukemia and in a subset of myelodysplastic syndromes. The underlying mechanisms, illustrated in the text and although quite diverse in different diseases, provide the rationale for new therapeutic strategies combining different NF-kB or proteasome inhibitors. It has, therefore, been proposed that inhibition of NF-kB could be an adjuvant therapy for cancer and many phase I/II clinical studies are ongoing with different inhibitors. This review highlights the in vitro and in vivo results of NF-kB inhibition in myeloid malignancies.
The in vivo pharmacological profile of CS‐747, a novel antiplatelet agent with platelet ADP receptor antagonist properties (2000)

1. CS-747 is a novel antiplatelet agent that generates an active metabolite, R-99224, in vivo. CS-747 itself was totally inactive in vitro. This study examined in vivo pharmacological profiles of CS-747 after single oral administration to rats. 2. Orally administered CS-747 (0.3 - 10 mg kg(-1)) partially but significantly decreased [(3)H]-2-methylthio-ADP binding to rat platelets. CS-747 (3 mg kg(-1), p.o.) treatment neutralized ADP-induced decreases of cyclic AMP concentrations induced by prostaglandin E(1), suggesting that metabolites of CS-747 interfere with G(i)-linked P2T receptor. 3. CS-747 (0.3 and 3 mg kg(-1), p.o.) markedly inhibited ex vivo washed platelet aggregation in response to ADP but not to thrombin. CS-747 also exhibited a marked inhibition of ADP-induced ex vivo platelet aggregation in PRP with a rapid onset (<0.5 h) and long duration (>3 days) of action (ED(50) at 4 h=1.2 mg kg(-1)). 4. R-99224 (IC(50)=45 microM) inhibited in vitro PRP aggregation in a concentration-related manner. 5. CS-747 prevented thrombus formation in a dose-related manner with an ED(50) value of 0.68 mg kg(-1). CS-747 was more potent than clopidogrel (6.2 mg kg(-1)) and ticlopidine (>300 mg kg(-1)). 6. CS-747, clopidogrel, and ticlopidine prolonged the bleeding time. The order of potency of these agents in this activity was the same as that in antiaggregatory and antithrombotic activities. 7. These findings indicate that CS-747 is an orally active and a potent antiplatelet and antithrombotic agent with a rapid onset and long duration of action, and warrants clinical evaluations of the agent.
Functional topology of a surface loop shielding the catalytic center in lipoprotein lipase (1992)

Lipoprotein lipase (LPL), hepatic lipase, and pancreatic lipase show high sequence homology to one another. The crystal structure of pancreatic lipase suggests that it contains a trypsin-like Asp-His-Ser catalytic triad at the active center, which is shielded by a disulfide bridge-bounded surface loop that must be repositioned before the substrate can gain access to the catalytic residues. By sequence alignment, the homologous catalytic triad in LPL corresponds to Asp156-His241-Ser132, absolutely conserved residues, and the homologous surface loop to residues 217-238, a poorly conserved region. To verify these assignments, we expressed in vitro wild-type LPL and mutant LPLs having single amino acid mutations involving residue Asp156 (to His, Ser, Asn, Ala, Glu, or Gly), His241 (to Asn, Ala, Arg, Gln, or Trp), or Ser132 (to Gly, Ala, Thu, or Asp) individually. All 15 mutant LPLs were totally devoid of enzyme activity, while wild-type LPL and other mutant LPLs containing substitutions in other positions were fully active. We further replaced the 22-residue LPL loop which shields the catalytic center either partially (replacing 6 of 22 residues) or completely with the corresponding hepatic lipase loop. The partial loop-replacement chimeric LPL was found to be fully active, and the complete loop-replacement mutant had approximately 60% activity, although the primary sequence of the hepatic lipase loop is quite different. In contrast, replacement with the pancreatic lipase loop completely inactivated the enzyme. Our results are consistent with Asp156-His241-Ser132 being the catalytic triad in lipoprotein lipase.(ABSTRACT TRUNCATED AT 250 WORDS)
Homocysteine Impairs the Nitric Oxide Synthase Pathway (2001)

Homocysteine post-translationally inhibits DDAH enzyme activity, causing ADMA to accumulate and inhibit nitric oxide synthesis. This may explain the known effect of homocysteine to impair endothelium-mediated nitric oxide-dependent vasodilatation.
First-principles nonequilibrium analysis of STM-induced molecular negative-differential resistance on Si(100) (2008)

We report on theoretical investigations of scanning tunneling microscopy (STM)- induced molecular negative-differential resistance (NDR) on heavily $p$-type doped Si(100). Calculations are performed using the density functional theory (DFT) local density approximation (LDA) within the Keldysh nonequilibrium Green's function (NEGF) formalism. The nonequilibrium Hamiltonian is determined self-consistently for molecules on a Si(100) substrate and below a Pt(100) STM tip. We investigate in detail the nonequilibrium conditions which are likely to produce electronic $p$-type resonant NDR. The discussion is divided into two parts. First, we discuss STM distance dependence and its relation to $p$-type resonant NDR. It is shown that under high bias conditions electron tunneling is dominated by tunneling near the top of the vacuum barrier thereby preventing resonant NDR at large STM imaging distances. Second, we discuss the self-consistent bias profile and its effect on $p$-type NDR. It is shown that molecular charging effects may prevent the highest occupied molecular orbital from passing the silicon electrochemical potential, though bistable effects beyond the self-consistent NEGF-LDA method cannot be ruled out.
Effects of the 21-aminosteroid U74006F on experimental head injury in mice (1988)

The ability of a novel non-glucocorticoid 21-aminosteroid U74006F to inhibit lipid peroxidation of central nervous system tissue in vitro and to enhance the early neurological recovery and survival of mice after a severe concussive head injury is described. In the in vitro studies, U74006F was found to be an extremely potent inhibitor of lipid peroxidation in an assay system where the glucocorticoid steroid methylprednisolone and the non-glucocortoid steroids U72099E and U75718A were almost completely ineffective. In the head-injury studies, unanesthetized male CF-1 mice were subjected to a 900 gm-cm closed head injury produced by a 50-gm weight being dropped 18 cm. This concussive injury resulted in immediate unconsciousness (loss of righting reflex) in all animals and death in approximately 30%. Survivors received a tail vein injection of either vehicle or U74006F (0.001 to 30 mg/kg) within 5 minutes postinjury. Their neurological status was evaluated 1 hour later using a grip test. The grip-test score indicated that intravenous administration of a single dose of U74006F resulted in a significant improvement by as much as 168.6% in the neurological status 1 hour postinjury over a broad dose range (0.003 to 30 mg/kg). A 1-mg/kg dose given intravenously within 5 minutes and again at 1 1/2 hours after a severe injury, in addition to improving early recovery, also increased the 1-week survival rate to 78.6% compared to 27.3% in vehicle-treated mice (p less than 0.02). The compound was also effective in enhancing early recovery after a more moderate injury. This study demonstrates that early treatment after severe concussive head injury with a potent inhibitor of iron-dependent lipid peroxidation can significantly benefit the injured brain in mice and promote both early neurological recovery and long-term survival.
Distribution and modulation of the cellular receptor for transforming growth factor-beta. (1987)

Scatchard analyses of the binding of transforming growth factor-beta (TGF-beta) to a wide variety of different cell types in culture revealed the universal presence of high affinity (Kd = 1-60 pM) receptors for TGF-beta on every cell type assayed, indicating a wide potential target range for TGF-beta action. There was a strong (r = +0.85) inverse relationship between the receptor affinity and the number of receptors expressed per cell, such that at low TGF-beta concentrations, essentially all cells bound a similar number of TGF-beta molecules per cell. The binding of TGF-beta to various cell types was not altered by many agents that affect the cellular response to TGF-beta, suggesting that modulation of TGF-beta binding to its receptor may not be a primary control mechanism in TGF-beta action. Similarly, in vitro transformation resulted in only relatively small changes in the cellular binding of TGF-beta, and for those cell types that exhibited ligand-induced down-regulation of the receptor, down-regulation was not extensive. Thus the strong conservation of binding observed between cell types is also seen within a given cell type under a variety of conditions, and receptor expression appears to be essentially constitutive. Finally, the biologically inactive form of TGF-beta, which constitutes greater than 98% of autocrine TGF-beta secreted by all of the twelve different cell types assayed, was shown to be unable to bind to the receptor without prior activation in vitro. It is proposed that this may prevent premature interaction of autocrine ligand and receptor in the Golgi apparatus.
Cell-Penetrating Peptides, PepFects, Show No Evidence of Toxicity and ImmunogenicityIn VitroandIn Vivo (2011)

Cell-penetrating peptide based vehicles have been developed for the delivery of different payloads into the cells in culture and in animals. However, several biological features, among which is the tendency to trigger innate immune response, limit the development of highly efficient peptide-based drug delivery vectors. This study aims to evaluate the influence of transportan 10 (TP10) and its chemically modified derivatives, PepFects (PFs), on the innate immune response of the host system. PFs have shown high efficiency in nucleic acid delivery in vitro and in vivo; hence, the estimation of their possible toxic side effects would be of particular interest. In this study, we analyzed cytotoxic and immunogenic response of PF3, PF4, and PF6 peptides in monocytic leukemia and peripheral blood mononuclear cell lines. In comparison with amphipathic PFs, TP10, TAT, stearyl-(RxR)(4) peptides, and the most widely used transfection reagents Lipofectamine 2000 and Lipofectamine RNAiMAX were also analyzed in this study. IL-1β, IL-18, and TNF-α cytokine release was detected using highly sensitive enzyme-linked immunosorbent assay (ELISA). Cell viability was detected by measuring the activity of cellular enzymes that reduce water-soluble tetrazolium salts to formazan dyes and apoptosis was evaluated by measuring the levels of caspase-1 and caspase-3/7 over untreated cells. All peptides were found to be nontoxic and nonimmunogenic in vitro at the concentrations of 10 μM and 5 μM, respectively, and at a dose of 5 mg/kg in vivo, suggesting that these CPPs exhibit a promising potential in the delivery of therapeutic molecules into the cell without risks of toxicity and inflammatory reactions.
Molecular Basis of Neurotrophin−Receptor Interactions (2003)

ADVERTISEMENT RETURN TO ISSUEPerspectiveNEXTMolecular Basis of Neurotrophin−Receptor InteractionsMookda Pattarawarapan and Kevin BurgessView Author Information Texas A & M University, Department of Chemistry, P.O. Box 30012, College Station, Texas 77841-3012 Cite this: J. Med. Chem. 2003, 46, 25, 5277–5291Publication Date (Web):November 14, 2003Publication History Received9 May 2003Published online14 November 2003Published inissue 1 December 2003https://pubs.acs.org/doi/10.1021/jm030221qhttps://doi.org/10.1021/jm030221qreview-articleACS PublicationsCopyright © 2003 American Chemical SocietyRequest reuse permissionsArticle Views1177Altmetric-Citations57LEARN 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 SUBJECTS:Genetics,Monomers,Oligomers,Peptides and proteins,Receptors Get e-Alerts
Convolutional networks and applications in vision (2010)

Intelligent tasks, such as visual perception, auditory perception, and language understanding require the construction of good internal representations of the world (or "features")? which must be invariant to irrelevant variations of the input while, preserving relevant information. A major question for Machine Learning is how to learn such good features automatically. Convolutional Networks (ConvNets) are a biologically-inspired trainable architecture that can learn invariant features. Each stage in a ConvNets is composed of a filter bank, some nonlinearities, and feature pooling layers. With multiple stages, a ConvNet can learn multi-level hierarchies of features. While ConvNets have been successfully deployed in many commercial applications from OCR to video surveillance, they require large amounts of labeled training samples. We describe new unsupervised learning algorithms, and new non-linear stages that allow ConvNets to be trained with very few labeled samples. Applications to visual object recognition and vision navigation for off-road mobile robots are described.
Lithium dodecyl sulfate/polyacrylamide gel electrophoresis of thylakoid membranes at 4°C: Characterizations of two additional chlorophyll a-protein complexes (1979)

Lithium dodecyl sulfate/polyacrylamide gel electrophoresis of Chlamydomonas reinhardtii thylakoid membranes at room temperature gave two chlorophyll-protein complexes, CP I and CP II, as had been reported previously. However, when the electrophoresis was performed at 4 degrees C, there was an increase in the amount of chlorophyll associated with CP I and CP II, and in addition, three other chlorophyll-protein complexes appeared. Two of these complexes, designated CP III and CP IV, were characterized and found to be similar in their compositions. Each complex contains four to five molecules of chlorophyll a, one molecule of beta-carotene, and one polypeptide chain. The apoprotein of CP III is polypeptide 5 (M(r) 50,000) and that of CP IV is polypeptide 6 (M(r) 47,000); the two polypeptides are structurally unrelated. Chlorophyll-protein complexes similar to C. reinhardtii CP III and CP IV were also detected in higher plants (e.g., Pisum sativum). The apoproteins of the higher plant complexes are immunochemically related to those of the C. reinhardtii complexes, as shown by crossed immunoelectrophoresis. Absorption spectra of CP III and CP IV at -196 degrees C revealed a component at 682 nm. This observation, together with the previous results on photosystem II mutants [Chua, N.-H. & Bennoun, P. (1975) Proc. Natl. Acad. Sci. USA 72, 2175-2179], provides indirect evidence that CP III and CP IV may be involved in the primary photochemistry of photosystem II.
INTRA-ARTICULAR THIOTEPA THERAPY IN RHEUMATOID ARTHRITIS (1964)

Journal Article INTRA-ARTICULAR THIOTEPA THERAPY IN RHEUMATOID ARTHRITIS Get access M. E. FEARNLEY M. E. FEARNLEY Orpington HospitalKent Search for other works by this author on: Oxford Academic PubMed Google Scholar Rheumatology, Volume 7, Issue 8, November 1964, Pages 294–298, https://doi.org/10.1093/rheumatology/7.8.294 Published: 01 November 1964
Photonic Sampling of RF and Microwave Signals (1998)

The views expressed in this report are those of the author and do not reflect the oppical policy or position of the Department of Defense or the United States Government.
FIRE-RETARDANT-TREATED STRANDBOARD: PROPERTIES AND FIRE PERFORMANCE (2008)

This study evaluated a series of single-layer, randomly oriented strandboard panels made with one resin type, a single resin loading level, and four fire-retardant-treatment levels.The fire retardant (FR) evaluated was a pH-buffered combination of boric acid and organic phosphate.Siberian larch strands were separated into five batches.One batch of strands served as the untreated control group and was not treated with water or FR; the four other batches were individually treated using a vacuum-pressure-soak process of the strands in water or three progressively higher concentrations of FR solutions.Targeted water-or FRloading levels were no FR (0% FR-weight gain, water-treated control), 32 kg/m 3 FR (5% weight gain), 64 kg/m 3 FR (10% weight gain), and 96 kg/m 3 FR (15% weight gain).All water-or FR-treated strands were redried to less than 8% moisture content prior to diphenylmethane diisocyanate (MDI) resin application in rotary blenders using an aerosol sprayer.Three replicate specimens for each treatment level of 12.5-mm-thick, randomly oriented strandboard at a density of 650 kg/m 3 were evaluated.FR-treated strandboard had higher dry-and wet-internal bond strength and lower flexural strength than matched untreated strandboard.A Class B flame-spread rating was achieved near 10% FR-loading.These results suggest that better ratings seem possible at higher loadings.
Presence of C-type natriuretic peptide in cultured human endothelial cells and plasma (1992)

The present study was undertaken to investigate the presence of C-type natriuretic peptide (CNP) immunoreactivity in cultured human vascular endothelial cells and in human plasma. CNP immunoreactivity was present in cultured human aortic endothelial cells by both immunohistochemical staining and by radioimmunoassay. With the utilization of gel permeation chromatography, this immunoreactivity proved to be consistent with the higher molecular weight CNP-53. CNP immunoreactivity was also present in human plasma (n = 22) at low picogram concentrations (6.5 +/- 0.2 pg/ml) by specific radioimmunoassay. This immunoreactivity was consistent with the lower molecular weight CNP-22 by gel permeation chromatography. These findings suggest that the vascular endothelium may be the site of CNP production. The isolation of different molecular forms of CNP in tissue and plasma may be consistent with a storage form of the peptide in endothelial cells CNP-53, while CNP-22 circulates in plasma. In summary, the present study is consistent with CNP being a peptide of endothelial cell origin.
Measurement of isometric muscle strength: a reproducibility study of maximal voluntary contraction in normal subjects and amyotrophic lateral sclerosis patients (2000)

Amyotrophic lateral sclerosis (ALS) is a degenerative disease of unknown cause, resulting in the progressive loss of voluntary motor activity. Traditional methods of evaluating patients with ALS (neurologic assessment, manual muscle testing and rating scales) involve subjective elements and lack the sensitivity needed to detect small but meaningful changes in deterioration and therapeutic efficacy. This paper presents a recently developed strength measurement instrument, useful for the long-term monitoring of muscle strength deterioration in ALS. In addition, a reproducibility study to assess the intra- and interobserver reliability of maximal voluntary isometric contraction is reported. The strength measurement instrument consists of a strain gauge force transducer, a bridge amplifier and a mechanical structure to counteract movements. A personal computer acquires the strength signal during each voluntary contraction and automatically computes the maximal value. Reproducibility of measurement was assessed in 18 normal subjects tested twice, on successive days, with the same examiner and under the same conditions. The interexaminer reproducibility of measurement was assessed in a group of 13 normal subjects and 10 ALS patients. Each subject of the two groups was independently examined by three examiners. The two reproducibility studies showed a high intraclass correlation coefficient (0.91-0.97) and low SEM and measurement error (3-10%) in all muscle regions tested. The Bland and Altman plots confirmed these results.
Recombinant Anti-Botulinum Neurotoxin A Single-Chain Variable Fragment Antibody Generated Using a Phage Display System (2003)

A recombinant single-chain fragment variable antibody (scFv) to botulinum A neurotoxin (BoNT/A) was developed. BALB/C mice were immunized with BoNT/A. Splenomic RNA was isolated from the hyperimmune mice and used to prepare a cDNA library, from which the variable regions of the heavy and light chain antibody genes were generated and connected by a DNA linker. The resulting scFv genes were cloned into the phagemid vector pCANTAB5 in order to construct phage display scFv libraries. Individual anti-BoNT/A phage clones were isolated from the phage display libraries by immunoaffinity selection using immobilized BoNT/A and further evaluated by enzyme-linked immunosorbant assay, immunoprecipitation and Western blotting. Forty-eight clones were found to be BoNT/A-reactive. The most reactive clone, designated D12, was selected for further study. The scFv gene of D12 was subcloned into a Pichia pastoris vector, and expression in yeast was evaluated.
Tumorigenicity assay essential for facilitating safety studies of hiPSC-derived cardiomyocytes for clinical application (2019)

Transplantation of cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSC-CMs) is a promising treatment for heart failure, but residual undifferentiated hiPSCs and malignant transformed cells may lead to tumor formation. Here we describe a highly sensitive tumorigenicity assay for the detection of these cells in hiPSC-CMs. The soft agar colony formation assay and cell growth analysis were unable to detect malignantly transformed cells in hiPSC-CMs. There were no karyotypic abnormalities during hiPSCs subculture and differentiation. The hiPSC markers TRA1-60 and LIN28 showed the highest sensitivity for detecting undifferentiated hiPSCs among primary cardiomyocytes. Transplantation of hiPSC-CMs with a LIN28-positive fraction > 0.33% resulted in tumor formation in nude rats, whereas no tumors were formed when the fraction was < 0.1%. These findings suggested that combination of these in vitro and in vivo tumorigenecity assays can verify the safety of hiPSC-CMs for cell transplantation therapy.
Using collaborative filtering to weave an information tapestry (1992)

Tapestry is an experimental mail system developed at the Xerox Palo Alto Research