gebhart/patrepeval huggingface dataset:
Function of the c-Met receptor tyrosine kinase in carcinogenesis and associated therapeutic opportunities (2018)

c-Met is a receptor tyrosine kinase belonging to the MET (MNNG HOS transforming gene) family, and is expressed on the surfaces of various cells. Hepatocyte growth factor (HGF) is the ligand for this receptor. The binding of HGF to c-Met initiates a series of intracellular signals that mediate embryogenesis and wound healing in normal cells. However, in cancer cells, aberrant HGF/c-Met axis activation, which is closely related to c-Met gene mutations, overexpression, and amplification, promotes tumor development and progression by stimulating the PI3K/AKT, Ras/MAPK, JAK/STAT, SRC, Wnt/β-catenin, and other signaling pathways. Thus, c-Met and its associated signaling pathways are clinically important therapeutic targets. In this review, we elaborate on the molecular structure of c-Met and HGF and the mechanism through which their interaction activates the PI3K/AKT, Ras/MAPK, and Wnt signaling pathways. We also summarize the connection between c-Met and RON and EGFR, which are also receptor tyrosine kinases. Finally, we introduce the current therapeutic drugs that target c-Met in primary tumors, and their use in clinical research.
Differential Histone H3 Lys-9 and Lys-27 Methylation Profiles on the X Chromosome (2004)

Histone H3 tail modifications are among the earliest chromatin changes in the X-chromosome inactivation process. In this study we investigated the relative profiles of two important repressive marks on the X chromosome: methylation of H3 lysine 9 (K9) and 27 (K27). We found that both H3K9 dimethylation and K27 trimethylation characterize the inactive X in somatic cells and that their relative kinetics of enrichment on the X chromosome as it undergoes inactivation are similar. However, dynamic changes of H3K9 and H3K27 methylation on the inactivating X chromosome compared to the rest of the genome are distinct, suggesting that these two modifications play complementary and perhaps nonredundant roles in the establishment and/or maintenance of X inactivation. Furthermore, we show that a hotspot of H3K9 dimethylation 5' to Xist also displays high levels of H3 tri-meK27. However, analysis of this region in G9a mutant embryonic stem cells shows that these two methyl marks are dependent on different histone methyltransferases.
Human colonic intraepithelial and lamina proprial lymphocytes: cytotoxicity in vitro and the potential effects of the isolation method on their functional properties. (1981)

Colonic mucosal lymphoid cells, selectively enriched for intraepithelial (IEL) or lamina proprial lymphocytes (LPL), were isolated by sequential EDTA-collagenase treatment of resected human colons. Cytotoxic activities of colonic and peripheral blood lymphoid cells (PBL) were tested in three different assays, using chicken erythrocytes (CRBC) and Chang cells as targets. Antibody-dependent cell-mediated cytotoxicity (ADCC) and PHA-induced cytotoxicity (MICC) for both targets were shown by all the isolates of PBL, as was spontaneous cell-mediated cytotoxicity (SCMC) for Chang cells. However, no SCMC or ADCC for Chang cells was found with LPL, and IEL showed minimal or no activity in either assay. PBL, LPL and IEL demonstrated MICC for Chang cells but, contrasting with PBL and LPL, IEL showed no MCC for CRBC. No significant differences were found between the cytotoxic capabilities of colonic lymphoid cells from patients with inflammatory bowel disease and those from patients with other colonic diseases. Importantly, control studies with PBL showed that SCMC for Chang cells and ADCC for CRBC and Chang cells were reduced by collagenase treatment used in the isolation, of LPL. Also, SCMC for Chang cells was reduced by the treatment of PBL with EDTA. In contrast, neither EDTA nor collagenase reduced MICC for CRBC or Chang cells. Both forms of treatment induced variable degrees of cell losses in the PBL. By analogy, it can be implied that the isolation of intestinal mononuclear cells using EDTA and collagenase may influence some of their cytotoxic activities in vitro. This raises an important caveat in the interpretation of such studies.
Construction of a Large Naïve Human Phage-Displayed Fab Library Through One-Step Cloning (2008)

Antibody-based therapeutics is attracting more attention in the post-genome era, in contrast to a diminution in the initial high expectation for rapid development of gene-based therapeutic modalities. In support to the antibody-based therapeutics, the advent of recent technologies has made human antibody screening and production progressively more economic. Among those technologies, phage-display antibody library has been successfully applied in the antibody-based drug development both as fully human antibody sources and tools for antibody engineering. Building up a high-quality antibody library with a large library size and high diversity has been crucial for successful isolation of antibodies. Here we describe an efficient strategy for the construction of a large naïve phage-display human Fab library with one-step cloning. Optimization of each key step is extensively discussed and simplified protocols for library panning and Fab production are also described.
Peripheral Aromatic L-Amino Acids Decarboxylase Inhibitor in Parkinsonism. I. EFFECT ON O-METHYLATED METABOLITES OF L-DOPA-2-14C (1972)

The effects of MK-486, an inhibitor of peripheral aromatic L-amino acids decarboxylase, on the urinary metabolites derived from orally administered L-Dopa-2-(14)C were studied in three Parkinsonian patients. Treatment with MK-486 before L-Dopa-2-(14)C markedly reduced radioactivity found in catecholamines fraction by 70-80% during 48 hr, but increased 3-O-methyldopa fraction by threefold, as compared with a nonpretreated base line value. Pretreatment with MK-486 for a period of 1 wk resulted in less inhibition of O-methylated amine and acid metabolite fractions than that measured after a single dose of the inhibitor.
Context-based adaptive binary arithmetic coding in JVT/H.26L (2003)

In this paper a new adaptive entropy coding scheme for video compression is presented. It utilizes an adaptive arithmetic coding technique to better match the first order entropy of the coded symbols and to keep track of nonstationary symbol statistics. In addition, remaining symbol redundancies are exploited by context modeling to further reduce the bit-rate. A novel approach for coding of transform coefficients and a table look-up method for probability estimation and arithmetic coding is presented. Our new approach has been integrated in the current JVT test model (JM) to demonstrate the performance gain, and it was adopted as a part of the current JVT/H.26L draft.
Antifungals targeted to the cell wall (1997)

Serious fungal infections are increasingly common in immunocompromised patients and existing antifungals do not completely satisfy the medical need. The latter have either considerable toxicity, e.g., amphotericin, which is, however, less toxic in lipid formulations, or have limited activity, e.g., azoles. Cell wall acting antifungals are inherently selective and fungicidal; two classes of compounds--nikkomycin Z targeted at chitin synthase, and echinocandin LY 303366 and pneumocandin L-743,872 targeted at alpha-1,3-glucan synthase--are currently in clinical development.
Vascular leukocytes contribute to tumor vascularization (2004)

There is no proof that hematopoietic cells contribute significantly to vasculogenesis in postnatal life. Here we report a novel leukocyte subset within ovarian carcinoma that coexpresses endothelial and dendritic cell markers. Fluorescence-activated cell sorter (FACS) analysis identified a high frequency of VE-cadherin+ CD45+ leukocytes (39% of host cells) in 10 of 10 solid tumors evaluated. This population represented less than 1% of nontumor cells in ascites and peripheral blood. At the protein level, more than 86% of these cells expressed the endothelial markers P1H12, CD34, and CD31 and leukocyte markers CD11c and major histocompatibility complex (MHC) class II. At the mRNA level, we detected TEM1, TEM7, and Thy-1, specific markers of angiogenic endothelium. Finally, this population has the capacity to generate functional blood vessels in vivo. Because of its mixed phenotype, we named this population vascular leukocytes (VLCs). Our data provide an important link between hematopoietic endothelial precursors and vascular development in postnatal life and a possible novel therapeutic target.
MicroRNA Microarray Identifies Let-7i as a Novel Biomarker and Therapeutic Target in Human Epithelial Ovarian Cancer (2008)

MicroRNAs (miRNA) are approximately 22-nucleotide noncoding RNAs that negatively regulate protein-coding gene expression in a sequence-specific manner via translational inhibition or mRNA degradation. Our recent studies showed that miRNAs exhibit genomic alterations at a high frequency and their expression is remarkably deregulated in ovarian cancer, strongly suggesting that miRNAs are involved in the initiation and progression of this disease. In the present study, we performed miRNA microarray to identify the miRNAs associated with chemotherapy response in ovarian cancer and found that let-7i expression was significantly reduced in chemotherapy-resistant patients (n = 69, P = 0.003). This result was further validated by stem-loop real-time reverse transcription-PCR (n = 62, P = 0.015). Both loss-of-function (by synthetic let-7i inhibitor) and gain-of-function (by retroviral overexpression of let-7i) studies showed that reduced let-7i expression significantly increased the resistance of ovarian and breast cancer cells to the chemotherapy drug, cis-platinum. Finally, using miRNA microarray, we found that decreased let-7i expression was significantly associated with the shorter progression-free survival of patients with late-stage ovarian cancer (n = 72, P = 0.042). This finding was further validated in the same sample set by stem-loop real-time reverse transcription-PCR (n = 62, P = 0.001) and in an independent sample set by in situ hybridization (n = 53, P = 0.049). Taken together, our results strongly suggest that let-7i might be used as a therapeutic target to modulate platinum-based chemotherapy and as a biomarker to predict chemotherapy response and survival in patients with ovarian cancer.
Reprogramming Control of an Allosteric Signaling Switch Through Modular Recombination (2003)

Many eukaryotic signaling proteins are composed of simple modular binding domains, yet they can display sophisticated behaviors such as allosteric gating and multi-input signal integration, properties essential for complex cellular circuits. To understand how such behavior can emerge from combinations of simple domains, we engineered variants of the actin regulatory protein N-WASP (neuronal Wiskott-Aldrich syndrome protein) in which the "output" domain of N-WASP was recombined with heterologous autoinhibitory "input" domains. Synthetic switch proteins were created with diverse gating behaviors in response to nonphysiological inputs. Thus, this type of modular framework can facilitate the evolution or engineering of cellular signaling circuits.
Free-radical chain addition reactions of aldehydes with perfluoro ketones and chloro perfluoro ketones (1967)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFree-radical chain addition reactions of aldehydes with perfluoro ketones and chloro perfluoro ketonesWilbert H. Urry, A. Nishihara, and J. H. Y. NiuCite this: J. Org. Chem. 1967, 32, 2, 347–352Publication Date (Print):February 1, 1967Publication History Published online1 May 2002Published inissue 1 February 1967https://pubs.acs.org/doi/10.1021/jo01288a021https://doi.org/10.1021/jo01288a021research-articleACS PublicationsRequest reuse permissionsArticle Views315Altmetric-Citations24LEARN 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
[Research on heterocyclic compounds. V. Imidazo/2,1-b/thiazole-6-ascetic acids and imidazo/2,1-b/benzothiazole-2-acetic acids]. (1976)

We have prepared a group of ethyl imidazo [2,1-b]thiazole-6- and imidazo[2,1-b]benzothiazole-2-acetates, starting from some substituted 2-aminothiazoles and 2-aminobenzothiazoles, by reaction with ethyl 4-bromoacetoacetate. From these esters we have obtained the corresponding acetic acids, and we have tested their anti-inflammatory activity.
Efficiently delivering online services over integrated infrastructure (2016)

We present Footprint, a system for delivering online services in the integrated setting, where the same provider operates multiple elements of the infrastructure (e.g., proxies, data centers, and the wide area network). Such integration can boost system efficiency and performance by finely modulating how traffic enters and traverses the infrastructure. But fully realizing its benefits requires managing complex dynamics of service workloads. For instance, when a group of users are directed to a new proxy, their ongoing sessions continue to arrive at the old proxy, and this load at the old proxy declines gradually. Footprint harnesses such dynamics using a high-fidelity model that is also efficient to solve. Simulations based on a partial deployment of Footprint in Microsoft's infrastructure show that, compared to the current method, it can carry at least 50% more traffic and reduce user delays by at least 30%.
A compensatory base change in human U2 snRNA can suppress a branch site mutation. (1989)

We have developed an assay to test whether U2 snRNA can base-pair with the branch site during mammalian mRNA splicing. The beta 110 point mutation (GG----AG) within the first intron of human beta-globin generates a new 3' splice site that is preferentially used. We show here that use of the normal 3' splice site can be restored either by improving the match of a cryptic branch site to the branch site consensus or by introducing mutant U2 snRNAs with greater complementarity to the cryptic branch site. These data indicate that human U2 snRNA can form base pairs with the mRNA precursor; however, base pairing appears to be optional because some mammalian branch sites do not match the consensus.
Intercellular adhesion molecule-1 dimerization and its consequences for adhesion mediated by lymphocyte function associated-1. (1995)

Intercellular adhesion molecule-1 (ICAM-1, CD54) is a ligand for the integrins lymphocyte function associated-1 (LFA-1, CD11a/CD18) and complement receptor-3 (Mac-1, CD11b/CD18) making it an important participant in many immune and inflammatory processes. Modified recombinant soluble ICAM-1 formed dimers. This result indicated that the ectodomain of ICAM-1 contains homophilic interaction sites. Soluble ICAM-1 dimers bind to solid-phase purified LFA-1 with high avidity (dissociation constant [Kd] = 8 nM) in contrast to soluble ICAM-1 monomers whose binding was not measurable. Cell surface ICAM-1 was found to be dimeric based on two distinct criteria. First, a monoclonal antibody specific for monomeric soluble ICAM-1, CA7, binds normal ICAM-1 poorly at the cell surface; this antibody, however, binds strongly to two mutant forms of ICAM-1 when expressed at the cell surface, thus identifying elements required for dimer formation. Second, chemical cross-linking of cell surface ICAM-1 on transfected cells and tumor necrosis factor-activated endothelial cells results in conversion of a portion of ICAM-1 to a covalent dimer. Cell surface ICAM-1 dimers are more potent ligands for LFA-1-dependent adhesion than ICAM-1 monomers. While many extracellular matrix-associated ligands of integrins are multimeric, this is the first evidence of specific, functionally important homodimerization of a cell surface integrin ligand.
High-level IL-10 production by monoclonal antibody-stimulated human T cells. (1995)

We investigated interleukin-10 (IL-10) production in freshly isolated mononuclear cells and purified T cells in response to stimulation with monoclonal antibodies (mAb) recognizing CD3, CD2 and CD28, or with the bacterial products Staphylococcus aureus cells (SAC), staphylococcal enterotoxin (SEA) and lipopolysaccharide (LPS). IL-10 production was compared with that of IL-2, IL-4 and interferon-gamma (IFN-gamma). Similar to the other cytokines, in peripheral blood mononuclear cells (PBMC) from adult donors the highest IL-10 levels were produced in response to CD2 plus CD28 stimulation, within 72-96 hr of stimulation. Levels of IL-10 in response to CD2 plus CD28 stimulation (1.9 +/- 1 ng/ml) exceeded those in response to SEA (0.25 +/- 0.16 ng/ml), SAC (0.43 +/- 0.42 ng/ml), or LPS (0.19 +/- 0.14 ng/ml) stimulation. With adult purified T cells, high levels of IL-10 and IL-4 were measured following CD3 plus CD28 stimulation, and the amounts of both T-helper type-2 (Th2) cytokines decreased following the addition of phorbol myristate acetate (PMA), whereas the synthesis of the Th1 cytokines IL-2 and IFN-gamma was enhanced. When PBMC were stimulated with a CD3 mAb and different other cytokines were added, strong enhancement of IL-10 production was seen upon the addition of IL-2, IL-4, IL-7, IL-12 and IFN-gamma, whereas inhibition was found with transforming growth factor-beta 1 (TGF-beta 1). These data illustrate that in freshly isolated PBMC large amounts of IL-10 can be induced rapidly by appropriate mAb stimulation, and that even in freshly isolated cells IL-4 and IL-10 show signs of parallel regulation.
Blob population dynamics during immiscible two-phase flows in reconstructed porous media (2013)

We study the dynamics of nonwetting liquid blobs during immiscible two-phase flows in stochastically reconstructed porous domains predominantly saturated by a wetting fluid. The flow problem is solved explicitly using a Lattice-Boltzmann model that captures both the bulk phase and interfacial dynamics of the process. We show that the nonwetting blobs undergo a continuous life cycle of dynamic breaking up and coalescence producing two populations of blobs, a mobile and a stranded one, that exchange continuously mass between them. The process reaches a ``steady state'' when the rates of coalescence and breaking up become equal, and the macroscopic flow variables remain practically constant with time. At steady state, mass partitioning between mobile and immobile populations depends strongly on the applied Bond number $\mathrm{Bo}$ and the initial nonwetting phase distributions. Three flow regimes are identified: a single-phase flow Darcy-type regime at low $\mathrm{Bo}$ numbers, a non-Darcy two-phase flow regime at intermediate values of $\mathrm{Bo}$, where the capillary number scales as $\mathrm{Ca}\ensuremath{\propto}{\mathrm{Bo}}^{2}$, and a Darcy-type two-phase flow regime at higher values of $\mathrm{Bo}$. Our numerical results are found to be in good agreement with recent experimental and theoretical works.
Space experiments with particle accelerators: SEPAC (1986)

The SEPAC instruments consist of an electron accelerator, a plasma accelerator, a neutral gas (N2) release device, particle and field diagnostic instruments, and a low light level television system. These instruments are used to accomplish multiple experiments: to study beam-particle interactions and other plasma processes; as probes to investigate magnetospheric processes; and as perturbation devices to study energy coupling mechanisms in the magnetosphere, ionosphere, and upper atmosphere.
Synthesis of Guanosine-3'-(5-bromo-4-chloroindol-3-yl)p-hosphate (G-3'-BCIP) (1996)

N -2-Benzoyl-5'- O -dimethoxytrityl-2'- O -tetrahydropyranylguanosine ( 5 ) and 1-acetyl-5-bromo-4-chloroindol-3-yl-3-phosphorodichloridate ( 7 ) were synthesized and coupled to give the title compound 9 .
miR‐29 suppression of osteonectin in osteoblasts: Regulation during differentiation and by canonical Wnt signaling (2009)

The matricellular protein osteonectin, secreted protein acidic and rich in cysteine (SPARC, BM-40), is the most abundant non-collagenous matrix protein in bone. Matricellular proteins play a fundamental role in the skeleton as regulators of bone remodeling. In the skeleton, osteonectin is essential for the maintenance of bone mass and for balancing bone formation and resorption in response to parathyroid hormone (PTH). It promotes osteoblast differentiation and cell survival. Mechanisms regulating the expression of osteonectin in the skeleton and in other tissues remain poorly understood. We found that the proximal region of the mouse osteonectin 3' untranslated region (UTR) contains a well-conserved, dominant regulatory motif that interacts with microRNAs (miRs)-29a and -29c. Transfection of osteoblastic cells with miR-29a inhibitors increased osteonectin protein levels, whereas transfection of miR-29a precursor RNA decreased osteonectin. miR-29a and -29c were increased during osteoblastic differentiation in vitro. The up-regulation of these miRNAs correlated with decreased osteonectin protein during the matrix maturation and mineralization phases of late differentiation. In contrast, osteonectin transcript levels remained relatively constant during this process, implying repression of translation. Treatment of osteoblasts with LiCl induced miR-29a and -29c expression and decreased osteonectin synthesis. When cells were treated with Dickkopf-1 (Dkk-1), miR-29a and -29c expression was repressed. These data suggest that canonical Wnt signaling, which is increased during osteoblastic differentiation, induces expression of miR-29. Osteonectin and miR-29 are co-expressed in extra-skeletal tissues, and the post-transcriptional mechanisms regulating osteonectin in osteoblasts are likely to be active in other cell systems.
The Role of Metal−Nanotube Contact in the Performance of Carbon Nanotube Field-Effect Transistors (2005)

Single-wall carbon nanotube field-effect transistors (CNFETs) have been shown to behave as Schottky barrier (SB) devices. It is not clear, however, what factors control the SB size. Here we present the first statistical analysis of this issue. We show that a large data set of more than 100 devices can be consistently accounted by a model that relates the on-current of a CNFET to a tunneling barrier whose height is determined by the nanotube diameter and the nature of the source/drain metal contacts. Our study permits identification of the desired combination of tube diameter and type of metal that provides the optimum performance of a CNFET.
Procalcitonin release patterns in a baboon model of trauma and sepsis: Relationship to cytokines and neopterin (2000)

PCT is detectable in the baboon as in humans, both in hemorrhagic shock and sepsis. PCT levels are significantly higher in sepsis than in hemorrhage, a finding that is probably related to the differences in endotoxin. The baboon can be used for the study of PCT kinetics in both models; PCT kinetics are clearly different from other markers of sepsis, either IL-6 or neopterin, in both models. There are significant differences between survivors and nonsurvivors in the sepsis model.