gebhart/patrepeval huggingface dataset:
State‐dependent NMDA receptor antagonism by Ro 8‐4304, a novel NR2B selective, non‐competitive, voltage‐independent antagonist (1998)

1. Subunit-selective blockade of N-methyl-D-aspartate (NMDA) receptors provides a potentially attractive strategy for neuroprotection in the absence of undesirable side effects. Here, we describe a novel NR2B-selective NMDA antagonist, 4-¿3-[4-(4-fluoro-phenyl)-3,6-dihydro-2H-pyridin-1-yl]-2-hydroxy-propoxy ¿-benzamide (Ro 8-4304), which exhibits >100 fold higher affinity for recombinant NR1(001)/NR2B than NR1(001)/NR2A receptors. 2. Ro 8-4304 is a voltage-independent, non-competitive antagonist of NMDA receptors in rat cultured cortical neurones and exhibits a state-dependent mode of action similar to that described for ifenprodil. 3. The apparent affinity of Ro 8-4304 for the NMDA receptor increased in an NMDA concentration-dependent manner so that Ro 8-4304 inhibited 10 and 100 microM NMDA responses with IC50s of 2.3 and 0.36 microM, respectively. Currents elicited by 1 microM NMDA were slightly potentiated in the presence of 10 microM Ro 8-4304, and Ro 8-4304 binding slowed the rate of glutamate dissociation from NMDA receptors. 4. These results were predicted by a reaction scheme in which Ro 8-4304 exhibits a 14 and 23 fold higher affinity for the activated and desensitized states of the NMDA receptor, respectively, relative to the agonist-unbound resting state. Additionally, Ro 8-4304 binding resulted in a 3 4 fold increase in receptor affinity for glutamate site agonists. 5. Surprisingly, whilst exhibiting a similar affinity for NR2B-containing NMDA receptors as ifenprodil, Ro 8-4304 exhibited markedly faster kinetics of binding and unbinding to the NMDA receptor. This spectrum of kinetic behaviour reveals a further important feature of this emerging class of NR2B-selective compounds.
SH2-Directed Ligands of the Lck Tyrosine Kinase (2000)

Two separate libraries, prepared via parallel synthesis, were employed to identify low-molecular-weight SH2-targeted ligands for the Lck tyrosine protein kinase. These libraries were constructed to furnish non-amino acid analogues of the (1) Glu-Glu and (2) Ile residues of the Lck SH2 domain peptide ligand Ac-pTyr-Glu-Glu-Ile-amide. The lead compound acquired in this study exhibits a dissociation constant for the Lck SH2 domain that is comparable to that displayed by Ac-pTyr-Glu-Glu-Ile-amide. These results demonstrate that the standard amino acid residues Glu-Glu-Ile can be completely replaced with non-amino acid moieties without loss of SH2 affinity.
Isolation and characterization of a high molecular weight glycoprotein from human blood platelets. (1978)

In this episode, Noah and Vivian discuss their thoughts and feelings about web3 lingo. GM. WAGMI. Diamond Hands. Rekt. So many words, so little time, so many feelings. \nNoah recalls work from photographer Aaron Ferguson, who had a collection of photographs of GM spray painted around his city. Aaron discusses his thoughts behind the photographs, his general feelings about web3 lingo, toxic positivity, NFT community, and favorite web3 term. \nA few more voicemails come into the hotline, with the callers discussing terms they do not like, including GM, GN, Ser, and LFG. This leads to a rapid fire discussion with ...
Luteinizing hormone-releasing hormone agonist triptorelin antagonizes signal transduction and mitogenic activity of epidermal growth factor in human ovarian and endometrial cancer cell lines (1996)

This study was designed to elucidate the signal transduction mechanisms, mediating the antiproliferative effects of analogs of luteinizing hormone releasing hormone (LHRH) on cell lines derived from human cancers of the ovary (EFO-21, EFO-27) and the endometrium (HEC-1A, Ishikawa). The LHRH agonist triptorelin had no measurable effects on the activity of phospholipase C, protein kinase C, or adenylate cyclase in all 4 cell lines, though these enzymes could be activated through pharmacological stimuli. The proliferation of EFO-21, EFO-27 and HEC-1A cells in serum/phenol red-free medium was significantly stimulated by epidermal growth factor (EGF). This mitogenic effect of EGF was dose dependently antagonized by triptorelin, without affecting the concentrations of EGF receptors. Net tyrosine phosphorylation induced by 1 nM EGF was nearly completely suppressed by simultaneous addition of 10 mu M triptorelin or preincubation for 48 h with 100 nM triptorelin. This inhibitory effect of the LHRH agonist on EGF-induced net tyrosine phosphorylation was partly antagonized by exposure to 100 mu M sodium vandate, an inhibitor of phosphotyrosine phosphatase. In EFO-21, EFO-27, and HEC-1A cells exposure to 100 nM EGF for 5 min induced an approximately 5-fold increase in activity of mitogen activated protein kinase (MAP-kinase)/extracellular signal regulated kinase (ERK) which was virtually nullified, when the cells were exposed for 15 min to 10 mu M triptorelin. These data suggest that LHRH signal transduction mechanisms based on the activation of phospholipase C, protein kinase C, and adenylate cyclase, which operate in the pituitary gonadotroph, are not necessarily involved in the mediation of the antiproliferative effects of triptorelin in these ovarian and endometrial cancer cell lines. Instead our findings support the hypothesis that triptorelin interferes with mitogenic signal transduction, probably through antagonizing tyrosine kinase activity of the EGF receptor.
The post-translational modification of ras p21 is important for Raf-1 activation. (1994)

Raf-1, a serine/threonine kinase, is required for the mitogenic action of ras p21. It has been recently demonstrated that ras p21 directly associates with Raf-1. The C-terminal region of ras p21 is modified by farnesylation and carboxyl methylation. This modification is necessary for ras p21 function. To elucidate the role of post-translational modification of ras p21 in Raf-1 activation, we examined ras p21-dependent Raf-1 activity in baculovirus/Sf9 cells overexpressing Raf-1 and ras p21. Coexpression of Raf-1 with v-ras p21 in Sf9 cells stimulated the autophosphorylating activity of Raf-1. The activity of Raf-1, as assessed by its ability to activate extracellular signal-regulated kinase kinase (MEK) in vitro, was also increased when Raf-1 was coexpressed with v-ras p21. However, neither the autophosphorylating activity of Raf-1 nor its ability to activate MEK was stimulated by v-ras p21 mutants which are not post-translationally modified. Raf-1 formed a complex with v-ras p21 and the v-ras p21 mutants in Sf9 cells. These results indicate that the post-translational modification of ras p21 is necessary for Raf-1 activation but that the association of Raf-1 with ras p21 is not sufficient to activate Raf-1.
Ultrasound imaging for the rheumatologist VII. Ultrasound imaging in rheumatoid arthritis. (2007)

The present review provides an update of the available data and discusses research issues of ultrasound (US) imaging in rheumatoid arthritis (RA). Currently the principal indications for using US in the assessment of patients with RA include: detection of sub-clinical synovitis, demonstration of bone erosion undetected by conventional radiography, detailed assessment of tendon pathology and guided injection and aspiration of joints and soft tissues. Future potential applications are likely to include short and long term therapy monitoring and early detection of cartilaginous changes in RA. The main priorities requiring the attention of investigators include: addressing validity issues, especially those related to criterion and discriminator validity, development of international consensus on scoring systems, evaluation of the role of power Doppler in the assessment of disease activity, development of a specific training programme for rheumatologists performing US and investigation of the potential of 3D US using a volumetric probe.
Core Gut Bacteria Analysis of Healthy Mice (2019)

Previous studies revealed that there existed great individual variations of gut microbiota in mice, and the gut bacteria of mice were changed with the occurrence and development of diseases. To identify the core gut bacteria in healthy mice and explore their relationships with the host phenotypes would help to understand the underlying mechanisms. In this study, we identified 37 genus-level core bacteria from feces of 101 healthy mice with different ages, sexes, and mouse strains in three previous studies. They collectively represented nearly half of the total sequences, and predominantly included carbohydrate- and amino acids-metabolizing bacteria and immunomodulatory bacteria. Among them, <i>Anaerostipes</i> indwelt the gut of all healthy mice. Co-abundance analysis showed that these core genera were clustered into five groups (Group C1-C5), which were ecologically related. For example, the abundances of Group C2 including probiotics <i>Bifidobacterium</i> and <i>Lactobacillus</i> slightly positively correlated with those of Group C1. Principal component analysis (PCA) and multivariate analysis of variance test revealed that these core gut genera were distinguished with age and sex, and also associated with their health/disease state. Linear discriminant analysis effect size (LEfSe) method showed that bacteria in Group C1 and C2/C3 increased with the age in infancy and early adulthood, and were more abundant in female mice than in male ones. The metabolic syndrome (MS) induced by high fat diet (HFD) and accelerated postnatal growth would decrease Group C2 genera, whereas probiotics intervention would reverse HFD-induced reduction of Group C2. Spearman correlation analysis indicated that the principal components based on the abundance of the 37 core genera were significantly correlated with host characteristic parameters of MS. These results demonstrated that the 37 core genera in five co-abundance groups from healthy mice were related to host phenotypes. It was indicated that these prevalent gut bacterial genera could be representative of the healthy gut microbiome in gnotobiotic animal models, and might also be candidates of probiotics and fecal microbiota transplantation.
Heating rate influence on the synthesis of iron oxide nanoparticles: the case of decanoic acid (2010)

Iron oxide nanoparticles with uniform sizes between 13 nm and 180 nm can be selectively prepared through the "heating up" thermal decomposition method by using decanoic acid and carefully tuning the heating rate.
Bridging of β-catenin and glycogen synthase kinase-3β by Axin and inhibition of β-catenin-mediated transcription (1998)

Axin antagonizes the developmental effects of Wnt in vertebrates. We show here that Axin simultaneously binds two components of the Wnt pathway, beta-catenin and its negative regulator glycogen synthase kinase-3beta. In mammalian cells, Axin inhibits Wnt-1 stimulation of beta-catenin/lymphoid enhancer factor 1-dependent transcription. Axin also blocks beta-catenin-mediated transcription in colon cancer cells that have a mutation in the adenomatous polyposis coli gene. These findings suggest that Axin, by forming a complex with beta-catenin and glycogen synthase kinase-3beta, can block signaling stimulated by Wnt or by adenomatous polyposis coli mutations.
Query-URL bipartite based approach to personalized query recommendation (2008)

Query recommendation is considered an effective assistant in enhancing keyword based queries in search engines and Web search software. Conventional approach to query recommendation has been focused on query-term based analysis over the user access logs. In this paper, we argue that utilizing the connectivity of a query-URL bipartite graph to recommend relevant queries can significantly improve the accuracy and effectiveness of the conventional query-term based query recommendation systems. We refer to the Query-URL Bipartite based query reCommendation approach as QUBIC. The QUBIC approach has two unique characteristics. First, instead of operating on the original bipartite graph directly using biclique based approach or graph clustering, we extract an affinity graph of queries from the initial query-URL bipartite graph. The affinity graph consists of only queries as its vertices and its edges are weighted according to a query-URL vector based similarity (distance) measure. By utilizing the query affinity graph, we are able to capture the propagation of similarity from query to query by inducing an implicit topical relatedness between queries. We devise a novel rank mechanism for ordering the related queries based on the merging distances of a hierarchical agglomerative clustering. We compare our proposed ranking algorithm with both naïve ranking that uses the query-URL similarity measure directly, and the single-linkage based ranking method. In addition, we make it possible for users to interactively participate in the query recommendation process, to bridge the gap between the determinacy of actual similarity values and the indeterminacy of users ’ information needs, allowing the lists of related queries to be changed from user to user and query to query, thus personalizing the query recommendation on demand. The experimental results from two query collections demonstrate the effectiveness and feasibility of our approach. 1.
THE SIX MISTAKES EXECUTIVES MAKE IN RISK MANAGEMENT (2009)

We don’t live in the world for which conventional risk-management textbooks prepare us. No forecasting model predicted the impact of the current economic crisis, and its consequences continue to take establishment economists and business academics by surprise. Moreover, as we all know, the crisis has been compounded by the banks’ socalled risk-management models, which increased their exposure to risk instead of limiting it and rendered the global economic system more fragile than ever.
Electrospun TiO2 Nanofiber‐Based Cell Capture Assay for Detecting Circulating Tumor Cells from Colorectal and Gastric Cancer Patients (2012)

A nanostructured platform that combines electrospun TiO(2) nanofibers (TiNFs)-deposited substrate and cell-capture agent realizes significant capture of circulating tumor cells (CTCs). The enhanced local topographic interactions between the horizontally packed TiNFs deposited substrates and extracellular matrix scaffolds, in addition to anti-EpCAM/EpCAM biological recognition, contributes to the significantly enhanced capture efficiency compared to flat surfaces.
Translational frameshifting generates the gamma subunit of DNA polymerase III holoenzyme. (1990)

The dnaX gene (previously called dnaZX) of Escherichia coli has only one open reading frame for a 71-kDa polypeptide from which two distinct DNA polymerase III holoenzyme subunits, tau (71 kDa) and gamma (47 kDa), are produced. To determine how the gamma subunit is generated, we examined the influence of mutations in the dnaX gene on the pattern of tau and gamma production in overproducing cells. Important structural elements in dnaX mRNA include a stretch of six adenines (nucleotides 1425-1430), a stable hairpin structure (nucleotides 1437-1466), and a UGA stop codon in a -1 frame (nucleotides 1434-1436) between the stretch of adenines and the hairpin structure. Disruption of this stop codon generates a slightly larger gamma subunit, indicative of the use of a -1 stop codon farther downstream (nucleotides 1470-1472). These results suggest that a -1 frameshift during translation allows the use of this UGA codon to terminate translation of the gamma polypeptide. The amino acid composition, sequence, and mass spectra of a C-terminal peptide from mild digestion of the purified gamma protein with endoproteinase Lys-C confirms that this frameshift occurs at either of the two lysine codons in the region of the adenine stretch. Remarkable features of this frameshifting are its high frequency (i.e., about 80% in an overproducing cell) and the striking structural similarity to the frameshifting signal responsible for expression of the pol and pro genes in many retroviruses.
Phase II study of lapatinib in combination with vinorelbine, as first or second-line therapy in women with HER2 overexpressing metastatic breast cancer (2014)

The combination of lapatinib and vinorelbine was active, feasible and well tolerated in patients with HER2-positive advanced breast cancer.
Mixed-domain coding of speech at 3 kb/s (2002)

We present a speech coding algorithm called mixed-domain residual coding (MDRC) wherein a prototype pitch cycle in each frame of the speech residual is coded in the time-domain while interpolation of the residual signal is performed in the frequency-domain. A novel quantization scheme takes into account time scaling and differentially codes successive prototypes with a closed-loop perceptually-weighted search. A fixed-rate (3.15 kb/s) implementation of MDRC achieves quality better or comparable to higher rate coders such as FS 1016 CELP and IMBE.
Single-cell RNA-seq and V(D)J profiling of immune cells in COVID-19 patients (2020)

Coronavirus disease 2019 (COVID-19) has caused over 220,000 deaths so far and is still an ongoing global health problem. However, the immunopathological changes of key types of immune cells during and after virus infection remain unclear. Here, we enriched CD3+ and CD19+ lymphocytes from peripheral blood mononuclear cells of COVID-19 patients (severe patients and recovered patients at early or late stages) and healthy people (SARS-CoV-2 negative) and revealed transcriptional profiles and changes in these lymphocytes by comprehensive single-cell transcriptome and V(D)J recombination analyses. We found that although the T lymphocytes were decreased in the blood of patients with virus infection, the remaining T cells still highly expressed inflammatory genes and persisted for a while after recovery in patients. We also observed the potential transition from effector CD8 T cells to central memory T cells in recovered patients at the late stage. Among B lymphocytes, we analyzed the expansion trajectory of a subtype of plasma cells in severe COVID-19 patients and traced the source as atypical memory B cells (AMBCs). Additional BCR and TCR analyses revealed a high level of clonal expansion in patients with severe COVID-19, especially of B lymphocytes, and the clonally expanded B cells highly expressed genes related to inflammatory responses and lymphocyte activation. V-J gene usage and clonal types of higher frequency in COVID-19 patients were also summarized. Taken together, our results provide crucial insights into the immune response against patients with severe COVID-19 and recovered patients and valuable information for the development of vaccines and therapeutic strategies.
IRF-1 induced cell growth inhibition and interferon induction requires the activity of the protein kinase PKR. (1995)

Expression of the tumor suppressor IRF-1 results in the inhibition of cell growth and transcriptional activation of the IFN-beta gene. IFN production is not responsible for the IRF-1 mediated cell growth inhibition. It is shown here that activation of the IRF-1 causes induction of PKR expression. PKR is a serine/threonine kinase with tumor suppressor activity. IRF-1 mediated cell growth inhibition and IFN induction correlates with PKR expression. A catalytically inactive dominant negative PKR mutant abolishes both activities of IRF-1. These data demonstrate that the tumor suppressor activity of IRF-1 is mediated, at least in part, by PKR.
Syngeneic sensitization of mouse lymphocytes on monolayers of thyroid epithelial cells. III. Induction of thyroiditis by thyroid‐sensitized T lymphoblasts (1982)

During in vitro sensitization of CBA spleen lymphocytes on syngeneic monolayers of either thyroid epithelial cells (TEC) or fibroblasts, stimulation occurs, as assessed by thymidine incorporation and lymphoblast generation. When lymphoblasts generated on syngeneic TEC are injected either into thyroid lobes of intact CBA recipients or i.v., thyroiditis appears at least 21 days after injection. Thyroiditis is assessed by both optical and electron microscopic blind studies and by the presence of antibodies in the sera directed against mouse thyroglobulin. In contrast, control animals which received identical numbers of lymphoblasts generated on syngeneic fibroblasts behaved as normal. Thyroiditis was also induced using pure thyroid-sensitized T lymphoblasts. This is the first report showing the role of T lymphocytes in the induction of experimental autoimmune thyroiditis.
Electrical properties of lightly doped p-type silicon–germanium single crystals (1998)

Experimental results are presented on the electrical properties of lightly boron doped bulk Si1−xGex as a function of the Ge content x in the range 0&amp;lt;x&amp;lt;0.13. Calculations of the hole mobility in Si and in Si1−xGex and comparison with experimental results allow us to estimate the averaged scattering potential of the randomly distributed Ge atoms to be 0.55 eV. From Hall effect and capacitance–voltage measurements, a Hall factor around 0.8 at T=300 K is derived. Hall effect measurements in the temperature range 20–300 K enable us to determine the boron acceptor activation energy, which decreases from 45 meV at x=0 down to 32 meV for x=0.13, and to estimate the hole effective masses to be meff/m0≈0.45.
Hairpin, Dumbbell, and Single-Stranded Phosphodiester Oligonucleotides Exhibit Identical Uptake in T Lymphocyte Cell Lines (1996)

The cellular binding, uptake, and intracellular distribution of structured double-stranded phosphodiester oligonucleotides (decoys) have been examined in T lymphocytes using fluorescein-labeled molecules. Intracellular localization of hairpin and dumbbell decoys was similar to that of single-stranded oligonucleotides. At short incubation times, oligonucleotides were localized only in cytoplasmic vesicles, whereas at longer times, they were also found in the nucleus. Cellular uptake was dependent on temperature, time, and extracellular concentration. Oligonucleotide efflux was similar for all types of molecules and was very rapid (t1/2 = 10-15 minutes). These results imply that phosphodiester double-stranded oligonucleotides can enter cellular compartments of interest for their potential biologic function and, thus, provide a potential tool to control gene transcription.
Evidence for a system of general protein glycosylation in Campylobacter jejuni (1999)

A genetic locus from Campylobacter jejuni 81-176 (O:23, 36) has been characterized that appears to be involved in glycosylation of multiple proteins, including flagellin. The lipopolysaccharide (LPS) core of Escherichia coli DH5alpha containing some of these genes is modified such that it becomes immunoreactive with O:23 and O:36 antisera and loses reactivity with the lectin wheat germ agglutinin (WGA). Site-specific mutation of one of these genes in the E. coli host causes loss of O:23 and O:36 antibody reactivity and restores reactivity with WGA. However, site-specific mutation of each of the seven genes in 81-176 failed to show any detectable changes in LPS. Multiple proteins from various cellular fractions of each mutant showed altered reactivity by Western blot analyses using O:23 and O:36 antisera. The changes in protein antigenicity could be restored in one of the mutants by the presence of the corresponding wild-type allele in trans on a shuttle vector. Flagellin, which is known to be a glycoprotein, was one of the proteins that showed altered reactivity with O:23 and O:36 antiserum in the mutants. Chemical deglycosylation of protein fractions from the 81-176 wild type suggests that the other proteins with altered antigenicity in the mutants are also glycosylated.