gebhart/patrepeval huggingface dataset:
Convenient Polymer-Supported Synthetic Route to Heterobifunctional Polyethylene Glycols (1998)

Conventional synthesis of heterobifunctional poly(ethylene glycol) derivatives, especially of medium size, is a rather tedious task. A straightforward solid-phase methodology has been developed that is illustrated here by the synthesis of alpha-pyridyldithio-omega-hydroxy-poly(ethylene glycol)600. This derivative was prepared from resin-bound PEG600 with a global yield of 65% for 6 individual steps, i.e., with an average yield of 93%/step. Intermediate purification steps simply consisted of resin washing. Progress of each reaction toward completion could conveniently be monitored by 13C NMR of the resin-bound PEG derivatives. This example highlights both the versatility and efficiency of combining polymer-supported synthesis with direct 13C-NMR characterization of the intermediate compounds.
Wnt signaling plays an essential role in neuronal specification of the dorsal spinal cord (2002)

In the developing spinal cord, signals from the roof plate are required for the development of three classes of dorsal interneuron: D1, D2, and D3, listed from dorsal to ventral. Here, we demonstrate that absence of Wnt1 and Wnt3a, normally expressed in the roof plate, leads to diminished development of D1 and D2 neurons and a compensatory increase in D3 neuron populations. This occurs without significantly altered expression of BMP and related genes in the roof plate. Moreover, Wnt3a protein induces expression of D1 and D2 markers in the isolated medial region of the chick neural plate, and Noggin does not interfere with this induction. Thus, Wnt signaling plays a critical role in the specification of cell types for dorsal interneurons.
Prognostic significance of post-clopidogrel platelet reactivity assessed by a point-of-care assay on thrombotic events after drug-eluting stent implantation (2008)

High post-treatment platelet reactivity measured with a point-of-care platelet function assay is associated with post-discharge events after PCI with DES, including stent thrombosis. Investigation of alternative clopidogrel dosing regimens to reduce ischaemic events in high-risk patients identified by this assay is warranted.
CaSPA2is important for polarity establishment and maintenance inCandida albicans (2003)

Saccharomyces cerevisiae Spa2p is a component of polarisome that controls cell polarity. Here, we have characterized the role of its homologue, CaSpa2p, in the polarized growth in Candida albicans. During yeast growth, GFP-tagged CaSpa2p localized to distinct growth sites in a cell cycle-dependent manner, while during hyphal growth it persistently localized to hyphal tips throughout the cell cycle. Persistent tip localization of the protein was also observed in Catup1Delta and Canrg1Delta, mutants constitutive for filamentous growth. Caspa2Delta exhibited defects in polarity establishment and maintenance, such as random budding and failure to confine growth to a small surface area leading to round cells with wide, elongated bud necks and markedly thicker hyphae. It was also defective in nuclear positioning, presumably a result of defective interactions between cytoplasmic microtubules with certain polarity determinants. The highly conserved SHD-I and SHD-V domains were found to be important and responsible for different aspects of CaSpa2p function. Caspa2Delta exhibited no virulence in the mouse systemic candidiasis model. Because of the existence of distinct growth forms and the easy control of the switch between them in vitro, C. albicans may serve as a useful model in cell polarity research.
Patterns of relapse in large-cell lymphoma patients with bulk disease: implications for the use of adjuvant radiation therapy. (1989)

In patients with large-cell lymphoma (LCL) treated with combination chemotherapy, the presence of bulk disease has consistently been associated with a poorer response rate and a shortened survival. The optimal therapy for patients with bulk disease (greater than or equal to 10 cm) will depend on whether treatment failures result from inadequate tumor eradication in prior bulk sites or from distant dissemination. To address this issue, we have evaluated patterns of relapse in patients with bulk disease who relapsed after achieving a complete remission with methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (M- or m-BACOD). Eighty-one II, III, or IV patients with disease greater than or equal to 10 cm were identified; 45 of the 81 patients achieved a confirmed complete response (CR) and are included in the analysis. The 45 complete responders included 21 patients with localized (stage II) disease and 24 patients with advanced (stage III/IV) disease. Six of the 21 stage II complete responders and three of the 24 stage II/IV complete responders also received adjuvant radiation therapy following completion of M- or m-BACOD. Only one of the 21 patients with stage II disease relapsed, doing so in the site of prior bulk involvement. In contrast, nine of 24 patients with stage III/IV disease relapsed, although no patient failed solely in the site of prior bulk disease. Stage III/IV patients recurred in either a new site (one patient), a new and old site (five), an old non-bulk site (two), or both old non-bulk and bulk sites (one). These results indicate that advanced-stage bulk-disease patients do not consistently relapse in sites of prior bulk disease; therefore, this group of patients is unlikely to benefit from adjuvant radiation therapy administered following completion of combination chemotherapy. Although the low relapse rate and the addition of adjuvant radiation therapy in a subgroup of the stage II bulk-disease patients precludes a definitive analysis, our results further suggest that these patients may be effectively treated with combination chemotherapy alone.
A phase II study of FOLFIRI-3 (double infusion of irinotecan combined with LV5FU) after FOLFOX in advanced colorectal cancer patients (2006)

In advanced colorectal cancer previously treated with oxaliplatin, efficacy of irinotecan-based chemotherapy is poor and the best regimen is not defined. We designed FOLFIRI-3 and conducted a phase II study to establish its efficacy and safety in advanced colorectal cancer patients previously treated with FOLFOX. FOLFIRI-3 consisted of irinotecan 100 mg m-2 as a 60-min infusion on day 1, running concurrently with leucovorin 200 mg m-2 as a 2-h infusion on day 1, followed by 46-h continuous infusion of 5-fluorouracil (5FU) 2000 mg m-2, and irinotecan 100 mg m-2 repeated on day 3, at the end of the 5FU infusion, every 2 weeks. Sixty-five patients entered the study. The intent-to-treat objective response rate was 23% (95% CI 13-33%). Disease was stable in 37% of patients, progressed in 26% and was not assessable in 14%. From the start of FOLFIRI-3, median progression-free survival was 4.7 months and median survival 10.5 months. Main toxicities (% of patients) were grade 3-4 diarrhoea 23% and grade 4 neutropenia 11%. FOLFIRI-3 is a promising regimen achieving high response rate and progression-free survival in patients previously treated with FOLFOX with a moderate toxicity.
Vaccinology in the genome era (2009)

Vaccination has played a significant role in controlling and eliminating life-threatening infectious diseases throughout the world, and yet currently licensed vaccines represent only the tip of the iceberg in terms of controlling human pathogens. However, as we discuss in this Review, the arrival of the genome era has revolutionized vaccine development and catalyzed a shift from conventional culture-based approaches to genome-based vaccinology. The availability of complete bacterial genomes has led to the development and application of high-throughput analyses that enable rapid targeted identification of novel vaccine antigens. Furthermore, structural vaccinology is emerging as a powerful tool for the rational design or modification of vaccine antigens to improve their immunogenicity and safety.
5‐HT1D receptor agonists and human coronary artery reactivity in vitro: crossover comparisons of 5‐HT and sumatriptan with rizatriptan and L‐741,519 (1996)

1 Rizatriptan (MK‐462, ( N , N ‐dimethyl‐2‐[5‐(1,2,4‐triazol‐1‐ylmethyl)‐1H‐indol‐3‐yl]ethylamine)) and its structurally related analogue L‐741,519 ( N ‐methyl‐4‐[5‐(1,2,4‐triazol‐4‐yl)‐1H‐indol‐3‐yl]piperidine) are novel 5‐HT 1D ‐receptor agonists. Rizatriptan has shown efficacy as an anti‐migraine agent in clinical trials. Since angiographic studies in patients have shown that sumatriptan (an established 5‐HT 1D ‐receptor agonist) can cause coronary artery vasoconstriction, we compared the effects of rizatriptan and L‐741,519 with those of 5‐HT and sumatriptan on endothelium‐denuded segments of human coronary artery in vitro . 2 Coronary arteries were obtained from explanted hearts from patients undergoing cardiac transplantation ( n =16 viable arteries from 13 males, 3 females, aged 38–68 years) and arterial segments (5–6 mm in length) were mounted in organ baths for isometric tension recording. Each segment was first exposed to 45mm KCl and then to 5‐HT (1 nm–100 μm). Concentration–effect curves to rizatriptan and sumatriptan (Study 1, n =6 or 7 arteries) or sumatriptan and L‐741,519 (Study 2, n =8 arteries) were then performed in a consecutive and random manner. The response to repeated application of 5‐HT was obtained in separate segments. 3 One artery showed severe atheroma and was not included in the analysis. ANOVA showed that 5‐HT responsiveness varied significantly between arteries from different patients, but not between arterial segments from the same patient. Desensitization was seen consistently across all agonists but did not significantly affect inter‐agonist comparisons. 4 There was graded effectiveness in the ability of the agonists to cause contraction with the rank order of E max values being 5‐HTsumatriptan&gt;L‐741,519&gt;rizatriptan. In terms of E C 50 values, L‐741,519 was significantly more potent than sumatriptan. 5 The present study (using a ‘cross‐over’ experimental protocol) confirms our previous observation that rizatriptan is less effective than sumatriptan in causing contraction of human isolated coronary artery. Furthermore, it shows that the lower maximum contractile response to rizatriptan, compared with that of sumatriptan, is not merely the consequence of variability in response to 5‐HT 1D ‐ receptor agonists between patients or between segments from the same artery.
Metabolism and transport of glutamine and glucose in vascularly perfused small intestine of the rat (1977)

1. The metabolism and transport of glutamine and glucose were investigated in a preparation of rat small intestine perfused through the vascular bed in vitro and in situ. 2. With glucose (7.5mm) or glutamine (4.5mm) in the lumen, approx. 40% of the substrate taken up appears unchanged on the vascular side. When glutamine (1.5mm) is also added to the vascular perfusate, metabolism of glutamine is increased and there is uptake of glutamine from both the vascular bed and lumen. Orientation of substrate (vascular bed or lumen) influences the value of alanine production/glutamine utilization and lactate production/glucose utilization. 3. Deprivation of food and metabolic acidosis have no effect upon the utilization of glutamine by unit length of jejunum. In fed rats, glutamine utilization is 44% of glucose utilization, but in rats deprived of food it is 112% of glucose utilization. 4. Glucose utilization and lactate production are not significantly altered by the presence of glutamine in the vascular bed or lumen. 5. With glucose only in the vascular perfusate, glucose utilization is the same in jejunum and ileum. Glutamine metabolism in the ileum is 28% lower than in the jejunum. 6. Glutamine utilization is dependent on the concentration of glutamine in the vascular perfusate, but is not significantly affected by the absence of glucose. 7. Results are discussed in relation to the role of intestinal glutamine metabolism and with respect to some problems of the transepithelial movement of substrates that are both transported and metabolized.
The Synthesis and Antifungal Activity of Nitrogen Containing Hemiaminal Ethers of LY303366. (1998)

LY303366 (Fig. 1), currently in phase II clinical trials, is a semisynthetic, broad spectrum, fungicidal agent derived through extensive structure-activity relationship (SAR) studies based on the echinocandin B (ECB) nucleus 1∼3) . Possession of such potent activity against clinically important fungi such as Aspergillus fumigatus, Candida albicans and Candida parapsilosis has prompted subsequent SAR studies focused on two major properties. First, improving the water solubility (<0.1 mg/ml) associated with the molecule and secondly, addressing the instability which is observed under strongly basic conditions. This instability is attributed to the hemiaminal group and results in a ring opened, inactive product as shown previously 4) . To this end, derivatization of the hemiaminal to form an ether linkage with amino alcohols would address both areas via formation of a stable hemiaminal ether possessing a pendant basic amine for salt formation. A similar approach has been taken in the pneumocandin B 0 class of antifungal agents 5) .
R-spondins function as ligands of the orphan receptors LGR4 and LGR5 to regulate Wnt/β-catenin signaling (2011)

The Wnt/β-catenin signaling system plays essential roles in embryonic development and in the self-renewal and maintenance of adult stem cells. R-spondins (RSPOs) are a group of secreted proteins that enhance Wnt/β-catenin signaling and have pleiotropic functions in development and stem cell growth. LGR5, an orphan receptor of the G protein-coupled receptor (GPCR) superfamily, is specifically expressed in stem cells of the intestinal crypt and hair follicle. Knockout of LGR5 in the mouse results in neonatal lethality. LGR4, a receptor closely related to LGR5, also has essential roles in development, as its knockout leads to reduced viability and retarded growth. Overexpression of both receptors has been reported in several types of cancer. Here we demonstrate that LGR4 and LGR5 bind the R-spondins with high affinity and mediate the potentiation of Wnt/β-catenin signaling by enhancing Wnt-induced LRP6 phosphorylation. Interestingly, neither receptor is coupled to heterotrimeric G proteins or to β-arrestin when stimulated by the R-spondins, indicating a unique mechanism of action. The findings provide a basis for stem cell-specific effects of Wnt/β-catenin signaling and for the broad range of functions LGR4, LGR5, and the R-spondins have in normal and malignant growth.
Restoring E-Cadherin Expression Increases Sensitivity to Epidermal Growth Factor Receptor Inhibitors in Lung Cancer Cell Lines (2006)

The epidermal growth factor receptor (EGFR) is overexpressed in the majority of non-small cell lung cancers (NSCLC). EGFR tyrosine kinase inhibitors, such as gefitinib and erlotinib, produce 9% to 27% response rates in NSCLC patients. E-Cadherin, a calcium-dependent adhesion molecule, plays an important role in NSCLC prognosis and progression, and interacts with EGFR. The zinc finger transcriptional repressor, ZEB1, inhibits E-cadherin expression by recruiting histone deacetylases (HDAC). We identified a significant correlation between sensitivity to gefitinib and expression of E-cadherin, and ZEB1, suggesting their predictive value for responsiveness to EGFR-tyrosine kinase inhibitors. E-Cadherin transfection into a gefitinib-resistant line increased its sensitivity to gefitinib. Pretreating resistant cell lines with the HDAC inhibitor, MS-275, induced E-cadherin along with EGFR and led to a growth-inhibitory and apoptotic effect of gefitinib similar to that in gefitinib-sensitive NSCLC cell lines including those harboring EGFR mutations. Thus, combined HDAC inhibitor and gefitinib treatment represents a novel pharmacologic strategy for overcoming resistance to EGFR inhibitors in patients with lung cancer.
SYNTHESIS OF AMINO ACIDS IN ANIMAL ORGANISMS. I. SYNTHESIS OF GLYCOCOLL AND GLUTAMINE IN THE HUMAN ORGANISM (1922)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSYNTHESIS OF AMINO ACIDS IN ANIMAL ORGANISMS. I. SYNTHESIS OF GLYCOCOLL AND GLUTAMINE IN THE HUMAN ORGANISMGeorge J. Shiple and Carl P. SherwinCite this: J. Am. Chem. Soc. 1922, 44, 3, 618–624Publication Date (Print):March 1, 1922Publication History Published online1 May 2002Published inissue 1 March 1922https://pubs.acs.org/doi/10.1021/ja01424a021https://doi.org/10.1021/ja01424a021research-articleACS PublicationsRequest reuse permissionsArticle Views66Altmetric-Citations29LEARN 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
Abundance-based Classifier for the Prediction of Mass Spectrometric Peptide Detectability Upon Enrichment (PPA) (2014)

The function of a large percentage of proteins is modulated by post-translational modifications (PTMs). Currently, mass spectrometry (MS) is the only proteome-wide technology that can identify PTMs. Unfortunately, the inability to detect a PTM by MS is not proof that the modification is not present. The detectability of peptides varies significantly making MS potentially blind to a large fraction of peptides. Learning from published algorithms that generally focus on predicting the most detectable peptides we developed a tool that incorporates protein abundance into the peptide prediction algorithm with the aim to determine the detectability of every peptide within a protein. We tested our tool, "Peptide Prediction with Abundance" (PPA), on in-house acquired as well as published data sets from other groups acquired on different instrument platforms. Incorporation of protein abundance into the prediction allows us to assess not only the detectability of all peptides but also whether a peptide of interest is likely to become detectable upon enrichment. We validated the ability of our tool to predict changes in protein detectability with a dilution series of 31 purified proteins at several different concentrations. PPA predicted the concentration dependent peptide detectability in 78% of the cases correctly, demonstrating its utility for predicting the protein enrichment needed to observe a peptide of interest in targeted experiments. This is especially important in the analysis of PTMs. PPA is available as a web-based or executable package that can work with generally applicable defaults or retrained from a pilot MS data set.
Advances in Targeting HER3 as an Anticancer Therapy (2012)

HER3 (ErbB3) is a unique member of the human epidermal growth factor receptor (EGFR) family (ErbB family). It functions only through dimerization with other members of the ErbB family and modulates activity and sensitivity to targeted cancer therapies. This paper briefly describes the mechanism of HER3 in signal transduction and its potential role in acquired resistance to EGFR- and HER2-targeted therapies. We also consider recent developments in HER3-targeting therapeutics and their combination with inhibitors of other ErbB members in clinical applications.
The fabrication and characterization of Cu-nanoparticle immobilization on a hybrid chitosan derivative-carbon support as a novel electrochemical sensor: application for the sensitive enzymeless oxidation of glucose and reduction of hydrogen peroxide (2013)

New hybrid chitosan derivatives (chitosan (Chit)), amine group grafted chitosan (N-Chit), and thiol group grafted chitosan (S-Chit) modified-carbon (carbon nanotubes or graphite) were prepared and used as supports for Cu-nanoparticles. The synthesized materials were characterized with different methods such as transmission electron microscopy, Brunauer-Emmett-Teller and cyclic voltammetry. The electrocatalytic effect of the nanohybrid was investigated in the reduction of hydrogen peroxide and the oxidation of glucose. It was found that the Cu nanoparticles decorate on the modified chitosan-CNT (Cu@M-Chit-CNT) exhibit a remarkable catalytic performance for H<sub>2</sub>O<sub>2</sub> reduction and glucose oxidation. Hydrodynamic amperometry was used for the electrochemical determination of H<sub>2</sub>O<sub>2</sub> and glucose. The linear range for H<sub>2</sub>O<sub>2</sub> was from 0.1 to 1000 μmol L<sup>-1</sup> with a detection limit of 0.025 μmol L<sup>-1</sup>, whereas the linear range for glucose was from 0.5 to 1000 μmol L<sup>-1</sup> with a detection limit of 0.05 μmol L<sup>-1</sup>. In addition, Cu@N-Chit-CNT/GCE and Cu@Chit-CNT/GCE showed a good selectivity for H<sub>2</sub>O<sub>2</sub> and glucose detection in the presence of dopamine, ascorbic acid and uric acid. The kinetic parameters such as the electron transfer coefficient and the catalytic reaction rate constant were also determined for glucose and H<sub>2</sub>O<sub>2</sub>. Finally, the modified electrode is the most sensitive probe ever reported and can be used to achieve the real-time quantitative detection of H<sub>2</sub>O<sub>2</sub> and glucose for biological applications.
The Thermophone (1922)

Acoustic Efficiency of Thermophones of the Heated Foil or Wire Type.---Theoretical formul\ae{} are derived for the maximum value of the alternating pressure produced within the enclosure of any thermophone when a given alternating current, superposed on a direct current, is passed through the central foil or wire. The effect of certain simplifying assumptions which are made is shown to be small in practical cases. As an experimental verification of the formul\ae{}, an electrostatic transmitter was calibrated for a wide range of frequencies with four thermophones which differed greatly in their physical constants, the formul\ae{} being used to compute the pressures produced. The four calibrations thus obtained agree with each other closely and also with an independent calibration made with a pistonphone.Methods of Calibrating Acoustical Transmitters.---In addition to the pistonphone, the thermophone is now available. The circuits used in calibrating an electrostatic transmitter are given.Method of Measuring the Thermal Conductivity of a Gas by Using a Thermophone is Suggested.---It would have the advantage of avoiding difficulties due to convection.