gebhart/patrepeval huggingface dataset:
Phase I study of TH-302, investigational hypoxia-targeted drug, in combination with sunitinib. (2013)

e15557 Background: Tumors often consist of highly hypoxic subregions known to be resistant to chemotherapy and radiotherapy. TH-302 is an investigational hypoxia-targeted drug with a 2-nitroimidazole trigger designed to release the DNA alkylator bromo-isophosphoramide mustard (Br-IPM) when reduced in severe hypoxia. Preclinical models demonstrate that treatment with sunitinib increased the tumor hypoxic fraction, the therapeutic target of TH-302. Initiating TH-302 following sunitinib significantly increased the efficacy of sunitinib in these models. In this phase 1 dose escalation study, TH-302 was combined with standard dose sunitinib. Methods: Eligible patients (pts) for the study (NCT01381822) had advanced RCC, GIST or PNET tumors, evaluable disease by RECIST, ECOG ≤2 and acceptable hematologic, hepatic and renal function. Pts received TH-302 in combination with standard full doses of 50 mg PO sunitinib daily from Day 1 to Day 28 of a 6 week cycle. TH-302 was administered IV on Days 8, 15 and 22. TH-302 starting dose was 240 mg/m 2 . The study objectives were to determine the MTD, DLTs and RP2D and to evaluate the safety and preliminary efficacy of TH-302 when used in combination with sunitinib. Results: Ten pts were enrolled. Median age: 63 (range 27-72); Female (5)/ Male (5); ECOG 0 (5); ECOG 1 (5); Primary tumor: RCC (6), GIST (4). Median prior chemotherapies: 3 (range: 0-3) including prior sunitinib in 7 pts. No DLTs were observed in the 3 pts at the 240 mg/m 2 cohort and 1 pt of 5 DLT evaluable in the 340 mg/m 2 cohort had a DLT of stomatitis. Eight pts discontinued (progressive disease (6), pursued other treatment options, adverse event unrelated to study drugs). Three pts had a study drug related SAE (neutropenic sepsis, anemia, hyperthyroidism). Common TH-302 related AEs were nausea and mucosal toxicity and were mostly grade 1 or 2. Grade 3/4 thrombocytopenia and neutropenia were reported in 4 pts and 3 pts, respectively. One of 4 (25%) pts with GIST had a confirmed PR and 3 of 4 (75%) pts with RCC had PRs including 2 with confirmed PRs. Conclusions: TH-302 can be administered in combination with full dose sunitinib. Mucositis was dose limiting. There is preliminary evidence of activity of TH-302 in combination with sunitinib in RCC. Clinical trial information: NCT01381822.
Coupling of aryl Grignard reagents by electron transfer to unsaturated 1,4-dihalo compounds (1981)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCoupling of aryl Grignard reagents by electron transfer to unsaturated 1,4-dihalo compoundsStephen K. Taylor, Stephen G. Bennett, Karl J. Heinz, and Lauren K. LashleyCite this: J. Org. Chem. 1981, 46, 10, 2194–2196Publication Date (Print):May 1, 1981Publication History Published online1 May 2002Published inissue 1 May 1981https://pubs.acs.org/doi/10.1021/jo00323a050https://doi.org/10.1021/jo00323a050research-articleACS PublicationsRequest reuse permissionsArticle Views327Altmetric-Citations30LEARN 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
Locating facial features using threshold images (2002)

This paper describes a scheme for locating the eyes and the mouth on a facial image with slightly constrained background. The presented method reasonably assumes that only the facial image should be thresholded well enough that the hair and eyes can be distinctly separated from the cheeks. It first searches for all potential circles with specific radius as the candidates of the irises by performing the Hough transform on the binarized image, then sifts the candidates to detect the two eyes. It then roughly binds the mouth region according to the anthropometric standards and finally utilizes the integral projections to obtain the position of the mouth. The method has been tested on 223 face pictures with different illuminating conditions and varied head poses, and showed a quite satisfactory performance in both speed and accuracy.
Novel benzothiazole derivatives with a broad antifungal spectrum: design, synthesis and structure–activity relationships (2013)

N-Myristoyltransferase (NMT) is a new target for the development of novel antifungal agents. The benzothiazole derivative FR1335 is a highly potent NMT inhibitor with fungicidal activity. However, FTR1335 was only active against Candida albicans and its antifungal spectrum and solubility remained to be improved. Thus, a series of benzothiazole derivatives were designed and synthesized by modifying the scaffold and side chain of FTR1335. Interestingly, the antifungal spectrum of the target compounds was significantly expanded and also new structure–activity relationship information was obtained. Particularly, compound 6m showed good inhibitory activity against a wide range of fungal pathogens including systemic fungus and dermatophytes. Its antifungal activity against Cryptococcus neoformans and Candida glabrata was higher than that of fluconazole. Moreover, compound 6m also exhibited in vivo antifungal activity in a Caenorhabditis elegans-Candida albicans infection model, which represents a promising lead for further optimization.
A Locally Amplified Strain Sensor Based on a Piezoelectric Polymer and Organic Field-Effect Transistors (2011)

Piezoelectric sensors are useful for a range of applications, but passive arrays suffer from crosstalk and signal attenuation, which have complicated the development of array-based polyvinylidene difluoride (PVDF) sensors. We have used organic field-effect transistors, which are compatible with the low Curie temperature of a flexible piezoelectric polymer, i.e., PVDF, to monolithically fabricate transimpedance amplifiers directly on the sensor surface and convert the piezoelectric charge signal into a current signal, which can be detected even in the presence of parasitic capacitance. The device couples the voltage generated by the PVDF film under strain into the gate of organic thin-film transistors using an arrangement that allows the full piezoelectric voltage to couple to the channel while also increasing charge-retention time. A bipolar detector is created using ultraviolet-ozone treatment to shift the threshold voltage and increase the current of the transistor under both compressive and tensile strain. An array of devices that maps the strain field on a PVDF film surface is demonstrated.
Crystal Structure of Thermotoga maritima α-l-Fucosidase (2004)

Fucosylated glycoconjugates are involved in numerous biological events, and alpha-l-fucosidases, the enzymes responsible for their processing, are therefore of crucial importance. Deficiency in alpha-l-fucosidase activity is associated with fucosidosis, a lysosomal storage disorder characterized by rapid neurodegeneration, resulting in severe mental and motor deterioration. To gain insight into alpha-l-fucosidase function at the molecular level, we have determined the crystal structure of Thermotoga maritima alpha-l-fucosidase. This enzyme assembles as a hexamer and displays a two-domain fold, composed of a catalytic (beta/alpha)(8)-like domain and a C-terminal beta-sandwich domain. The structures of an enzyme-product complex and of a covalent glycosyl-enzyme intermediate, coupled with kinetic and mutagenesis studies, allowed us to identify the catalytic nucleophile, Asp(244), and the Brønsted acid/base, Glu(266). Because T. maritima alpha-l-fucosidase occupies a unique evolutionary position, being far more closely related to the mammalian enzymes than to any other prokaryotic homolog, a structural model of the human enzyme was built to document the structural consequences of the genetic mutations associated with fucosidosis.
Highly efficient microwave coupling devices for remote plasma applications (1994)

Microwave resonant cavities running at 2.45 GHz are now being investigated for use in the high power remote plasma processings. The present paper deals with the design of two coupling devices, e.g., one coaxial cavity and one TM012 mode cylindrical cavity, using an antenna coupling. Their main attractive feature is the ability to run at powers as high as 3 and 6 kW, respectively. A basic model used to describe the wave–plasma interaction is developed and leads to the main consequences for the cavities conception thanks to the deduced equivalent electrical circuits. Their high efficiency is experimentally demonstrated for nitrogen, oxygen, air, and argon.
Histological classification of gastric adenocarcinoma for epidemiological research: concordance between pathologists. (2001)

Epidemiology of gastric adenocarcinoma suggests that intestinal-type and diffuse-type cancers develop through distinct causal pathways. To examine the differences in risk factors and molecular changes between the histological types, reliable data on histological typing are essential. We evaluated the concordance between two pathologists in assessment of 95 gastric adenocarcinomas for Laurén classification and tumor grade. Two pathologists, each blinded to the other's assessment, reviewed H&E-stained slides of gastric tumor. The responses of the two pathologists for histological type were considered as concordant if they fell on one of the three categories (intestinal type, diffuse type, or other). Tumor grade was classified into three categories (well, moderately, or poorly differentiated). The pathologists agreed on the classification of histological type for 71 of 92 (77%) tumors. Kappa coefficient was 0.59 (95% confidence interval, 0.44-0.73). Concordance for tumor grade was 87%, with a kappa coefficient of 0.72 (95% confidence interval, 0.57-0.87). Both observed concordance and kappa coefficient for histological type and tumor grade were similar across three calendar periods of study. Interobserver agreement was virtually identical between tumors with biopsy specimens only and those with surgical specimens. Although the level of disagreement for histological type observed in this study is comparable with that in other studies, the resulting misclassification would lead to the reduction in observed differences in prevalence and odds ratio estimates between two histological types.
Structural and Dynamic Parameters Obtained from <sup>17</sup>O NMR, EPR, and NMRD Studies of Monomeric and Dimeric Gd<sup>3+</sup> Complexes of Interest in Magnetic Resonance Imaging:  An Integrated and Theoretically Self-Consistent Approach<sup>1</sup> (1996)

We present the results of new and previously published 17O NMR, EPR, and NMRD studies of aqueous solutions of the Gd3+ octaaqua ion and the commercial MRI contrast agents [Gd(DTPA)(H2O)]2- (MAGNEVIST, Schering AG, DTPA = 1,1,4,7,7-pentakis(carboxymethyl)-1,4,7-triazaheptane), [Gd(DTPA-BMA)(H2O)] (OMNISCAN, Sanofi Nycomed, DTPA-BMA = 1,7-bis[(N-methylcarbamoyl)methyl]-1,4,7-tris(carboxymethyl)-1,4,7-triazaheptane), and [Gd(DOTA)(H2O)]- (DOTAREM, Guerbet, DOTA = 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane). High-field EPR measurements at different concentrations give evidence of an intermolecular dipole−dipole electronic relaxation mechanism that has not previously been described for Gd3+ complexes. For the first time, the experimental data from the three techniques for each complex have been treated using a self-consistent theoretical model in a simultaneous multiple parameter least-squares fitting procedure. The lower quality of the fits compared to separate fits of the data for each of the three techniques shows that the increase in the number of adjustable parameters is outweighed by the increased constraint on the fits. The parameters governing the relaxivity of the complexes are thus determined with greater confidence than previously possible. The same approach was used to study two dimeric Gd3+ complexes [pip{Gd(DO3A)(H2O)}2] and [bisoxa{Gd(DO3A)(H2O)}2] (pip(DO3A)2 = bis(1,4-(1-(carboxymethyl)-1,4,7,10-tetraaza-4,7,10-tris(carboxymethyl)-1-cyclododecyl-1,4-diazacyclohexane, bisoxa(DO3A)2 = bis(1,4-(1-(carboxymethyl)-1,4,7,10-tetraaza-4,7,10-tris(carboxymethyl)-1-cyclododecyl))-1,10-diaza-3,6-dioxadecane) that are being developed as potential second-generation MRI contrast agents. These dimeric complexes are expected to have higher relaxivities than the monomeric contrast agents, due to their longer rotational correlation times. The results of this study show that further relaxivity gain for these complexes will be hindered by the slow rate of water exchange on the complexes. High-field EPR measurements suggest that there is a previously unrecorded intramolecular dipole−dipole mechanism of electronic relaxation, but that this additional contribution to electronic relaxation is of minor importance compared to the limiting effect of water exchange rates in the determination of proton relaxivity in MRI applications.
Physical and genetic interaction of filamin with presenilin in <i>Drosophila</i> (2000)

Presenilins were first identified as causative factors in early onset, familial Alzheimer's Disease (FAD). They are predicted to encode a highly conserved novel family of eight transmembrane domain proteins with a large hydrophilic loop between TM6 and TM7 that is the site of numerous FAD mutations. Here, we show that the loop region of Drosophila and human presenilins interacts with the C-terminal domain of Drosophila filamin. Furthermore, we show that Drosophila has at least two major filamin forms generated by alternative splicing from a gene that maps to position 89E10-89F4 on chromosome 3. The longest form is enriched in the central nervous system and ovaries, shares 41.7% overall amino acid identity with human filamin (ABP-280) and contains an N-terminal actin-binding domain. The shorter form is broadly expressed and encodes an alternatively spliced form of the protein lacking the actin-binding domain. Finally, we show that presenilin and filamin are expressed in overlapping patterns in Drosophila and that dominant adult phenotypes produced by overexpression of presenilin can be suppressed by overexpression of filamin in the same tissue. Taken together, these results suggest that presenilin and filamin functionally interact during development.
Regulating insulin signaling and β-cell function through IRS proteinsThis paper is one of a selection of papers published in this Special Issue, entitled Second Messengers and Phosphoproteins—12th International Conference. (2006)

Diabetes mellitus is a complex disorder that arises from various causes, including dysregulated glucose sensing and impaired insulin secretion (maturity onset diabetes of youth, MODY), autoimmune-mediated beta-cell destruction (type 1), or insufficient compensation for peripheral insulin resistance (type 2). Type 2 diabetes is the most prevalent form that usually occurs at middle age; it afflicts more than 30 million people over the age of 65, but is appearing with greater frequency in children and adolescents. Dysregulated insulin signaling exacerbated by chronic hyperglycemia promotes a cohort of systemic disorders--including dyslipidemia, hypertension, cardiovascular disease, and female infertility. Understanding the molecular basis of insulin resistance can prevent these disorders and their inevitable progression to type 2 diabetes.
Characterization and biological roles of oviduct-specific, oestrogen-dependent glycoprotein (2002)

During late follicular growth, oestrus, fertilization and early embryonic development, the oviduct, under specific hormonal control, produces fluid and contributes secretory macromolecules that optimize the microenvironment for gamete maturation and transport, fertilization and early cleavage-stage embryonic development. This review describes the state of knowledge concerning the physiological and biochemical characterization of the major oviduct secreted protein, the oviduct-specific, oestrogen-dependent glycoprotein. The identification, localization within the oviduct, binding and association with oocytes, embryos and spermatozoa, hormonal control of gene expression, cloning, gene organization, protein sequences and post-translational modifications of oviduct-specific, oestrogen-dependent glycoprotein are discussed. Identification of biological functions for this glycoprotein, its interactions with spermatozoa, oocytes and embryos and its potential as a paracrine regulator of fertilization and development are also discussed.
Immunoblotting to Detect a Soluble Glycoprotein from Trifoliate Orange in a Citrus Hybrid (1988)

Abstract Polyclonal antibodies against the major soluble glycoprotein of trifoliate orange [ Poncirus trìfoliata (L.) Raf.] were produced in rabbits. The antisera were used to detect the glycoprotein in foliar protein extracts from a hybrid of Poncirus and Citrus genotypes by immunoblotting. One of the sera was found to be highly specific and was suited to indicate trifoliate gene expression. Cross-reacting bands in protein extracts from citrus callus tissue and in the medium of suspension cell cultures suggest that tissue culture systems can be used for biochemical studies of glycoproteins, but not for genotype characterization.
<title>Fluorescence-based visualization of electro-osmotic flow in microfabricated systems</title> (1999)

A recently developed imaging tool is employed to study scalar transport in microfabricated fluidic manifolds. Using the two-color fluorescence-based method to generate molecular fluid flow tracers, we investigate electrokinetic flow through channel geometries commonly encountered in micro-total analytical system research and development.
Ultrafast laser-induced microstructure/nanostructure replication and optical properties (2012)

This paper demonstrates replication of ultrafast laser-induced micro/nano surface textures on poly(dimethylsiloxane) (PDMS). The surface texture replication process reduces the processing steps for microtexturing while improving light trapping. Two methods are demonstrated to replicate surface microtexture, a simple mold method and an embossing method. The laser microtextured silicon and titanium surfaces with micro to nanoscale features have been successfully replicated. Optical characterization of the replicated microtextured PDMS surfaces is performed and the results agree with model predictions. The replicated microtextured PDMS film is applied on a silicon surface and optical characterization shows that surface reflectance can be suppressed over 55% compared to the control value.
Silicon-aluminum oxynitride composite films deposited by reactive ion beam sputtering (2002)

Amorphous Silicon-Aluminum Oxynitride (SIALON) films were deposited by a reactive ion beam sputtering (IBS) method with neutralizer. The properties for insulating films were examined for these SIALON films. Auger analysis shows that the deposited SIALON films have uniform composition of atoms in the depth. The etching rate of the films by hydrofluoric acid 30 nm/min under the deposition condition above 30% of oxygen partial pressure. This rate is lower than that of Si/sub 3/N/sub 4/ films deposited by CVD and SIALON films deposited here are thought to be more dense than the films deposited by CVD. Breakdown electric field strength of the films increases with increasing oxygen partial pressure and reaches to the maximum value of 2 MV/cm at 30-40% oxygen. The high breakdown strength, low dielectric loss and dense film can be obtained by controlling oxygen pressure in IBS. These facts suggest that the SIALON film deposited by IBS is expected to be useful for the passivation of electronic devices.
QoS in GPRS (2000)

Mobile telephony has been for many years the most popular application supported by mobile systems such as the Global System for Mobile communications (GSM). Recently, the use of mobile data applications such as the GSM Short Message Service (SMS) has gained popularity. However, the GSM system can only support data services up to 9.6 kbit/s, circuit switched. The General Packet Radio Service (GPRS), developed by the European Telecommunications Standards Institute (ETSI), is a new packet switched data service for GSM that can allow bitrates, theoretically up to 170 kbit/s per user. However, commercial GPRS systems will be able to support rates up to 115 kbit/s. This document presents current developments and research activities in the area of Quality of Service (QoS) provisioning in GPRS Release 1998 and Release 1999. Moreover, new procedures that are used to enable the interworking between the GPRS QoS framework and the IntServ framework and as well the interworking between the GPRS QoS framework and the Diffserv framework are introduced.
Antihyperalgesic activity of a novel nonpeptide bradykinin B<sub>1</sub> receptor antagonist in transgenic mice expressing the human B<sub>1</sub> receptor (2005)

We describe the properties of a novel nonpeptide kinin B1 receptor antagonist, NVP-SAA164, and demonstrate its in vivo activity in models of inflammatory pain in transgenic mice expressing the human B1 receptor. NVP-SAA164 showed high affinity for the human B1 receptor expressed in HEK293 cells (K(i) 8 nM), and inhibited increases in intracellular calcium induced by desArg10kallidin (desArg10KD) (IC50 33 nM). While a similar high affinity was observed in monkey fibroblasts (K(i) 7.7 nM), NVP-SAA164 showed no affinity for the rat B1 receptor expressed in Cos-7 cells. In transgenic mice in which the native B1 receptor was deleted and the gene encoding the human B1 receptor was inserted (hB1 knockin, hB1-KI), hB1 receptor mRNA was induced in tissues following LPS treatment. No mRNA encoding the mouse or human B1 receptor was detected in mouse B1 receptor knockout (mB1-KO) mice following LPS treatment. Freund's complete adjuvant-induced mechanical hyperalgesia was similar in wild-type and hB(1)-KI mice, but was significantly reduced in mB1-KO animals. Mechanical hyperalgesia induced by injection of the B1 agonist desArg10KD into the contralateral paw 24 h following FCA injection was similar in wild-type and hB1-KI mice, but was absent in mB1-KO animals. Oral administration of NVP-SAA164 produced a dose-related reversal of FCA-induced mechanical hyperalgesia and desArg10KD-induced hyperalgesia in hB1-KI mice, but was inactive against inflammatory pain in wild-type mice. These data demonstrate the use of transgenic technology to investigate the in vivo efficacy of species selective agents and show that NVP-SAA164 is a novel orally active B1 receptor antagonist, providing further support for the utility of B1 receptor antagonists in inflammatory pain conditions in man.