Is da Vinci Xi Better than da Vinci Si in Robotic Rectal Cancer Surgery? Comparison of the 2 Generations of da Vinci Systems.

PubMed

Ozben, Volkan; Cengiz, Turgut B; Atasoy, Deniz; Bayraktar, Onur; Aghayeva, Afag; Erguner, Ilknur; Baca, Bilgi; Hamzaoglu, Ismail; Karahasanoglu, Tayfun

2016-10-01

We aimed to compare perioperative outcomes for procedures using the latest generation of da Vinci robot versus its previous version in rectal cancer surgery. Fifty-three patients undergoing robotic rectal cancer surgery between January 2010 and March 2015 were included. Patients were classified into 2 groups (Xi, n=28 vs. Si, n=25) and perioperative outcomes were analyzed. The groups had significant differences including operative procedure, hybrid technique and redocking (P>0.05). In univariate analysis, the Xi group had shorter console times (265.7 vs. 317.1 min, P=0.006) and total operative times (321.6 vs. 360.4 min, P=0.04) and higher number of lymph nodes harvested (27.5 vs. 17.0, P=0.008). In multivariate analysis, Xi robot was associated with a shorter console time (odds ratio: 0.09, P=0.004) with no significant differences regarding other outcomes. Both generations of da Vinci robot led to similar short-term outcomes in rectal cancer surgery, but the Xi robot allowed shorter console times.

The DaNa2.0 Knowledge Base Nanomaterials—An Important Measure Accompanying Nanomaterials Development

PubMed Central

Bohmer, Nils; Marquardt, Clarissa; Nau, Katja; Steinbach, Christoph

2018-01-01

Nanotechnology is closely related to the tailored manufacturing of nanomaterials for a huge variety of applications. However, such applications with newly developed materials are also a reason for concern. The DaNa2.0 project provides information and support for these issues on the web in condensed and easy-to-understand wording. Thus, a key challenge in the field of advanced materials safety research is access to correct and reliable studies and validated results. For nanomaterials, there is currently a continuously increasing amount of publications on toxicological issues, but criteria to evaluate the quality of these studies are necessary to use them e.g., for regulatory purposes. DaNa2.0 discusses scientific results regarding 26 nanomaterials based on actual literature that has been selected after careful evaluation following a literature criteria checklist. This checklist is publicly available, along with a selection of standardized operating protocols (SOPs) established by different projects. The spectrum of information is rounded off by further articles concerning basics or crosscutting topics in nanosafety research. This article is intended to give an overview on DaNa2.0 activities to support reliable toxicity testing and science communication alike. PMID:29596351

GROWTH FACTORS AND COX2 IN WOUND HEALING: AN EXPERIMENTAL STUDY WITH EHRLICH TUMORS.

PubMed

Salgado, Flávio L L; Artigiani-Neto, Ricardo; Lopes-Filho, Gaspar de Jesus

2016-01-01

late scarring by fibroblasts and FGF. A cicatrização é fenômeno biológico inato, e a carcinogênese adquirido, mas com elementos humorais e celulares comuns. A carcinogênese interfere de forma negativa na cicatrização. Avaliar as modificações histológicas nas cicatrizes laparotômicas de camundongos Balb/c sadios como controles, e com a neoplasia de Ehrlich, em suas diferentes formas de apresentação. Foram utilizados 54 camundongos, divididos em três grupos de 18 animais cada um. O primeiro era controle; o segundo com a neoplasia de Ehrlich em sua forma ascítica; e o terceiro na forma subcutânea. Sete dias após a inoculação do tumor, todos os 54 camundongos foram submetidos à laparotomia e reoperados no sétimo dia de pós-operatório, com ressecção da cicatriz e posterior eutanásia. As cicatrizes foram encaminhadas para estudo histológico com técnicas imunoistoquímicas para avaliar Cox-2 (ciclo-oxigenase 2), VEGF (fator de crescimento do endotélio vascular) e FGF (fator de crescimento dos fibroblastos) e analisadas de forma semiquantitativana tanto na cicatriz laparotômica como na parede abdominal mais distante do local operado. Avaliando o peso, observou-se a correta inoculação do tumor e o aumento de peso no grupo com a neoplasia na modalidade ascítica. Os estudos histológicos mostraram que os grupos com a neoplasia apresentaram maior presença da Cox-2 em relação ao controle, estatisticamente significante. No estudo da Cox-2 da parede abdominal foi o local em que o grupo ascítico apresentou a diferença mais expressiva. O VEGF não apresentou diferenças significantes entre os três grupos, independentemente do local estudado. O FGF teve aumento significante nos animais com neoplasia. Os achados histológicos encontrados tanto na cicatriz das laparotomias quanto na parede abdominal mostraram que com a neoplasia de Ehrlich houve resposta inflamatória exacerbada, traduzida por expressão mais intensa da Cox-2 e maior prolifera

11 CFR 111.13 - Service of subpoenas, orders and notifications (2 U.S.C. 437d(a) (3), (4)).

Code of Federal Regulations, 2010 CFR

2010-01-01

... 11 Federal Elections 1 2010-01-01 2010-01-01 false Service of subpoenas, orders and notifications (2 U.S.C. 437d(a) (3), (4)). 111.13 Section 111.13 Federal Elections FEDERAL ELECTION COMMISSION GENERAL COMPLIANCE PROCEDURE (2 U.S.C. 437g, 437d(a)) Enforcement § 111.13 Service of subpoenas, orders...

The local effect of octreotide on mechanical pain sensitivity is more sensitive in DA rats than DA.1U rats.

PubMed

Yao, Fan-Rong; Wang, Hui-Sheng; Guo, Yuan; Zhao, Yan

2016-02-01

A recent study by the authors indicated that major histocompatibility complex (MHC) genes are associated with the differences in basal pain sensitivity and in formalin model between Dark-Agouti (DA) and novel congenic DA.1U rats, which have the same genetic background as DA rats except for the u alleles of MHC. The objective of the present study is to investigate whether there is a difference in the pristane-induced arthritis (PIA) model and local analgesic effect of octreotide (OCT) between DA and DA.1U rats. The hindpaw mechanical withdrawal threshold (MWT) and heat withdrawal latency (HWL) were observed. The C unit firings of the tibial nerve evoked by non-noxious and noxious toe movements were recorded by electrophysiological methods in normal and PIA models in DA and DA.1U rats before and after local OCT administration. The expression of somatostatin receptor 2A (SSTR2A) was observed by immunohistochemistry. The results demonstrate that DA rats have a higher mechanical sensitivity than DA.1U rats after PIA. Local OCT administration significantly elevated MWT in DA rats under normal and PIA sate, but not in DA.1U rats. The electrophysiological experiments showed OCT significantly attenuated the firings of C units evoked by non-noxious and noxious stimulation in DA rats more than those in DA.1U rats both in normal and PIA states. In addition, the expression of SSTR2A in the dorsal horn of the spinal cord was significantly higher in DA than in DA.1U rats. All of the findings suggest a higher local analgesic effect of OCT in DA rats than DA.1U rats, which might be associated with the MHC genes. © 2016 John Wiley & Sons Australia, Ltd.

[Analysis of the therapeutic efficacy and prognosis for acute myeloid leukemia M2a patients treated by IA and DA regimens].

PubMed

Wang, Fan; Yuan, Hai-Long; Duan, Xian-Lin; Wang, Lei; Cao, Hai-Zhou; Xu, Jian-Li; Qu, Jian-Hua

2014-08-01

This study was purposed to compare the therapeutic efficacy and prognosis of acute myeloid leukemia M2a (AML-M2a) patients treated by idarubicin (IDA) combined with cytarabine (Ara-C) (IA) and daunorubicin (DNR) combined cytarabine (Ara-C) (DA) regimens. The clinical data of 65 patients with AML-M2a in our hospital were collected from May 2009 to May 2013 and analyzed. The results indicated the complete remission in IA group was slightly higher than that in DA group, there was no statistically significant difference(P > 0.05); leukocyte minimum value in IA group [(0.58 ± 0.40)×10(9)/L] was obviously lower than that in DA group [(0.99 ± 0.67)×10(9)/L] (P < 0.05); neutrophil minimum value in IA group [(0.19 ± 0.09)×10(9)/L] was significantly lower than that in DA group [(0.21 ± 0.16)×10(9)/L] (P < 0.05); the neutropenia duration in IA group (12.59 ± 5.31)d was much longer than that in DA group (9.17 ± 7.04)d (P < 0.05). The median survival time of patients in IA group was 36.67 months, which was obviously longer than that of patients in DA group (21.45 months) (P < 0.05). The lactate dehydrogenase (LDH) value and chemotherapy regimens were the independently risk factor affecting the prognosis of AML-M2a patients. It is concluded that as compared with DA regimen, the IA regimen can prolong the median survival time and has better long-term therapeutic efficacy, thus it can be used as the first chemotherapy regimen for treatment of AML-M2a.

Quadrupole Ion Mass Spectrometer for Masses of 2 to 50 Da

NASA Technical Reports Server (NTRS)

Helms, William; Griffin, Timothy P.; Ottens, Andrew; Harrison, Willard

2005-01-01

A customized quadrupole ion-trap mass spectrometer (QITMS) has been built to satisfy a need for a compact, rugged instrument for measuring small concentrations of hydrogen, helium, oxygen, and argon in a nitrogen atmosphere. This QITMS can also be used to perform quantitative analyses of other gases within its molecular-mass range, which is 2 to 50 daltons (Da). (More precisely, it can be used to perform quantitative analysis of gases that, when ionized, are characterized by m/Z ratios between 2 and 50, where m is the mass of an ion in daltons and Z is the number of fundamental electric charges on the ion.

Understanding and Interpreting Japanese NP1 "wa" NP2 "da" Sentences: Mechanism and Contextual Factors

ERIC Educational Resources Information Center

Yoshida, Megumi

2013-01-01

This dissertation investigates the contextual factors that affect the understanding and interpretation of one Japanese topicalized construction, NP[subscript 1] wa NP[subscript 2] da sentences, by native speakers of Japanese. The construction allows two possibilities in the relation between the NP[subscript 1] and the NP[subscript 2]. When the two…

Iterative random vs. Kennard-Stone sampling for IR spectrum-based classification task using PLS2-DA

NASA Astrophysics Data System (ADS)

Lee, Loong Chuen; Liong, Choong-Yeun; Jemain, Abdul Aziz

2018-04-01

External testing (ET) is preferred over auto-prediction (AP) or k-fold-cross-validation in estimating more realistic predictive ability of a statistical model. With IR spectra, Kennard-stone (KS) sampling algorithm is often used to split the data into training and test sets, i.e. respectively for model construction and for model testing. On the other hand, iterative random sampling (IRS) has not been the favored choice though it is theoretically more likely to produce reliable estimation. The aim of this preliminary work is to compare performances of KS and IRS in sampling a representative training set from an attenuated total reflectance - Fourier transform infrared spectral dataset (of four varieties of blue gel pen inks) for PLS2-DA modeling. The `best' performance achievable from the dataset is estimated with AP on the full dataset (APF, error). Both IRS (n = 200) and KS were used to split the dataset in the ratio of 7:3. The classic decision rule (i.e. maximum value-based) is employed for new sample prediction via partial least squares - discriminant analysis (PLS2-DA). Error rate of each model was estimated repeatedly via: (a) AP on full data (APF, error); (b) AP on training set (APS, error); and (c) ET on the respective test set (ETS, error). A good PLS2-DA model is expected to produce APS, error and EVS, error that is similar to the APF, error. Bearing that in mind, the similarities between (a) APS, error vs. APF, error; (b) ETS, error vs. APF, error and; (c) APS, error vs. ETS, error were evaluated using correlation tests (i.e. Pearson and Spearman's rank test), using series of PLS2-DA models computed from KS-set and IRS-set, respectively. Overall, models constructed from IRS-set exhibits more similarities between the internal and external error rates than the respective KS-set, i.e. less risk of overfitting. In conclusion, IRS is more reliable than KS in sampling representative training set.

DA1 receptors modulation in rat isolated trachea.

PubMed

Cabezas, Gloria A; Velasco, Manuel

2010-01-01

We have previously demonstrated that low dose of inhaled dopamine (0.5-2 microg kg(-1) min(-1)) induces broncodilatacion in patients with acute asthma attack, suggesting that this dopamine effect is mediated by dopaminergic rather than by adrenergic receptors. To understand better these dopamine effect, rat tracheal smooth muscle was used as a model to evaluate the responses of beta2-, alpha1-, alpha2-adrenergic and DA1 and DA2 dopaminergic antagonists. Tracheal rings from male Sprague-Dawley rats (n = 90) were excised and placed in an organ bath containing modified Krebs-Ringer bicarbonate buffer at 37 degrees C, and gassed with O2 (95%) and CO2 (5%). Contractile responses were recorded with an isometric transducer in a polygraph (Letica, Spain). Contraction was induced by accumulative doses of acetylcholine (0.1, 0.3, 1, 3, 10 mM) or by electric field stimulation (10 Hz at 2 milliseconds), and accumulative doses of dopamine were added to the bath. Low concentration (0.1-0.3 mM) elicited a small initial contraction, followed by a marked relaxation. Cholinergic contraction was completely reversed at 6 mM of dopamine. This biphasic dopaminergic response was not blocked by incubation with beta2-adrenergic antagonist propranolol (0.1 microM), alpha1-antagonist, terazosin (0.1 mM), alpha2-antagonist, yohimbine (0.1 mM), or by DA2 antagonist metoclopramide (1-8 mM); DA1 antagonist SCH23390 (0.1 microM) produced a sustained increase of basal tone but did not block initial dopaminergic contraction and partially inhibited bronchodilator effect of dopamine. Dopaminergic relaxation in rat trachea is mediated by DA1 rather than by DA2 receptors; and adrenergic receptors are not involved in such dopamine-induced response. Finally, DA1 antagonist SCH23390 exerts intrinsic contractile activity on airway smooth muscle that deserves further research.

Biochemical characterization of a halophilic, alkalithermophilic protease from Alkalibacillus sp. NM-Da2.

PubMed

Abdel-Hamed, Asmaa R; Abo-Elmatty, Dina M; Wiegel, Juergen; Mesbah, Noha M

2016-11-01

An extracellular, halophilic, alkalithermophilic serine protease from the halo-alkaliphilic Alkalibacillus sp. NM-Da2 was purified to homogeneity by ethanol precipitation and anion-exchange chromatography. The purified protease was a monomeric enzyme with an approximate molecular mass of 35 kDa and exhibited maximal activity at 2.7 M NaCl, pH 55 °C 9 and 56 °C. The protease showed great temperature stability, retaining greater than 80 % of initial activity after 2 h incubation at 55 °C. The protease was also extremely pH tolerant, retaining 80 % of initial activity at pH 55 °C 10.5 after 30 min incubation. Protease hydrolyzed complex substrates, displaying activity on yeast extract, tryptone, casein, gelatin and peptone. Protease activity was inhibited at casein concentrations greater than 1.2 mg/mL. The enzyme was stable and active in 40 % (v/v) solutions of isopropanol, ethanol and benzene and was stable in the presence of the polysorbate surfactant Tween 80. Activity was stimulated with the oxidizing agent hydrogen peroxide. Inhibition with phenyl methylsulfonylfluoride indicates it is a serine protease. Synthetic saline wastewater treated with the protease showed 50 % protein removal after 5 h. Being halophilic, alkaliphilic and thermophilic, in addition to being resistant to organic solvents, this protease has potential for various applications in biotechnological and pharmaceutical industries.

32 CFR 516.25 - DA Form 4.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 3 2010-07-01 2010-07-01 true DA Form 4. 516.25 Section 516.25 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY AID OF CIVIL AUTHORITIES AND PUBLIC RELATIONS LITIGATION Reporting Legal Proceedings to HQDA § 516.25 DA Form 4. (a) General. The DA Form 4 (See figure C-2...

Design, Modelling and Teleoperation of a 2 mm Diameter Compliant Instrument for the da Vinci Platform.

PubMed

Francis, P; Eastwood, K W; Bodani, V; Looi, T; Drake, J M

2018-05-07

This work explores the feasibility of creating and accurately controlling an instrument for robotic surgery with a 2 mm diameter and a three degree-of-freedom (DoF) wrist which is compatible with the da Vinci platform. The instrument's wrist is composed of a two DoF bending notched-nitinol tube pattern, for which a kinematic model has been developed. A base mechanism for controlling the wrist is designed for integration with the da Vinci Research Kit. A basic teleoperation task is successfully performed using two of the miniature instruments. The performance and accuracy of the instrument suggest that creating and accurately controlling a 2 mm diameter instrument is feasible and the design and modelling proposed in this work provide a basis for future miniature instrument development.

Release of carrot plasma membrane-associated phosphatidylinositol kinase by phospholipase A2 and activation by a 70 kDa protein.

PubMed

Gross, W; Yang, W; Boss, W F

1992-02-19

Plasma membranes were isolated from carrot (Daucus carota L.) cells grown in suspension culture and treated with phospholipase A2 from snake or bee venom for 10 min. As a result of this treatment, phosphatidylinositol kinase activity was recovered in the soluble fraction. There was no detectable diacylglycerol kinase or phosphatidylinositol monophosphate kinase activity released from the membranes after the phospholipase A2 treatment. Treating the plasma membranes with phospholipase C or D did not release PI kinase activity. The phospholipase A2-released PI kinase was activated over 2-fold by a heat stable, soluble 70 kDa protein. The partially purified 70 kDa activator increases the Vmax but does not affect the Km of the phospholipase A2-released PI kinase.

76 FR 12627 - Airworthiness Directives; Diamond Aircraft Industries GmbH Models DA 42, DA 42 NG, and DA 42 M-NG...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-08

... Industries GmbH Models DA 42, DA 42 NG, and DA 42 M-NG Airplanes AGENCY: Federal Aviation Administration (FAA... on Diamond aeroplanes, the majority of which were DA 40. In additional, at least 18 doors have been... conditions) while the aeroplane was parked. All DA 40 and DA 42 aeroplanes have a system installed that...

Effect of shorter dark adaptation on ISCEV standard DA 0.01 and DA 3 skin ERGs in healthy adults.

PubMed

Hamilton, R; Graham, K

2016-08-01

To quantify dark-adapted (DA) skin ERG changes during 20 min of dark adaptation. Sixteen healthy adult subjects were dark-adapted for 20 min during which ISCEV standard dim (0.01 phot cd s m(-2)) white flash ERGs were recorded at 1, 2, 3, 4, 5, 10, 15 and 20 min, and bright (3 phot cd s m(-2)) white ERGs were recorded at 2, 5, 10, 15 and 20 min without mydriasis and using skin electrodes. Amplitudes and peak times were normalised to 20 min values. Halving dark adaptation from 20 to 10 min had no measureable effect on the DA 3 ERG and caused a 10 % amplitude loss (range 0-23 %) only for the DA 0.01 ERG b-wave amplitude. No significant peak time changes resulted, nor increased parameter variability. Reducing dark adaptation from 20 to 10 min or even less has an effect on only DA 0.01 ERGs. Shorter dark adaptation than 20 min may not compromise the clinical utility of the ERG providing clinics adhere to the usual standards of adequate reference data.

Iron abundance in the hot DA white dwarfs Feige 24 and G191 B2B

NASA Technical Reports Server (NTRS)

Vennes, Stephane; Chayer, Pierre; Thorstensen, John R.; Bowyer, Stuart; Shipman, Harry L.

1992-01-01

Attention is given to model calculations of the far- and extreme-UV line spectra of highly ionized Fe species (Fe IV, Fe V, and Fe VI) for hot high-gravity H-rich stars. A spectral analysis of 31 hr of exposure of the DA white dwarf Feige 24 with IUE in the echelle mode reveals the presence of Fe with an abundance relative to H by number of (5-10) x 10 exp -6 with an uncertainty dominated by the determination of stellar parameters. An analysis of IUE data from the white dwarf G191 B2B results in a similar Fe abundance if this star shares similar atmospheric parameters (Teff, g) with Feige 24. Fe is thus the second most abundant photospheric element in hot DA white dwarfs.

Origin of the DA and non-DA white dwarf stars

NASA Technical Reports Server (NTRS)

Shipman, Harry L.

1989-01-01

Various proposals for the bifurcation of the white dwarf cooling sequence are reviewed. 'Primordial' theories, in which the basic bifurcation of the white dwarf sequence is rooted in events predating the white dwarf stage of stellar evolution, are discussed, along with the competing 'mixing' theories in which processes occurring during the white dwarf stage are responsible for the existence of DA or non-DA stars. A new proposal is suggested, representing a two-channel scenario. In the DA channel, some process reduces the hydrogen layer mass to the value of less than 10 to the -7th. The non-DA channel is similar to that in the primordial scenario. These considerations suggest that some mechanism operates in both channels to reduce the thickness of the outermost layer of the white dwarf. It is also noted that accretion from the interstellar medium has little to do with whether a particular white dwarf becomes a DA or a non-DA star.

A geochemical and geophysical approach to derive a conceptual circulation model of CO2-rich mineral waters: A case study of Vilarelho da Raia, northern Portugal

NASA Astrophysics Data System (ADS)

Marques, J. M.; Santos, Monteiro; Graça, R. C.; Castro, R.; Aires-Barros, L.; Mendes Victor, L. A.

2001-11-01

The Vilarelho da Raia-Chaves region, located in northern Portugal adjacent to the Spanish border, is characterized by both hot and cold CO2-rich mineral waters issuing from springs and drilled wells. The present paper updates the conceptual circulation model of the Vilarelho da Raia cold CO2-rich mineral waters. Vilarelho da Raia mineral waters, dominated by Na and HCO3 ions, have formed mainly by interaction with CO2 of deep-seated mantle origin. The δ18O, δ2H and 3H values indicate that these waters are the result of meteoric waters infiltrating into Larouco Mountain, NW of Vilarelho da Raia, circulating at shallow depths in granitic rocks and moving into Vilarelho da Raia area. The conceptual geochemical and geophysical circulation model indicates that the hot and cold CO2-rich mineral waters of Chaves (76 °C) and Vilarelho da Raia (17 °C) should be considered manifestations of similar but not the same geohydrological systems. Résumé. La région de Vilarelho da Raia - Chaves, située au Portugal près de la frontière Espagnole, est caractérisée par des eaux carbogazeuses, chaudes et froides, émergeant à des sources et dans des puits. Ce travail constitue une mise au point du modèle conceptuel de circulation des eaux minérales carbogazeuses froides de Vilarelho da Raia. Les eaux minérales de Vilarelho da Raia, dans lesquelles les ions Na and HCO3 sont dominants, résultent principalement d'interactions avec du CO2 d'origine mantellique. Les δ18O, les δ2H, et les teneurs en 3H indiquent que ces eaux proviennent de l'infiltration d'eaux météoriques dans le Mont Larouco au NW de Vilarelho da Raia, circulant à faible profondeur dans les granites en direction de la région de Vilarelho da Raia. Le modèle de circulation géochimique et géophysique conduit à penser que les eaux minérales carbogazeuses chaudes et froides de Chaves (76 °C) et de Vilarelho da Raia (17 °C) doivent être considérées comme des manifestations de systèmes hydrog

Pharmacological Modulation of 5-HT2C Receptor Activity Produces Bidirectional Changes in Locomotor Activity, Responding for a Conditioned Reinforcer, and Mesolimbic DA Release in C57BL/6 Mice.

PubMed

Browne, Caleb J; Ji, Xiaodong; Higgins, Guy A; Fletcher, Paul J; Harvey-Lewis, Colin

2017-10-01

Converging lines of behavioral, electrophysiological, and biochemical evidence suggest that 5-HT 2C receptor signaling may bidirectionally influence reward-related behavior through an interaction with the mesolimbic dopamine (DA) system. Here we directly test this hypothesis by examining how modulating 5-HT 2C receptor activity affects DA-dependent behaviors and relate these effects to changes in nucleus accumbens (NAc) DA release. In C57BL/6 mice, locomotor activity and responding for a conditioned reinforcer (CRf), a measure of incentive motivation, were examined following treatment with three 5-HT 2C receptor ligands: the agonist CP809101 (0.25-3 mg/kg), the antagonist SB242084 (0.25-1 mg/kg), or the antagonist/inverse agonist SB206553 (1-5 mg/kg). We further tested whether doses of these compounds that changed locomotor activity and responding for a CRf (1 mg/kg CP809101, 0.5 mg/kg SB242084, or 2.5 mg/kg SB206553) also altered NAc DA release using in vivo microdialysis in anesthetized mice. CP809101 reduced locomotor activity, responding for a CRf, and NAc DA release. In contrast, both SB242084 and SB206553 enhanced locomotor activity, responding for a CRf, and NAc DA release, although higher doses of SB206553 produced opposite behavioral effects. Pretreatment with the non-selective DA receptor antagonist α-flupenthixol prevented SB242084 from enhancing responding for a CRf. Thus blocking tonic 5-HT 2C receptor signaling can release serotonergic inhibition of mesolimbic DA activity and enhance reward-related behavior. The observed bidirectional effects of 5-HT 2C receptor ligands may have important implications when considering the 5-HT 2C receptor as a therapeutic target for psychiatric disorders, particularly those presenting with motivational dysfunctions.

The role of adenosine A1 and A2A receptors in the caffeine effect on MDMA-induced DA and 5-HT release in the mouse striatum.

PubMed

Górska, A M; Gołembiowska, K

2015-04-01

3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") popular as a designer drug is often used with caffeine to gain a stronger stimulant effect. MDMA induces 5-HT and DA release by interaction with monoamine transporters. Co-administration of caffeine and MDMA may aggravate MDMA-induced toxic effects on DA and 5-HT terminals. In the present study, we determined whether caffeine influences DA and 5-HT release induced by MDMA. We also tried to find out if adenosine A1 and A2A receptors play a role in the effect of caffeine by investigating the effect of the selective adenosine A1 and A2A receptor antagonists, DPCPX and KW 6002 on DA and 5-HT release induced by MDMA. Mice were treated with caffeine (10 mg/kg) and MDMA (20 or 40 mg/kg) alone or in combination. DA and 5-HT release in the mouse striatum was measured using in vivo microdialysis. Caffeine exacerbated the effect of MDMA on DA and 5-HT release. DPCPX or KW 6002 co-administered with MDMA had similar influence as caffeine, but KW 6002 was more potent than caffeine or DPCPX. To exclude the contribution of MAO inhibition by caffeine in the caffeine effect on MDMA-induced increase in DA and 5-HT, we also tested the effect of the nonxanthine adenosine receptor antagonist CGS 15943A lacking properties of MAO activity modification. Our findings indicate that adenosine A1 and A2A receptor blockade may account for the caffeine-induced exacerbation of the MDMA effect on DA and 5-HT release and may aggravate MDMA toxicity.

DA-Raf-Mediated Suppression of the Ras--ERK Pathway Is Essential for TGF-β1-Induced Epithelial-Mesenchymal Transition in Alveolar Epithelial Type 2 Cells.

PubMed

Watanabe-Takano, Haruko; Takano, Kazunori; Hatano, Masahiko; Tokuhisa, Takeshi; Endo, Takeshi

2015-01-01

Myofibroblasts play critical roles in the development of idiopathic pulmonary fibrosis by depositing components of extracellular matrix. One source of lung myofibroblasts is thought to be alveolar epithelial type 2 cells that undergo epithelial-mesenchymal transition (EMT). Rat RLE-6TN alveolar epithelial type 2 cells treated with transforming growth factor-β1 (TGF-β1) are converted into myofibroblasts through EMT. TGF-β induces both canonical Smad signaling and non-canonical signaling, including the Ras-induced ERK pathway (Raf-MEK-ERK). However, the signaling mechanisms regulating TGF-β1-induced EMT are not fully understood. Here, we show that the Ras-ERK pathway negatively regulates TGF-β1-induced EMT in RLE-6TN cells and that DA-Raf1 (DA-Raf), a splicing isoform of A-Raf and a dominant-negative antagonist of the Ras-ERK pathway, plays an essential role in EMT. Stimulation of the cells with fibroblast growth factor 2 (FGF2), which activated the ERK pathway, prominently suppressed TGF-β1-induced EMT. An inhibitor of MEK, but not an inhibitor of phosphatidylinositol 3-kinase, rescued the TGF-β1-treated cells from the suppression of EMT by FGF2. Overexpression of a constitutively active mutant of a component of the Ras-ERK pathway, i.e., H-Ras, B-Raf, or MEK1, interfered with EMT. Knockdown of DA-Raf expression with siRNAs facilitated the activity of MEK and ERK, which were only weakly and transiently activated by TGF-β1. Although DA-Raf knockdown abrogated TGF-β1-induced EMT, the abrogation of EMT was reversed by the addition of the MEK inhibitor. Furthermore, DA-Raf knockdown impaired the TGF-β1-induced nuclear translocation of Smad2, which mediates the transcription required for EMT. These results imply that intrinsic DA-Raf exerts essential functions for EMT by antagonizing the TGF-β1-induced Ras-ERK pathway in RLE-6TN cells.

Evaluation of the Efficacy and Safety of DA-9601 versus Its New Formulation, DA-5204, in Patients with Gastritis: Phase III, Randomized, Double-Blind, Non-Inferiority Study.

PubMed

Choi, Yoon Jin; Lee, Dong Ho; Choi, Myung Gyu; Lee, Sung Joon; Kim, Sung Kook; Song, Geun Am; Rhee, Poong Lyul; Jung, Hwoon Yong; Kang, Dae Hwan; Lee, Yong Chan; Lee, Si Hyung; Choi, Suck Chei; Shim, Ki Nam; Seol, Sang Yong; Moon, Jeong Seop; Shin, Yong Woon; Kim, Hyun Soo; Lee, Soo Teik; Cho, Jin Woong; Choi, Eun Kwang; Lee, Oh Young; Jang, Jin Seok

2017-11-01

This study compared the efficacy of DA-9601 (Dong-A ST Co., Seoul, Korea) and its new formulation, DA-5204 (Dong-A ST Co.), for treating erosive gastritis. This phase III, randomized, multicenter, double-blind, non-inferiority trial randomly assigned 434 patients with endoscopically proven gastric mucosal erosions into two groups: DA-9601 3 times daily or DA-5,204 twice daily for 2 weeks. The final analysis included 421 patients (DA-5204, 209; DA-9601, 212). The primary endpoint (rate of effective gastric erosion healing) and secondary endpoints (cure rate of endoscopic erosion and gastrointestinal [GI] symptom relief) were assessed using endoscopy after the treatment. Drug-related adverse events (AEs), including GI symptoms, were also compared. At week 2, gastric healing rates with DA-5204 and DA-9601 were 42.1% (88/209) and 42.5% (90/212), respectively. The difference between the groups was -0.4% (95% confidence interval, -9.8% to 9.1%), which was above the non-inferiority margin of -14%. The cure rate of gastric erosion in both groups was 37.3%. The improvement rates of GI symptoms with DA-5204 and DA-9601 were 40.4% and 40.8%, respectively. There were no statistically significant differences between the two groups in both secondary endpoints. AEs were reported in 18 (8.4%) patients in the DA-5204 group and 19 (8.8%) in the DA-9601 group. Rates of AE were not different between the two groups. No serious AE or adverse drug reaction (ADR) occurred. These results demonstrate the non-inferiority of DA-5204 compared to DA-9601. DA-5204 is as effective as DA-9601 in the treatment of erosive gastritis. Registered randomized clinical trial at ClinicalTrials.gov (NCT02282670). © 2017 The Korean Academy of Medical Sciences.

The major histocompatibility complex genes impact pain response in DA and DA.1U rats.

PubMed

Guo, Yuan; Yao, Fan-Rong; Cao, Dong-Yuan; Li, Li; Wang, Hui-Sheng; Xie, Wen; Zhao, Yan

2015-08-01

Our recent studies have shown that the difference in basal pain sensitivity to mechanical and thermal stimulation between Dark-Agouti (DA) rats and a novel congenic DA.1U rats is major histocompatibility complex (MHC) genes dependent. In the present study, we further used DA and DA.1U rats to investigate the role of MHC genes in formalin-induced pain model by behavioral, electrophysiological and immunohistochemical methods. Behavioral results showed biphasic nociceptive behaviors increased significantly following the intraplantar injection of formalin in the hindpaw of DA and DA.1U rats. The main nociceptive behaviors were lifting and licking, especially in DA rats (P<0.001 and P<0.01). The composite pain scores (CPS) in DA rats were significantly higher than those in DA.1U rats in both phases of the formalin test (P<0.01). Electrophysiological results also showed the biphasic increase in discharge rates of C and Aδ fibers of L5 dorsal root in the two strains, and the net change of the discharge rate of DA rats was significantly higher than that of DA.1U rats (P<0.05). The mechanical thresholds decreased after formalin injection in both strains (P<0.01), and the net change in the mechanical threshold in DA was greater than that in DA.1U rats (P<0.05). The expression of RT1-B, representation of MHC class II molecule, in laminae I-II of L4/5 spinal cord in DA rats was significantly higher than that in DA.1U rats in the respective experimental group (P<0.05). These results suggested that both DA and DA.1U rats exhibited nociceptive responses in formalin-induced pain model and DA rats were more sensitive to noxious chemical stimulus than DA.1U rats, indicating that MHC genes might contribute to the difference in pain sensitivity. Copyright © 2015 Elsevier Inc. All rights reserved.

PKC phosphorylates residues in the N-terminal of the DA transporter to regulate amphetamine-induced DA efflux.

PubMed

Wang, Qiang; Bubula, Nancy; Brown, Jason; Wang, Yunliang; Kondev, Veronika; Vezina, Paul

2016-05-27

The DA transporter (DAT), a phosphoprotein, controls extracellular dopamine (DA) levels in the central nervous system through transport or reverse transport (efflux). Multiple lines of evidence support the claim that PKC significantly contributes to amphetamine-induced DA efflux. Other signaling pathways, involving CaMKII and ERK, have also been shown to regulate DAT mediated efflux. Here we assessed the contribution of putative PKC residues (S4, S7, S13) in the N-terminal of the DAT to amphetamine-induced DA efflux by transfecting DATs containing different serine to alanine (S-A) point mutations into DA pre-loaded HEK-293 cells and incubating these cells in amphetamine (2μM). The effects of a S-A mutation at the non-PKC residue S12 and a threonine to alanine (T-A) mutation at the ERK T53 residue were also assessed for comparison. WT-DATs were used as controls. In an initial experiment, we confirmed that inhibiting PKC with Go6976 (130nM) significantly reduced amphetamine-induced DA efflux. In subsequent experiments, cells transfected with the S4A, S12A, S13A, T53A and S4,7,13A mutants showed a reduction in amphetamine-induced DA efflux similar to that observed with Go6976. Interestingly, cells transfected with the S7A mutant, identified by some as a PKC-PKA residue, showed unperturbed WT-DAT levels of amphetamine-induced DA efflux. These results indicate that phosphorylation by PKC of select residues in the DAT N-terminal can regulate amphetamine-induced efflux. PKC can act either independently or in concert with other kinases such as ERK to produce this effect. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Evaluation of simultaneous organic matters and nutrients removal from municipal wastewater using a novel bioreactor (D-A2O) system.

PubMed

Ye, Changbing; Zhou, Zhiming; Li, Ming; Liu, Qin; Xu, Tiantian; Li, Jia

2018-07-15

A novel bioreactor, the divisional influent dual-anaerobic-anoxic/oxic (D-A 2 O) system, was applied to treat municipal wastewater. This new system improved the removal efficiency of simultaneous organic matters and nutrients, and provided a reduction in the system's energy costs and sludge yield. Results from the reactor's 18 months of operation demonstrated the following optimal conditions for the 4 key parameters of the system: (1) a divisional ratio (DR) of 8:2 between the influent flow volumes fed into the anaerobic and anoxic tanks, (2) a hydraulic retention time (HRT) of 6 h, (3) a R:r ratio of 200%:100% between the mixed liquor return ratio (R) and the return activated sludge ratio (r), and (4) an alternative operating time (t A/B ) of 1 h for the A/B anaerobic-anoxia series. Under optimal conditions, the system showed a high removal efficiency for the chemical oxygen demand (COD), total nitrogen (TN), ammonia nitrogen (NH 3 -N), and total phosphorus (TP) removals, with the average removal efficiencies (with a standard deviation of less than 3%) being 95.23%, 80.64%, 90.42%, and 90.03%, respectively. The final concentration ranges of COD, TN, NH 3 -N, and TP in the effluent were 26-48 mg L -1 , 6.11-11.03 mg L -1 , 2.93-4.04 mg L -1 , and 0.21-0.45 mg L -1 , respectively. The concentrations of the pollutants in the effluent from the D-A 2 O system were lower than those required for Level 1A (Chinese quality of wastewater discharge standard GB18918-2002). According to the results, we concluded that the divisional influent dual-anaerobic-anoxic system (which integrated the A 2 O and sequencing batch reactor (SBR) process) was successfully provided sufficient carbon sources for denitrification and phosphorus uptake without external carbon addition. Compared to the conventional anaerobic-anoxic/oxic (A 2 O) process, the D-A 2 O system offers a high removal efficiency, simple operation, and significant energy saving of about 0.276 kWh m -3

Virtual reality training improves da Vinci performance: a prospective trial.

PubMed

Cho, Jae Sung; Hahn, Koo Yong; Kwak, Jung Myun; Kim, Jin; Baek, Se Jin; Shin, Jae Won; Kim, Seon Hahn

2013-12-01

The DV-Trainer™ (a virtual reality [VR] simulator) (Mimic Technologies, Inc., Seattle, WA) is one of several different robotic surgical training methods. We designed a prospective study to determine whether VR training could improve da Vinci(®) Surgical System (Intuitive Surgical, Inc., Sunnyvale, CA) performance. Surgeons (n=12) were enrolled using a randomized protocol. Groups 1 (VR training) and 2 (control) participated in VR and da Vinci exercises. Participants' time and moving distance were combined to determine a composite score: VR index=1000/(time×moving distance). The da Vinci exercises included needle control and suturing. Procedure time and error were measured. A composite index (DV index) was computed and used to measure da Vinci competency. After the initial trial with both the VR and da Vinci exercises, only Group 1 was trained with the VR simulator following our institutional curriculum for 3 weeks. All members of both groups then participated in the second trial of the VR and da Vinci exercises and were scored in the same way as in the initial trial. In the initial trial, there was no difference in the VR index (Group 1 versus Group 2, 8.9 ± 3.3 versus 9.4 ± 3.7; P=.832) and the DV index (Group 1 versus Group 2, 3.85 ± 0.73 versus 3.66 ± 0.65; P=.584) scores between the two groups. At the second time point, Group 1 showed increased VR index scores in comparison with Group 2 (19.3 ± 4.5 versus 9.7 ± 4.1, respectively; P=.001) and improved da Vinci performance skills as measured by the DV index (5.80 ± 1.13 versus 4.05 ± 1.03, respectively; P=.028) and by suturing time (7.1 ± 1.54 minutes versus 10.55 ± 1.93 minutes, respectively; P=.018). We found that VR simulator training can improve da Vinci performance. VR practice can result in an early plateau in the learning curve for robotic practice under controlled circumstances.

M1/M2 muscarinic receptor selectivity using potassium (K/sup +/)-stimulated release of (/sup 3/H)-dopamine (DA) and (/sup 14/C)-acetyl-choline (ACH) in striatum

DOE Office of Scientific and Technical Information (OSTI.GOV)

DeHaven, D.L.; Steranka, L.R.

Raiteri et al have suggested that muscarinic receptor subtypes can be differentiated in striatal synaptosomes by the release of DA (M1) or ACh (M2). The authors attempted to replicate this finding and to characterize responses of selective and non-selective cholinergic agonists and antagonists using K+-stimulated release of transmitters from rat striatal slices. The non-selective agonists ACh, carbachol and oxotremorine stimulated release of (/sup 3/H)-DA and inhibited release of (/sup 14/C)-ACh with EC50 values of 10.6, 9.2 and 4.2 ..mu..M (DA) and 1.2, 0.77 and 0.43 ..mu..M (ACh), respectively. The M1 agonist McN-A-343-11 selectively inhibited release of DA with an EC50more » value of 4.8 ..mu..M. Pilocarpine was ineffective in this system. The M1 antagonist pirenzepine reversed the effects of 10/sup -4/ M carbachol on release with an eight-fold selectivity for release of (/sup 3/H)-DA (IC50 = 0.77 ..mu..M) vs (/sup 14/C)-ACh (IC50 = 6.3 ..mu..M). These results suggest that although this system can determine relative subtype selectivities, the results obtained in this assay do not always correlate with those obtained from phosphatidyl inositol turnover or adenylate cyclase activity.« less

[Anesthesia experiences on laparoscopic nephrectomy with da Vinci S robotics].

PubMed

Mou, Ling; Lan, Zhixun

2015-09-01

To summarize the clinical anesthesia experiences in 20 patients who underwent laparoscopic nephrectomy with da Vinci S robotics.
 Anesthesia data of 20 patients from Sichuan Provincial People's Hospital, who underwent laparoscopic nephrectomy with da Vinci S robotics from August 2014 to November 2014, were analyzed and summarized. The anesthesia time, operation time, CO(2) pneumoperitoneum time, PaCO(2) and PETCO(2) were recorded.
 All patients were anesthetized and underwent surgery with da Vinci S robotics. The anesthesia time was (220±14) min, the operation time was (187±11) min, and the CO(2) pneumoperitoneum time was (180±13) min. The PaCO(2) and PETCO(2) were significantly elevated at 1.5 h after operation compared with those at the baseline (before pneumoperitoneum) (P<0.05). The pH value was significantly decreased at 2.5 h after operation compared to that at the baseline (P<0.05). The peak airway pressure of inspiration was significantly elevated at 0.5 h after the beginning of pneumoperitoneum compared to that at the baseline (P<0.05).
 The hemodynamics is stable during the laparoscopic nephrectomy with da vinci S robotics. However, the duration of CO(2) pneumoperitoneum is significantly increased compared to that of other surgical procedures, resulting in high airway resistance and acid-base disturbance.

Involvement of PKA/DARPP-32/PP1α and β- arrestin/Akt/GSK-3β Signaling in Cadmium-Induced DA-D2 Receptor-Mediated Motor Dysfunctions: Protective Role of Quercetin.

PubMed

Gupta, Richa; Shukla, Rajendra K; Pandey, Ankita; Sharma, Tanuj; Dhuriya, Yogesh K; Srivastava, Pranay; Singh, Manjul P; Siddiqi, Mohammad Imran; Pant, Aditya B; Khanna, Vinay K

2018-02-06

Given increasing risk of cadmium-induced neurotoxicity, the study was conducted to delineate the molecular mechanisms associated with cadmium-induced motor dysfunctions and identify targets that govern dopaminergic signaling in the brain involving in vivo, in vitro, and in silico approaches. Selective decrease in dopamine (DA)-D2 receptors on cadmium exposure was evident which affected the post-synaptic PKA/DARPP-32/PP1α and β-arrestin/Akt/GSK-3β signaling concurrently in rat corpus striatum and PC12 cells. Pharmacological inhibition of PKA and Akt in vitro demonstrates that both pathways are independently modulated by DA-D2 receptors and associated with cadmium-induced motor deficits. Ultrastructural changes in the corpus striatum demonstrated neuronal degeneration and loss of synapse on cadmium exposure. Further, molecular docking provided interesting evidence that decrease in DA-D2 receptors may be due to direct binding of cadmium at the competitive site of dopamine on DA-D2 receptors. Treatment with quercetin resulted in the alleviation of cadmium-induced behavioral and neurochemical alterations. This is the first report demonstrating that cadmium-induced motor deficits are associated with alteration in postsynaptic dopaminergic signaling due to a decrease in DA-D2 receptors in the corpus striatum. The results further demonstrate that quercetin has the potential to alleviate cadmium-induced dopaminergic dysfunctions.

The discovery of Ni V in the photospheres of the hot DA white dwarfs RE 2214-492 and G191-B2B

NASA Technical Reports Server (NTRS)

Holberg, J. B.; Hubeny, I.; Barstow, M. A.; Lanz, T.; Sion, E. M.; Tweedy, R. W.

1994-01-01

We have co-added six recently obtained International Ultraviolet Explorer (IUE) echelle spectra of the hot DA white dwarf RE 2214-492 and 10 existing archive spectra of the well-known hot DA, G191-B2B. We find that both stars contain numerous weak features due to Ni V. Nickel is thus the second iron-group element to be found in the spectra of the very hottest DA white dwarfs. In addition to Ni V, we also observe Al III in both stars and present evidence for the possible presence of Ni IV and Fe IV in RE 2214-492. The presence of Ni and Al, together with previously reported elements, will contribute significantly to both the EUV opacity and to the apparent complexity of the UV spectra of these stars. Using Non-Local Thermodynamic Equilibrium (NLTE) model atmospheres we estimate the Ni abundances in RE 2214-492 the G191-B2B to be log(Ni/H) = -5.5 +/- 0.3 and -6.0 +/- 0.3, respectively.

A Customizable Importer for the Clinical Data Warehouses PaDaWaN and I2B2.

PubMed

Fette, Georg; Kaspar, Mathias; Dietrich, Georg; Ertl, Maximilian; Krebs, Jonathan; Stoerk, Stefan; Puppe, Frank

2017-01-01

In recent years, clinical data warehouses (CDW) storing routine patient data have become more and more popular to support scientific work in the medical domain. Although CDW systems provide interfaces to import new data, these interfaces have to be used by processing tools that are often not included in the systems themselves. In order to establish an extraction-transformation-load (ETL) workflow, already existing components have to be taken or new components have to be developed to perform the load part of the ETL. We present a customizable importer for the two CDW systems PaDaWaN and I2B2, which is able to import the most common import formats (plain text, CSV and XML files). In order to be run, the importer only needs a configuration file with the user credentials for the target CDW and a list of XML import configuration files, which determine how already exported data is indented to be imported. The importer is provided as a Java program, which has no further software requirements.

75 FR 52292 - Airworthiness Directives; Diamond Aircraft Industries GmbH Models DA 40 and DA 40F Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-25

... Industries GmbH Models DA 40 and DA 40F Airplanes AGENCY: Federal Aviation Administration (FAA), Department... new airworthiness directive (AD) for all Diamond Aircraft Industries GmbH Models DA 40 and DA 40F... received information from Diamond Aircraft Industries GmbH that the Models DA 40 and DA 40F airplanes have...

Structures of (5′S)-8,5′-Cyclo-2′-deoxyguanosine Mismatched with dA or dT

PubMed Central

2012-01-01

Diastereomeric 8,5′-cyclopurine 2′-deoxynucleosides, containing a covalent bond between the deoxyribose and the purine base, are induced in DNA by ionizing radiation. They are suspected to play a role in the etiology of neurodegeneration in xeroderma pigmentosum patients. If not repaired, the S-8,5′-cyclo-2′-deoxyguanosine lesion (S-cdG) induces Pol V-dependent mutations at a frequency of 34% in Escherichia coli. Most are S-cdG → A transitions, suggesting mis-incorporation of dTTP opposite the lesion during replication bypass, although low levels of S-cdG → T transversions, arising from mis-incorporation of dATP, are also observed. We report the structures of 5′-d(GTGCXTGTTTGT)-3′·5′-d(ACAAACAYGCAC)-3′, where X denotes S-cdG and Y denotes either dA or dT, corresponding to the situation following mis-insertion of either dTTP or dATP opposite the S-cdG lesion. The S-cdG·dT mismatch pair adopts a wobble base pairing. This provides a plausible rationale for the S-cdG → A transitions. The S-cdG·dA mismatch pair differs in conformation from the dG·dA mismatch pair. For the S-cdG·dA mismatch pair, both S-cdG and dA intercalate, but no hydrogen bonding is observed between S-cdG and dA. This is consistent with the lower levels of S-cdG → T transitions in E. coli. PMID:22309170

The strainrange partitioning behavior of an advanced gas turbine disk alloy, AF2-1DA

NASA Technical Reports Server (NTRS)

Halford, G. R.; Nachtigall, A. J.

1979-01-01

The low-cycle, creep-fatigue characteristics of the advanced gas turbine disk alloy, AF2-1DA have been determined at 1400 F and are presented in terms of the method of strainrange partitioning (SRP). The mean stresses which develop in the PC and CP type SRP cycles at the lowest inelastic strainrange were observed to influence the cyclic lives to a greater extent than the creep effects and hence interfered with a conventional interpretation of the results by SRP. A procedure is proposed for dealing with the mean stress effects on life which is compatible with SRP.

Fluorescence growth of self-polymerized fluorescence polydopamine for ratiometric visual detection of DA.

PubMed

Yu, Miao; Lu, Yang; Tan, Zhenjiang

2017-06-01

In this work, a novel and facile ratiometric fluorescence probe was prepared for the visual detection of dopamine (DA). In this detection system, red-emission CdTe@SiO 2 (r-QDs@SiO 2 ) was used as steady core of the probe and inverse microemulsion method was applied to synthesize uniform r-QDs@SiO 2 , this step could protect CdTe from contacting with human skin directly. Polydopamine (PDA) acted as response signal to detect DA, a very handy method which just combined polyethyleneimine (PEI) with DA together to synthesize PDA, this way for synthesis of PDA was much time-saving and non-toxic than any other methods. Differently from traditional analysis processes, the products of this experiment were also the analysis substances in final. Under optimum measurement conditions, the dual-emission ratiometric fluorescence probe was used for detections of DA in a concentration ranged from 10μM to 80μM with a detection limit of 0.12μM, with addition of DA the color of the probe changed from red to green watched by naked eyes. In addition, the developed probe was also used for detections of DA in human serum samples successfully. This study provides a simple, time-saving and non-toxic approach for detections of DA without the requirement of complex equipment. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of omeprazole or cola beverage on the pharmacokinetics of oral DA-8159, a new erectogenic, in rats.

PubMed

Lee, Joo H; Bae, Soo K; Kwon, Jong W; Kim, Won B; Lee, Myung G

2005-12-01

The changes in pharmacokinetics of DA-8159 by omeprazole with respect to inhibition of CYP3A1/2 in rats were evaluated. After oral administration of DA-8159 at dose of 30 mg/kg to rats pretreated with oral omeprazole at 30 mg/kg for 1 week, the total area under the plasma concentration-time curve from time zero to time infinity (AUC) of DA-8159 was significantly greater (37.5% increase) than that in control rats. This could be due to inhibition of metabolism of DA-8159 by inhibition of CYP3A1/2 by omeprazole. The AUC(DA-8164 (a metabolite of DA-8159))/AUC(DA-8159) ratio was also smaller (32.4% decrease) with omeprazole. After oral administration of DA-8159 at a dose of 30 mg/kg to rats without or with cola beverage, the pharmacokinetic parameters of DA-8159 and DA-8164 were not significantly different between two groups of rats. This suggested that cola beverage did not have any considerable effects on CYP3A1/2 in rats.

Generation of oxyradicals (O2. and H2O2), mitochondrial activity and induction of apoptosis of PBMC of Cyprinus carpio carpio treated in vivo with halomethanes and with recombinant HSP60 kDa and with LPS of Klebsiella pneumoniae.

PubMed

Uraga-Tovar, D Italibi; Domínguez-López, M Lilia; Madera-Sandoval, Ruth L; Nájera-Martínez, Minerva; García-Latorre, Ethel; Vega-López, Armando

2014-10-01

Halomethanes (HM) can be immunotoxic in mammals; however, in the fish immune system HM effects are unknown. In the current study, we evaluated the mitochondrial activity (MA) by MTT, induction of apoptosis by SubG0 technique and quantified serum ROS concentration (O2. and H2O2) and ROS production in PBMC of Cyprinus carpio carpio treated i.p. with CH2Cl2, CHCl3 and BrCHCl2 (0.004-40.0 mg/kg) for 96 h. Positive controls were recombinant heat shock protein of 60 kDa (rHSP60 kDa) of Klebsiella pneumoniae and its LPS. In addition, for in vitro PBMC cultures, two culture media and two sources of sera were tested. Both positive controls increased the MA more than 4-fold as well as the production of O2. (26-fold) and H2O2 (5-fold) compared to their controls. HM induced different effects on MA, ROS production and an induction of apoptosis, depending on the chlorination patterns and the dose; however, a systemic damage prevails. To fish treated with CH2Cl2, the apoptosis was related with serum ROS concentration and with MA. In contrast, in fish dosed with CHCl3 relationships were not found, deducing a systemic damage. However, in fish treated with BrCHCl2, serum O2. concentration and in vitro ROS generation performed by PBMC were involved in the induction of apoptosis of these cells but not with MA suggesting also immunotoxic effects. The current study demonstrated that HMs are immunomodulators increasing an acute inflammatory response and that rHSP60kDA of K. pneumoniae and its LPS are appropriate antigens to assess the immune response of C. c. carpio.

DA-9701 on gastric motility in patients with Parkinson's disease: A randomized controlled trial.

PubMed

Shin, Cheol Min; Lee, Yoon Jin; Kim, Jong-Min; Lee, Jee Young; Kim, Kyung-Joon; Choi, Yoon Jin; Kim, Nayoung; Lee, Dong Ho

2018-04-21

To evaluate the effect of DA-9701, a novel prokinetic drug, on gastric motility evaluated by magnetic resonance imaging in patients with Parkinson's disease (PD). Forty PD patients were randomly allocated to receive either domperidone or DA-9701. Their gastric functions were evaluated using magnetic resonance imaging before and after 4-week treatment period. Information on levodopa daily dose, disease duration, and Unified PD Rating Scale scores was collected. In 18 patients (domperidone: 9, DA-9701: 9), plasma levodopa concentrations were determined. Primary outcome was assessed by a one-sided 95% confidence interval to show non-inferiority of DA-9701 vs. domperidone with a pre-determined non-inferiority margin of -10%. Thirty-eight participants (19 men and 19 women; mean age, 67.1 years) completed the study protocol (domperidone: DA-9701 = 19:19). Gastric emptying rate at 120 min (2-hr GER) was comparable between the 2 groups; it was not correlated with levodopa daily dose or disease duration or Unified PD Rating Scale scores (all p > 0.05). DA-9701 was not inferior to domperidone in changes of 2-hr GERs before and after the treatment (absolute difference, 4.0 %; one-sided 95% confidence interval, - 3.7 to infinity). However, a significant increase in 2-hr GER was observed only in DA-9701 group (54.5% and 61.8%, before and after treatment, respectively, p < 0.05). Plasma levodopa concentration showed an insignificant but increasing trend in DA-9701 group. There were neither adverse reactions nor deteriorations of parkinsonian symptoms observed in the study participants. DA-9701 can be used for the patients with PD to enhance gastric motility without aggravating PD symptoms (ClinicalTrials.gov number: NCT03022201). Copyright © 2018 Elsevier Ltd. All rights reserved.

Da Vinci-assisted abdominal cerclage.

PubMed

Barmat, Larry; Glaser, Gretchen; Davis, George; Craparo, Frank

2007-11-01

To report the first placement of an abdominal cervicoisthmic cerclage using the da Vinci robot. Case report. Tertiary-care hospital. A 39-year-old female with a history of cervical insufficiency who required a cerclage and was not a candidate for transvaginal cerclage placement. Abdominal cervicoisthmic cerclage placement using the da Vinci robot. Ability to safely and successfully place an abdominal cerclage using the da Vinci robot. Abdominal cerclage was successfully placed using the da Vinci robot. The patient had minimal blood loss and was discharged to home on the same day as surgery. Da Vinci robot-assisted abdominal cerclage placement is an innovative application of robotic surgery and may alter the standard of care for women who require this surgery.

Cloning, expression and activation of a truncated 92-kDa gelatinase minienzyme.

PubMed

Kröger, M; Tschesche, H

1997-09-01

The matrix metalloproteinases (MMPs) are a family of highly homologous zinc-endopeptidases that degrade extracellular matrix components. Human 92-kDa gelatinase (MMP-9) represents one of the MMPs that cleaves native collagen type IV. As a basis for structural investigations, the short form (catalytic domain, amino acid residues 113-450) of the 92-kDa gelatinase cDNA was cloned and expressed in E. coli as a minienzyme. By combination of reverse transcription (RT) and polymerase chain reaction (PCR), the truncated 92-kDa gelatinase-cDNA was amplified from the corresponding mRNA derived from ovarian carcinoma cells. The cDNA fragment obtained was cloned in E. coli and sequenced. With the exception of one nucleotide inversion at position 745 (gt-->tg) the cDNA sequence was identical to the nucleotide sequence of the 92-kDa gelatinase as has been previously reported. The protein was expressed in E. coli using the vector pET-12b. The recombinant protein was stored in inclusion bodies and extracted as a 38 kDa species from the inclusion bodies by solubilization in 8 M urea. The product was purified by affinity chromatography and gel filtration. Amino-terminal sequence analysis confirmed the identity with the catalytic domain of 92-kDa gelatinase. The recombinant protein was refolded in the presence of Ca2+ and Zn2+ and yielded an active minienzyme with gelatinolytic activity. It degrades the native substrate collagen type IV and the synthetic substrate Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 x AcOH like the full-length 92-kDa gelatinase. The catalytic activity could be inhibited by the specific MMP inhibitors TIMP-1 and TIMP-2.

Towards a Standardized Line List for G 191-B2B and other DA Type Objects

NASA Astrophysics Data System (ADS)

Preval, S. P.; Barstow, M. A.; Holberg, J. B.; Dickinson, N. J.

2013-01-01

We present a comprehensive analysis of the far UV spectrum of G 191-B2B over the range of 900-1700Å using co-added data from the FUSE and STIS archives. While previous identifications made by Holberg et al. (2003) are reaffirmed in this work, it is found that many previously unidentified lines can now be attributed to Fe, Ni, and a few lighter metals. Future work includes extending this detailed analysis to a wider range of DA objects, in the expectation that a more complete analysis of their atmospheres can be realised.

A randomized, double-blind, placebo-controlled, phase II clinical trial to investigate the efficacy and safety of oral DA-1229 in patients with type 2 diabetes mellitus who have inadequate glycaemic control with diet and exercise.

PubMed

Jung, Chang Hee; Park, Cheol-Young; Ahn, Kyu-Joeng; Kim, Nan-Hee; Jang, Hak-Chul; Lee, Moon-Kyu; Park, Joong-Yeol; Chung, Choon-Hee; Min, Kyung-Wan; Sung, Yeon-Ah; Park, Jeong-Hyun; Kim, Sung Jin; Lee, Hyo Jung; Park, Sung-Woo

2015-03-01

DA-1229 is a novel, potent and selective dipeptidyl peptidase-4 (DPP-IV) inhibitor that is orally bioavailable. We aimed to evaluate the optimal dose, efficacy and safety of DA-1229, in Korean subjects with type 2 diabetes mellitus suboptimally controlled with diet and exercise. We enrolled 158 patients (mean age, 53 years and a mean BMI, 25.6 kg/m(2) ). The mean baseline fasting plasma glucose level, HbA1c and duration of diabetes were 8.28 mmol/L, 7.6% (60 mmol/mol) and 3.9 years, respectively. After 2 or 6 weeks of an exercise and diet program followed by 2 weeks of a placebo period, the subjects were randomized into one of four groups for a 12-week active treatment period: placebo, 2.5, 5 or 10 mg of DA-1229. All three doses of DA-1229 significantly reduced HbA1c from baseline compared to the placebo group (-0.09 in the placebo group vs. -0.56, -0.66 and -0.61% in 2.5, 5 and 10-mg groups, respectively) but without any significant differences between the doses. Insulin secretory function, as assessed by homeostasis model assessment β-cell, the insulinogenic index, 2-h oral glucose tolerance test (OGTT) C-peptide and post-OGTT C-peptide area under the curve (AUC)0-2h, significantly improved with DA-1229 treatment. The incidence of adverse events was similar between the treatment groups and DA-1229 did not affect body weight or induce hypoglycaemic events. DA-1229 monotherapy (5 mg for 12 weeks) improved HbA1c, fasting plasma glucose level, OGTT results and β-cell function. This drug was well tolerated in Korean subjects with type 2 diabetes mellitus. © 2014 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons, Ltd.

Effects of DA-Phen, a dopamine-aminoacidic conjugate, on alcohol intake and forced abstinence.

PubMed

Sutera, Flavia Maria; De Caro, Viviana; Cannizzaro, Carla; Giannola, Libero Italo; Lavanco, Gianluca; Plescia, Fulvio

2016-09-01

The mesolimbic dopamine (DA) system plays a key role in drug reinforcement and is involved in the development of alcohol addiction. Manipulation of the DAergic system represents a promising strategy to control drug-seeking behavior. Previous studies on 2-amino-N-[2-(3,4-dihydroxy-phenyl)-ethyl]-3-phenyl-propionamide (DA-Phen) showed in vivo effects as a DA-ergic modulator. This study was aimed at investigate DA-Phen effects on operant behavior for alcohol seeking behavior, during reinstatement following subsequent periods of alcohol deprivation. For this purpose, male Wistar rats were tested in an operant paradigm of self-administration; behavioral reactivity and anxiety like-behavior during acute abstinence were evaluated. A characterization of DA-Phen CNS targeting by its quantification in the brain was also carried out. Our findings showed that DA-Phen administration was able to reduce relapse in alcohol drinking by 50% and reversed the alterations in behavioral reactivity and emotionality observed during acute abstinence. In conclusion, DA-Phen can reduce reinstatement of alcohol drinking in an operant-drinking paradigm following deprivation periods and reverse abstinence-induced behavioral phenotype. DA-Phen activity seems to be mediated by the modulation of the DAergic transmission. However further studies are needed to characterize DA-Phen pharmacodynamic and pharmacokinetic properties, and its potential therapeutic profile in alcohol addiction. Copyright © 2016 Elsevier B.V. All rights reserved.

D-amphetamine (A)-induced dopamine (DA) release is not strictly dependent on newly-synthesized transmitter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parker, E.; Cubeddu, L.

1986-03-05

A is thought to exert its stimulant effects by releasing DA from a newly synthesized transmitter pool. This hypothesis was evaluated directly by measuring the basal efflux and electrically-evoked release of endogenous DA and dihydroxyphenylacetic acid (DOPAC). In striatal slices from reserpine-treated rabbits A increased DA efflux, reduced DOPAC efflux, and inhibited electrically-evoked /sup 3/H-ACh release in a concentration-dependent manner. These effects could not be mimicked by inhibition of neuronal uptake or MAO, but were blocked by inhibition of DA synthesis or neuronal uptake, and were potentiated by inhibition of MAO. In slices with intact vesicular transmitter stores A inducedmore » DA efflux was 2-fold greater than that seen in slices having no vesicular stores. Inhibition of DA synthesis reduced A-induced DA efflux by 60%, but had little effect on the ability of A to inhibit /sup 3/H-ACh release. A also increased the electrical stimulation-evoked overflow of DA (an effect which was attenuated slightly by synthesis inhibition), and potently inhibited DOPAC overflow. These results suggest that: 1) A facilitates efflux of axoplasmic DA by an accelerated exchange diffusion mechanism. The releasable axoplasmic pool is derived from newly synthesized and vesicular transmitter pools; 2) postsynaptic indices of transmitter release may be misleading; and 3) A increases electrically-evoked DA release possibly by inhibiting neuronal uptake.« less

Comparative effect of lurasidone and blonanserin on cortical glutamate, dopamine, and acetylcholine efflux: role of relative serotonin (5-HT)2A and DA D2 antagonism and 5-HT1A partial agonism.

PubMed

Huang, Mei; Panos, John J; Kwon, Sunoh; Oyamada, Yoshihiro; Rajagopal, Lakshmi; Meltzer, Herbert Y

2014-03-01

Atypical antipsychotic drugs (AAPDs) have been suggested to be more effective in improving cognitive impairment in schizophrenia than typical APDs, a conclusion supported by differences in receptor affinities and neurotransmitter efflux in the cortex and the hippocampus. More potent serotonin (5-HT)2A than dopamine (DA) D2 receptors antagonism, and direct or indirect 5-HT1A agonism, characterize almost all AAPDs. Blonanserin, an AAPD, has slightly greater affinity for D2 than 5-HT2A receptors. Using microdialysis and ultra performance liquid chromatography-mass spectrometry/mass spectrometry, we compared the abilities of the typical APD, haloperidol, three AAPDs, blonanserin, lurasidone, and olanzapine, and a selective 5-HT1A partial agonist, tandospirone, and all, except haloperidol, were found to ameliorate the cognitive deficits produced by the N-methyl-d-aspartate antagonist, phencyclidine, altering the efflux of neurotransmitters and metabolites in the rat cortex and nucleus accumbens. Blonanserin, lurasidone, olanzapine, and tandospirone, but not haloperidol, increased the efflux of cortical DA and its metabolites, homovanillic acid and 3,4-dihydroxyphenylacetic acid. Olanzapine and lurasidone increased the efflux of acetylcholine; lurasidone increased glutamate as well. None of the compounds significantly altered the efflux of 5-HT or its metabolite, 5-hydroxyindole acetic acid, or GABA, serine, and glycine. The ability to increase cortical DA efflux was the only shared effect of the compounds which ameliorates the deficit in cognition in rodents following phencyclidine. © 2013 International Society for Neurochemistry.

Fatigue Crack Growth Characteristics of Thin Sheet Titanium Alloy Ti 6-2-2-2-2

NASA Technical Reports Server (NTRS)

Smith, Stephen W.; Piascik, Robert S.

2001-01-01

Fatigue crack growth rates of Ti 6-2-2-2-2 as a function of stress ratio, temperature (24 or 177 C), tensile orientation and environment (laboratory air or ultrahigh vacuum) are presented. Fatigue crack growth rates of Ti 6-2-2-2-2 are also compared with two more widely used titanium alloys (Timetal 21S and Ti 6Al-4V). The fatigue crack growth rate (da/dN) of Ti 6-2-2-2-2 in laboratory air is dependent upon stress ratio (R), particularly in the near-threshold and lower-Paris regimes. For low R (less than approximately 0.5), da/dN is influenced by crack closure behavior. At higher R (> 0.5), a maximum stress-intensity factor (K(sub max)) dependence is observed. Fatigue crack growth behavior is affected by test temperature between 24 and 177 C. For moderate to high applied cyclic-stress-intensity factors (delta-K), the slope of the log da/dN versus log delta-K curve is lower in 177 C laboratory air than 24 C laboratory air. The difference in slope results in lower values of da/dN for exposure to 177 C laboratory air compared to room temperature laboratory air. The onset of this temperature effect is dependent upon the applied R. This temperature effect has not been observed in ultrahigh vacuum. Specimen orientation has been shown to affect the slope of the log da/dN versus log delta-K curve in the Paris regime.

The ATLAS PanDA Pilot in Operation

NASA Astrophysics Data System (ADS)

Nilsson, P.; Caballero, J.; De, K.; Maeno, T.; Stradling, A.; Wenaus, T.; ATLAS Collaboration

2011-12-01

The Production and Distributed Analysis system (PanDA) [1-2] was designed to meet ATLAS [3] requirements for a data-driven workload management system capable of operating at LHC data processing scale. Submitted jobs are executed on worker nodes by pilot jobs sent to the grid sites by pilot factories. This paper provides an overview of the PanDA pilot [4] system and presents major features added in light of recent operational experience, including multi-job processing, advanced job recovery for jobs with output storage failures, gLExec [5-6] based identity switching from the generic pilot to the actual user, and other security measures. The PanDA system serves all ATLAS distributed processing and is the primary system for distributed analysis; it is currently used at over 100 sites worldwide. We analyze the performance of the pilot system in processing real LHC data on the OSG [7], EGI [8] and Nordugrid [9-10] infrastructures used by ATLAS, and describe plans for its evolution.

75 FR 75868 - Airworthiness Directives; Diamond Aircraft Industries GmbH Models DA 40 and DA 40F Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-07

... Airworthiness Directives; Diamond Aircraft Industries GmbH Models DA 40 and DA 40F Airplanes AGENCY: Federal... of the Thielert Engine Owners Group commented that the Model DA 42 has the same door design and the same unsafe condition. He recommended that the AD also apply to the Model DA 42. The FAA has discussed...

DA-Raf, a dominant-negative antagonist of the Ras-ERK pathway, is a putative tumor suppressor.

PubMed

Kanno, Emiri; Kawasaki, Osamu; Takahashi, Kazuya; Takano, Kazunori; Endo, Takeshi

2018-01-01

Activating mutations of RAS genes, particularly KRAS, are detected with high frequency in human tumors. Mutated Ras proteins constitutively activate the ERK pathway (Raf-MEK-ERK phosphorylation cascade), leading to cellular transformation and tumorigenesis. DA-Raf1 (DA-Raf) is a splicing variant of A-Raf and contains the Ras-binding domain (RBD) but lacks the kinase domain. Accordingly, DA-Raf antagonizes the Ras-ERK pathway in a dominant-negative fashion and suppresses constitutively activated K-Ras-induced cellular transformation. Thus, we have addressed whether DA-Raf serves as a tumor suppressor of Ras-induced tumorigenesis. DA-Raf(R52Q), which is generated from a single nucleotide polymorphism (SNP) in the RBD, and DA-Raf(R52W), a mutant detected in a lung cancer, neither bound to active K-Ras nor interfered with the activation of the ERK pathway. They were incapable of suppressing activated K-Ras-induced cellular transformation and tumorigenesis in mice, in which K-Ras-transformed cells were transplanted. Furthermore, although DA-Raf was highly expressed in lung alveolar epithelial type 2 (AE2) cells, its expression was silenced in AE2-derived lung adenocarcinoma cell lines with oncogenic KRAS mutations. These results suggest that DA-Raf represents a tumor suppressor protein against Ras-induced tumorigenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Evolution of the ATLAS PanDA workload management system for exascale computational science

NASA Astrophysics Data System (ADS)

Maeno, T.; De, K.; Klimentov, A.; Nilsson, P.; Oleynik, D.; Panitkin, S.; Petrosyan, A.; Schovancova, J.; Vaniachine, A.; Wenaus, T.; Yu, D.; Atlas Collaboration

2014-06-01

An important foundation underlying the impressive success of data processing and analysis in the ATLAS experiment [1] at the LHC [2] is the Production and Distributed Analysis (PanDA) workload management system [3]. PanDA was designed specifically for ATLAS and proved to be highly successful in meeting all the distributed computing needs of the experiment. However, the core design of PanDA is not experiment specific. The PanDA workload management system is capable of meeting the needs of other data intensive scientific applications. Alpha-Magnetic Spectrometer [4], an astro-particle experiment on the International Space Station, and the Compact Muon Solenoid [5], an LHC experiment, have successfully evaluated PanDA and are pursuing its adoption. In this paper, a description of the new program of work to develop a generic version of PanDA will be given, as well as the progress in extending PanDA's capabilities to support supercomputers and clouds and to leverage intelligent networking. PanDA has demonstrated at a very large scale the value of automated dynamic brokering of diverse workloads across distributed computing resources. The next generation of PanDA will allow other data-intensive sciences and a wider exascale community employing a variety of computing platforms to benefit from ATLAS' experience and proven tools.

Leonardo Da Vinci and stroke - vegetarian diet as a possible cause.

PubMed

Oztürk, Serefnur; Altieri, Marta; Troisi, Pina

2010-01-01

Leonardo da Vinci (April 15, 1452 to May 2, 1519) was an Italian Renaissance architect, musician, anatomist, inventor, engineer, sculptor, geometer, and painter. It has been gleaned from the many available historical documents that da Vinci was a vegetarian who respected and loved animals, and that he suffered from right hemiparesis in the last 5 years of his life. A vegetarian diet has both positive and negative influences on the cerebrovascular system. In this report, a possible relation between a vegetarian diet and stroke is discussed from various perspectives as related to Leonardo da Vinci's stroke. Copyright (c) 2010 S. Karger AG, Basel.

da Vinci decoded: does da Vinci stereopsis rely on disparity?

PubMed

Tsirlin, Inna; Wilcox, Laurie M; Allison, Robert S

2012-11-01

In conventional stereopsis, the depth between two objects is computed based on the retinal disparity in the position of matching points in the two eyes. When an object is occluded by another object in the scene, so that it is visible only in one eye, its retinal disparity cannot be computed. Nakayama and Shimojo (1990) found that a precept of quantitative depth between the two objects could still be established for such stimuli and proposed that this precept is based on the constraints imposed by occlusion geometry. They named this and other occlusion-based depth phenomena "da Vinci stereopsis." Subsequent research found quantitative depth based on occlusion geometry in several other classes of stimuli grouped under the term da Vinci stereopsis. However, Nakayama and Shimojo's findings were later brought into question by Gillam, Cook, and Blackburn (2003), who suggested that quantitative depth in their stimuli was perceived based on conventional disparity. In order to understand whether da Vinci stereopsis relies on one type of mechanism or whether its function is stimulus dependent we examine the nature and source of depth in the class of stimuli used by Nakayama and Shimojo (1990). We use three different psychophysical and computational methods to show that the most likely source for depth in these stimuli is occlusion geometry. Based on these experiments and previous data we discuss the potential mechanisms responsible for processing depth from monocular features in da Vinci stereopsis.

Effect of 14-kDa and 47-kDa protein molecules of age garlic extract on peritoneal macrophages.

PubMed

Daneshmandi, Saeed; Hajimoradi, Monire; Ahmadabad, Hasan Namdar; Hassan, Zuhair Mohammad; Roudbary, Maryam; Ghazanfari, Tooba

2011-03-01

Garlic (Allium sativum), traditionally being used as a spice worldwide, has different applications and is claimed to possess beneficial effects in several health ailments such as tumor and atherosclerosis. Garlic is also an immunomodulator and its different components are responsible for different properties. The present work aimed to assess the effect of protein fractions of garlic on peritoneal macrophages. 14-kDa and 47-kDa protein fractions of garlic were purified. Mice peritoneal macrophages were lavaged and cultured in a microtiter plate and exposed to different concentrations of garlic proteins. MTT assay was performed to evaluate the viability of macrophage. The amount of nitric oxide (NO) was detected in culture supernatants of macrophages by Griess reagent and furthermore, the cytotoxicity study of culture supernatants was carried out on WEHI-164 fibrosarcoma cell line as tumor necrosis factor-α bioassay. MTT assay results for both 14-kDa and 47-kDa protein fractions of stimulated macrophages were not significant (P > 0.05). Both 14-kDa and 47-kDa fractions significantly suppressed production of NO from macrophages (P = 0.007 and P = 0.003, respectively). Cytotoxicity of macrophages' supernatant on WEHI-164 fibrosarcoma cells was not affected by garlic protein fractions (P = 0.066 for 14-kDa and P = 0.085 for 47-kDa fractions). according to our finding, 14-kDa and 47-kDa fractions of aged garlic extract are able to suppress NO production from macrophages, which can be used as a biological advantage. These molecules had no cytotoxic effect on macrophages and do not increase tumoricidal property of macrophages.

Impact of 2D and 3D vision on performance of novice subjects using da Vinci robotic system.

PubMed

Blavier, A; Gaudissart, Q; Cadière, G B; Nyssen, A S

2006-01-01

The aim of this study was to evaluate the impact of 3D and 2D vision on performance of novice subjects using da Vinci robotic system. 224 nurses without any surgical experience were divided into two groups and executed a motor task with the robotic system in 2D for one group and with the robotic system in 3D for the other group. Time to perform the task was recorded. Our data showed significant better time performance in 3D view (24.67 +/- 11.2) than in 2D view (40.26 +/- 17.49, P < 0.001). Our findings emphasized the advantage of 3D vision over 2D view in performing surgical task, encouraging the development of efficient and less expensive 3D systems in order to improve the accuracy of surgical gesture, the resident training and the operating time.

2MASS Photometry of the Hot DA White Dwarf Stars in the Palomar Green Survey

NASA Astrophysics Data System (ADS)

Holberg, J. B.; Magargal, K.

2003-12-01

The Palomar Green (PG) Survey is a complete, magnitude limited survey of UV excess objects that continues to provide well-defined sample populations for many types of objects, in particular hot white dwarf stars. The 2MASS All-Sky Survey limiting JHK magnitudes are reasonably well matched to the B magnitude limits of the PG survey. The 2MASS survey, therefore, constitutes an excellent source of uniform, high-quality of photometry, that can be used in conjunction with the PG Survey. The 2MASS Point Source Catalog in the All-Sky Data Release was searched for over 340 hot DA white dwarfs in the PG sample. The resulting JHK colors and apparent magnitudes are used to determine photometric distances for these stars and to place limits on the existence of possible cool binary companions. This publication makes use of data products from the Two Micron All Sky Survey, which is a joint project of the University of Massachusetts and the Infrared Processing and Analysis Center/California Institute of Technology, funded by the National Aeronautics and Space Administration and the National Science Foundation.

Using iPSC-derived human DA neurons from opioid-dependent subjects to study dopamine dynamics.

PubMed

Sheng, Yang; Filichia, Emily; Shick, Elizabeth; Preston, Kenzie L; Phillips, Karran A; Cooperman, Leslie; Lin, Zhicheng; Tesar, Paul; Hoffer, Barry; Luo, Yu

2016-08-01

The dopaminergic (DA) system plays important roles in addiction. However, human DA neurons from drug-dependent subjects were not available for study until recent development in inducible pluripotent stem cells (iPSCs) technology. In this study, we produced DA neurons differentiated using iPSCs derived from opioid-dependent and control subjects carrying different 3' VNTR (variable number tandem repeat) polymorphism in the human dopamine transporter (DAT or SLC6A3). In addition, the effects of valproic acid (VPA) exposures on iPSC-derived human DA neurons are also examined. We present the first evidence suggesting that the 3' VNTR polymorphism in the hDAT gene affects DAT expression level in iPSC-derived human DA neurons. In human DA neurons, which provide an appropriate cellular milieu, VPA treatment alters the expression of several genes important for dopaminergic neuron function including DAT, Nurr1, and TH; this might partly explain its action in regulating addictive behaviors. VPA treatment also significantly increased DA D2 receptor (Drd2) expression, especially in the opioid-dependent iPSC cell lines. Our data suggest that human iPSC-derived DA neurons may be useful in in vitro experimental model to examine the effects of genetic variation in gene regulation, to examine the underlying mechanisms in neurological disorders including drug addiction, and to serve as a platform for therapeutic development.

U2 small nuclear ribonucleoprotein particle (snRNP) auxiliary factor of 65 kDa, U2AF65, can promote U1 snRNP recruitment to 5' splice sites.

PubMed Central

Förch, Patrik; Merendino, Livia; Martínez, Concepción; Valcárcel, Juan

2003-01-01

The splicing factor U2AF(65), U2 small nuclear ribonucleoprotein particle (snRNP) auxillary factor of 65 kDa, binds to pyrimidine-rich sequences at 3' splice sites to recruit U2 snRNP to pre-mRNAs. We report that U2AF(65) can also promote the recruitment of U1 snRNP to weak 5' splice sites that are followed by uridine-rich sequences. The arginine- and serine-rich domain of U2AF(65) is critical for U1 recruitment, and we discuss the role of its RNA-RNA annealing activity in this novel function of U2AF(65). PMID:12558503

Specific cytoarchitectureal changes in hippocampal subareas in daDREAM mice.

PubMed

Mellström, Britt; Kastanauskaite, Asta; Knafo, Shira; Gonzalez, Paz; Dopazo, Xose M; Ruiz-Nuño, Ana; Jefferys, John G R; Zhuo, Min; Bliss, Tim V P; Naranjo, Jose R; DeFelipe, Javier

2016-02-29

Transcriptional repressor DREAM (downstream regulatory element antagonist modulator) is a Ca(2+)-binding protein that regulates Ca(2+) homeostasis through gene regulation and protein-protein interactions. It has been shown that a dominant active form (daDREAM) is implicated in learning-related synaptic plasticity such as LTP and LTD in the hippocampus. Neuronal spines are reported to play important roles in plasticity and memory. However, the possible role of DREAM in spine plasticity has not been reported. Here we show that potentiating DREAM activity, by overexpressing daDREAM, reduced dendritic basal arborization and spine density in CA1 pyramidal neurons and increased spine density in dendrites in dentate gyrus granule cells. These microanatomical changes are accompanied by significant modifications in the expression of specific genes encoding the cytoskeletal proteins Arc, Formin 1 and Gelsolin in daDREAM hippocampus. Our results strongly suggest that DREAM plays an important role in structural plasticity in the hippocampus.

A Influência da Escola e da Mídia na Obtenção dos Conhecimentos Astronômicos

NASA Astrophysics Data System (ADS)

da Cunha, W. S.; Voelzke, M. R.; Amaral, L. H.

2006-08-01

O universo em que vivemos possui segredos jamais imaginados pelo homem, fruto da pequena proporção que ocupamos diante de um cosmos infinito. A astronomia funciona como um instrumento que sacia a sede humana em desvendar esses segredos, estudando as galáxias, quasares, pulsares além da existência de todos os elementos que preenchem o espaço cósmico, o vácuo, não mais vazio como se pensou em outros tempos. A mídia explora esse campo de forma mística e também científica. A difusão adequada e dentro dos padrões educacionais vigentes, de conceitos astronômicos, se faz necessária, devido sua presença nos conteúdos escolares, centros de ciência e na mídia, de modo geral. A reforma do Currículo Básico da Escola Pública da maioria dos Estados brasileiros introduziu conceitos astronômicos desde a pré-escola até o Ensino Médio. Num estudo realizado com 1.032 alunos do Ensino Médio de seis escolas estaduais, revelou-se através da aplicação de um questionário que abordava conheciment os básicos em astronomia, como estes foram adquiridos e qual era a infra-estrutura oferecida pela escola: para 66,2% dos entrevistados o professor já fez alguma apresentação a respeito de astronomia. O presente estudo revelou também que 44,5% dos alunos entrevistados adquiriram seus conhecimentos astronômicos na escola, 28,1% através da televisão e 27,4% afirmaram que seus conhecimentos foram obtidos através de outros tipos de mídia (internet, filmes e revistas). Embora o estudo revele claramente que há certo equilíbrio na forma em que os alunos obtiveram seus conhecimentos astronômicos, a mídia ainda explora e muitas vezes desperta o interesse pela astronomia com assuntos que não fazem parte de nosso cotidiano como, por exemplo, o homem na Lua, os projetos espaciais e a primeira viagem de um astronauta brasileiro no espaço. Porém, em certos casos, a mídia pode promover conhecimentos incompletos ou mesmo equivocados sobre os conceitos que envolvam

The Effect of DA-6034 on Intestinal Permeability in an Indomethacin-Induced Small Intestinal Injury Model.

PubMed

Kwak, Dong Shin; Lee, Oh Young; Lee, Kang Nyeong; Jun, Dae Won; Lee, Hang Lak; Yoon, Byung Chul; Choi, Ho Soon

2016-05-23

DA-6034 has anti-inflammatory activities and exhibits cytoprotective effects in acute gastric injury models. However, explanations for the protective effects of DA-6034 on intestinal permeability are limited. This study sought to investigate the effect of DA-6034 on intestinal permeability in an indomethacin-induced small intestinal injury model and its protective effect against small intestinal injury. Rats in the treatment group received DA-6034 from days 0 to 2 and indomethacin from days 1 to 2. Rats in the control group received indomethacin from days 1 to 2. On the fourth day, the small intestines were examined to compare the severity of inflammation. Intestinal permeability was evaluated by using fluorescein isothiocyanate-labeled dextran. Western blotting was performed to confirm the association between DA-6034 and the extracellular signal-regulated kinase (ERK) pathway. The inflammation scores in the treatment group were lower than those in the control group, but the difference was statistically insignificant. Hemorrhagic lesions in the treatment group were broader than those in the control group, but the difference was statistically insignificant. Intestinal permeability was lower in the treatment group than in the control group. DA-6034 enhanced extracellular signal-regulated kinase expression, and intestinal permeability was negatively correlated with ERK expression. DA-6034 may decrease intestinal permeability in an indomethacin-induced intestinal injury model via the ERK pathway.

Desenvolvimento de modelo clínico para predição da possibilidade de identificação da artéria de Adamkiewicz por angiotomografia

PubMed Central

Amato, Alexandre Campos Moraes; Parga, José Rodrigues; Stolf, Noedir Antônio Groppo

2018-01-01

Resumo Contexto Diferenças morfológicas da artéria de Adamkiewicz (AKA) entre a população portadora e não portadora de doença aórtica têm importância clínica, influenciando as complicações neuroisquêmicas da medula espinhal em procedimentos operatórios. Ainda não é conhecida a correlação entre parâmetros clínicos e a previsibilidade da identificação dessa artéria pela angiotomografia. Objetivo Desenvolver um modelo matemático que, através de parâmetros clínicos correlacionados com aterosclerose, possa prever a probabilidade de identificação da AKA em pacientes submetidos a angiotomografias. Método Estudo observacional transversal utilizando banco de imagens e dados de pacientes. Foi feita análise estatística multivariada e criado modelo matemático logit de predição para identificação da AKA. Variáveis significativas foram utilizadas na montagem da fórmula para cálculo da probabilidade de identificação. O modelo foi calibrado, e a discriminação foi avaliada pela curva receiver operating characteristic (ROC). A seleção das variáveis explanatórias foi guiada pela maior área na curva ROC (p = 0,041) e pela significância combinada das variáveis. Resultados Foram avaliados 110 casos (54,5% do sexo masculino, com idade média de 60,97 anos e etnia com coeficiente B -2,471, M -1,297, N -0,971), com AKA identificada em 60,9%. Índice de massa corporal: 27,06 ± 0,98 (coef. -0,101); fumantes: 55,5% (coef. -1,614/-1,439); diabéticos: 13,6%; hipertensos: 65,5% (coef. -1,469); dislipidêmicos: 58,2%; aneurisma aórtico: 38,2%; dissecção aórtica: 12,7%; e trombo mural: 24,5%. Constante de 6,262. Fórmula para cálculo da probabilidade de detecção: (e−(Coef. Etnia+(Coef. IMC×IMC)+Coef.fumante+Coef.HAS+Coef.dislip+Constante)+1)−1 . O modelo de predição foi criado e disponibilizado no link https://vascular.pro/aka-model . Conclusão Com as covariáveis etnia, índice de massa corporal, tabagismo, hipertens

Pharmacokinetics and tolerability of DA-8031, a novel selective serotonin reuptake inhibitor for premature ejaculation in healthy male subjects.

PubMed

Shin, Dongseong; Lee, SeungHwan; Yi, Sojeong; Yoon, Seo Hyun; Cho, Joo-Youn; Bahng, Mi Young; Jang, In-Jin; Yu, Kyung-Sang

2017-01-01

DA-8031 is a selective serotonin reuptake inhibitor under development for the treatment of premature ejaculation. This is the first-in-human study aimed at evaluating the pharmacokinetics and tolerability of DA-8031 and its metabolites (M1, M2, M4, and M5) in the plasma and urine after administration of a single oral dose in healthy male subjects. A dose block-randomized, double-blind, placebo-controlled, single ascending dose study was conducted. Subjects received either placebo or a single dose of DA-8031 at 5, 10, 20, 40, 60, 80, or 120 mg. DA-8031 and its four metabolites were analyzed in the plasma and urine for pharmacokinetic evaluation. The effect of genetic polymorphisms of cytochrome-P450 (CYP) enzymes on the pharmacokinetics of DA-8031 was evaluated. After a single dose, plasma DA-8031 reached the maximum concentration at a median of 2-3 h and was eliminated with terminal elimination half-life of 17.9-28.7 h. The mean renal clearance was 3.7-5.6 L/h. Dose-proportional pharmacokinetics was observed over the dose range of 20-80 mg. Among the metabolites, M4 had the greatest plasma concentration, followed by M5 and M1. Subjects with CYP2D6 intermediate metabolizer had significantly greater dose-normalized C max and AUC 0- t of DA-8031 as well as smaller metabolic ratios than those subjects with CYP2D6 extensive metabolizer. The most common adverse events were nausea, dizziness, and headache, and no serious adverse events were reported. In conclusion, the systemic exposure of DA-8031 was increased proportionally to the dose within 20-80 mg. Genetic polymorphisms of CYP2D6 had an effect on the systemic exposure of DA-8031. DA-8031 was well tolerated after single doses of 80 mg or less.

ATLAS WORLD-cloud and networking in PanDA

NASA Astrophysics Data System (ADS)

Barreiro Megino, F.; De, K.; Di Girolamo, A.; Maeno, T.; Walker, R.; ATLAS Collaboration

2017-10-01

The ATLAS computing model was originally designed as static clouds (usually national or geographical groupings of sites) around the Tier 1 centres, which confined tasks and most of the data traffic. Since those early days, the sites’ network bandwidth has increased at 0(1000) and the difference in functionalities between Tier 1s and Tier 2s has reduced. After years of manual, intermediate solutions, we have now ramped up to full usage of World-cloud, the latest step in the PanDA Workload Management System to increase resource utilization on the ATLAS Grid, for all workflows (MC production, data (re)processing, etc.). We have based the development on two new site concepts. Nuclei sites are the Tier 1s and large Tier 2s, where tasks will be assigned and the output aggregated, and satellites are the sites that will execute the jobs and send the output to their nucleus. PanDA dynamically pairs nuclei and satellite sites for each task based on the input data availability, capability matching, site load and network connectivity. This contribution will introduce the conceptual changes for World-cloud, the development necessary in PanDA, an insight into the network model and the first half-year of operational experience.

Effects of porcine 25 kDa amelogenin and its proteolytic derivatives on bone sialoprotein expression.

PubMed

Nakayama, Y; Yang, L; Mezawa, M; Araki, S; Li, Z; Wang, Z; Sasaki, Y; Takai, H; Nakao, S; Fukae, M; Ogata, Y

2010-10-01

Amelogenins are hydrophobic proteins that are the major component of developing enamel. Enamel matrix derivative has been used for periodontal regeneration. Bone sialoprotein is an early phenotypic marker of osteoblast differentiation. In this study, we examined the ability of porcine amelogenins to regulate bone sialoprotein transcription. To determine the molecular basis of the transcriptional regulation of the bone sialoprotein gene by amelogenins, we conducted northern hybridization, transient transfection analyses and gel mobility shift assays using the osteoblast-like ROS 17/2.8 cells. Amelogenins (100 ng/mL) up-regulated bone sialoprotein mRNA at 3 h, with maximal mRNA expression occurring at 12 h (25 and 20 kDa) and 6 h (13 and 6 kDa). Amelogenins (100 ng/mL, 12 h) increased luciferase activities in pLUC3 (nucleotides -116 to +60), and 6 kDa amelogenin up-regulated pLUC4 (nucleotides -425 to +60) activity. The tyrosine kinase inhibitor inhibited amelogenin-induced luciferase activities, whereas the protein kinase A inhibitor abolished 25 kDa amelogenin-induced bone sialoprotein transcription. The effects of amelogenins were abrogated by 2-bp mutations in the fibroblast growth factor 2 response element (FRE). Gel-shift assays with radiolabeled FRE, homeodomain-protein binding site (HOX) and transforming growth factor-beta1 activation element (TAE) double-strand oligonucleotides revealed increased binding of nuclear proteins from amelogenin-stimulated ROS 17/2.8 cells at 3 h (25 and 13 kDa) and 6 h (20 and 6 kDa). These results demonstrate that porcine 25 kDa amelogenin and its proteolytic derivatives stimulate bone sialoprotein transcription by targeting FRE, HOX and TAE in the bone sialoprotein gene promoter, and that full-length amelogenin and amelogenin cleavage products are able to regulate bone sialoprotein transcription via different signaling pathways. (c) 2010 John Wiley & Sons A/S.

Ca2+-induced changes in the secondary structure of a 60 kDa phosphoinositide-specific phospholipase C from bovine brain cytosol.

PubMed Central

Herrero, C; Cornet, M E; Lopez, C; Barreno, P G; Municio, A M; Moscat, J

1988-01-01

The purification to homogeneity of a 60 kDa phosphoinositide-specific phospholipase C from bovine brain cytosol is reported here. This enzyme exhibits the same properties, in terms of response to Ca2+, as does the cytosolic activity in a variety of cell types. We show here that Ca2+ does not appear to modulate the binding of the enzyme to the substrate, but induces dramatic changes in its secondary structure. Therefore we suggest that a decrease in the alpha-helix content of this enzyme correlates with its ability to be activated by Ca2+. Images Fig. 1. PMID:2850798

The da Vinci robot.

PubMed

Moran, Michael E

2006-12-01

One might assume from the title of this paper that the nuances of a complex mechanical robot will be discussed, and this would be correct. On the other hand, the date of the design and possible construction of this robot was 1495, a little more than five centuries ago. The key point in the title is the lack of a trademarked name, as Leonardo was the designer of this sophisticated system. His notes from the Codex Altanticus represent the foundation of this report. English translations of da Vinci's notebooks are currently available. Beginning in the 1950s, investigators at the University of California began to ponder the significance of some of da Vinci's markings on what appeared to be technical drawings. Such markings also occur in his Codex Atlanticus (the largest single collection of da Vinci's sheets, consisting of 1119 separate pages and 481 folios) along with a large number of other mechanical devices. Continuing research at the Instituto e Museo di Storia della Scienza in Florence has yielded a great deal of information about Leonardo's intentions with regard to his mechanical knight. It is now known that da Vinci's robot would have had the outer appearance of a Germanic knight. It had a complex core of mechanical devices that probably was human powered. The robot had two independent operating systems. The first had three degree-of-freedom legs, ankles, knees, and hips. The second had four degrees of freedom in the arms with articulated shoulders, elbows, wrists, and hands. A mechanical analog-programmable controller within the chest provided the power and control for the arms. The legs were powered by an external crank arrangement driving the cable, which connected to key locations near each lower extremity's joints. Da Vinci also is known to have devised a programmable front-wheel-drive automobile with rack-and-pinion suspension mechanisms at age 26. He would recall this device again, when, at age 40, he is thought to have built a programmable automated

Biochemical characterization of the 49 kDa penicillin-binding protein of Mycobacterium smegmatis.

PubMed Central

Mukherjee, T; Basu, D; Mahapatra, S; Goffin, C; van Beeumen, J; Basu, J

1996-01-01

The 49 kDa penicillin-binding protein (PBP) of Mycobacterium smegmatis catalyses the hydrolysis of the peptide or S-ester bond of carbonyl donors R1-CONH-CHR2-COX-CHR2-COO- (where X is NH or S). In the presence of a suitable amino acceptor, the reaction partitions between the transpeptidation and hydrolysis pathways, with the amino acceptor, behaving as a simple alternative nucleophile at the level of the acyl-enzyme. By virtue of its N-terminal sequence similarity, the 49 kDa PBP represents one of the class of monofunctional low-molecular-mass PBPs. An immunologically related protein of M(r) 52,000 is present in M. tuberculosis. The 49 kDa PBP is sensitive towards amoxycillin, imipenem, flomoxef and cefoxitin. PMID:8947487

Anti-inflammatory effect of garlic 14-kDa protein on LPS-stimulated-J774A.1 macrophages.

PubMed

Rabe, Shahrzad Zamani Taghizadeh; Ghazanfari, Tooba; Siadat, Zahra; Rastin, Maryam; Rabe, Shahin Zamani Taghizadeh; Mahmoudi, Mahmoud

2015-04-01

Garlic 14-kDa protein is purified from garlic (Allium sativum L.) which is used in traditional medicine and exerts various immunomodulatory activities. The present study investigated the suppressive effect of garlic 14-kDa protein on LPS-induced expression of pro-inflammatory mediators and underlying mechanism in inflammatory macrophages. J774A.1 macrophages were treated with 14-kDa protein (5-30 μg/ml) with/without LPS (1 μg/ml) and the production of inflammatory mediators such as prostaglandin E2 (PGE2), TNF-α, and IL-1β released were measured using ELISA. Nitric oxide (NO) production was determined using the Griess method. The anti-inflammatory activity of 14-kDa protein was examined by measuring inducible nitric oxide synthase and cyclooxygenase-2 proteins using western blot. The expression of nuclear NF-κB p65 subunit was assessed by western blot. Garlic 14-kDa protein significantly inhibited the excessive production of NO, PGE, TNF-α, and IL-1β in lipopolysaccharide (LPS)-activated J774A.1 macrophages in a concentration-related manner without cytotoxic effect. Western blot analysis demonstrated that garlic 14-kDa protein suppressed corresponding inducible NO synthase expression and activated cyclooxygenase-2 protein expression. The inhibitory effect was mediated partly by a reduction in the activity and expression of transcription factor NF-κB protein. Our results suggested, for the first time, garlic 14-kDa protein exhibits anti-inflammatory properties in macrophages possibly by suppressing the inflammatory mediators via the inhibition of transcription factor NF-κB signaling pathway. The traditional use of garlic as anti-inflammatory remedy could be ascribed partly to 14-kDa protein content. This protein might be a useful candidate for controlling inflammatory diseases and further investigations in vivo.

Hidden sketches by Leonardo da Vinci revealed

NASA Astrophysics Data System (ADS)

Dumé, Belle

2009-02-01

Three drawings on the back of Leonardo da Vinci's The Virgin and Child with St Anne (circa 1508) have been discovered by researchers led by Michel Menu from the Centre de Recherche et de Restauration des Musées de France (C2RMF) and the Louvre Museum in Paris.

Da Vinci Xi Robot–Assisted Penetrating Keratoplasty

PubMed Central

Chammas, Jimmy; Sauer, Arnaud; Pizzuto, Joëlle; Pouthier, Fabienne; Gaucher, David; Marescaux, Jacques; Mutter, Didier; Bourcier, Tristan

2017-01-01

Purpose This study aims (1) to investigate the feasibility of robot-assisted penetrating keratoplasty (PK) using the new Da Vinci Xi Surgical System and (2) to report what we believe to be the first use of this system in experimental eye surgery. Methods Robot-assisted PK procedures were performed on human corneal transplants using the Da Vinci Xi Surgical System. After an 8-mm corneal trephination, four interrupted sutures and one 10.0 monofilament running suture were made. For each procedure, duration and successful completion of the surgery as well as any unexpected events were assessed. The depth of the corneal sutures was checked postoperatively using spectral-domain optical coherence tomography (SD-OCT). Results Robot-assisted PK was successfully performed on 12 corneas. The Da Vinci Xi Surgical System provided the necessary dexterity to perform the different steps of surgery. The mean duration of the procedures was 43.4 ± 8.9 minutes (range: 28.5–61.1 minutes). There were no unexpected intraoperative events. SD-OCT confirmed that the sutures were placed at the appropriate depth. Conclusions We confirm the feasibility of robot-assisted PK with the new Da Vinci Surgical System and report the first use of the Xi model in experimental eye surgery. Operative time of robot-assisted PK surgery is now close to that of conventional manual surgery due to both improvement of the optical system and the presence of microsurgical instruments. Translational Relevance Experimentations will allow the advantages of robot-assisted microsurgery to be identified while underlining the improvements and innovations necessary for clinical use. PMID:28660096

Da Vinci Xi Robot-Assisted Penetrating Keratoplasty.

PubMed

Chammas, Jimmy; Sauer, Arnaud; Pizzuto, Joëlle; Pouthier, Fabienne; Gaucher, David; Marescaux, Jacques; Mutter, Didier; Bourcier, Tristan

2017-06-01

This study aims (1) to investigate the feasibility of robot-assisted penetrating keratoplasty (PK) using the new Da Vinci Xi Surgical System and (2) to report what we believe to be the first use of this system in experimental eye surgery. Robot-assisted PK procedures were performed on human corneal transplants using the Da Vinci Xi Surgical System. After an 8-mm corneal trephination, four interrupted sutures and one 10.0 monofilament running suture were made. For each procedure, duration and successful completion of the surgery as well as any unexpected events were assessed. The depth of the corneal sutures was checked postoperatively using spectral-domain optical coherence tomography (SD-OCT). Robot-assisted PK was successfully performed on 12 corneas. The Da Vinci Xi Surgical System provided the necessary dexterity to perform the different steps of surgery. The mean duration of the procedures was 43.4 ± 8.9 minutes (range: 28.5-61.1 minutes). There were no unexpected intraoperative events. SD-OCT confirmed that the sutures were placed at the appropriate depth. We confirm the feasibility of robot-assisted PK with the new Da Vinci Surgical System and report the first use of the Xi model in experimental eye surgery. Operative time of robot-assisted PK surgery is now close to that of conventional manual surgery due to both improvement of the optical system and the presence of microsurgical instruments. Experimentations will allow the advantages of robot-assisted microsurgery to be identified while underlining the improvements and innovations necessary for clinical use.

Complete daVinci versus laparoscopic pyeloplasty: cost analysis.

PubMed

Bhayani, Sam B; Link, Richard E; Varkarakis, John M; Kavoussi, Louis R

2005-04-01

Computer-assisted pyeloplasty with the daVinci system is an emerging technique to treat ureteropelvic junction (UPJ) obstruction. A relative cost analysis was performed assessing this technology in comparison with purely laparoscopic pyeloplasty. Eight patients underwent computer-assisted (daVinci) dismembered pyeloplasty (CP) via a transperitoneal four-port approach. They were compared with 13 patients who underwent purely laparoscopic pyeloplasty (LP). All patients had a primary UPJ obstruction and were matched for age, sex, and body mass index. The cost of equipment and capital depreciation for both procedures, as well as assessment of room set-up time, takedown time, and personnel were analyzed. Surgeons and nursing staff for both groups were experienced in both laparoscopy and daVinci procedures. One- and two-way financial analysis was performed to assess relative costs. The mean set-up and takedown time was 71 minutes for CP and 49 minutes for LP. The mean length of stay was 2.3 days for CP and 2.5 days for LP. The mean operating room (OR) times for CP and LP were 176 and 210 minutes, respectively. There were no complications in either group. One-way cost analysis with an economic model showed that LP is more cost effective than CP at our hospital if LP OR time is <338 minutes. With adjustment to a volume of 500 daVinci cases/year, CP is still not as cost effective as LP. Two-way sensitivity analysis shows that in-room time must still be <130 minutes and yearly cases must be >500 to obtain cost equivalence for CP. Perioperative parameters for CP are encouraging. However, the costs are a clear disadvantage. In our hospital, it is more cost effective to teach and perform LP than to perform CP.

Pharmacological action of DA-9701 on the motility of feline stomach circular smooth muscle.

PubMed

Nguyen, Thanh Thao; Song, Hyun Ju; Ko, Sung Kwon; Sohn, Uy Dong

2015-03-01

DA-9701, a new prokinetic agent for the treatment of functional dyspepsia, is formulated with Pharbitis semen and Corydalis tuber. This study wasconducted to determine the pharmacological action of DA-9701 and to identify the receptors involved in DA-9701 -induced contractile responsesin the feline gastric corporal, fundic and antral circular smooth muscle. Concentration-response curve to DA-9701 was established. The tissue trips were exposed to methylsergide, ketanserin, ondansetron, GR 113808, atropine and dopamine before administration of DA-9701. The contractile force was determined before and after administration of drugs by a polygraph.DA-9701 enhanced the spontaneous contractile amplitude of antrum, corpus and fundus. However, it did not change the spontaneous contractile frequency of antrum and corpus, but concentration-dependently reduced that of fundus. In the fundus, DA-9701 -induced tonic contractions were inhibited by dopamine, methylsergide, ketanserine, ondansetron or GR 113808 respectively, but not by atropine, indicating that the contractile responses are mediated by multiple receptors: 5-HT2, 5-HT3, 5-HT4, and dopamine receptors. In the corpus, DA-9701-induced contractions were blocked by atropine, dopamine or GR 113808, but not by methysergide, ketanserin or ondansetron, indicating that they are involved in receptors on both, smooth muscles and neurons: 5-HT4 and dopamine receptors. However, contractile responses to DA-9701 are mainly mediated by dopamine receptors in the antrum. These results suggest that DA-9701 has important roles in gastric accommodation by enhancing tonic activity of fundus, and in gastric emptying and gastrointestinal transit by phasic contractions of corpus and antrum mediated by multiple receptors.

Geomagnetic observations on tristan da cunha, south atlantic ocean

USGS Publications Warehouse

Matzka, J.; Olsen, N.; Maule, C.F.; Pedersen, L.W.; Berarducci, A.M.; Macmillan, S.

2009-01-01

Few geomagnetic ground observations exist of the Earth's strongest core field anomaly, the South Atlantic Anomaly (SAA). The geomagnetic repeat station on the island Tristan da Cunha, located half-way between South Africa and South America at 37?? 05' S, 12?? 18' W, is therefore of crucial importance. We have conducted several sets of repeat station measurements during magnetically quiet conditions (Kp 2o or less) in 2004. The procedures are described and the results are compared to those from earlier campaigns and to the predictions of various global field models. Features of the local crustal bias field and the solar quiet daily variation are discussed. We also evaluate the benefit of continuous magnetic field recordings from Tristan da Cunha, and argue that such a data set is a very valuable addition to geomagnetic satellite data. Recently, funds were set up to establish and operate a magnetometer station on Tristan da Cunha during the Swarm magnetic satellite mission (2011-2014).

[Freud's identification with men who had 2 mothers: Oedipus, Leonardo da Vinci, Michealangelo and Moses].

PubMed

Harsch, H E

1994-02-01

In view of the fact that as a child Sigmund Freud was looked after by two mothers--his actual mother and a nursemaid--it is hardly surprising that traces of this pre-oedipal situation, fraught as it was with traumatisation and loss, should be discernible in the works of the creator of psychoanalysis. Freud's continued preoccupation with the Oedipus myth, his interest in "great men" like da Vinci and Michelangelo, and finally his identification with the figure of Moses are pointers not only to the paternal dimension (as long suggested by Freud's biographers) but also to the maternal dimension and its significance for Freud's life and work. The author demonstrates that those mythical and historical figures which Freud identified with--Oedipus, da Vinci, Michelangelo, Moses--themselves all had two mothers and sublimated this traumatic experience into outstanding achievements, the same being true of Freud himself "who solved the famous riddle and was a most powerful man".

[Short-term efficacy of da Vinci robotic surgical system on rectal cancer in 101 patients].

PubMed

Zeng, Dong-Zhu; Shi, Yan; Lei, Xiao; Tang, Bo; Hao, Ying-Xue; Luo, Hua-Xing; Lan, Yuan-Zhi; Yu, Pei-Wu

2013-05-01

To investigate the feasibility and safety of da Vinci robotic surgical system in rectal cancer radical operation, and to summarize its short-term efficacy and clinical experience. Data of 101 cases undergoing da Vinci robotic surgical system for rectal cancer radical operation from March 2010 to September 2012 were retrospectively analyzed. Evaluation was focused on operative procedure, complication, recovery and pathology. All the 101 cases underwent operation successfully and safely without conversion to open procedure. Rectal cancer radical operation with da Vinci robotic surgical system included 73 low anterior resections and 28 abdominoperineal resections. The average operative time was (210.3±47.2) min. The average blood lose was (60.5±28.7) ml without transfusion. Lymphadenectomy harvest was 17.3±5.4. Passage of first flatus was (2.7±0.7) d. Distal margin was (5.3±2.3) cm without residual cancer cells. The complication rate was 6.9%, including anastomotic leakage(n=2), perineum incision infection(n=2), pulmonary infection (n=2), urinary retention (n=1). There was no postoperative death. The mean follow-up time was(12.9±8.0) months. No local recurrence was found except 2 cases with distant metastasis. Application of da Vinci robotic surgical system in rectal cancer radical operation is safe and patients recover quickly The short-term efficacy is satisfactory.

Revisiting shape selectivity in liquid chromatography for polycyclic aromatic hydrocarbons (PAHs) - six-ring and seven-ring Cata-condensed PAH isomers of molecular mass 328 Da and 378 Da.

PubMed

Oña-Ruales, Jorge O; Sander, Lane C; Wilson, Walter B; Wise, Stephen A

2018-01-01

The relationship of reversed-phase liquid chromatography (RPLC) retention on a polymeric C 18 stationary phase and the shape of polycyclic aromatic hydrocarbons (PAHs) was investigated for three-ring to seven-ring cata-condensed isomers. We report the first RPLC separation for six-ring and seven-ring cata-condensed PAH isomers. Correlations of LC retention and shape parameters (length-to-breath ratio, L/B and thickness, T) were investigated for 2 three-ring isomers (molecular mass 178 Da), 5 four-ring isomers (molecular mass 228 Da), 11 five-ring isomers (molecular mass 278 Da), 17 six-ring isomers (molecular mass 328 Da), and 20 seven-ring isomers (molecular mass 378 Da). Significant linear correlations were found for all isomer groups (r = 0.71 to 0.94). Nonplanarity of the PAH isomers was found to influence retention (i.e., nonplanar isomers eluting earlier than expected based on L/B) and linear correlations of retention vs. T for isomer groups containing nonplanar isomers were significant (r = 0.71 to 0.86). Graphical abstract.

Leonardo da Vinci's drapery studies: characterization of lead white pigments by µ-XRD and 2D scanning XRF

NASA Astrophysics Data System (ADS)

Gonzalez, Victor; Calligaro, Thomas; Pichon, Laurent; Wallez, Gilles; Mottin, Bruno

2015-11-01

This work focuses on the composition and microstructure of the lead white pigment employed in a set of paintworks, using a combination of µ-XRD and 2D scanning XRF, directly applied on five drapery studies attributed to Leonardo da Vinci (1452-1519) and conserved in the Département des Arts Graphiques, Musée du Louvre and in the Musée des Beaux- Arts de Rennes. Trace elements present in the composition as well as in the lead white highlights were imaged by 2D scanning XRF. Mineral phases were determined in a fully noninvasive way using a special µ-XRD diffractometer. Phase proportions were estimated by Rietveld refinement. The analytical results obtained will contribute to differentiate lead white qualities and to highlight the artist's technique.

A 120-kDa alkaline peptidase from Trypanosoma cruzi is involved in the generation of a novel Ca(2+)-signaling factor for mammalian cells.

PubMed

Burleigh, B A; Andrews, N W

1995-03-10

Trypomastigotes, the infective stages of the intracellular parasite Trypanosoma cruzi, induce rapid and repetitive cytosolic free Ca2+ transients in fibroblasts. Buffering or depletion of intracellular free Ca2+ inhibits cell entry by trypomastigotes, indicating a role for this signaling event in invasion. We show here that the majority of the Ca(2+)-signaling activity is associated with the soluble fraction of parasites disrupted by sonication. Distinct cell types from different species are responsive to this soluble factor, and intracellular free Ca2+ transients occur rapidly and reach concentrations comparable to responses induced by thrombin and bombesin. The Ca(2+)-signaling activity does not bind concanavalin A and is strongly inhibited by a specific subset of protease inhibitors. The only detectable protease in the fractions with Ca(2+)-signaling activity is an unusual alkaline peptidase of 120 kDa, to which no function had been previously assigned. The activity of the protease and cell invasion by trypomastigotes are blocked by the same specific inhibitors that impair Ca(2+)-signaling, suggesting that the enzyme is required for generating the response leading to infection. We demonstrate that the 120-kDa peptidase is not sufficient for triggering Ca(2+)-signaling, possibly being involved in the processing of precursors present only in infective trypomastigotes. These findings indicate a biological function for a previously identified unusual protozoan protease and provide the first example of a proteolytically generated parasite factor with characteristics of a mammalian hormone.

Leonardo da Vinci and the Downburst.

NASA Astrophysics Data System (ADS)

Gedzelman, Stanley David

1990-05-01

Evidence from the drawings, experiments, and writings of Leonardo da Vinci are presented to demonstrate that da Vinci recognized and, possibly, discovered the downburst and understood its associated airflow. Other early references to vortex flows resembling downbursts are mentioned.

Computerized Dynamic Assessment (C-DA): Diagnosing L2 Development According to Learner Responsiveness to Mediation

ERIC Educational Resources Information Center

Poehner, Matthew E.; Zhang, Jie; Lu, Xiaofei

2015-01-01

Dynamic assessment (DA) derives from the sociocultural theory of mind as elaborated by Russian psychologist L. S. Vygotsky. By offering mediation when individuals experience difficulties and carefully tracing their responsiveness, Vygotsky (1998) proposed that diagnoses may uncover abilities that have fully formed as well as those still in the…

Test Review: TestDaF

ERIC Educational Resources Information Center

Norris, John; Drackert, Anastasia

2018-01-01

The Test of German as a Foreign Language (TestDaF) plays a critical role as a standardized test of German language proficiency. Developed and administered by the Society for Academic Study Preparation and Test Development (g.a.s.t.), TestDaF was launched in 2001 and has experienced persistent annual growth, with more than 44,000 test takers in…

Overview of ATLAS PanDA Workload Management

NASA Astrophysics Data System (ADS)

Maeno, T.; De, K.; Wenaus, T.; Nilsson, P.; Stewart, G. A.; Walker, R.; Stradling, A.; Caballero, J.; Potekhin, M.; Smith, D.; ATLAS Collaboration

2011-12-01

The Production and Distributed Analysis System (PanDA) plays a key role in the ATLAS distributed computing infrastructure. All ATLAS Monte-Carlo simulation and data reprocessing jobs pass through the PanDA system. We will describe how PanDA manages job execution on the grid using dynamic resource estimation and data replication together with intelligent brokerage in order to meet the scaling and automation requirements of ATLAS distributed computing. PanDA is also the primary ATLAS system for processing user and group analysis jobs, bringing further requirements for quick, flexible adaptation to the rapidly evolving analysis use cases of the early datataking phase, in addition to the high reliability, robustness and usability needed to provide efficient and transparent utilization of the grid for analysis users. We will describe how PanDA meets ATLAS requirements, the evolution of the system in light of operational experience, how the system has performed during the first LHC data-taking phase and plans for the future.

Overview of ATLAS PanDA Workload Management

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maeno T.; De K.; Wenaus T.

2011-01-01

The Production and Distributed Analysis System (PanDA) plays a key role in the ATLAS distributed computing infrastructure. All ATLAS Monte-Carlo simulation and data reprocessing jobs pass through the PanDA system. We will describe how PanDA manages job execution on the grid using dynamic resource estimation and data replication together with intelligent brokerage in order to meet the scaling and automation requirements of ATLAS distributed computing. PanDA is also the primary ATLAS system for processing user and group analysis jobs, bringing further requirements for quick, flexible adaptation to the rapidly evolving analysis use cases of the early datataking phase, in additionmore » to the high reliability, robustness and usability needed to provide efficient and transparent utilization of the grid for analysis users. We will describe how PanDA meets ATLAS requirements, the evolution of the system in light of operational experience, how the system has performed during the first LHC data-taking phase and plans for the future.« less

Vi-da: vitiligo diagnostic assistance mobile application

NASA Astrophysics Data System (ADS)

Nugraha, G. A.; Nurhudatiana, A.; Bahana, R.

2018-03-01

Vitiligo is a skin disorder in which white patches of depigmentation appear on different parts of the body. Usually, patients come to hospitals or clinics to have their vitiligo conditions assessed. This can be very tiring to the patients, as vitiligo treatments usually take a relatively long period of time, which can range from months to years. To address this challenge, we present in this paper a prototype of an Android-based mobile application called Vi-DA, which stands for Vitiligo Diagnostic Assistance. Vi-DA consists of three subsystems, which are user sign-up subsystem, camera and image analysis subsystem, and progress report subsystem. The mobile application was developed in Java programming language and uses MySQL as the database system. Vi-DA adopts a vitiligo segmentation algorithm to segment input image into normal skin area, vitiligo skin area, and non-skin area. Results showed that Vi-DA gave comparable results to the previous system implemented in Matlab. User acceptance testing results also showed that all respondents agreed on the usefulness of the system and agreed to use Vi-DA again in the future. Vi-DA benefits both dermatologists and patients as not only a computer-aided diagnosis (CAD) tool but also as a smart application that can be used for self-assessment at home.

Metaproteomics of Microbiota in Naturally Fermented Soybean Paste, Da-jiang.

PubMed

Zhang, Ping; Zhang, Pengfei; Xie, Mengxi; An, Feiyu; Qiu, Boshu; Wu, Rina

2018-05-01

Da-jiang is a typical traditional fermented soybean product in China. At present, the proteins in da-jiang are needed to be explored. The composition and species of microbial proteins in traditional fermented da-jiang were analyzed by metaproteomics based on sodium dodecyl sulfonate-polyacrylamide gel electrophoresis (SDS-PAGE) and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). The results showed that the number and variety of microbial proteins in the traditional fermented da-jiang from different regions were different. The production site influences the fermentation in da-jiang. Then we analyzed the functions of the microbial proteins identified in da-jiang, and found that they were mainly involved in the process of protein synthesis, glycometabolism and nucleic acid synthesis. In addtion, we compared the proteins composition in different da-jiang. There are 51 common proteins of naturally fermented da-jiang, and 25 common microbial sources. The main commonly microbial sources of fungal proteins are Saccharomyces cerevisiae and Schizosaccharomyces; the main commonly microbial sources of bacterial proteins are Enterococcus faecalis, Leuconostoc mesenteroides, Acinetobacter baumannii, and Bacillus subtilis. These common microbes play the predominant role in da-jiang fermentation. The present results help us to understand the fermentation of da-jiang and improve the quality and safety of final products in the future. The study illustrated metaproteome of microbiota in traditional fermented soybean paste, da-jiang, by sodium dodecyl sulfonate-polyacrylamide gel electrophoresis (SDS-PAGE) and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). A method of extracting metaproteome from microbiota in da-jiang was attempted. The findings help to understand the fermentation of da-jiang and improve the quality and safety of da-jiang in fermented industry. © 2018 Institute of Food Technologists®.

A Proposal to Build Evaluation Capacity at the Bunche-Da Vinci Learning Partnership Academy

ERIC Educational Resources Information Center

King, Jean A.

2005-01-01

The author describes potential evaluation capacity-building activities in contrast to the specifics of an evaluation design. Her response to the case of the Bunche-Da Vinci Learning Partnership Academy is developed in three parts: (1) an initial framing of the Bunche-Da Vinci situation; (2) what should be done before signing a contract; and (3)…

Beyond the Classic VTA: Extended Amygdala Projections to DA-Striatal Paths in the Primate

PubMed Central

Fudge, Julie L; Kelly, Emily A; Pal, Ria; Bedont, Joseph L; Park, Lydia; Ho, Brian

2017-01-01

The central extended amygdala (CEA) has been conceptualized as a ‘macrosystem’ that regulates various stress-induced behaviors. Consistent with this, the CEA highly expresses corticotropin-releasing factor (CRF), an important modulator of stress responses. Stress alters goal-directed responses associated with striatal paths, including maladaptive responses such as drug seeking, social withdrawal, and compulsive behavior. CEA inputs to the midbrain dopamine (DA) system are positioned to influence striatal functions through mesolimbic DA-striatal pathways. However, the structure of this amygdala-CEA-DA neuron path to the striatum has been poorly characterized in primates. In primates, we combined neuronal tracer injections into various arms of the circuit through specific DA subpopulations to assess: (1) whether the circuit connecting amygdala, CEA, and DA cells follows CEA intrinsic organization, or a more direct topography involving bed nucleus vs central nucleus divisions; (2) CRF content of the CEA-DA path; and (3) striatal subregions specifically involved in CEA-DA-striatal loops. We found that the amygdala-CEA-DA path follows macrostructural subdivisions, with the majority of input/outputs converging in the medial central nucleus, the sublenticular extended amygdala, and the posterior lateral bed nucleus of the stria terminalis. The proportion of CRF+ outputs is >50%, and mainly targets the A10 parabrachial pigmented nucleus (PBP) and A8 (retrorubal field, RRF) neuronal subpopulations, with additional inputs to the dorsal A9 neurons. CRF-enriched CEA-DA projections are positioned to influence outputs to the ‘limbic-associative’ striatum, which is distinct from striatal regions targeted by DA cells lacking CEA input. We conclude that the concept of the CEA is supported on connectional grounds, and that CEA termination over the PBP and RRF neuronal populations can influence striatal circuits involved in associative learning. PMID:28220796

Beyond the Classic VTA: Extended Amygdala Projections to DA-Striatal Paths in the Primate.

PubMed

Fudge, Julie L; Kelly, Emily A; Pal, Ria; Bedont, Joseph L; Park, Lydia; Ho, Brian

2017-07-01

The central extended amygdala (CEA) has been conceptualized as a 'macrosystem' that regulates various stress-induced behaviors. Consistent with this, the CEA highly expresses corticotropin-releasing factor (CRF), an important modulator of stress responses. Stress alters goal-directed responses associated with striatal paths, including maladaptive responses such as drug seeking, social withdrawal, and compulsive behavior. CEA inputs to the midbrain dopamine (DA) system are positioned to influence striatal functions through mesolimbic DA-striatal pathways. However, the structure of this amygdala-CEA-DA neuron path to the striatum has been poorly characterized in primates. In primates, we combined neuronal tracer injections into various arms of the circuit through specific DA subpopulations to assess: (1) whether the circuit connecting amygdala, CEA, and DA cells follows CEA intrinsic organization, or a more direct topography involving bed nucleus vs central nucleus divisions; (2) CRF content of the CEA-DA path; and (3) striatal subregions specifically involved in CEA-DA-striatal loops. We found that the amygdala-CEA-DA path follows macrostructural subdivisions, with the majority of input/outputs converging in the medial central nucleus, the sublenticular extended amygdala, and the posterior lateral bed nucleus of the stria terminalis. The proportion of CRF+ outputs is >50%, and mainly targets the A10 parabrachial pigmented nucleus (PBP) and A8 (retrorubal field, RRF) neuronal subpopulations, with additional inputs to the dorsal A9 neurons. CRF-enriched CEA-DA projections are positioned to influence outputs to the 'limbic-associative' striatum, which is distinct from striatal regions targeted by DA cells lacking CEA input. We conclude that the concept of the CEA is supported on connectional grounds, and that CEA termination over the PBP and RRF neuronal populations can influence striatal circuits involved in associative learning.

Evolution of the ATLAS PanDA Production and Distributed Analysis System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maeno, T.; De, K.; Wenaus, T.

2012-12-13

Evolution of the ATLAS PanDA Production and Distributed Analysis System T Maeno1,5, K De2, T Wenaus1, P Nilsson2, R Walker3, A Stradling2, V Fine1, M Potekhin1, S Panitkin1 and G Compostella4 Published under licence by IOP Publishing Ltd Journal of Physics: Conference Series, Volume 396, Part 3 Article PDF References Citations Metrics 101 Total downloads Cited by 8 articles Turn on MathJax Share this article Article information Abstract The PanDA (Production and Distributed Analysis) system has been developed to meet ATLAS production and analysis requirements for a data-driven workload management system capable of operating at LHC data processing scale. PanDAmore » has performed well with high reliability and robustness during the two years of LHC data-taking, while being actively evolved to meet the rapidly changing requirements for analysis use cases. We will present an overview of system evolution including automatic rebrokerage and reattempt for analysis jobs, adaptation for the CernVM File System, support for the multi-cloud model through which Tier-2 sites act as members of multiple clouds, pledged resource management and preferential brokerage, and monitoring improvements. We will also describe results from the analysis of two years of PanDA usage statistics, current issues, and plans for the future.« less

Biosynthesis of 2′-Chloropentostatin and 2′-Amino-2′-Deoxyadenosine Highlights a Single Gene Cluster Responsible for Two Independent Pathways in Actinomadura sp. Strain ATCC 39365

PubMed Central

Gao, Yaojie; Xu, Gudan; Wu, Pan; Liu, Jin; Cai, You-sheng; Deng, Zixin

2017-01-01

ABSTRACT 2′-Chloropentostatin (2′-Cl PTN, 2′-chloro-2′-deoxycoformycin) and 2′-amino-2′-deoxyadenosine (2′-amino dA) are two adenosine-derived nucleoside antibiotics coproduced by Actinomadura sp. strain ATCC 39365. 2′-Cl PTN is a potent adenosine deaminase (ADA) inhibitor featuring an intriguing 1,3-diazepine ring, as well as a chlorination at C-2′ of ribose, and 2′-amino dA is an adenosine analog showing bioactivity against RNA-type virus infection. However, the biosynthetic logic of them has remained poorly understood. Here, we report the identification of a single gene cluster (ada) essential for the biosynthesis of 2′-Cl PTN and 2′-amino dA. Further systematic genetic investigations suggest that 2′-Cl PTN and 2′-amino dA are biosynthesized by independent pathways. Moreover, we provide evidence that a predicted cation/H+ antiporter, AdaE, is involved in the chlorination step during 2′-Cl PTN biosynthesis. Notably, we demonstrate that 2′-amino dA biosynthesis is initiated by a Nudix hydrolase, AdaJ, catalyzing the hydrolysis of ATP. Finally, we reveal that the host ADA (designated ADA1), capable of converting adenosine/2′-amino dA to inosine/2′-amino dI, is not very sensitive to the powerful ADA inhibitor pentostatin. These findings provide a basis for the further rational pathway engineering of 2′-Cl PTN and 2′-amino dA production. IMPORTANCE 2′-Cl PTN/PTN and 2′-amino dA have captivated the great interests of scientists, owing to their unusual chemical structures and remarkable bioactivities. However, the precise logic for their biosynthesis has been elusive for decades. Actually, the identification and elucidation of their biosynthetic pathways not only enrich the biochemical repertoire of novel enzymatic reactions but may also lay solid foundations for the pathway engineering and combinatorial biosynthesis of this family of purine nucleoside antibiotics to generate novel hybrid analogs with improved features. PMID

A phase IIa study of rhLTα-Da in combination with cisplatin and fluorouracil for patients with metastatic esophageal squamous cell carcinoma or gastric adenocarcinoma.

PubMed

Wang, Feng-Hua; Wang, Yun; Chen, Zhen-Dong; Chen, Jian-Hua; Qin, Feng-Zhan; Jiang, Wen-Qi; Li, Yu-Hong

2016-11-01

Recombinant human lymphotoxin-α derivative (rhLTα-Da) is a lymphotoxin-α derivative missing 27 N-terminal amino acid residues. This multicenter phase IIa trial was conducted to evaluate the safety, efficacy and pharmacokinetics of rhLTα-Da with cisplatin (DDP) and 5-fluorouracil (5-Fu) for metastatic esophageal squamous cell cancer (ESCC) and gastric adenocarcinoma (GC). Two different rhLTα-Da doses (10 µg/m 2 /d and 20 µg/m 2 /d) in combination with DDP and 5-Fu were evaluated in this study. The first 6 ESCC and 6 GC patients were given 10 µg/m 2 /d rhLTα-Da followed by DDP (15 mg/m 2 /d) and 5-Fu (750 mg/m 2 /d) on days 1-5. The next 6 ESCC and 6 GC patients were given 20 µg/m 2 /d rhLTα-Da after fewer than 2 of the 6 patients who received the 10 µg/m 2 /d dose exhibited dose-limiting rhLTα-Da-related toxicities. The treatment was 21 days a cycle until a maximum of 6. The rhLTα-Da pharmacokinetic analyses were performed. Twelve ESCC and 12 GC patients were enrolled. The toxicities were controllable and reversible. The most common adverse events related to rhLTα-Da were chills (37.5 %, 9/24) and fever (16.7 %, 4/24) (all grades 1-2). The overall response rates in the 10- and 20-µg/m 2 /d groups were 50 % (6/12) and 33.3 % (4/12), respectively, and the overall response rates of the ESCC and GC patients were 66.7 % (8/12) and 16.7 % (2/12), respectively. rhLTα-Da in combination with DDP and 5-Fu exhibited a tolerable toxicity profile. The addition of rhLTα-Da may enhance the anti-tumor efficacy of platinum-based chemotherapy in metastatic ESCC.

2D Hexagonal Boron Nitride (2D-hBN) Explored for the Electrochemical Sensing of Dopamine.

PubMed

Khan, Aamar F; Brownson, Dale A C; Randviir, Edward P; Smith, Graham C; Banks, Craig E

2016-10-04

Crystalline 2D hexagonal boron nitride (2D-hBN) nanosheets are explored as a potential electrocatalyst toward the electroanalytical sensing of dopamine (DA). The 2D-hBN nanosheets are electrically wired via a drop-casting modification process onto a range of commercially available carbon supporting electrodes, including glassy carbon (GC), boron-doped diamond (BDD), and screen-printed graphitic electrodes (SPEs). 2D-hBN has not previously been explored toward the electrochemical detection/electrochemical sensing of DA. We critically evaluate the potential electrocatalytic performance of 2D-hBN modified electrodes, the effect of supporting carbon electrode platforms, and the effect of "mass coverage" (which is commonly neglected in the 2D material literature) toward the detection of DA. The response of 2D-hBN modified electrodes is found to be largely dependent upon the interaction between 2D-hBN and the underlying supporting electrode material. For example, in the case of SPEs, modification with 2D-hBN (324 ng) improves the electrochemical response, decreasing the electrochemical oxidation potential of DA by ∼90 mV compared to an unmodified SPE. Conversely, modification of a GC electrode with 2D-hBN (324 ng) resulted in an increased oxidation potential of DA by ∼80 mV when compared to the unmodified electrode. We explore the underlying mechanisms of the aforementioned examples and infer that electrode surface interactions and roughness factors are critical considerations. 2D-hBN is utilized toward the sensing of DA in the presence of the common interferents ascorbic acid (AA) and uric acid (UA). 2D-hBN is found to be an effective electrocatalyst in the simultaneous detection of DA and UA at both pH 5.0 and 7.4. The peak separations/resolution between DA and UA increases by ∼70 and 50 mV (at pH 5.0 and 7.4, respectively, when utilizing 108 ng of 2D-hBN) compared to unmodified SPEs, with a particularly favorable response evident in pH 5.0, giving rise to a

The rare DAT coding variant Val559 perturbs DA neuron function, changes behavior, and alters in vivo responses to psychostimulants.

PubMed

Mergy, Marc A; Gowrishankar, Raajaram; Gresch, Paul J; Gantz, Stephanie C; Williams, John; Davis, Gwynne L; Wheeler, C Austin; Stanwood, Gregg D; Hahn, Maureen K; Blakely, Randy D

2014-11-04

Despite the critical role of the presynaptic dopamine (DA) transporter (DAT, SLC6A3) in DA clearance and psychostimulant responses, evidence that DAT dysfunction supports risk for mental illness is indirect. Recently, we identified a rare, nonsynonymous Slc6a3 variant that produces the DAT substitution Ala559Val in two male siblings who share a diagnosis of attention-deficit hyperactivity disorder (ADHD), with other studies identifying the variant in subjects with bipolar disorder (BPD) and autism spectrum disorder (ASD). Previously, using transfected cell studies, we observed that although DAT Val559 displays normal total and surface DAT protein levels, and normal DA recognition and uptake, the variant transporter exhibits anomalous DA efflux (ADE) and lacks capacity for amphetamine (AMPH)-stimulated DA release. To pursue the significance of these findings in vivo, we engineered DAT Val559 knock-in mice, and here we demonstrate in this model the presence of elevated extracellular DA levels, altered somatodendritic and presynaptic D2 DA receptor (D2R) function, a blunted ability of DA terminals to support depolarization and AMPH-evoked DA release, and disruptions in basal and psychostimulant-evoked locomotor behavior. Together, our studies demonstrate an in vivo functional impact of the DAT Val559 variant, providing support for the ability of DAT dysfunction to impact risk for mental illness.

The rare DAT coding variant Val559 perturbs DA neuron function, changes behavior, and alters in vivo responses to psychostimulants

PubMed Central

Mergy, Marc A.; Gowrishankar, Raajaram; Gresch, Paul J.; Gantz, Stephanie C.; Williams, John; Davis, Gwynne L.; Wheeler, C. Austin; Stanwood, Gregg D.; Hahn, Maureen K.; Blakely, Randy D.

2014-01-01

Despite the critical role of the presynaptic dopamine (DA) transporter (DAT, SLC6A3) in DA clearance and psychostimulant responses, evidence that DAT dysfunction supports risk for mental illness is indirect. Recently, we identified a rare, nonsynonymous Slc6a3 variant that produces the DAT substitution Ala559Val in two male siblings who share a diagnosis of attention-deficit hyperactivity disorder (ADHD), with other studies identifying the variant in subjects with bipolar disorder (BPD) and autism spectrum disorder (ASD). Previously, using transfected cell studies, we observed that although DAT Val559 displays normal total and surface DAT protein levels, and normal DA recognition and uptake, the variant transporter exhibits anomalous DA efflux (ADE) and lacks capacity for amphetamine (AMPH)-stimulated DA release. To pursue the significance of these findings in vivo, we engineered DAT Val559 knock-in mice, and here we demonstrate in this model the presence of elevated extracellular DA levels, altered somatodendritic and presynaptic D2 DA receptor (D2R) function, a blunted ability of DA terminals to support depolarization and AMPH-evoked DA release, and disruptions in basal and psychostimulant-evoked locomotor behavior. Together, our studies demonstrate an in vivo functional impact of the DAT Val559 variant, providing support for the ability of DAT dysfunction to impact risk for mental illness. PMID:25331903

Role for VGLUT2 in selective vulnerability of midbrain dopamine neurons

PubMed Central

Steinkellner, Thomas; Farino, Zachary J.; Sonders, Mark S.; Villeneuve, Michael; Freyberg, Robin J.; Przedborski, Serge; Lu, Wei; Hnasko, Thomas S.

2018-01-01

Parkinson’s disease is characterized by the loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNc). DA neurons in the ventral tegmental area are more resistant to this degeneration than those in the SNc, though the mechanisms for selective resistance or vulnerability remain poorly understood. A key to elucidating these processes may lie within the subset of DA neurons that corelease glutamate and express the vesicular glutamate transporter VGLUT2. Here, we addressed the potential relationship between VGLUT expression and DA neuronal vulnerability by overexpressing VGLUT in DA neurons of flies and mice. In Drosophila, VGLUT overexpression led to loss of select DA neuron populations. Similarly, expression of VGLUT2 specifically in murine SNc DA neurons led to neuronal loss and Parkinsonian behaviors. Other neuronal cell types showed no such sensitivity, suggesting that DA neurons are distinctively vulnerable to VGLUT2 expression. Additionally, most DA neurons expressed VGLUT2 during development, and coexpression of VGLUT2 with DA markers increased following injury in the adult. Finally, conditional deletion of VGLUT2 made DA neurons more susceptible to Parkinsonian neurotoxins. These data suggest that the balance of VGLUT2 expression is a crucial determinant of DA neuron survival. Ultimately, manipulation of this VGLUT2-dependent process may represent an avenue for therapeutic development. PMID:29337309

Pharmacological profile of DA-6886, a novel 5-HT4 receptor agonist to accelerate colonic motor activity in mice.

PubMed

Lee, Min Jung; Cho, Kang Hun; Park, Hyun Min; Sung, Hyun Jung; Choi, Sunghak; Im, Weonbin

2014-07-15

DA-6886, the gastrointestinal prokinetic benzamide derivative is a novel 5-HT4 receptor agonist being developed for the treatment of constipation-predominant irritable bowel syndrome (IBS-C). The purpose of this study was to characterize in vitro and in vivo pharmacological profile of DA-6886. We used various receptor binding assay, cAMP accumulation assay, organ bath experiment and colonic transit assay in normal and chemically constipated mice. DA-6886 exhibited high affinity and selectivity to human 5-HT4 receptor splice variants, with mean pKi of 7.1, 7.5, 7.9 for the human 5-HT4a, 5-HT4b and 5-HT4d, respectively. By contrast, DA-6886 did not show significant affinity for several receptors including dopamine D2 receptor, other 5-HT receptors except for 5-HT2B receptor (pKi value of 6.2). The affinity for 5-HT4 receptor was translated into functional agonist activity in Cos-7 cells expressing 5-HT4 receptor splice variants. Furthermore, DA-6886 induced relaxation of the rat oesophagus preparation (pEC50 value of 7.4) in a 5-HT4 receptor antagonist-sensitive manner. The evaluation of DA-6886 in CHO cells expressing hERG channels revealed that it inhibited hERG channel current with an pIC50 value of 4.3, indicating that the compound was 1000-fold more selective for the 5-HT4 receptor over hERG channels. In the normal ICR mice, oral administration of DA-6886 (0.4 and 2mg/kg) resulted in marked stimulation of colonic transit. Furthermore, in the loperamide-induced constipation mouse model, 2mg/kg of DA-6886 significantly improved the delay of colonic transit, similar to 10mg/kg of tegaserod. Taken together, DA-6886 is a highly potent and selective 5-HT4 receptor agonist to accelerate colonic transit in mice, which might be therapeutic agent having a favorable safety profile in the treatment of gastrointestinal motor disorders such as IBS-C and chronic constipation. Copyright © 2014 Elsevier B.V. All rights reserved.

[Trattamento del disturbo da uso di alcol da un punto di vista psicologico].

PubMed

Coriale, Giovanna; Fiorentino, Daniela; De Rosa, Francesca; Solombrino, Simona; Scalese, Bruna; Ciccarelli, Rosaria; Attilia, Fabio; Vitali, Mario; Musetti, Alessia; Fiore, Marco; Ceccanti, Mauro

2018-01-01

RIASSUNTO. L'elaborazione del piano di trattamento rappresenta un momento molto delicato e complesso del processo terapeutico del disturbo da abuso di alcol (DUA). È la fase in cui le informazioni raccolte da un'équipe di professionisti (medici, psicologi e assistenti sociali) (modello bio-psico-sociale del DUA) vengono messe insieme per decidere il percorso terapeutico più adatto. Per quanto riguarda la parte psicologica, è di notevole importanza scegliere un trattamento clinico in grado di ridurre al minimo la mancata adesione al trattamento e, per i soggetti che rimangono in trattamento, di garantirne l'efficacia. Se da una parte, le tecniche psicoanalitiche e comportamentali hanno fornito le basi della terapia psicologica dell'alcolismo, dall'altra, gli approcci basati sull'evidenza scientifica sono stati elaborati a partire dai principi del colloquio motivazionale e della terapia cognitivo-comportamentale. In questo articolo viene fornita una panoramica dei trattamenti che sono risultati più efficaci nel trattare il DUA e delle modalità temporali più adeguate per monitorare l'efficacia del trattamento.

N-Acetyltransferase 2 Genotypes Are Associated With Diisocyanate-Induced Asthma.

PubMed

Yucesoy, Berran; Kissling, Grace E; Johnson, Victor J; Lummus, Zana L; Gautrin, Denyse; Cartier, André; Boulet, Louis-Philippe; Sastre, Joaquin; Quirce, Santiago; Tarlo, Susan M; Cruz, Maria-Jesus; Munoz, Xavier; Luster, Michael I; Bernstein, David I

2015-12-01

To investigate whether genetic variants of N-acetyltransferase (NAT) genes are associated with diisocyanate asthma (DA). The study population consisted of 354 diisocyanate-exposed workers. Genotyping was performed using a 5'-nuclease polymerase chain reaction assay. The NAT2 rs2410556 and NAT2 rs4271002 variants were significantly associated with DA in the univariate analysis. In the first logistic regression model comparing DA+ and asymptomatic worker groups, the rs2410556 (P = 0.004) and rs4271002 (P < 0.001) single nucleotide polymorphisms and the genotype combination, NAT2 rs4271002*NAT1 rs11777998, showed associations with DA risk (P = 0.014). In the second model comparing DA+ and DA- groups, NAT2 rs4271002 variant and the combined genotype, NAT1 rs8190845*NAT2 rs13277605, were significantly associated with DA risk (P = 0.022, P = 0.036, respectively). These findings suggest that variations in the NAT2 gene and their interactions contribute to DA susceptibility.

Pharmacokinetics and brain distribution of tetrahydropalmatine and tetrahydroberberine after oral administration of DA-9701, a new botanical gastroprokinetic agent, in rats.

PubMed

Jung, Ji Won; Kwon, Yong Sam; Jeong, Jin Seok; Son, Miwon; Kang, Hee Eun

2015-01-01

DA-9701, a new botanical gastroprokinetic agent, has potential for the management of delayed gastric emptying in Parkinson's disease if it has no central anti-dopaminergic activity. Therefore, we examined the pharmacokinetics of DA-9701 components having dopamine D2 receptor antagonizing activity, tetrahydropalmatine (THP) and tetrahydroberberine (THB), following various oral doses (80-328 mg/kg) of DA-9701. The distribution of THP and THB to the brain and/or other tissues was also evaluated after single or multiple oral administrations of DA-9701. Oral administration of DA-9701 yielded dose-proportional area under the plasma concentration-time curve (AUC0-8 h) and maximum plasma concentration (Cmax) values for THP and THB, indicating linear pharmacokinetics (except for THB at the lowest dose). THP and THB's large tissue-to-plasma concentration ratios indicated considerable tissue distribution. High concentrations of THP and THB in the stomach and small intestine suggest an explanation for DA-9701's potent gastroprokinetic activity. The maximum concentrations of THP and THB in brain following multiple oral DA-9701 for 7 d (150 mg/kg/d) was observed at 30 min after the last oral DA-9701 treatment: 131±67.7 ng/g for THP and 6.97±4.03 ng/g for THB. Although both THP and THB pass through the blood-brain barrier, as indicated by brain-to-plasma concentration ratios greater than unity (approximately 2-4), oral administration of DA-9701 at the effective dose in humans is not expected to lead to sufficient brain concentrations to exert central dopamine D2 receptor antagonism.

Production of Thermoalkaliphilic Lipase from Geobacillus thermoleovorans DA2 and Application in Leather Industry

PubMed Central

Abol Fotouh, Deyaa M.; Bayoumi, Reda A.; Hassan, Mohamed A.

2016-01-01

Thermophilic and alkaliphilic lipases are meeting a growing global attention as their increased importance in several industrial fields. Over 23 bacterial strains, novel strain with high lipolytic activity was isolated from Southern Sinai, Egypt, and it was identified as Geobacillus thermoleovorans DA2 using 16S rRNA as well as morphological and biochemical features. The lipase was produced in presence of fatty restaurant wastes as an inducing substrate. The optimized conditions for lipase production were recorded to be temperature 60°C, pH 10, and incubation time for 48 hrs. Enzymatic production increased when the organism was grown in a medium containing galactose as carbon source and ammonium phosphate as nitrogen source at concentrations of 1 and 0.5% (w/v), respectively. Moreover, the optimum conditions for lipase production such as substrate concentration, inoculum size, and agitation rate were found to be 10% (w/v), 4% (v/v), and 120 rpm, respectively. The TA lipase with Triton X-100 had the best degreasing agent by lowering the total lipid content to 2.6% as compared to kerosene (7.5%) or the sole crude enzyme (8.9%). It can be concluded that the chemical leather process can be substituted with TA lipase for boosting the quality of leather and reducing the environmental hazards. PMID:26881066

Production of Thermoalkaliphilic Lipase from Geobacillus thermoleovorans DA2 and Application in Leather Industry.

PubMed

Abol Fotouh, Deyaa M; Bayoumi, Reda A; Hassan, Mohamed A

2016-01-01

Thermophilic and alkaliphilic lipases are meeting a growing global attention as their increased importance in several industrial fields. Over 23 bacterial strains, novel strain with high lipolytic activity was isolated from Southern Sinai, Egypt, and it was identified as Geobacillus thermoleovorans DA2 using 16S rRNA as well as morphological and biochemical features. The lipase was produced in presence of fatty restaurant wastes as an inducing substrate. The optimized conditions for lipase production were recorded to be temperature 60°C, pH 10, and incubation time for 48 hrs. Enzymatic production increased when the organism was grown in a medium containing galactose as carbon source and ammonium phosphate as nitrogen source at concentrations of 1 and 0.5% (w/v), respectively. Moreover, the optimum conditions for lipase production such as substrate concentration, inoculum size, and agitation rate were found to be 10% (w/v), 4% (v/v), and 120 rpm, respectively. The TA lipase with Triton X-100 had the best degreasing agent by lowering the total lipid content to 2.6% as compared to kerosene (7.5%) or the sole crude enzyme (8.9%). It can be concluded that the chemical leather process can be substituted with TA lipase for boosting the quality of leather and reducing the environmental hazards.

VerSeDa: vertebrate secretome database

PubMed Central

Cortazar, Ana R.; Oguiza, José A.

2017-01-01

Based on the current tools, de novo secretome (full set of proteins secreted by an organism) prediction is a time consuming bioinformatic task that requires a multifactorial analysis in order to obtain reliable in silico predictions. Hence, to accelerate this process and offer researchers a reliable repository where secretome information can be obtained for vertebrates and model organisms, we have developed VerSeDa (Vertebrate Secretome Database). This freely available database stores information about proteins that are predicted to be secreted through the classical and non-classical mechanisms, for the wide range of vertebrate species deposited at the NCBI, UCSC and ENSEMBL sites. To our knowledge, VerSeDa is the only state-of-the-art database designed to store secretome data from multiple vertebrate genomes, thus, saving an important amount of time spent in the prediction of protein features that can be retrieved from this repository directly. Database URL: VerSeDa is freely available at http://genomics.cicbiogune.es/VerSeDa/index.php PMID:28365718

VerSeDa: vertebrate secretome database.

PubMed

Cortazar, Ana R; Oguiza, José A; Aransay, Ana M; Lavín, José L

2017-01-01

Based on the current tools, de novo secretome (full set of proteins secreted by an organism) prediction is a time consuming bioinformatic task that requires a multifactorial analysis in order to obtain reliable in silico predictions. Hence, to accelerate this process and offer researchers a reliable repository where secretome information can be obtained for vertebrates and model organisms, we have developed VerSeDa (Vertebrate Secretome Database). This freely available database stores information about proteins that are predicted to be secreted through the classical and non-classical mechanisms, for the wide range of vertebrate species deposited at the NCBI, UCSC and ENSEMBL sites. To our knowledge, VerSeDa is the only state-of-the-art database designed to store secretome data from multiple vertebrate genomes, thus, saving an important amount of time spent in the prediction of protein features that can be retrieved from this repository directly. VerSeDa is freely available at http://genomics.cicbiogune.es/VerSeDa/index.php. © The Author(s) 2017. Published by Oxford University Press.

[First experience in the thyroid and parathyroid surgery using the da Vinci® system].

PubMed

Al Kadah, B; Siemer, S; Schick, B

2014-01-01

Endoscopic surgery for the treatment of thyroid and parathyroid pathologies is gaining increasing attention. The da Vinci® system has been already widely used in different fields of medicine including recently thyroid and parathyroid surgery. Herein we report our first experiences in endoscopic surgery of thyroid and parathyroid pathologies using the da Vinci® system. 8 patients presenting with struma nodosa in 6 cases and parathyroid adenomas in 2 cases have been treated using the da Vinci® system at the ENT department of Homburg/Saar University. The skin incision to introduce the instruments with the da Vinci® system were axilar or at the lateral segment of the clavicle. The neurovascular structures like inferior laryngeal nerve as well as the pathologies were clearly 3-dimensional visualized in all 8 cases. No paralysis of the vocal cord was observed. All patients had in histological examination a benign pathology. The endoscopic surgery of the thyroid and parathyroid gland can be performed using the da Vinci® system and offers an excellent, intraoperative, 3-dimensional visualization of the neurovascular structures. Additionally the da Vinci® system enables skin incisions within considerable distance from the thyroid and parathyroid gland. © Georg Thieme Verlag KG Stuttgart · New York.

Yarkovsky-driven Impact Predictions: Apophis and 1950 DA

NASA Astrophysics Data System (ADS)

Farnocchia, Davide; Chesley, S. R.; Chodas, P.; Milani, A.

2013-05-01

Abstract (2,250 Maximum Characters): Orbit determination for Near-Earth Asteroids presents unique technical challenges due to the imperative of early detection and careful assessment of the risk posed by specific Earth close approaches. The occurrence of an Earth impact can be decisively driven by the Yarkovsky effect, which is the most important nongravitational perturbation as it causes asteroids to undergo a secular variation in semimajor axis resulting in a quadratic effect in anomaly. We discuss the cases of (99942) Apophis and (29075) 1950 DA. The relevance of the Yarkovsky effect for Apophis is due to a scattering close approach in 2029 with minimum geocentric distance ~38000 km. For 1950 DA the influence of the Yarkovsky effect in 2880 is due to the long time interval preceding the impact. We use the available information on the asteroids' physical models as a starting point for a Monte Carlo method that allow us to measure how the Yarkovsky effect affects orbital predictions. For Apophis we map onto the 2029 close approach b-plane and analyze the keyholes corresponding to resonant close approaches. For 1950 DA we use the b-plane corresponding to the possible impact in 2880. We finally compute the impact probability from the mapped probability density function on the considered b-plane.

Increased susceptibility of ethanol-treated gastric mucosa to naproxen and its inhibition by DA-9601, an Artemisia asiatica extract

PubMed Central

Oh, Tae Young; Ahn, Gook Jun; Choi, Seul Min; Ahn, Byoung Ok; Kim, Won Bae

2005-01-01

AIM: To examine the effect of DA-9601, a new gastroprotective agent, on the vulnerability of ethanol-treated rat’s stomach to naproxen (NAP). METHODS: Male Sprague-Dawley rats were pretreated with 1 mL of 50% ethanol twice a day for 5 d and then NAP (50 mg/kg) was administered. DA-9601 was administered 1 h before NAP. Four hours after NAP, the rats were killed to examine gross injury index (mm2), histologic change and to determine mucosal levels of malondialdehyde (MDA), prostaglandin E2 (PGE2), glutathione (GSH) and myeloperoxidase (MPO). RESULTS: Pretreatment of ethanol significantly increased NAP-induced gastric lesions, as well as an increase in MDA and MPO. On the contrary, mucosal PGE2 and GSH contents were decreased dramatically by ethanol pretreatment, which were aggravated by NAP. DA-9601 significantly reduced NAP-induced gastric injury grossly and microscopically, regardless of pretreatment with ethanol. DA-9601 preserved, or rather, increased mucosal PGE2 and GSH in NAP-treated rats (P<0.05), with reduction in mucosal MDA and MPO levels. CONCLUSION: These results suggest that repeated alcohol consumption renders gastric mucosa more susceptible to NSAIDs though, at least in part, reduction of endogenous cytoprotectants including PGE2 and GSH, and increase in MPO activation, and that DA-9601, a new gastroprotectant, can reduce the increased vulnerability of ethanol consumers to NSAIDs-induced gastric damage via the mechanism in which PGE2 and GSH are involved. PMID:16437715

Increased susceptibility of ethanol-treated gastric mucosa to naproxen and its inhibition by DA-9601, an Artemisia asiatica extract.

PubMed

Oh, Tae Young; Ahn, Gook Jun; Choi, Seul Min; Ahn, Byoung Ok; Kim, Won Bae

2005-12-21

To examine the effect of DA-9601, a new gastroprotective agent, on the vulnerability of ethanol-treated rat's stomach to naproxen (NAP). Male Sprague-Dawley rats were pretreated with 1 mL of 50% ethanol twice a day for 5 d and then NAP (50 mg/kg) was administered. DA-9601 was administered 1 h before NAP. Four hours after NAP, the rats were killed to examine gross injury index (mm2), histologic change and to determine mucosal levels of malondialdehyde (MDA), prostaglandin E2 (PGE2), glutathione (GSH) and myeloperoxidase (MPO). Pretreatment of ethanol significantly increased NAP-induced gastric lesions, as well as an increase in MDA and MPO. On the contrary, mucosal PGE2 and GSH contents were decreased dramatically by ethanol pretreatment, which were aggravated by NAP. DA-9601 significantly reduced NAP-induced gastric injury grossly and microscopically, regardless of pretreatment with ethanol. DA-9601 preserved, or rather, increased mucosal PGE2 and GSH in NAP-treated rats (P<0.05), with reduction in mucosal MDA and MPO levels. These results suggest that repeated alcohol consumption renders gastric mucosa more susceptible to NSAIDs though, at least in part, reduction of endogenous cytoprotectants including PGE2 and GSH, and increase in MPO activation, and that DA-9601, a new gastroprotectant, can reduce the increased vulnerability of ethanol consumers to NSAIDs-induced gastric damage via the mechanism in which PGE2 and GSH are involved.

A relevant IgE-reactive 28kDa protein identified from Salsola kali pollen extract by proteomics is a natural degradation product of an integral 47kDa polygalaturonase.

PubMed

Mas, Salvador; Oeo-Santos, Carmen; Cuesta-Herranz, Javier; Díaz-Perales, Araceli; Colás, Carlos; Fernández, Javier; Barber, Domingo; Rodríguez, Rosalía; de Los Ríos, Vivian; Barderas, Rodrigo; Villalba, Mayte

2017-08-01

A highly prevalent IgE-binding protein band of 28kDa is observed when Salsola kali pollen extract is incubated with individual sera from Amaranthaceae pollen sensitized patients. By an immunoproteomic analysis of S. kali pollen extract, we identified this protein band as an allergenic polygalacturonase enzyme. The allergen, named Sal k 6, exhibits a pI of 7.14 and a molecular mass of 39,554.2Da. It presents similarities to Platanaceae, Poaceae, and Cupressaceae allergenic polygalacturonases. cDNA-encoding sequence was subcloned into the pET41b vector and produced in bacteria as a His-tag fusion recombinant protein. The far-UV CD spectrum determined that rSal k 6 was folded. Immunostaining of the S. kali pollen protein extract with a rSal k 6-specific pAb and LC-MS/MS proteomic analyses confirmed the co-existence of the 28kDa band together with an allergenic band of about 47kDa in the pollen extract. Therefore, the 28kDa was assigned as a natural degradation product of the 47kDa integral polygalacturonase. The IgE-binding inhibition to S. kali pollen extract using rSal k 6 as inhibitor showed that signals directed to both protein bands of 28 and 47kDa were completely abrogated. The average prevalence of rSal k 6 among the three populations analyzed was 30%, with values correlating well with the levels of grains/m 3 of Amaranthaceae pollen. Sal k 6 shares IgE epitopes with Oleaceae members (Fraxinus excelsior, Olea europaea and Syringa vulgaris), with IgE-inhibition values ranging from 20% to 60%, respectively. No IgE-inhibition was observed with plant-derived food extracts. Copyright © 2017 Elsevier B.V. All rights reserved.

Raven surgical robot training in preparation for da vinci.

PubMed

Glassman, Deanna; White, Lee; Lewis, Andrew; King, Hawkeye; Clarke, Alicia; Glassman, Thomas; Comstock, Bryan; Hannaford, Blake; Lendvay, Thomas S

2014-01-01

The rapid adoption of robotic assisted surgery challenges the pace at which adequate robotic training can occur due to access limitations to the da Vinci robot. Thirty medical students completed a randomized controlled trial evaluating whether the Raven robot could be used as an alternative training tool for the Fundamentals of Laparoscopic Surgery (FLS) block transfer task on the da Vinci robot. Two groups, one trained on the da Vinci and one trained on the Raven, were tested on a criterion FLS block transfer task on the da Vinci. After robotic FLS block transfer proficiency training there was no statistically significant difference between path length (p=0.39) and economy of motion scores (p=0.06) between the two groups, but those trained on the da Vinci did have faster task times (p=0.01). These results provide evidence for the value of using the Raven robot for training prior to using the da Vinci surgical system for similar tasks.

Construção de um catálogo de aglomerados abertos para estudo da dinâmica da estrutura espiral da Galáxia

NASA Astrophysics Data System (ADS)

Carlos, I. M.; Lépine, J. R. D.

2003-08-01

Os aglomerados abertos são objetos de grande valor para o estudo da dinâmica da Galáxia devido esses objetos terem uma faixa de idade relativamente ampla. O trabalho visa estudar a dinâmica da estrutura espiral da Galáxia principalmente através do uso desses aglomerados, uma vez que o estudo da cinemática desses objetos é fundamental para esse objetivo. Nosso grupo trabalha no sentido de construir uma base de dados de aglomerados abertos contendo coordenadas, distância, idade, movimentos próprios e velocidades radiais e já disponibiliza uma nova versão do catálogo de aglomerados abertos o qual é uma compilação de edições anteriores, principalmente Lynga (1987), Mermilliod (1995) e ESO-B (Lauberts 1982). Nossa amostra possui cerca de 1630 aglomerados, mas nem todos os parâmetros acima citados foram determinados em sua totalidade. Para determinarmos esses parâmetros, derivamos as cores intrínsecas das estrelas membro de cada aglomerado a partir de seus tipos espectrais (busca feita no SIMBAD) obtendo assim o excesso de cor individual. A distribuição dos excessos de cor foi então utilizada para derivarmos o avermelhamento médio para cada aglomerado. De maneira similar, os tipos espectrais foram usados para estimar as magnitudes absolutas, e com as magnitudes absolutas e aparentes determinamos a respectiva distribuição do módulo de distância e finalmente a distância. Para determinar as idades foram confeccionados os diagramas cor-magnitude das estrelas de cada aglomerado onde foram superpostas a Seqüência Principal de Idade Zero (ZAMS). Superpomos a ZAMS de Schmidt-Kaler e isócronas de composição solar. Essas isócronas foram usadas para determinação das idades dos aglomerados. Uma vez que não temos ainda resultados finais, apresentamos então alguns diagramas cor-magnitude os quais foram usados para determinação, principalmente, da distância e idade dos aglomerados.

Tristan da Cunha Island

NASA Image and Video Library

2018-05-25

Tristan da Cunha is both a remote group of volcanic islands in the south Atlantic, and the main island. It is the most remote inhabited island group in the world, 2400 km from the nearest inhabited land. Tristan has a population of about 250 inhabitants, and is part of the British overseas territory of Saint Helena, Ascension and Tristan da Cunha. In 1961 the eruption of Queen Mary's Peak forced the evacuation of the entire population for two years. The image was acquired October 7, 2017, and is located at 37.1 degrees south, 12.3 degrees west. https://photojournal.jpl.nasa.gov/catalog/PIA22506

A fused-ring acceptor unit in d-a copolymers benefits photovoltaic performance.

PubMed

Zuo, Chuantian; Cao, Jiamin; Ding, Liming

2014-08-01

Pentacyclic lactam acceptor unit TPTI invented by our group is proved to be a good building block for efficient D-A copolymers used in organic solar cells. Here, two D-A copolymers PBTTPTI and PTTTPTI are developed by copolymerizing TPTI with 2,2'-bithiophene (BT) or thieno[3,2-b]thiophene (TT). PBTTPTI and PTTTPTI exhibit good solubility and strong interchain π-π interaction even in dilute solution. They possess deep HOMO levels (ca. -5.3 eV), partial crystallinity, and good hole mobilities. Blending with PC71 BM, PBTTPTI and PTTTPTI give decent power conversion efficiencies (PCE) up to 6.83% and 5.86%, with outstanding fill factors (FF) of 74.3% and 71.3%, respectively. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Training and Health. Leonardo da Vinci Series: Good Practices.

ERIC Educational Resources Information Center

Commission of the European Communities, Brussels (Belgium). Directorate-General for Education and Culture.

This document profiles programs in the fields of health and medicine that are offered through the European Commission's Leonardo da Vinci program. The following programs are profiled: (1) CYTOTRAIN (a transnational vocational training program in cervical cancer screening); (2) Apollo (a program of open and distance learning for paramedical…

2D and 3D optical diagnostic techniques applied to Madonna dei Fusi by Leonardo da Vinci

NASA Astrophysics Data System (ADS)

Fontana, R.; Gambino, M. C.; Greco, M.; Marras, L.; Materazzi, M.; Pampaloni, E.; Pelagotti, A.; Pezzati, L.; Poggi, P.; Sanapo, C.

2005-06-01

3D measurement and modelling have been traditionally applied to statues, buildings, archeological sites or similar large structures, but rarely to paintings. Recently, however, 3D measurements have been performed successfully also on easel paintings, allowing to detect and document the painting's surface. We used 3D models to integrate the results of various 2D imaging techniques on a common reference frame. These applications show how the 3D shape information, complemented with 2D colour maps as well as with other types of sensory data, provide the most interesting information. The 3D data acquisition was carried out by means of two devices: a high-resolution laser micro-profilometer, composed of a commercial distance meter mounted on a scanning device, and a laser-line scanner. The 2D data acquisitions were carried out using a scanning device for simultaneous RGB colour imaging and IR reflectography, and a UV fluorescence multispectral image acquisition system. We present here the results of the techniques described, applied to the analysis of an important painting of the Italian Reinassance: `Madonna dei Fusi', attributed to Leonardo da Vinci.

A Comparative study for striatal-direct and -indirect pathway neurons to DA depletion-induced lesion in a PD rat model.

PubMed

Zheng, Xuefeng; Wu, Jiajia; Zhu, Yaofeng; Chen, Si; Chen, Zhi; Chen, Tao; Huang, Ziyun; Wei, Jiayou; Li, Yanmei; Lei, Wanlong

2018-04-16

Striatal-direct and -indirect Pathway Neurons showed different vulnerability in basal ganglia disorders. Therefore, present study aimed to examine and compare characteristic changes of densities, protein and mRNA levels of soma, dendrites, and spines between striatal-direct and -indirect pathway neurons after DA depletion by using immunohistochemistry, Western blotting, real-time PCR and immunoelectron microscopy techniques. Experimental results showed that: 1) 6OHDA-induced DA depletion decreased the soma density of striatal-direct pathway neurons (SP+), but no significant changes for striatal-indirect pathway neurons (ENK+). 2) DA depletion resulted in a decline of dendrite density for both striatal-direct (D1+) and -indirect (D2+) pathway neurons, and D2+ dendritic density declined more obviously. At the ultrastructure level, the densities of D1+ and D2+ dendritic spines reduced in the 6OHDA groups compared with their control groups, but the density of D2+ dendritic spines reduced more significant than that of D1. 3) Striatal DA depletion down-regulated protein and mRNA expression levels of SP and D1, on the contrary, ENK and D2 protein and mRNA levels of indirect pathway neurons were up-regulated significantly. Present results suggested that indirect pathway neurons be more sensitive to 6OHDA-induced DA depletion. Copyright © 2018 Elsevier Ltd. All rights reserved.

[Clinical application of Da Vinci surgical system in China].

PubMed

Jin, Zhenyu

2014-01-01

Da Vinci robotic surgical system leads the development of minimally invasive surgical techniques. By using Da Vinci surgical robot for minimally invasive surgery, it brings a lot of advantages to the surgeons. Since 2008, Da Vinci surgeries have been performed in 14 hospitals in domestic cities such as Beijing and Shanghai. Until the end of 2012, 3 551 cases of Da Vinci robotic surgery have been performed, covering various procedures of various surgical departments including the department of general surgery, urology, cardiovascular surgery, thoracic surgery, gynecology, and etc. Robotic surgical technique has made remarkable achievements.

A comparative study of DA-9601 and misoprostol for prevention of NSAID-associated gastroduodenal injury in patients undergoing chronic NSAID treatment.

PubMed

Lee, Oh Young; Kang, Dae-Hwan; Lee, Dong Ho; Chung, Il-Kwun; Jang, Jae Young; Jang, Jae-Young; Kim, Jin-Il; Cho, Jin-Woong; Rew, Jong-Sun; Lee, Kang-Moon; Kim, Kyoung Oh; Choi, Myung-Gyu; Lee, Sang-Woo; Lee, Soo-Teik; Kim, Tae-Oh; Shin, Yong-Woon; Seol, Sang-Yong

2014-10-01

Misoprostol is reported to prevent non-steroidal anti-inflammatory drug (NSAID)-associated gastroduodenal complications. There is, however, limited information regarding the efficacy of DA-9601 in this context. We performed a comparative study on the relative efficacy of DA-9601 and misoprostol for prevention of NSAID-associated complications. In this multicenter, double-blinded, active-controlled, stratified randomized, parallel group, non-inferiority trial, 520 patients who were to be treated with an NSAID (aceclofenac, 100 mg, twice daily) over a 4-week period were randomly assigned to groups for coincidental treatment with DA-9601 (60 mg, thrice daily) (236 patients for full analysis) or misoprostol (200 μg, thrice daily) (242 patients for full analysis). [corrected]. The primary endpoint was the gastric protection rate, and secondary endpoints were the duodenal protection rate and ulcer incidence rate. Endpoints were assessed by endoscopy after the 4-week treatment period. Drug-related adverse effects, including gastrointestinal (GI) symptoms, were also compared. At week 4, the gastric protection rates with DA-9601 and misoprostol were 81.4 % (192/236) and 89.3 % (216/242), respectively. The difference between the groups was -14.2 %, indicating non-inferiority of DA-9601 to misoprostol. Adverse event rates were not different between the two groups; however, the total scores for GI symptoms before and after administration were significantly lower in the DA-9601 group than in the misoprostol group (-0.2 ± 2.8 vs 1.2 ± 3.2; p < 0.0001). DA-9601 is as effective as misoprostol in preventing NSAID-associated gastroduodenal complications, and has a superior adverse GI effect profile.

Structural analysis and cross-protective efficacy of recombinant 87 kDa outer membrane protein (Omp87) of Pasteurella multocida serogroup B:2.

PubMed

Kumar, Abhinendra; Yogisharadhya, Revanaiah; Ramakrishnan, Muthannan A; Viswas, K N; Shivachandra, Sathish B

2013-12-01

Pasteurella multocida serogroup B:2, a causative agent of haemorrhagic septicaemia (HS) in cattle and buffalo especially in tropical regions of Asian and African countries, is known to possess several outer membrane proteins (OMPs) as immunogenic antigens. In the present study, omp87 gene encoding for 87 kDa OMP (Omp87) protein of P. multocida serogroup B:2 strain P52, has been amplified (∼2304 bp), cloned in to pET32a vector and over-expressed in recombinant Escherichia coli as fusion protein. The recombinant Omp87 protein (∼102 kDa) including N-terminus hexa-histidine tag was purified under denaturing condition. Immunization of mice with rOmp87 resulted in increased antigen specific IgG titres in serum and provided protection of 66.6 and 83.3% following homologous (B:2) and heterologous (A:1) challenge, respectively. A homology model of Omp87 revealed the presence of two distinct domains; N-terminal domain with four POTRA repeats in the periplasmic space and a pore forming C-terminal β-barrel domain (β1- β16) in the outer membrane of P. multocida, which belong to Omp85-TpsB transporter superfamily of OMPs. The study indicated the potential possibilities to use rOmp87 protein along with suitable adjuvant in developing subunit vaccine for haemorrhagic septicaemia and pasteurellosis in livestock. Copyright © 2013 Elsevier Ltd. All rights reserved.

Randomized, Controlled, Multi-center Trial: Comparing the Safety and Efficacy of DA-9701 and Itopride Hydrochloride in Patients With Functional Dyspepsia.

PubMed

Choi, Myung-Gyu; Rhee, Poong-Lyul; Park, Hyojin; Lee, Oh Young; Lee, Kwang Jae; Choi, Suck Chei; Seol, Sang Young; Chun, Hoon Jai; Rew, Jong-Sun; Lee, Dong Ho; Song, Geun Am; Jung, Hwoon Yong; Jeong, Hyung Yong; Sung, In Kyung; Lee, Joon Seong; Lee, Soo Teik; Kim, Sung Kook; Shin, Yong Woon

2015-07-30

Therapies of functional dyspepsia (FD) are limited. DA-9701 is a novel prokinetic agent formulated with Pharbitis semen and Corydalis Tuber. We aimed to assess the efficacy of DA-9701 compared with itopride in FD patients. Patients with FD randomly received either itopride 50 mg or DA-9701 30 mg t.i.d after a 2-week baseline period. After 4 weeks of treatment, 2 primary efficacy endpoints were analyzed: the change from baseline in composite score of the 8 dyspep-tic symptoms and the overall treatment effect. Impact on patients' quality of life was assessed using the Nepean Dyspepsia Index (NDI) questionnaire. We randomly assigned 464 patients with 455 having outcome data. The difference of the composite score change of the 8 symptoms between the 2 groups was 0.62, indicating that DA-9701 was not inferior to itopride. The overall treatment effect response rate was not different between the groups. When responder was defined as ≥ 5 of the 7 Likert scale, responder rates were 37% of DA-9701 and 36% of itopride group. Patients receiving DA-9701 experienced similar mean percentage of days with adequate relief during the 4-week treatment period compared with those receiving itopride (56.8% vs 59.1%). Both drugs increased the NDI score of 5 domains without any difference in change of the NDI score between the groups. The safety profile of both drugs was comparable. DA-9701 significantly improves symptoms in patients with FD. DA-9701 showed non-inferior efficacy to itopride with com-parable safety.

Randomized, Controlled, Multi-center Trial: Comparing the Safety and Efficacy of DA-9701 and Itopride Hydrochloride in Patients With Functional Dyspepsia

PubMed Central

Choi, Myung-Gyu; Rhee, Poong-Lyul; Park, Hyojin; Lee, Oh Young; Lee, Kwang Jae; Choi, Suck Chei; Seol, Sang Young; Chun, Hoon Jai; Rew, Jong-Sun; Lee, Dong Ho; Song, Geun Am; Jung, Hwoon Yong; Jeong, Hyung Yong; Sung, In Kyung; Lee, Joon Seong; Lee, Soo Teik; Kim, Sung Kook; Shin, Yong Woon

2015-01-01

Background/Aims Therapies of functional dyspepsia (FD) are limited. DA-9701 is a novel prokinetic agent formulated with Pharbitis semen and Corydalis Tuber. We aimed to assess the efficacy of DA-9701 compared with itopride in FD patients. Methods Patients with FD randomly received either itopride 50 mg or DA-9701 30 mg t.i.d after a 2-week baseline period. After 4 weeks of treatment, 2 primary efficacy endpoints were analyzed: the change from baseline in composite score of the 8 dyspeptic symptoms and the overall treatment effect. Impact on patients’ quality of life was assessed using the Nepean Dyspepsia Index (NDI) questionnaire. Results We randomly assigned 464 patients with 455 having outcome data. The difference of the composite score change of the 8 symptoms between the 2 groups was 0.62, indicating that DA-9701 was not inferior to itopride. The overall treatment effect response rate was not different between the groups. When responder was defined as ≥ 5 of the 7 Likert scale, responder rates were 37% of DA-9701 and 36% of itopride group. Patients receiving DA-9701 experienced similar mean percentage of days with adequate relief during the 4-week treatment period compared with those receiving itopride (56.8% vs 59.1%). Both drugs increased the NDI score of 5 domains without any difference in change of the NDI score between the groups. The safety profile of both drugs was comparable. Conclusions DA-9701 significantly improves symptoms in patients with FD. DA-9701 showed non-inferior efficacy to itopride with comparable safety. PMID:26130637

Synergistic effects of melatonin and deprenyl against MPTP-induced mitochondrial damage and DA depletion.

PubMed

Khaldy, Hoda; Escames, Germaine; León, Josefa; Bikjdaouene, Leila; Acuña-Castroviejo, Darío

2003-01-01

Previous studies showed a synergistic effect of melatonin and deprenyl against dopamine (DA) autoxidation in vitro. Since oxidative stress is implicated in Parkinson's disease (PD), we explored the effects of melatonin plus deprenyl administration in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD in C57/Bl6 mice. Melatonin, but not deprenyl prevents the inhibition of mitochondrial complex I and the oxidative damage in nigrostriatal neurons induced by MPTP. With the dose used deprenyl recovers 50% DA levels and tyrosine hydroxylase activity depressed by the neurotoxin, normalizing locomotor activity of mice. Melatonin, which was unable to counteract MPTP-induced DA depletion and inhibition of tyrosine hydroxylase activity, potentiates the effect of deprenyl on catecholamine turnover and mice ambulatory activity. These results suggest a dissociation of complex I inhibition from DA depletion in this model of Parkinson's disease. The data also support that a combination of melatonin, which improves mitochondrial electron transport chain and reduces oxidative damage, and deprenyl, which promotes the specific function of the rescued neurons, i.e. DA turnover, may be a promising strategy for the treatment of PD.

[da Vinci surgical system].

PubMed

Watanabe, Gou; Ishikawa, Norihiro

2014-07-01

The da Vinci surgical system was developed by Intuitive Surgical Inc. in the United States as an endoscopic surgical device to assist remote control surgeries. In 1998, the Da Vinci system was first used for cardiothoracic procedures. Currently a combination of robot-assisted internal thoracic artery harvest together with coronary artery bypass grafting (CABG) through a mini-incision (ThoraCAB) or totally endoscopic procedures including anastomoses under robotic assistance (TECAB) are being conducted for the treatment of coronary artery diseases. With the recent advances in catheter interventions, hybrid procedures combining catheter intervention with ThoraCAB or TECAB are anticipated in the future.On the other hand, with the decrease in number of coronary artery bypass surgeries, the share of valvular surgeries is expected to increase in the future. Among them, mitral valvuloplasty for mitral regurgitation is anticipated to be conducted mainly by low-invasive procedures, represented by minimally invasive cardiac surgery( MICS) and robot-assisted surgery. Apart from the intrinsic good surgical view, robotic-assisted systems offer additional advantages of the availability of an amplified view and the easy to observe the mitral valve in the physiological position. Thus, robotic surgical surgeries that make complicated procedures easier are expected to accomplish further developments in the future. Furthermore, while the number of surgeries for atrial septal defects has decreased dramatically following the widespread use of Amplatzer septal occluder, robotic surgery may become a good indication for cases in which the Amplatzer device is not indicated. In Japan, clinical trial of the da Vinci robotic system for heart surgeries has been completed. Statutory approval of the da Vinci system for mitral regurgitation and atrial septal defects is anticipated in the next few years.

NADH:ubiquinone oxidoreductase from bovine heart mitochondria. cDNA sequences of the import precursors of the nuclear-encoded 39 kDa and 42 kDa subunits.

PubMed Central

Fearnley, I M; Finel, M; Skehel, J M; Walker, J E

1991-01-01

The 39 kDa and 42 kDa subunits of NADH:ubiquinone oxidoreductase from bovine heart mitochondria are nuclear-coded components of the hydrophobic protein fraction of the enzyme. Their amino acid sequences have been deduced from the sequences of overlapping cDNA clones. These clones were amplified from total bovine heart cDNA by means of the polymerase chain reaction, with the use of complex mixtures of oligonucleotide primers based upon fragments of protein sequence determined at the N-terminals of the proteins and at internal sites. The protein sequences of the 39 kDa and 42 kDa subunits are 345 and 320 amino acid residues long respectively, and their calculated molecular masses are 39,115 Da and 36,693 Da. Both proteins are predominantly hydrophilic, but each contains one or two hydrophobic segments that could possibly be folded into transmembrane alpha-helices. The bovine 39 kDa protein sequence is related to that of a 40 kDa subunit from complex I from Neurospora crassa mitochondria; otherwise, it is not related significantly to any known sequence, including redox proteins and two polypeptides involved in import of proteins into mitochondria, known as the mitochondrial processing peptidase and the processing-enhancing protein. Therefore the functions of the 39 kDa and 42 kDa subunits of complex I are unknown. The mitochondrial gene product, ND4, a hydrophobic component of complex I with an apparent molecular mass of about 39 kDa, has been identified in preparations of the enzyme. This subunit stains faintly with Coomassie Blue dye, and in many gel systems it is not resolved from the nuclearcoded 36 kDa subunit. Images Fig. 1. PMID:1832859

The 29-kDa proteins phosphorylated ion thrombin-activated human platelets are forms of the estrogen receptor-related 27-kDa heat shock protein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mendelsohn, M.E.; Yan Zhu; O'Neill, S.

Thrombin plays a critical role in platelet activation, hemostasis, and thrombosis. Cellular activation by thrombin leads to the phosphorylation of multiple proteins, most of which are unidentified. The authors have characterized several 29-kDa proteins that are rapidly phosphorylated following exposure of intact human platelets to thrombin. A murine monoclonal antibody raised to an unidentified estrogen receptor-related 29-kDa protein selectively recognized these proteins as well as a more basic, unphosphorylated 27-kDa protein. Cellular activation by thrombin led to a marked shift in the proportion of protein from the 27-kDa unphosphorylated form to the 29-kDa phosphoprotein species. Using this antibody, they isolatedmore » and sequenced a human cDNA clone encoding a protein that was identical to the mammalian 27-kDa heat shock protein (HSP27), a protein of uncertain function that is known to be phosphorylated to several forms and to be transcriptionally induced by estrogen. The 29-kDa proteins were confirmed to be phosphorylated forms of HSP27 by immunoprecipitation studies. Thus, the estrogen receptor-related protein is HSP27, and the three major 20-kDa proteins phosphorylated in thrombin-activated platelets are forms of HSP27. These data suggest a role for HSP27 in the signal transduction events of platelet activation.« less

Recombinant expression, isolation, and proteolysis of extracellular matrix-secreted phosphoprotein-24 kDa.

PubMed

Murray, Elsa J Brochmann; Murray, Samuel S; Simon, Robert; Behnam, Keyvan

2007-01-01

Secreted phosphoprotein-24 kDa (spp24) is an extracellular matrix protein first cloned from bone. Bovine spp24 is transcribed as a 203 amino acid residue protein that undergoes cleavage of a secretory peptide to form the mature protein (spp24, residues 24 to 203). While not osteogenic itself, spp24 is degraded to a pro-osteogenic protein, spp18.5, in bone. Both spp18.5 and spp24 contain a cyclic TRH1 (TGF-beta receptor II homology-1) domain similar to that found in the receptor itself and in fetuin. A synthetic peptide corresponding to the TRH1 domain of spp18.5 and spp24 specifically binds BMP-2 and enhances the rate and magnitude of BMP-2-induced ectopic bone formation in vivo. The parental protein, spp24, exhibits a high affinity for bone and mineral complexes, but its abundance there is low, suggesting that it is rapidly degraded. The availability of recombinant spp24 and its degradation products would facilitate the elucidation of their structure:function relationships. We describe here the expression of His(6)-tagged bovine spp24 (residues 24 to 203) in E. coli, its purification by high-resolution IMAC (immobilized metal affinity chromatography), and the characterization of the full-length recombinant 21.5 kDa protein and its two major 16 kDa and 14.5 kDa degradation products (spp24, residues 24 to 157, and spp24, residues 24 to 143) by mass spectroscopy. The recombinant spp24 protein was resistant to proteolysis by MC3T3-E1 osteoblastic cell extracts in the absence of calcium; however, in the presence of 4 mM Ca, it can undergo essentially complete proteolysis to small peptides, bypassing the 16 kDa and 14.5 kDa intermediates. This confirms the proteolytic susceptibility of spp24. It also suggests that the levels of spp24 in bone may be regulated, in part, by calcium-dependent proteolysis mediated by osteoblastic cells.

Molecular cloning and developmental expression of the catalytic and 65-kDa regulatory subunits of protein phosphatase 2A in Drosophila.

PubMed Central

Mayer-Jaekel, R E; Baumgartner, S; Bilbe, G; Ohkura, H; Glover, D M; Hemmings, B A

1992-01-01

cDNA clones encoding the catalytic subunit and the 65-kDa regulatory subunit of protein phosphatase 2A (PR65) from Drosophila melanogaster have been isolated by homology screening with the corresponding human cDNAs. The Drosophila clones were used to analyze the spatial and temporal expression of the transcripts encoding these two proteins. The Drosophila PR65 cDNA clones contained an open reading frame of 1773 nucleotides encoding a protein of 65.5 kDa. The predicted amino acid sequence showed 75 and 71% identity to the human PR65 alpha and beta isoforms, respectively. As previously reported for the mammalian PR65 isoforms, Drosophila PR65 is composed of 15 imperfect repeating units of approximately 39 amino acids. The residues contributing to this repeat structure show also the highest sequence conservation between species, indicating a functional importance for these repeats. The gene encoding Drosophila PR65 was located at 29B1,2 on the second chromosome. A major transcript of 2.8 kilobase (kb) encoding the PR65 subunit and two transcripts of 1.6 and 2.5 kb encoding the catalytic subunit could be detected throughout Drosophila development. All of these mRNAs were most abundant during early embryogenesis and were expressed at lower levels in larvae and adult flies. In situ hybridization of different developmental stages showed a colocalization of the PR65 and catalytic subunit transcripts. The mRNA expression is high in the nurse cells and oocytes, consistent with a high equally distributed expression in early embryos. In later embryonal development, the expression remains high in the nervous system and the gonads but the overall transcript levels decrease. In third instar larvae, high levels of mRNA could be observed in brain, imaginal discs, and in salivary glands. These results indicate that protein phosphatase 2A transcript levels change during development in a tissue and in a time-specific manner. Images PMID:1320961

DaCHS: Data Center Helper Suite

NASA Astrophysics Data System (ADS)

Demleitner, Markus

2018-04-01

DaCHS, the Data Center Helper Suite, is an integrated package for publishing astronomical data sets to the Virtual Observatory. Network-facing, it speaks the major VO protocols (SCS, SIAP, SSAP, TAP, Datalink, etc). Operator-facing, many input formats, including FITS/WCS, ASCII files, and VOTable, can be processed to publication-ready data. DaCHS puts particular emphasis on integrated metadata handling, which facilitates a tight integration with the VO's Registry

Respostas religiosas à aids no Brasil: impressões de pesquisa acerca da Pastoral de DST/Aids da Igreja Católica1

PubMed Central

Seffner, Fernando; Silva, Cristiane Gonçalves Meireles da; Maksud, Ívia; Garcia, Jonathan; Rios, Luís Felipe; Natividade, Marcelo; Borges, Priscila Rodrigues; Parker, Richard; Terto, Veriano

2009-01-01

O texto encontra-se estruturado em quatro partes. Na primeira delas, apresentamos um conjunto de considerações e informações acerca da situação da aids no Brasil, das relações entre religião, sexualidade, aids e estado laico, bem como uma descrição mais clara do Projeto Respostas Religiosas ao HIV/Aids no Brasil, do qual este texto apresenta algumas impressões de pesquisa preliminares. A seguir, dedicamos um item a apresentação da Pastoral de DST/Aids, sua história, estrutura e objetivos. No item seguinte problematizamos diversas questões em particular no âmbito das relações Estado e Igreja, relações entre agentes de pastoral e hierarquia da Igreja, e questões ligadas mais diretamente à sexualidade e aids, todas referenciadas ao trabalho da Pastoral de DST/Aids. Ao final, apresentamos a bibliografia e fontes consultadas. PMID:20442806

PCA as a practical indicator of OPLS-DA model reliability.

PubMed

Worley, Bradley; Powers, Robert

Principal Component Analysis (PCA) and Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) are powerful statistical modeling tools that provide insights into separations between experimental groups based on high-dimensional spectral measurements from NMR, MS or other analytical instrumentation. However, when used without validation, these tools may lead investigators to statistically unreliable conclusions. This danger is especially real for Partial Least Squares (PLS) and OPLS, which aggressively force separations between experimental groups. As a result, OPLS-DA is often used as an alternative method when PCA fails to expose group separation, but this practice is highly dangerous. Without rigorous validation, OPLS-DA can easily yield statistically unreliable group separation. A Monte Carlo analysis of PCA group separations and OPLS-DA cross-validation metrics was performed on NMR datasets with statistically significant separations in scores-space. A linearly increasing amount of Gaussian noise was added to each data matrix followed by the construction and validation of PCA and OPLS-DA models. With increasing added noise, the PCA scores-space distance between groups rapidly decreased and the OPLS-DA cross-validation statistics simultaneously deteriorated. A decrease in correlation between the estimated loadings (added noise) and the true (original) loadings was also observed. While the validity of the OPLS-DA model diminished with increasing added noise, the group separation in scores-space remained basically unaffected. Supported by the results of Monte Carlo analyses of PCA group separations and OPLS-DA cross-validation metrics, we provide practical guidelines and cross-validatory recommendations for reliable inference from PCA and OPLS-DA models.

Women and Technical Professions. Leonardo da Vinci Series: Good Practices.

ERIC Educational Resources Information Center

Commission of the European Communities, Brussels (Belgium). Directorate-General for Education and Culture.

This document profiles programs for women in technical professions that are offered through the European Commission's Leonardo da Vinci program. The following programs are profiled: (1) Artemis and Diana (vocational guidance programs to help direct girls toward technology-related careers); (2) CEEWIT (an Internet-based information and…

Direct voltammetric specific recognition of dopamine using AlIII-DA complexes at the hanging mercury drop electrode.

PubMed

Zhang, Fuping; Zhang, Min; Cheng, Jiongjia; Yang, Li; Ji, Ming; Bi, Shuping

2007-11-01

In this paper, we firstly report the direct voltammetric recognition and determination of dopamine (DA) by using Al(III)-DA complexes at the hanging mercury drop electrode (HMDE). A new sensitive cathodic peak of Al(III)-DA can be detected at -900 mV (vs. SCE) in 0.1 M NH(4)Cl-NH(3).H(2)O-0.1 M KCl buffer solution at pH 8.5. This unique -900 mV cathodic peak arises from the specific interaction between Al(III) and DA on the HMDE, whereas other substances with similar structures, such as L-dopa, epinephrine (EP), norepinephrine (NE), catechols, caffeic acid (CA), trihydric phenols and tiron, do not yield any new peak on the voltammograms in the potential range from -100 to -1200 mV when Al(III) is added. The distinct voltammetric characteristic of the recognition of DA can effectively inhibit the interferences of both ascorbic acid and uric acid in the DA determination by the direct electrochemistry, which is a major difficulty when a solid electrode is used. The proposed method can be anticipated as an effective means for the recognition of DA in the elucidation of the mechanisms of Parkinson's disease (PD) and Alzheimer's disease (AD) in the presence of Al(III).

32 CFR 516.25 - DA Form 4.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 3 2013-07-01 2013-07-01 false DA Form 4. 516.25 Section 516.25 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY AID OF CIVIL AUTHORITIES AND PUBLIC... attached to a properly prepared and sealed DA Form 4 are self-authenticating. (See Fed. R. Evid. 902). (b...

32 CFR 516.25 - DA Form 4.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 3 2014-07-01 2014-07-01 false DA Form 4. 516.25 Section 516.25 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY AID OF CIVIL AUTHORITIES AND PUBLIC... attached to a properly prepared and sealed DA Form 4 are self-authenticating. (See Fed. R. Evid. 902). (b...

32 CFR 516.25 - DA Form 4.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 3 2011-07-01 2009-07-01 true DA Form 4. 516.25 Section 516.25 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY AID OF CIVIL AUTHORITIES AND PUBLIC RELATIONS... properly prepared and sealed DA Form 4 are self-authenticating. (See Fed. R. Evid. 902). (b) Preparation at...

32 CFR 516.25 - DA Form 4.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 3 2012-07-01 2009-07-01 true DA Form 4. 516.25 Section 516.25 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY AID OF CIVIL AUTHORITIES AND PUBLIC RELATIONS... properly prepared and sealed DA Form 4 are self-authenticating. (See Fed. R. Evid. 902). (b) Preparation at...

Tree Branching: Leonardo da Vinci's Rule versus Biomechanical Models

PubMed Central

Minamino, Ryoko; Tateno, Masaki

2014-01-01

This study examined Leonardo da Vinci's rule (i.e., the sum of the cross-sectional area of all tree branches above a branching point at any height is equal to the cross-sectional area of the trunk or the branch immediately below the branching point) using simulations based on two biomechanical models: the uniform stress and elastic similarity models. Model calculations of the daughter/mother ratio (i.e., the ratio of the total cross-sectional area of the daughter branches to the cross-sectional area of the mother branch at the branching point) showed that both biomechanical models agreed with da Vinci's rule when the branching angles of daughter branches and the weights of lateral daughter branches were small; however, the models deviated from da Vinci's rule as the weights and/or the branching angles of lateral daughter branches increased. The calculated values of the two models were largely similar but differed in some ways. Field measurements of Fagus crenata and Abies homolepis also fit this trend, wherein models deviated from da Vinci's rule with increasing relative weights of lateral daughter branches. However, this deviation was small for a branching pattern in nature, where empirical measurements were taken under realistic measurement conditions; thus, da Vinci's rule did not critically contradict the biomechanical models in the case of real branching patterns, though the model calculations described the contradiction between da Vinci's rule and the biomechanical models. The field data for Fagus crenata fit the uniform stress model best, indicating that stress uniformity is the key constraint of branch morphology in Fagus crenata rather than elastic similarity or da Vinci's rule. On the other hand, mechanical constraints are not necessarily significant in the morphology of Abies homolepis branches, depending on the number of daughter branches. Rather, these branches were often in agreement with da Vinci's rule. PMID:24714065

Tree branching: Leonardo da Vinci's rule versus biomechanical models.

PubMed

Minamino, Ryoko; Tateno, Masaki

2014-01-01

This study examined Leonardo da Vinci's rule (i.e., the sum of the cross-sectional area of all tree branches above a branching point at any height is equal to the cross-sectional area of the trunk or the branch immediately below the branching point) using simulations based on two biomechanical models: the uniform stress and elastic similarity models. Model calculations of the daughter/mother ratio (i.e., the ratio of the total cross-sectional area of the daughter branches to the cross-sectional area of the mother branch at the branching point) showed that both biomechanical models agreed with da Vinci's rule when the branching angles of daughter branches and the weights of lateral daughter branches were small; however, the models deviated from da Vinci's rule as the weights and/or the branching angles of lateral daughter branches increased. The calculated values of the two models were largely similar but differed in some ways. Field measurements of Fagus crenata and Abies homolepis also fit this trend, wherein models deviated from da Vinci's rule with increasing relative weights of lateral daughter branches. However, this deviation was small for a branching pattern in nature, where empirical measurements were taken under realistic measurement conditions; thus, da Vinci's rule did not critically contradict the biomechanical models in the case of real branching patterns, though the model calculations described the contradiction between da Vinci's rule and the biomechanical models. The field data for Fagus crenata fit the uniform stress model best, indicating that stress uniformity is the key constraint of branch morphology in Fagus crenata rather than elastic similarity or da Vinci's rule. On the other hand, mechanical constraints are not necessarily significant in the morphology of Abies homolepis branches, depending on the number of daughter branches. Rather, these branches were often in agreement with da Vinci's rule.

40 CFR 60.42Da - Standard for particulate matter (PM).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 6 2010-07-01 2010-07-01 false Standard for particulate matter (PM). 60.42Da Section 60.42Da Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR....42Da Standard for particulate matter (PM). (a) On and after the date on which the initial performance...

40 CFR 60.42Da - Standard for particulate matter (PM).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 6 2011-07-01 2011-07-01 false Standard for particulate matter (PM). 60.42Da Section 60.42Da Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR....42Da Standard for particulate matter (PM). (a) On and after the date on which the initial performance...

Isoform composition and stoichiometry of the approx. 90-kDa heat shock protein associated with glucocorticoid receptors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mendel, D.B.; Orti, E.

1988-05-15

The authors observed that the approx. 90-kDa non-steroid-binding component of nonactivated glucocorticoid receptors purified from WEHI-7 mouse thymoma cells (which has been identified as the approx. 90-kDa heat shock protein) consistently migrates as a doublet during polyacrylamide gel electrophoresis under denaturing and reducing conditions. It has recently been reported that murine Meth A cells contain a tumor-specific transplantation antigen (TSTA) which is related or identical to the approx. 90-kDa heat shock protein. The observation that TSTA and the approx. 90-kDa heat shock protein isolated from these cells exists as two isoforms of similar molecular mass and charge has suggested thatmore » the doublet observed is also due to the existence of two isoforms. They have therefore conducted this study to determine whether TSTA and the approx. 90-kDa component of glucocorticoid receptors are indeed related, to establish whether the receptor preferentially binds one isoform of the approx. 90-kDa heat shock protein, and to investigate the stoichiometry of the nonactivated receptor complex. They used the BuGr1 and AC88 monoclonal antibodies to purify, respectively, receptor-associated and free approx. 90-kDa heat shock protein from WEHI-7 cells grown for 48 h with (/sup 35/S)methionine to metabolically label proteins to steady state. The long-term metabolic labeling approach has also enabled them to directly determine that the purified non-activated glucocorticoid receptor contains a single steroid-binding protein and two approx. 90-kDa non-steroid-binding subunits. The consistency with which a approx. 1:2 stoichiometric ratio of steroid binding to approx. 90-kDa protein is observed supports the view that the approx. 90-kDa heat shock protein is a true component of nonactivated glucocorticoid-receptor complexes.« less

The role of transparency in da Vinci stereopsis.

PubMed

Zannoli, Marina; Mamassian, Pascal

2011-10-15

The majority of natural scenes contains zones that are visible to one eye only. Past studies have shown that these monocular regions can be seen at a precise depth even though there are no binocular disparities that uniquely constrain their locations in depth. In the so-called da Vinci stereopsis configuration, the monocular region is a vertical line placed next to a binocular rectangular occluder. The opacity of the occluder has been mentioned to be a necessary condition to obtain da Vinci stereopsis. However, this opacity constraint has never been empirically tested. In the present study, we tested whether da Vinci stereopsis and perceptual transparency can interact using a classical da Vinci configuration in which the opacity of the occluder varied. We used two different monocular objects: a line and a disk. We found no effect of the opacity of the occluder on the perceived depth of the monocular object. A careful analysis of the distribution of perceived depth revealed that the monocular object was perceived at a depth that increased with the distance between the object and the occluder. The analysis of the skewness of the distributions was not consistent with a double fusion explanation, favoring an implication of occlusion geometry in da Vinci stereopsis. A simple model that includes the geometry of the scene could account for the results. In summary, the mechanism responsible to locate monocular regions in depth is not sensitive to the material properties of objects, suggesting that da Vinci stereopsis is solved at relatively early stages of disparity processing. Copyright © 2011 Elsevier Ltd. All rights reserved.

Apoptosis of lactotrophs induced by D2 receptor activation is estrogen dependent.

PubMed

Radl, Daniela B; Zárate, Sandra; Jaita, Gabriela; Ferraris, Jimena; Zaldivar, Verónica; Eijo, Guadalupe; Seilicovich, Adriana; Pisera, Daniel

2008-01-01

Dopamine (DA) inhibits prolactin release and reduces lactotroph proliferation by activating D2 receptors. DA and its metabolite, 6-hydroxydopamine (6-OHDA), induce apoptosis in different cell types. DA receptors and DA transporter (DAT) were implicated in this action. Considering that estradiol sensitizes anterior pituitary cells to proapoptotic stimuli, we investigated the effect of estradiol on the apoptotic action of DA and 6-OHDA in anterior pituitary cells, and the involvement of the D2 receptor and DAT in the proapoptotic effect of DA. Viability of cultured anterior pituitary cells from ovariectomized rats was determined by MTS assay. Apoptosis was evaluated by Annexin-V/flow cytometry and TUNEL. Lactotrophs were identified by immunocytochemistry. DA induced apoptosis of lactotrophs in an estrogen-dependent manner. In contrast, estradiol was not required to trigger the apoptotic action of 6-OHDA. Cabergoline, a D2 receptor agonist, induced lactotroph apoptosis, while sulpiride, a D2 receptor antagonist, blocked DA-induced cell death. The blockade of DAT by GBR12909 did not affect the apoptotic action of DA, but inhibited 6-OHDA-induced apoptosis. These data show that DA, through D2 receptor activation, induces apoptosis of estrogen-sensitized anterior pituitary cells, and suggest that DA contributes to the control of lactotroph number not only by inhibiting proliferation but also by inducing apoptosis. 2008 S. Karger AG, Basel.

Agarose and Polyacrylamide Gel Electrophoresis Methods for Molecular Mass Analysis of 5–500 kDa Hyaluronan

PubMed Central

Bhilocha, Shardul; Amin, Ripal; Pandya, Monika; Yuan, Han; Tank, Mihir; LoBello, Jaclyn; Shytuhina, Anastasia; Wang, Wenlan; Wisniewski, Hans-Georg; de la Motte, Carol; Cowman, Mary K.

2011-01-01

Agarose and polyacrylamide gel electrophoresis systems for the molecular mass-dependent separation of hyaluronan (HA) in the size range of approximately 5–500 kDa have been investigated. For agarose-based systems, the suitability of different agarose types, agarose concentrations, and buffers systems were determined. Using chemoenzymatically synthesized HA standards of low polydispersity, the molecular mass range was determined for each gel composition, over which the relationship between HA mobility and logarithm of the molecular mass was linear. Excellent linear calibration was obtained for HA molecular mass as low as approximately 9 kDa in agarose gels. For higher resolution separation, and for extension to molecular masses as low as approximately 5 kDa, gradient polyacrylamide gels were superior. Densitometric scanning of stained gels allowed analysis of the range of molecular masses present in a sample, and calculation of weight-average and number-average values. The methods were validated for polydisperse HA samples with viscosity-average molecular masses of 112, 59, 37, and 22 kDa, at sample loads of 0.5 µg (for polyacrylamide) to 2.5 µg (for agarose). Use of the methods for electrophoretic mobility shift assays was demonstrated for binding of the HA-binding region of aggrecan (recombinant human aggrecan G1-IGD-G2 domains) to a 150 kDa HA standard. PMID:21684248

Effect of DA-9701 on the Normal Motility and Clonidine-induced Hypomotility of the Gastric Antrum in Rats.

PubMed

Kang, Je Wook; Han, Dae Kyeong; Kim, Ock Nyun; Lee, Kwang Jae

2016-04-30

DA-9701 is a novel prokinetic agent. In the present study, we investigated the effect of DA-9701 on the motility of the gastric antrum in the normal and clonidine-induced hypomotility in an in vivo animal model. A strain gauge force transducer was sutured on the gastric antrum to measure the contractile activity in rats. A total of 28 rats were subclassified into the 4 groups: (1) the placebo group, (2) the DA-9701 group, (3) the placebo group in the clonidine-pretreated rats, and (4) the DA-9701 group in the clonidine-pretreated rats. After the basal recording, either placebo (3% [w/v] hydroxypropylmethyl cellulose) or DA-9701 was administered. Contractile signals were measured after the administration and after a meal. In the clonidinepretreated rats, either placebo or DA-9701 was administered. Contractile signals were measured after the administration and after a meal. Oral administration of DA-9701 did not significantly alter the motility index of the gastric antrum in the preprandial and postprandial periods, compared with the placebo group. The administration of clonidine decreased the motility index of the gastric antrum in the preprandial and postprandial periods, compared with the administration of placebo. This reduction of the antral motility by the administration of clonidine was not observed in the clonidine-pretreated DA-9701 group. The percentage of the motility index in the postprandial period was significantly greater in the clonidine-pretreated DA-9701 group, compared with the clonidine-pretreated placebo group. DA-9701 improves the hypomotility of the gastric antrum induced by clonidine, suggesting its gastroprokinetic effect in the pathologic condition.

Effect of DA-9701 on the Normal Motility and Clonidine-induced Hypomotility of the Gastric Antrum in Rats

PubMed Central

Kang, Je Wook; Han, Dae Kyeong; Kim, Ock Nyun; Lee, Kwang Jae

2016-01-01

Background/Aims DA-9701 is a novel prokinetic agent. In the present study, we investigated the effect of DA-9701 on the motility of the gastric antrum in the normal and clonidine-induced hypomotility in an in vivo animal model. Methods A strain gauge force transducer was sutured on the gastric antrum to measure the contractile activity in rats. A total of 28 rats were subclassified into the 4 groups: (1) the placebo group, (2) the DA-9701 group, (3) the placebo group in the clonidine-pretreated rats, and (4) the DA-9701 group in the clonidine-pretreated rats. After the basal recording, either placebo (3% [w/v] hydroxypropylmethyl cellulose) or DA-9701 was administered. Contractile signals were measured after the administration and after a meal. In the clonidine-pretreated rats, either placebo or DA-9701 was administered. Contractile signals were measured after the administration and after a meal. Results Oral administration of DA-9701 did not significantly alter the motility index of the gastric antrum in the preprandial and postprandial periods, compared with the placebo group. The administration of clonidine decreased the motility index of the gastric antrum in the preprandial and postprandial periods, compared with the administration of placebo. This reduction of the antral motility by the administration of clonidine was not observed in the clonidine-pretreated DA-9701 group. The percentage of the motility index in the postprandial period was significantly greater in the clonidine-pretreated DA-9701 group, compared with the clonidine-pretreated placebo group. Conclusions DA-9701 improves the hypomotility of the gastric antrum induced by clonidine, suggesting its gastroprokinetic effect in the pathologic condition. PMID:26755679

Compensatory T-type Ca2+ channel activity alters D2-autoreceptor responses of Substantia nigra dopamine neurons from Cav1.3 L-type Ca2+ channel KO mice.

PubMed

Poetschke, Christina; Dragicevic, Elena; Duda, Johanna; Benkert, Julia; Dougalis, Antonios; DeZio, Roberta; Snutch, Terrance P; Striessnig, Joerg; Liss, Birgit

2015-09-18

The preferential degeneration of Substantia nigra dopamine midbrain neurons (SN DA) causes the motor-symptoms of Parkinson's disease (PD). Voltage-gated L-type calcium channels (LTCCs), especially the Cav1.3-subtype, generate an activity-related oscillatory Ca(2+) burden in SN DA neurons, contributing to their degeneration and PD. While LTCC-blockers are already in clinical trials as PD-therapy, age-dependent functional roles of Cav1.3 LTCCs in SN DA neurons remain unclear. Thus, we analysed juvenile and adult Cav1.3-deficient mice with electrophysiological and molecular techniques. To unmask compensatory effects, we compared Cav1.3 KO mice with pharmacological LTCC-inhibition. LTCC-function was not necessary for SN DA pacemaker-activity at either age, but rather contributed to their pacemaker-precision. Moreover, juvenile Cav1.3 KO but not WT mice displayed adult wildtype-like, sensitised inhibitory dopamine-D2-autoreceptor (D2-AR) responses that depended upon both, interaction of the neuronal calcium sensor NCS-1 with D2-ARs, and on voltage-gated T-type calcium channel (TTCC) activity. This functional KO-phenotype was accompanied by cell-specific up-regulation of NCS-1 and Cav3.1-TTCC mRNA. Furthermore, in wildtype we identified an age-dependent switch of TTCC-function from contributing to SN DA pacemaker-precision in juveniles to pacemaker-frequency in adults. This novel interplay of Cav1.3 L-type and Cav3.1 T-type channels, and their modulation of SN DA activity-pattern and D2-AR-sensitisation, provide new insights into flexible age- and calcium-dependent activity-control of SN DA neurons and its pharmacological modulation.

Amphetamine Self-Administration Attenuates Dopamine D2 Autoreceptor Function

PubMed Central

Calipari, Erin S; Sun, Haiguo; Eldeeb, Khalil; Luessen, Deborah J; Feng, Xin; Howlett, Allyn C; Jones, Sara R; Chen, Rong

2014-01-01

Dopamine D2 autoreceptors located on the midbrain dopaminergic neurons modulate dopamine (DA) neuron firing, DA release, and DA synthesis through a negative-feedback mechanism. Dysfunctional D2 autoreceptors following repeated drug exposure could lead to aberrant DA activity in the ventral tegmental area (VTA) and projection areas such as nucleus accumbens (NAcc), promoting drug-seeking and -taking behavior. Therefore, it is important to understand molecular mechanisms underlying drug-induced changes in D2 autoreceptors. Here, we reported that 5 days of amphetamine (AMPH) self-administration reduced the ability of D2 autoreceptors to inhibit DA release in the NAcc as determined by voltammetry. Using the antibody-capture [35S]GTPγS scintillation proximity assay, we demonstrated for the first time that midbrain D2/D3 receptors were preferentially coupled to Gαi2, whereas striatal D2/D3 receptors were coupled equally to Gαi2 and Gαo for signaling. Importantly, AMPH abolished the interaction between Gαi2 and D2/D3 receptors in the midbrain while leaving striatal D2/D3 receptors unchanged. The disruption of the coupling between D2/D3 receptors and Gαi2 by AMPH is at least partially explained by the enhanced RGS2 (regulator of G-protein signaling 2) activity resulting from an increased RGS2 trafficking to the membrane. AMPH had no effects on the midbrain expression and trafficking of other RGS proteins such as RGS4 and RGS8. Our data suggest that midbrain D2/D3 receptors are more susceptible to AMPH-induced alterations. Reduced D2 autoreceptor function could lead to enhanced DA signaling and ultimately addiction-related behavior. RGS2 may be a potential non-dopaminergic target for pharmacological intervention of dysfunctional DA transmission and drug addiction. PMID:24513972

Amphetamine self-administration attenuates dopamine D2 autoreceptor function.

PubMed

Calipari, Erin S; Sun, Haiguo; Eldeeb, Khalil; Luessen, Deborah J; Feng, Xin; Howlett, Allyn C; Jones, Sara R; Chen, Rong

2014-07-01

Dopamine D2 autoreceptors located on the midbrain dopaminergic neurons modulate dopamine (DA) neuron firing, DA release, and DA synthesis through a negative-feedback mechanism. Dysfunctional D2 autoreceptors following repeated drug exposure could lead to aberrant DA activity in the ventral tegmental area (VTA) and projection areas such as nucleus accumbens (NAcc), promoting drug-seeking and -taking behavior. Therefore, it is important to understand molecular mechanisms underlying drug-induced changes in D2 autoreceptors. Here, we reported that 5 days of amphetamine (AMPH) self-administration reduced the ability of D2 autoreceptors to inhibit DA release in the NAcc as determined by voltammetry. Using the antibody-capture [(35)S]GTPγS scintillation proximity assay, we demonstrated for the first time that midbrain D2/D3 receptors were preferentially coupled to Gαi2, whereas striatal D2/D3 receptors were coupled equally to Gαi2 and Gαo for signaling. Importantly, AMPH abolished the interaction between Gαi2 and D2/D3 receptors in the midbrain while leaving striatal D2/D3 receptors unchanged. The disruption of the coupling between D2/D3 receptors and Gαi2 by AMPH is at least partially explained by the enhanced RGS2 (regulator of G-protein signaling 2) activity resulting from an increased RGS2 trafficking to the membrane. AMPH had no effects on the midbrain expression and trafficking of other RGS proteins such as RGS4 and RGS8. Our data suggest that midbrain D2/D3 receptors are more susceptible to AMPH-induced alterations. Reduced D2 autoreceptor function could lead to enhanced DA signaling and ultimately addiction-related behavior. RGS2 may be a potential non-dopaminergic target for pharmacological intervention of dysfunctional DA transmission and drug addiction.

Characterization of the transacylase activity of rat liver 60-kDa lysophospholipase-transacylase. Acyl transfer from the sn-2 to the sn-1 position.

PubMed

Sugimoto, H; Yamashita, S

1999-05-18

Rat liver 60-kDa lysophospholipase-transacylase catalyzes not only the hydrolysis of 1-acyl-sn-glycero-3-phosphocholine, but also the transfer of its acyl chain to a second molecule of 1-acyl-sn-glycero-3-phosphocholine to form phosphatidylcholine (H. Sugimoto, S. Yamashita, J. Biol. Chem. 269 (1994) 6252-6258). Here we report the detailed characterization of the transacylase activity of the enzyme. The enzyme mediated three types of acyl transfer between donor and acceptor lipids, transferring acyl residues from: (1) the sn-1 to -1(3); (2) sn-1 to -2; and (3) sn-2 to -1 positions. In the sn-1 to -1(3) transfer, the sn-1 acyl residue of 1-acyl-sn-glycero-3-phosphocholine was transferred to the sn-1(3) positions of glycerol and 2-acyl-sn-glycerol, producing 1(3)-acyl-sn-glycerol and 1,2-diacyl-sn-glycerol, respectively. In the sn-1 to -2 transfer, the sn-1 acyl residue of 1-acyl-sn-glycero-3-phosphocholine was transferred to not only the sn-2 positions of 1-acyl-sn-glycero-3-phosphocholine, but also 1-acyl-sn-glycero-3-phosphoethanolamine, producing phosphatidylcholine and phosphatidylethanolamine, respectively. 1-Acyl-sn-glycero-3-phospho-myo-inositol and 1-acyl-sn-glycero-3-phosphoserine were much less effectively transacylated by the enzyme. In the sn-2 to -1 transfer, the sn-2 acyl residue of 2-acyl-sn-glycero-3-phosphocholine was transferred to the sn-1 position of 2-acyl-sn-glycero-3-phosphocholine and 2-acyl-sn-glycero-3-phosphoethanolamine, producing phosphatidylcholine and phosphatidylethanolamine, respectively. Consistently, the enzyme hydrolyzed the sn-2 acyl residue from 2-acyl-sn-glycero-3-phosphocholine. By the sn-2 to -1 transfer activity, arachidonic acid was transferred from the sn-2 position of donor lipids to the sn-1 position of acceptor lipids, thus producing 1-arachidonoyl phosphatidylcholine. When 2-arachidonoyl-sn-glycero-3-phosphocholine was used as the sole substrate, diarachidonoyl phosphatidylcholine was synthesized at a rate of 0

32 CFR 644.425 - Authority and procedure for disposal of surplus property by DA to eligible public agencies.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 4 2010-07-01 2010-07-01 true Authority and procedure for disposal of surplus property by DA to eligible public agencies. 644.425 Section 644.425 National Defense Department of Defense... property by DA to eligible public agencies. FPMR 101-47.303-2 provides that the disposal agency shall allow...

DA Negatively Regulates IGF-I Actions Implicated in Cognitive Function via Interaction of PSD95 and nNOS in Minimal Hepatic Encephalopathy

PubMed Central

Ding, Saidan; Zhuge, Weishan; Wang, Xuebao; Yang, Jianjing; Lin, Yuanshao; Wang, Chengde; Hu, Jiangnan; Zhuge, Qichuan

2017-01-01

Insulin-like growth factor I (IGF-I) has been positively correlated with cognitive ability. Cognitive decline in minimal hepatic encephalopathy (MHE) was shown to be induced by elevated intracranial dopamine (DA). The beneficial effect of IGF-I signaling in MHE remains unknown. In this study, we found that IGF-I content was reduced in MHE rats and that IGF-I administration mitigated cognitive decline of MHE rats. A protective effect of IGF-I on the DA-induced interaction between postsynaptic density protein 95 (PSD95) and neuronal nitric oxide synthase (nNOS) was found in neurons. Ribosomal S6 protein kinase (RSK) phosphorylated nNOS in response to IGF-I by recruiting extracellular signal-regulated kinase (ERK1/2). In turn, DA inactivated the ERK1/2/RSK pathway and stimulated the PSD95–nNOS interaction by downregulating IGF-I. Inhibition of the interaction between PSD95 and nNOS ameliorated DA-induced memory impairment. As DA induced deficits in the ERK1/2/RSK pathway and the interaction between PSD95 and nNOS in MHE brains, IGF-I administration exerted a protective effect via interruption of the interaction between PSD95 and nNOS. These results suggest that IGF-I antagonizes DA-induced cognitive loss by disrupting PSD95–nNOS interactions in MHE. PMID:28932186

DA Negatively Regulates IGF-I Actions Implicated in Cognitive Function via Interaction of PSD95 and nNOS in Minimal Hepatic Encephalopathy.

PubMed

Ding, Saidan; Zhuge, Weishan; Wang, Xuebao; Yang, Jianjing; Lin, Yuanshao; Wang, Chengde; Hu, Jiangnan; Zhuge, Qichuan

2017-01-01

Insulin-like growth factor I (IGF-I) has been positively correlated with cognitive ability. Cognitive decline in minimal hepatic encephalopathy (MHE) was shown to be induced by elevated intracranial dopamine (DA). The beneficial effect of IGF-I signaling in MHE remains unknown. In this study, we found that IGF-I content was reduced in MHE rats and that IGF-I administration mitigated cognitive decline of MHE rats. A protective effect of IGF-I on the DA-induced interaction between postsynaptic density protein 95 (PSD95) and neuronal nitric oxide synthase (nNOS) was found in neurons. Ribosomal S6 protein kinase (RSK) phosphorylated nNOS in response to IGF-I by recruiting extracellular signal-regulated kinase (ERK1/2). In turn, DA inactivated the ERK1/2/RSK pathway and stimulated the PSD95-nNOS interaction by downregulating IGF-I. Inhibition of the interaction between PSD95 and nNOS ameliorated DA-induced memory impairment. As DA induced deficits in the ERK1/2/RSK pathway and the interaction between PSD95 and nNOS in MHE brains, IGF-I administration exerted a protective effect via interruption of the interaction between PSD95 and nNOS. These results suggest that IGF-I antagonizes DA-induced cognitive loss by disrupting PSD95-nNOS interactions in MHE.

An improvement of LLNA:DA to assess the skin sensitization potential of chemicals.

PubMed

Zhang, Hongwei; Shi, Ying; Wang, Chao; Zhao, Kangfeng; Zhang, Shaoping; Wei, Lan; Dong, Li; Gu, Wen; Xu, Yongjun; Ruan, Hongjie; Zhi, Hong; Yang, Xiaoyan

2017-01-01

We developed a modified local lymph node assay based on ATP (LLNA:DA), termed the Two-Stage LLNA:DA, to further reduce the animal numbers in the identification of sensitizers. In the Two-Stage LLNA:DA procedure, 13 chemicals ranging from non-sensitizers to extreme sensitizers were selected. The first stage used reduced LLNA:DA (rLLNA:DA) to screen out sensitive chemicals. The second stage used LLNA:DA based on OECD 442 (A) to classify those potential sensitizers screened out in the first stage. In the first stage, the SIs of the methyl methacrylate, salicylic acid, methyl salicylate, ethyl salicylate, isopropanol and propanediol were below 1.8 and need not to be tested in the second step. Others continued to be tested by LLNA:DA. In the second stage, sodium lauryl sulphate and xylene were classified as weak sensitizers. a-hexyl cinnamic aldehyde and eugenol were moderate sensitizers. Benzalkonium chloride and glyoxal were strong sensitizers, and phthalic anhydride was an extreme sensitizer. The 9/9, 11/12, 10/11, and 8/13 (positive or negative only) categories of the Two-Stage LLNA:DA were consistent with those from the other methods (LLNA, LLNA:DA, GPMT/BT and HMT/HPTA), suggesting that Two-Stage LLNA:DA have a high coincidence rate with reported data. In conclusion, The Two-Stage LLNA:DA is in line with the "3R" rules, and can be a modification of LLNA:DA but needs more study.

The effect of adenosine A(2A) receptor antagonists on hydroxyl radical, dopamine, and glutamate in the striatum of rats with altered function of VMAT2.

PubMed

Gołembiowska, Krystyna; Dziubina, Anna

2012-08-01

It has been shown that a decreased vesicular monoamine transporter (VMAT2) function and the disruption of dopamine (DA) storage is an early contributor to oxidative damage of dopamine neurons in Parkinson's disease (PD). In our previous study, we demonstrated that adenosine A(2A) receptor antagonists suppressed oxidative stress in 6-hydroxydopamine-treated rats suggesting that this effect may account for neuroprotective properties of drugs. In the present study, rats were injected with reserpine (10 mg/kg sc) and 18 h later the effect of the adenosine A(2A) receptor antagonists 8-(3-chlorostyryl)caffeine (CSC) and 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM 241385) on extracellular DA, glutamate and hydroxyl radical formation was studied in the rat striatum using in vivo microdialysis. By disrupting VMAT2 function, reserpine depleted DA stores, and increased glutamate and hydroxyl radical levels in the rat striatum. CSC (1 mg/kg) but not ZM 241385 (3 mg/kg) increased extracellular DA level and production of hydroxyl radical in reserpinised rats. Both antagonists decreased the reserpine-induced increase in extracellular glutamate. L-3,4-Dihydroxyphenylalanine (L-DOPA) (25 mg/kg) significantly enhanced extracellular DA, had no effect on reserpine-induced hydroxyl radical production and decreased extracellular glutamate concentration. CSC but not ZM 241385 given jointly with L-DOPA increased the effect of L-DOPA on extracellular DA and augmented the reserpine-induced hydroxyl radical production. CSC and ZM 241385 did not influence extracellular glutamate level, which was decreased by L-DOPA. It seems that by decreasing the MAO-dependent DA metabolism rate, CSC raised cytosolic DA and by DA autoxidation, it induced hydroxyl radical overproduction. Thus, the methylxanthine A(2A) receptor antagonists bearing properties of MAO-B inhibitor, like CSC, may cause a risk of oxidative stress resulting from dysfunctional DA storage

Role of dopamine D2 receptors in human reinforcement learning.

PubMed

Eisenegger, Christoph; Naef, Michael; Linssen, Anke; Clark, Luke; Gandamaneni, Praveen K; Müller, Ulrich; Robbins, Trevor W

2014-09-01

Influential neurocomputational models emphasize dopamine (DA) as an electrophysiological and neurochemical correlate of reinforcement learning. However, evidence of a specific causal role of DA receptors in learning has been less forthcoming, especially in humans. Here we combine, in a between-subjects design, administration of a high dose of the selective DA D2/3-receptor antagonist sulpiride with genetic analysis of the DA D2 receptor in a behavioral study of reinforcement learning in a sample of 78 healthy male volunteers. In contrast to predictions of prevailing models emphasizing DA's pivotal role in learning via prediction errors, we found that sulpiride did not disrupt learning, but rather induced profound impairments in choice performance. The disruption was selective for stimuli indicating reward, whereas loss avoidance performance was unaffected. Effects were driven by volunteers with higher serum levels of the drug, and in those with genetically determined lower density of striatal DA D2 receptors. This is the clearest demonstration to date for a causal modulatory role of the DA D2 receptor in choice performance that might be distinct from learning. Our findings challenge current reward prediction error models of reinforcement learning, and suggest that classical animal models emphasizing a role of postsynaptic DA D2 receptors in motivational aspects of reinforcement learning may apply to humans as well.

Role of Dopamine D2 Receptors in Human Reinforcement Learning

PubMed Central

Eisenegger, Christoph; Naef, Michael; Linssen, Anke; Clark, Luke; Gandamaneni, Praveen K; Müller, Ulrich; Robbins, Trevor W

2014-01-01

Influential neurocomputational models emphasize dopamine (DA) as an electrophysiological and neurochemical correlate of reinforcement learning. However, evidence of a specific causal role of DA receptors in learning has been less forthcoming, especially in humans. Here we combine, in a between-subjects design, administration of a high dose of the selective DA D2/3-receptor antagonist sulpiride with genetic analysis of the DA D2 receptor in a behavioral study of reinforcement learning in a sample of 78 healthy male volunteers. In contrast to predictions of prevailing models emphasizing DA's pivotal role in learning via prediction errors, we found that sulpiride did not disrupt learning, but rather induced profound impairments in choice performance. The disruption was selective for stimuli indicating reward, whereas loss avoidance performance was unaffected. Effects were driven by volunteers with higher serum levels of the drug, and in those with genetically determined lower density of striatal DA D2 receptors. This is the clearest demonstration to date for a causal modulatory role of the DA D2 receptor in choice performance that might be distinct from learning. Our findings challenge current reward prediction error models of reinforcement learning, and suggest that classical animal models emphasizing a role of postsynaptic DA D2 receptors in motivational aspects of reinforcement learning may apply to humans as well. PMID:24713613

MATERNAL ATRAZINE (ATR) ALTERS HYPOTHALAMIC DOPAMINE (HYP-DA) AND SERUM PROLACTIN (SPRL) IN MALE PUPS

EPA Science Inventory

Maternal Atrazine (ATR) alters hypothalamic dopamine (HYP-DA) and serum prolactin (sPRL) in male pups. 1Christopher Langdale, 2Tammy Stoker and 2Ralph Cooper. 1 Dept. of Cell Biology, North Carolina State University College of Veterinary Medicine, Raleigh, NC. 2 Endocrinology ...

Evaluation of the transporter-mediated herb-drug interaction potential of DA-9801, a standardized dioscorea extract for diabetic neuropathy, in human in vitro and rat in vivo.

PubMed

Song, Im-Sook; Kong, Tae Yeon; Jeong, Hyeon-Uk; Kim, Eun Nam; Kwon, Soon-Sang; Kang, Hee Eun; Choi, Sang-Zin; Son, Miwon; Lee, Hye Suk

2014-07-17

Drug transporters play important roles in the absorption, distribution, and elimination of drugs and thereby, modulate drug efficacy and toxicity. With a growing use of poly pharmacy, concurrent administration of herbal extracts that modulate transporter activities with drugs can cause serious adverse reactions. Therefore, prediction and evaluation of drug-drug interaction potential is important in the clinic and in the drug development process. DA-9801, comprising a mixed extract of Dioscoreae rhizoma and Dioscorea nipponica Makino, is a new standardized extract currently being evaluated for diabetic peripheral neuropathy in a phase II clinical study. The inhibitory effects of DA-9801 on the transport functions of organic cation transporter (OCT)1, OCT2, organic anion transporter (OAT)1, OAT3, organic anion transporting polypeptide (OATP)1B1, OATP1B3, P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP) were investigated in HEK293 or LLC-PK1 cells. The effects of DA-9801 on the pharmacokinetics of relevant substrate drugs of these transporters were also examined in vivo in rats. DA-9801 inhibited the in vitro transport activities of OCT1, OCT2, OAT3, and OATP1B1, with IC50 values of 106, 174, 48.1, and 273 μg/mL, respectively, while the other transporters were not inhibited by 300 μg/mL DA-9801. To investigate whether this inhibitory effect of DA-9801 on OCT1, OCT2, and OAT3 could change the pharmacokinetics of their substrates in vivo, we measured the pharmacokinetics of cimetidine, a substrate for OCT1, OCT2, and OAT3, and of furosemide, a substrate for OAT1 and OAT3, by co-administration of DA-9801 at a single oral dose of 1,000 mg/kg. Pre-dose of DA-9801 5 min or 2 h prior to cimetidine administration decreased the Cmax of cimetidine in rats. However, DA-9801 did not affect the elimination parameters such as half-life, clearance, or amount excreted in the urine, suggesting that it did not inhibit elimination process of cimetidine, which is

Myelin management by the 18.5–kDa and 21.5–kDa classic myelin basic protein isoforms

PubMed Central

Harauz, George; Boggs, Joan M.

2013-01-01

The classic myelin basic protein (MBP) splice isoforms range in nominal molecular mass from 14 to 21.5 kDa, and arise from the gene in the oligodendrocyte lineage (Golli) in maturing oligodendrocytes. The 18.5-kDa isoform that predominates in adult myelin adheres the cytosolic surfaces of oligodendrocyte membranes together, and forms a two-dimensional molecular sieve restricting protein diffusion into compact myelin. However, this protein has additional roles including cytoskeletal assembly and membrane extension, binding to SH3-domains, participation in Fyn-mediated signaling pathways, sequestration of phosphoinositides, and maintenance of calcium homeostasis. Of the diverse post-translational modifications of this isoform, phosphorylation is the most dynamic, and modulates 18.5-kDa MBP’s protein-membrane and protein-protein interactions, indicative of a rich repertoire of functions. In developing and mature myelin, phosphorylation can result in microdomain or even nuclear targeting of the protein, supporting the conclusion that 18.5-kDa MBP has significant roles beyond membrane adhesion. The full-length, early-developmental 21.5-kDa splice isoform is predominantly karyophilic due to a non-traditional P-Y nuclear localization signal, with effects such as promotion of oligodendrocyte proliferation. We discuss in vitro and recent in vivo evidence for multifunctionality of these classic basic proteins of myelin, and argue for a systematic evaluation of the temporal and spatial distributions of these protein isoforms, and their modified variants, during oligodendrocyte differentiation. PMID:23398367

Long-term evolution of 1991 DA: A dynamically evolved extinct Halley-type comet

NASA Technical Reports Server (NTRS)

Hahn, Gerhard; Bailey, M. E.

1992-01-01

The long-term dynamical evolution of 21 variational orbits for the intermediate-period asteroid 1991 DA was followed for up to +/-10(exp 5) years from the present. 1991 DA is close to the 2:7 resonance with Jupiter; it has avoided close encounters, within 1 AU, with this planet for at least the past 30,000 years, even at the node crossing. The future evolution typically shows no close encounters with Jupiter within at least 50,000 years. This corresponds to the mean time between node crossings with either Jupiter or Saturn. Close encounters with Saturn and Jupiter lead to a chaotic evolution for the whole ensemble, while secular perturbations cause large-amplitude swings in eccentricity and inclination (the latter covering the range 15 deg approximately less than i approximately less than 85 deg) which correlate with deep excursions of the perihelion distance to values much less than 1 AU. These variations are similar to those found in P/Machholz and a variety of other high-inclination orbits, e.g., P/Hartley-IRAS. We emphasize the connection between the orbital evolution of 1991 DA and that of Halley-type comets. If 1991 DA was once a comet, it is not surprising that it is now extinct.

Experience with ATLAS MySQL PanDA database service

NASA Astrophysics Data System (ADS)

Smirnov, Y.; Wlodek, T.; De, K.; Hover, J.; Ozturk, N.; Smith, J.; Wenaus, T.; Yu, D.

2010-04-01

The PanDA distributed production and analysis system has been in production use for ATLAS data processing and analysis since late 2005 in the US, and globally throughout ATLAS since early 2008. Its core architecture is based on a set of stateless web services served by Apache and backed by a suite of MySQL databases that are the repository for all PanDA information: active and archival job queues, dataset and file catalogs, site configuration information, monitoring information, system control parameters, and so on. This database system is one of the most critical components of PanDA, and has successfully delivered the functional and scaling performance required by PanDA, currently operating at a scale of half a million jobs per week, with much growth still to come. In this paper we describe the design and implementation of the PanDA database system, its architecture of MySQL servers deployed at BNL and CERN, backup strategy and monitoring tools. The system has been developed, thoroughly tested, and brought to production to provide highly reliable, scalable, flexible and available database services for ATLAS Monte Carlo production, reconstruction and physics analysis.

Technical review of the da Vinci surgical telemanipulator.

PubMed

Freschi, C; Ferrari, V; Melfi, F; Ferrari, M; Mosca, F; Cuschieri, A

2013-12-01

The da Vinci robotic surgical telemanipulator has been utilized in several surgical specialties for varied procedures, and the users' experiences have been widely published. To date, no detailed system technical analyses have been performed. A detailed review was performed of all publications and patents about the technical aspects of the da Vinci robotic system. Published technical literature on the da Vinci system highlight strengths and weaknesses of the robot design. While the system facilitates complex surgical operations and has a low malfunction rate, the lack of haptic (especially tactile) feedback and collisions between the robotic arms remain the major limitations of the system. Accurate, preplanned positioning of access ports is essential. Knowledge of the technical aspects of the da Vinci robot is important for optimal use. We confirmed the excellent system functionality and ease of use for surgeons without an engineering background. Research and development of the surgical robot has been predominant in the literature. Future trends address robot miniaturization and intelligent control design. Copyright © 2012 John Wiley & Sons, Ltd.

Effects of DA-6034, a flavonoid derivative, on mucin-like glycoprotein and ocular surface integrity in a rabbit model.

PubMed

Choi, Seul Min; Seo, Mi Jeong; Lee, Yeong Geon; Lee, Min Jung; Jeon, Hyung Jun; Kang, Kyung Koo; Ahn, Byoung Ok; Yoo, Moohi

2009-01-01

This study was designed to assess whether DA-6034 (7-carboxymethyloxy-3',4',5-trimethoxy flavone monohydrate), a new synthetic derivative of eupatilin, increases secretion of mucin-like glycoprotein and some mucins species in conjunctiva and cornea, and contributes to the preservation of ocular surface integrity. Human conjunctival and corneal epithelial cells were incubated with DA-6034 (1-250 microM). To investigate mucin secreting activity more directly, isolated rat conjunctival goblet cells were also used. Corneal protection was investigated using a desiccation-induced rabbit model of dry eye syndrome. It was found that DA-6034 increased mucin-like glycoprotein levels of both conjunctival and corneal epithelial cells at concentrations above 100 microM. Using human conjunctival epithelial cells, it was demonstrated that treatment with DA-6034 (200 microM) significantly increased production of some mucins species including MUC1, MUC2, MUC4, MUC5AC, MUC5B, and MUC16. DA-6034 also significantly increased MUC5AC production from conjunctival goblet cells isolated from rats. In the rabbit desiccation model, an ophthalmic suspension containing 3% DA-6034 significantly reduced corneal damage induced by desiccation. These results suggest that DA-6034 is a good candidate for treatment of dry eye through maintaining ocular surface integrity, which might be related to mucin secretion.

A distância e o conteúdo estelar da região HII gigante G333.1-0.4 - vínculos para a taxa de formação estelar da galáxia

NASA Astrophysics Data System (ADS)

Figuerêdo, E.; Damineli, A.; Blum, R.; Conti, P.

2003-08-01

Neste trabalho apresentamos imagens de alta resolução angular da região HII gigante G333.1-0.4 obtidas através dos filtros J, H e K no telescópio de 4-m do CTIO. Este trabalho faz parte de um estudo de regiões HII gigantes no infravermelho próximo que tem por objetivo estudar a natureza da formação de estrelas massivas e traçar a estrutura espiral de nossa galáxia. Nossa determinação da distância é baseada no método da paralaxe espectroscópica de estrelas OB localizadas na seqüência principal de idade zero (ZAMS) do Diagrama HR. No caso de G333.1-0.4, a magnitude aparente das estrelas localizadas na ZAMS indica que a distância não pode ser maior do que o limite inferior determinado por técnica rádio (2,8 kpc). Resultados semelhantes foram encontrados para regiões estudadas anteriormente, reforçando a idéia de que a taxa de formação estelar na Via Láctea é menor do que o determinado a partir de dados rádio. Nossos resultados mais recentes sobre o conteúdo estelar de G333.1-0.4 revelaram vários objetos que possuem cores bastante avermelhadas (H-K > 2,0). Nós identificamos estes objetos usando os diagramas cor-cor e cor-magnitude dos aglomerados. Estes objetos apresentam um forte excesso em emissão na banda K e possivelmente se tratam de estrelas do tipo OB envolvidas por um disco/envelope circumestelar espesso. O estudo da função de massa inical desta região, em conjunto com resultados de nossos trabalhos anteriores, aponta para uma IMF independente da posição galática. A contagem de estrelas nos fornece um valor para o número de fótons no contínuo de Lyman que corrobora com a afirmação de que G333.1-0.4 se encontra mais próxima da menor distância determinada por rádio.

Pancreatic islets and insulinoma cells express a novel isoform of group VIA phospholipase A2 (iPLA2 beta) that participates in glucose-stimulated insulin secretion and is not produced by alternate splicing of the iPLA2 beta transcript.

PubMed

Ramanadham, Sasanka; Song, Haowei; Hsu, Fong-Fu; Zhang, Sheng; Crankshaw, Mark; Grant, Gregory A; Newgard, Christopher B; Bao, Shunzhong; Ma, Zhongmin; Turk, John

2003-12-02

Many cells express a group VIA 84 kDa phospholipase A(2) (iPLA(2)beta) that is sensitive to inhibition by a bromoenol lactone (BEL) suicide substrate. Inhibition of iPLA(2)beta in pancreatic islets and insulinoma cells suppresses, and overexpression of iPLA(2)beta in INS-1 insulinoma cells amplifies, glucose-stimulated insulin secretion, suggesting that iPLA(2)beta participates in secretion. Western blotting analyses reveal that glucose-responsive 832/13 INS-1 cells express essentially no 84 kDa iPLA(2)beta-immunoreactive protein but predominantly express a previously unrecognized immunoreactive iPLA(2)beta protein in the 70 kDa region that is not generated by a mechanism of alternate splicing of the iPLA(2)beta transcript. To determine if the 70 kDa-immunoreactive protein is a short isoform of iPLA(2)beta, protein from the 70 kDa region was digested with trypsin and analyzed by mass spectrometry. Such analyses reveal several peptides with masses and amino acid sequences that exactly match iPLA(2)beta tryptic peptides. Peptide sequences identified in the 70 kDa tryptic digest include iPLA(2)beta residues 7-53, suggesting that the N-terminus is preserved. We also report here that the 832/13 INS-1 cells express iPLA(2)beta catalytic activity and that BEL inhibits secretagogue-stimulated insulin secretion from these cells but not the incorporation of arachidonic acid into membrane PC pools of these cells. These observations suggest that the catalytic iPLA(2)beta activity expressed in 832/13 INS-1 cells is attributable to a short isoform of iPLA(2)beta and that this isoform participates in insulin secretory but not in membrane phospholipid remodeling pathways. Further, the finding that pancreatic islets also express predominantly a 70 kDa iPLA(2)beta-immunoreactive protein suggests that a signal transduction role of iPLA(2)beta in the native beta-cell might be attributable to a 70 kDa isoform of iPLA(2)beta.

Perfil dos Professores de Ciências Naturais do Recôncavo da Bahia - Alunos da Disciplina Terra e Universo no Curso de Ciências Naturais do Parfor

NASA Astrophysics Data System (ADS)

Lima, S. R.; Cerqueira Júnior, W.; Dutra, G.

2011-12-01

Este trabalho foi desenvolvido pelo projeto Astronomia no Recôncavo da Bahia, no Centro de Formação de Professores da Universidade Federal do Recôncavo da Bahia. Traçamos o perfil de um grupo de professores que lecionam conteúdos de Ciências Naturais no recôncavo, alunos do curso de Licenciatura em Ciências Naturais, oferecido dentro do Plano Nacional de Formação de Professores da Educação Básica. Nosso objetivo era avaliar se eles estão preparados para trabalhar conteúdos de Astronomia e identificar suas dificuldades. Os resultados serviram para orientar o professor da disciplina “Terra e Universo”, oferecida no segundo semestre de 2010. Durante a primeira aula da disciplina Terra e Universo, os alunos responderam a um questionário contendo questões abertas e fechadas, divididas em duas partes. A primeira procurando caracterizar profissionalmente os alunos enquanto professores da rede pública da região do Recôncavo Sul da Bahia e uma segunda parte procurando identificar conhecimentos básicos em Astronomia. Os resultados indicam uma predominância de professores do sexo feminino, com idade superior aos 40 anos, pardos e sem formação específica para o ensino de ciências. A maioria leciona há mais de 15 anos para turmas do 1º ao 5º ano, alguns lecionam para turmas de 6º ao 9º ano. Quase todos nunca participaram de um curso de formação continuada em Astronomia. Além disso, não estão habituados a ler revistas especializadas e nem livros com esta temática. Os que procuram ensinar temas voltados para a Astronomia têm, no livro didático, a maior fonte de informação sobre o assunto. As respostas também indicam uma deficiência em conteúdos básicos como a compreensão da esfericidade da Terra, noções de verticalidade e gravidade, incapacidade de identificar a Terra como um planeta, no Sistema Solar, em uma galáxia, no Universo. Estes resultados ressaltam a importância de disciplinas de Astronomia básica na formação dos

The Case: Bunche-Da Vinci Learning Partnership Academy

ERIC Educational Resources Information Center

Eisenberg, Nicole; Winters, Lynn; Alkin, Marvin C.

2005-01-01

The Bunche-Da Vinci case described in this article presents a situation at Bunche Elementary School that four theorists were asked to address in their evaluation designs (see EJ791771, EJ719772, EJ791773, and EJ792694). The Bunche-Da Vinci Learning Partnership Academy, an elementary school located between an urban port city and a historically…

Constitutive expression of DaCBF7, an Antarctic vascular plant Deschampsia antarctica CBF homolog, resulted in improved cold tolerance in transgenic rice plants.

PubMed

Byun, Mi Young; Lee, Jungeun; Cui, Li Hua; Kang, Yoonjee; Oh, Tae Kyung; Park, Hyun; Lee, Hyoungseok; Kim, Woo Taek

2015-07-01

Deschampsia antarctica is an Antarctic hairgrass that grows on the west coast of the Antarctic peninsula. In this report, we have identified and characterized a transcription factor, D. antarctica C-repeat binding factor 7 (DaCBF7), that is a member of the monocot group V CBF homologs. The protein contains a single AP2 domain, a putative nuclear localization signal, and the typical CBF signature. DaCBF7, like other monocot group V homologs, contains a distinct polypeptide stretch composed of 43 amino acids in front of the AP2 motif. DaCBF7 was predominantly localized to nuclei and interacted with the C-repeat/dehydration responsive element (CRT/DRE) core sequence (ACCGAC) in vitro. DaCBF7 was induced by abiotic stresses, including drought, cold, and salinity. To investigate its possible cellular role in cold tolerance, a transgenic rice system was employed. DaCBF7-overexpressing transgenic rice plants (Ubi:DaCBF7) exhibited markedly increased tolerance to cold stress compared to wild-type plants without growth defects; however, overexpression of DaCBF7 exerted little effect on tolerance to drought or salt stress. Transcriptome analysis of a Ubi:DaCBF7 transgenic line revealed 13 genes that were up-regulated in DaCBF7-overexpressing plants compared to wild-type plants in the absence of cold stress and in short- or long-term cold stress. Five of these genes, dehydrin, remorin, Os03g63870, Os11g34790, and Os10g22630, contained putative CRT/DRE or low-temperature responsive elements in their promoter regions. These results suggest that overexpression of DaCBF7 directly and indirectly induces diverse genes in transgenic rice plants and confers enhanced tolerance to cold stress. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Selective increase of in vivo firing frequencies in DA SN neurons after proteasome inhibition in the ventral midbrain.

PubMed

Subramaniam, Mahalakshmi; Kern, Beatrice; Vogel, Simone; Klose, Verena; Schneider, Gaby; Roeper, Jochen

2014-09-01

The impairment of protein degradation via the ubiquitin-proteasome system (UPS) is present in sporadic Parkinson's disease (PD), and might play a key role in selective degeneration of vulnerable dopamine (DA) neurons in the substantia nigra pars compacta (SN). Further evidence for a causal role of dysfunctional UPS in familial PD comes from mutations in parkin, which results in a loss of function of an E3-ubiquitin-ligase. In a mouse model, genetic inactivation of an essential component of the 26S proteasome lead to widespread neuronal degeneration including DA midbrain neurons and the formation of alpha-synuclein-positive inclusion bodies, another hallmark of PD. Studies using pharmacological UPS inhibition in vivo had more mixed results, varying from extensive degeneration to no loss of DA SN neurons. However, it is currently unknown whether UPS impairment will affect the neurophysiological functions of DA midbrain neurons. To answer this question, we infused a selective proteasome inhibitor into the ventral midbrain in vivo and recorded single DA midbrain neurons 2 weeks after the proteasome challenge. We found a selective increase in the mean in vivo firing frequencies of identified DA SN neurons in anesthetized mice, while those in the ventral tegmental area (VTA) were unaffected. Our results demonstrate that a single-hit UPS inhibition is sufficient to induce a stable and selective hyperexcitability phenotype in surviving DA SN neurons in vivo. This might imply that UPS dysfunction sensitizes DA SN neurons by enhancing 'stressful pacemaking'. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

The future of PanDA in ATLAS distributed computing

NASA Astrophysics Data System (ADS)

De, K.; Klimentov, A.; Maeno, T.; Nilsson, P.; Oleynik, D.; Panitkin, S.; Petrosyan, A.; Schovancova, J.; Vaniachine, A.; Wenaus, T.

2015-12-01

Experiments at the Large Hadron Collider (LHC) face unprecedented computing challenges. Heterogeneous resources are distributed worldwide at hundreds of sites, thousands of physicists analyse the data remotely, the volume of processed data is beyond the exabyte scale, while data processing requires more than a few billion hours of computing usage per year. The PanDA (Production and Distributed Analysis) system was developed to meet the scale and complexity of LHC distributed computing for the ATLAS experiment. In the process, the old batch job paradigm of locally managed computing in HEP was discarded in favour of a far more automated, flexible and scalable model. The success of PanDA in ATLAS is leading to widespread adoption and testing by other experiments. PanDA is the first exascale workload management system in HEP, already operating at more than a million computing jobs per day, and processing over an exabyte of data in 2013. There are many new challenges that PanDA will face in the near future, in addition to new challenges of scale, heterogeneity and increasing user base. PanDA will need to handle rapidly changing computing infrastructure, will require factorization of code for easier deployment, will need to incorporate additional information sources including network metrics in decision making, be able to control network circuits, handle dynamically sized workload processing, provide improved visualization, and face many other challenges. In this talk we will focus on the new features, planned or recently implemented, that are relevant to the next decade of distributed computing workload management using PanDA.

Expanded test method for peptides >2 kDa employing immunoaffinity purification and LC-HRMS/MS.

PubMed

Thomas, Andreas; Walpurgis, Katja; Tretzel, Laura; Brinkkötter, Paul; Fichant, Eric; Delahaut, Philippe; Schänzer, Wilhelm; Thevis, Mario

2015-01-01

Bioactive peptides with an approximate molecular mass of 2-12 kDa are of considerable relevance in sports drug testing. Such peptides have been used to manipulate several potential performance-enhancing processes in the athlete's body and include for example growth hormone releasing hormones (sermorelin, CJC-1293, CJC-1295, tesamorelin), synthetic/animal insulins (lispro, aspart, glulisine, glargine, detemir, degludec, bovine and porcine insulin), synthetic ACTH (synacthen), synthetic IGF-I (longR(3) -IGF-I) and mechano growth factors (human MGF, modified human MGF, 'full-length' MGF). A combined initial test method using one analytical procedure is a desirable tool in doping controls and related disciplines as requests for higher sample throughput with utmost comprehensiveness preferably at reduced costs are constantly issued. An approach modified from an earlier assay proved fit-for-purpose employing pre-concentration of all target analytes by means of ultrafiltration, immunoaffinity purification with coated paramagnetic beads, nano-ultra high performance liquid chromatography (UHPLC) separation, and subsequent detection by means of high resolution tandem mass spectrometry. The method was shown to be applicable to blood and urine samples, which represent the most common doping control specimens. The method was validated considering the parameters specificity, recovery (11-69%), linearity, imprecision (<25%), limit of detection (5-100 pg in urine, 0.1-2 ng in plasma), and ion suppression. The analysis of administration study samples for insulin degludec, detemir, aspart, and synacthen provided the essential data for the proof-of-principle of the method. Copyright © 2015 John Wiley & Sons, Ltd.

Identification of a major 50-kDa molecular weight human B-cell growth factor with Tac antigen-inducing activity on B cells.

PubMed

Kawano, M; Matsushima, K; Oppenheim, J J

1987-08-01

A bioassay was developed using human small B cells adherent to anti-human IgM (anti-mu)-coated wells. These B cells were stimulated to proliferate by culture supernatants of concanavalin A (Con A)-activated human peripheral blood lymphocytes (Con A Sup) even in the presence of high concentrations of anti-mu coated on assay wells. Human B-cell growth factor (BCGF) activities were partially purified from Con A Sup. Preparative chromatography (Sephacryl S-200 and isoelectrofocusing) yielded a major peak of BCGF activity for B cells adherent to anti-mu-coated wells with a molecular weight of 50,000 (50 kDa) and a pI 7.6. The 50-kDa BCGF was further purified by sequential chromatography using DEAE-Sephacel, CM-Sepharose, Sephacryl S-200, CM-high performance liquid chromatography (HPLC), and hydroxyapatite (HA)-HPLC. The HA-HPLC-purified 50-kDa BCGF was free of interleukin-1 (IL-1), interleukin-2 (IL-2), and interferon activities, but could support growth of BCL1 cells, similar to BCGF-II. Neither IL-1 nor interferon-gamma had any growth-stimulating effect in our B-cell proliferation assay with or without BCGF in Iscove's synthetic assay medium. BCGF-induced proliferation of B cells adherent to anti-mu-coated wells could be markedly augmented by the simultaneous or sequential addition of recombinant human IL-2 (rIL-2). When cultured for 3 days with 50-kDa BCGF, about 40% of B cells adherent to anti-mu-coated wells expressed Tac antigen, and monoclonal anti-Tac antibody inhibited rIL-2 enhancement of proliferation of 50-kDa BCGF-preactivated B cells. In addition, 50-kDa BCGF could induce Tac antigen on an Epstein-Barr virus-transformed B-cell line (ORSON) in the presence of a suboptimal dose of phorbol myristate acetate (PMA) and also on a natural killer-like cell line (YT cells). We have therefore identified a major 50-kDa BCGF activity with Tac antigen-inducing activity that also has a synergistic effect with IL-2 on normal B-cell proliferation.

Da Vinci Xi and Si platforms have equivalent perioperative outcomes during robot-assisted partial nephrectomy: preliminary experience.

PubMed

Abdel Raheem, Ali; Sheikh, Abulhasan; Kim, Dae Keun; Alatawi, Atalla; Alabdulaali, Ibrahim; Han, Woong Kyu; Choi, Young Deuk; Rha, Koon Ho

2017-03-01

The aims of this study were to compare the perioperative outcomes of da Vinci Xi to Si during robotic-assisted partial nephrectomy (RAPN) and to discuss the feasibility of our novel port placement scheme for the da Vinci Xi platform, to overcome the existing kinetic and technical difficulties we faced with the linear port placement in patients with a small body habitus. A retrospective data analysis of patients who underwent RPN using da Vinci Xi (n = 18) was carried out. The outcomes of the Xi group were compared with the Si group (n = 18) selected using a case-matched methodology. For da Vinci Xi, we applied the universal linear port placement in 12 patients and our modified port placement in the remaining 6 patients. The Xi group had a shorter mean docking time of 17.8 ± 2.6 min compared to the Si group of 20.5 ± 2.1 min (p = 0.002); otherwise, no significant difference was present with regard to the remaining perioperative variables (p > 0.05). The modified Xi port placement had a shorter mean console time of 70.8 ± 9.7 min compared to the universal linear port placement of 89.3 ± 17.2 min (p = 0.03). Moreover, it provided a broader field of vision with excellent robotic arms movement, minimizing collisions and allowing an easier and comfortable surgical assist. Da Vinci Xi appears to be feasible and safe during RPN with similar outcomes to Si. The novel Xi port placement makes surgery easier in patients with low BMI.

ECTA/DaSy Framework Self-Assessment Comparison Tool

ERIC Educational Resources Information Center

Center for IDEA Early Childhood Data Systems (DaSy), 2016

2016-01-01

The Self-Assessment Comparison (SAC) Tool is for state Part C and Section 619/Preschool programs to use to assess changes in the implementation of one or more components of the ECTA System Framework and/or subcomponenets of the DaSy Data System Framework. It is a companion to the ECTA/DaSy Framework Self-Assessment. Key features of the SAC are…

The ATLAS PanDA Monitoring System and its Evolution

NASA Astrophysics Data System (ADS)

Klimentov, A.; Nevski, P.; Potekhin, M.; Wenaus, T.

2011-12-01

The PanDA (Production and Distributed Analysis) Workload Management System is used for ATLAS distributed production and analysis worldwide. The needs of ATLAS global computing imposed challenging requirements on the design of PanDA in areas such as scalability, robustness, automation, diagnostics, and usability for both production shifters and analysis users. Through a system-wide job database, the PanDA monitor provides a comprehensive and coherent view of the system and job execution, from high level summaries to detailed drill-down job diagnostics. It is (like the rest of PanDA) an Apache-based Python application backed by Oracle. The presentation layer is HTML code generated on the fly in the Python application which is also responsible for managing database queries. However, this approach is lacking in user interface flexibility, simplicity of communication with external systems, and ease of maintenance. A decision was therefore made to migrate the PanDA monitor server to Django Web Application Framework and apply JSON/AJAX technology in the browser front end. This allows us to greatly reduce the amount of application code, separate data preparation from presentation, leverage open source for tools such as authentication and authorization mechanisms, and provide a richer and more dynamic user experience. We describe our approach, design and initial experience with the migration process.

Maximizing Use of Robot-Arm No. 3 in Da Vinci–Assisted Thoracic Surgery

PubMed Central

Kajiwara, Naohiro; Maeda, Junichi; Yoshida, Koichi; Kato, Yasufumi; Hagiwara, Masaru; Kakihana, Masatoshi; Ohira, Tatsuo; Kawate, Norihiko; Ikeda, Norihiko

2015-01-01

We have previously reported on the importance of appropriate robot-arm settings and replacement of instrument ports in robot-assisted thoracic surgery, because the thoracic cavity requires a large space to access all lesions in various areas of the thoracic cavity from the apex to the diaphragm and mediastinum and the chest wall.1–3 Moreover, it can be difficult to manipulate the da Vinci Surgical System using only arms No. 1 and No. 2 depending on the tumor location. However, arm No. 3 is usually positioned on the same side as arm No. 2, and sometimes it is only used as an assisting-arm to avoid conflict with other arms (Fig. 1). In this report, we show how robot-arm No. 3 can be used with maximum effectiveness in da Vinci-assisted thoracic surgery. PMID:26011219

Effects of DA-6034 on aqueous tear fluid secretion and conjunctival goblet cell proliferation.

PubMed

Choi, Seul Min; Lee, Yeong Geon; Seo, Mi Jung; Kang, Kyung Koo; Ahn, Byoung Ok; Yoo, Moohi

2009-06-01

This study was conducted to evaluate the effect of DA-6034, a potent secretagogue, on aqueous tear fluid secretion and its quality in normal rabbit. We also evaluated, in animal models of experimentally induced dry eye disease, its effectiveness over time to stimulate aqueous tear production by ocular ferning test and goblet cell proliferation. Aqueous tear production, total protein levels, and glycoprotein levels in normal rabbits were evaluated after topical application of DA-6034 (0.3, 1, and 3%). Moreover, time course aqueous tear volume measurement and ocular ferning test in tear fluid were performed in dry eyes of rabbits that had been given 1% atropine sulfate, topically. Altogether, tear fluid production and conjunctival goblet cell numbers were measured in dry eyes of mice that had been given topical scopolamine. Topical application of DA-6034 (0.3, 1, and 3%) significantly increased (P < 0.05) aqueous tear production in a concentration-dependent manner in normal rabbits. There was no change in total protein levels while glycoprotein levels were significantly increased (P < 0.05) at 3% DA-6034. The increase in aqueous tear fluid was significant (P < 0.05) and lasted for 2 h post-instillation in dry eyes of rabbits that had been given 1% atropine sulfate; 10-day repeated instillation of the drug in this model resulted in large and homogeneous fern-like tear patterns. In a mouse model, DA-6034 given as a 3% eyedrop solution significantly increased (P < 0.05) tear fluid production and conjunctival goblet cell number. These results suggest that DA-6034 accelerates not only tear secretion but also mucin production and may be a potential therapeutic agent for the treatment of dry eye disease.

32 CFR 643.121 - Private organizations on DA installations.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 4 2010-07-01 2010-07-01 true Private organizations on DA installations. 643.121 Section 643.121 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY... DA installations. (a) AR 210-1 defines and classifies private organizations, such as thrift shops and...

Use of the new da Vinci Xi® during robotic rectal resection for cancer: a pilot matched-case comparison with the da Vinci Si®.

PubMed

Morelli, Luca; Guadagni, Simone; Di Franco, Gregorio; Palmeri, Matteo; Caprili, Giovanni; D'Isidoro, Cristiano; Cobuccio, Luigi; Marciano, Emanuele; Di Candio, Giulio; Mosca, Franco

2017-03-01

The aim of this study was to compare the short-term outcomes of robotic rectal resection with total mesorectal excision (TME) for rectal cancer, with the use of the new da Vinci Xi® (Xi-RobTME group) and the da Vinci Si® (Si-RobTME group). Ten patients with histologically confirmed rectal cancer underwent robot-assisted TME with the use of the new da Vinci Xi. The outcomes of Xi-RobTME group were compared with a Si-RobTME group selected using a case-matched methodology. Overall operative times and mean hospital stays were shorter in the Xi-RobTME group. Surgeries were fully robotic with a complete take-down of the splenic flexure in all Xi-RobTME cases, while only four cases of the Si-RobTME group were fully robotic, with two cases of complete take-down of the splenic flexure. The new da Vinci Xi could offer some advantages with respect to the da Vinci Si in rectal resection for cancer. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

A 32 kDa viral attachment protein of lymphocystis disease virus (LCDV) specifically interacts with a 27.8 kDa cellular receptor from flounder (Paralichthys olivaceus).

PubMed

Zhong, Ying; Fei, Chenjie; Tang, Xiaoqian; Zhan, Wenbin; Sheng, Xiuzhen

2017-06-01

The 27.8 kDa protein in flounder gill (FG) cells was previously proved to be a receptor specific for lymphocystis disease virus (LCDV) entry and infection. In this paper, a 32 kDa viral attachment protein (VAP) of LCDV specifically binding to the 27.8 kDa receptor (27.8R) was found by far-Western blotting coupled with monoclonal antibodies (MAbs) against 27.8R. The 32 kDa protein was confirmed to be encoded by the open reading frame (ORF) 038 gene in LCDV-C, and predicted to contain a putative transmembrane region, multiple N-myristoylation and glycosylation sites and phosphorylation motifs. The expression plasmid of pET-32a-ORF038 was constructed and the recombinant VAP (rVAP) was obtained. Rabbit polyclonal antibodies against the rVAP were prepared and could recognize the rVAP and 32 kDa protein in LCDV. Immunogold electron microscopy showed that the 32 kDa protein was located on the surface of LCDV particles. Immunofluorescence assay demonstrated that the rVAP could bind to the 27.8R on the cell membrane of the FG monolayer and the anti-27.8R MAbs could block the rVAP binding. Pre-incubation of the rVAP with FG cells before LCDV infection, or pre-incubation of LCDV with the antibodies against the rVAP, could significantly decrease the LCDV copy numbers (P<0.05) and delay the emergence of cytopathic effects in FG cells in a dose-dependent manner. These results indicated for the first time that the 32 kDa protein functioned as an attachment protein for the initial attachment and entry of LCDV, and the interaction of the 32 kDa VAP with the 27.8R-initiated LCDV infection.

Selective Deletion of GRK2 Alters Psychostimulant-Induced Behaviors and Dopamine Neurotransmission

PubMed Central

Daigle, Tanya L; Ferris, Mark J; Gainetdinov, Raul R; Sotnikova, Tatyana D; Urs, Nikhil M; Jones, Sara R; Caron, Marc G

2014-01-01

GRK2 is a G protein-coupled receptor kinase (GRK) that is broadly expressed and is known to regulate diverse types of receptors. GRK2 null animals exhibit embryonic lethality due to a severe developmental heart defect, which has precluded the study of this kinase in the adult brain. To elucidate the specific role of GRK2 in the brain dopamine (DA) system, we used a conditional gene knockout approach to selectively delete GRK2 in DA D1 receptor (D1R)-, DA D2 receptor (D2R)-, adenosine 2A receptor (A2AR)-, or DA transporter (DAT)-expressing neurons. Here we show that select GRK2-deficient mice display hyperactivity, hyposensitivity, or hypersensitivity to the psychomotor effects of cocaine, altered striatal signaling, and DA release and uptake. Mice with GRK2 deficiency in D2R-expressing neurons also exhibited increased D2 autoreceptor activity. These findings reveal a cell-type-specific role for GRK2 in the regulation of normal motor behavior, sensitivity to psychostimulants, dopamine neurotransmission, and D2 autoreceptor function. PMID:24776686

Yarkovsky-driven Impact Predictions: Apophis and 1950 DA

NASA Astrophysics Data System (ADS)

Chesley, Steven R.; Farnocchia, D.; Chodas, P. W.; Milani, A.

2013-10-01

Orbit determination for Near-Earth Asteroids presents unique technical challenges due to the imperative of early detection and careful assessment of the risk posed by specific Earth close approaches. The occurrence of an Earth impact can be decisively driven by the Yarkovsky effect, which is the most important nongravitational perturbation as it causes asteroids to undergo a secular variation in semimajor axis resulting in a quadratic effect in anomaly. We discuss the cases of (99942) Apophis and (29075) 1950 DA. The relevance of the Yarkovsky effect for Apophis is due to a scattering close approach in 2029 with minimum geocentric distance ~38000 km. For 1950 DA the influence of the Yarkovsky effect in 2880 is due to the long time interval preceding the impact. We use the available information from the astrometry and the asteroids' physical models and dynamical evolution as a starting point for a Monte Carlo method that allows us to measure how the Yarkovsky effect affects orbital predictions. We also find that 1950 DA has a 98% likelihood of being a retrograde rotator. For Apophis we map onto the 2029 close approach b-plane and analyze the keyholes corresponding to resonant close approaches. For 1950 DA we use the b-plane corresponding to the possible impact in 2880. We finally compute the impact probability from the mapped probability density function on the considered b-plane. For Apophis we have 4 in a million chances of an impact in 2068, while the probability of Earth impact in 2880 for 1950 DA is 0.04%.

Diagnoses behind patients with hard-to-classify tremor and normal DaT-SPECT: a clinical follow up study.

PubMed

Menéndez-González, Manuel; Tavares, Francisco; Zeidan, Nahla; Salas-Pacheco, José M; Arias-Carrión, Oscar

2014-01-01

The [(123)I]ioflupane-a dopamine transporter radioligand-SPECT (DaT-SPECT) has proven to be useful in the differential diagnosis of tremor. Here, we investigate the diagnoses behind patients with hard-to-classify tremor and normal DaT-SPECT. Therefore, 30 patients with tremor and normal DaT-SPECT were followed up for 2 years. In 18 cases we were able to make a diagnosis. The residual 12 patients underwent a second DaT-SPECT, were then followed for additional 12 months and thereafter the diagnosis was reconsidered again. The final diagnoses included cases of essential tremor, dystonic tremor, multisystem atrophy, vascular parkinsonism, progressive supranuclear palsy, corticobasal degeneration, fragile X-associated tremor ataxia syndrome, psychogenic parkinsonism, iatrogenic parkinsonism and Parkinson's disease. However, for 6 patients the diagnosis remained uncertain. Larger series are needed to better establish the relative frequency of the different conditions behind these cases.

Functional and Structural Characterization of a Thermostable Phospholipase A2 from a Sparidae Fish (Diplodus annularis).

PubMed

Smichi, Nabil; Othman, Houcemeddine; Achouri, Neila; Noiriel, Alexandre; Arondel, Vincent; Srairi-Abid, Najet; Abousalham, Abdelkarim; Gargouri, Youssef; Miled, Nabil; Fendri, Ahmed

2017-03-22

Novel phospholipase (PLA 2 ) genes from the Sparidae family were cloned. The sequenced PLA 2 revealed an identity with pancreatic PLA 2 group IB. To better understand the structure/function relationships of these enzymes and their evolution, the Diplodus annularis PLA 2 (DaPLA 2 ) was overexpressed in E. coli. The refolded enzyme was purified by Ni-affinity chromatography and has a molecular mass of 15 kDa as determined by MALDI-TOF spectrometry. Interestingly, unlike the pancreatic type, the DaPLA 2 was active and stable at higher temperatures, which suggests its great potential in biotechnological applications. The 3D structure of DaPLA 2 was constructed to gain insights into the functional properties of sparidae PLA 2 . Molecular docking and dynamic simulations were performed to explain the higher thermal stability and the substrate specificity of DaPLA 2 . Using the monolayer technique, the purified DaPLA 2 was found to be active on various phospholipids ranging from 10 to 20 mN·m -1 , which explained the absence of the hemolytic activity for DaPLA 2 .

Da Vinci robot-assisted system for thymectomy: experience of 55 patients in China.

PubMed

Jun, Yi; Hao, Li; Demin, Li; Guohua, Dong; Hua, Jing; Yi, Shen

2014-09-01

Da Vinci robot-assisted thymectomy has been used in the past several years in China, however, practical experience in performing this approach in China remains limited. Thus, the study aimed to evaluate the experience of da Vinci robot-assisted thymectomy in China. From June 2010 to December 2012, 55 patients with diseases of the thymus underwent thymectomy using the da Vinci surgical HD robotic system. The clinical data of the da Vinci robot-assisted thymectomies were compared with the data of video-assisted thoracoscopic thymectomies in the same period. All da Vinci robot operations were successful. This is a retrospective analysis which demonstrated that compared with video-assisted thoracoscopic thymectomy in the same period, the clinical outcomes of da Vinci robot-assisted thymectomy were not significantly different. The da Vinci robot-assisted thymectomy is a safe, minimally invasive, and convenient operation, and shows promise for general thoracic surgery in China. Copyright © 2014 John Wiley & Sons, Ltd.

JCoDA: a tool for detecting evolutionary selection.

PubMed

Steinway, Steven N; Dannenfelser, Ruth; Laucius, Christopher D; Hayes, James E; Nayak, Sudhir

2010-05-27

The incorporation of annotated sequence information from multiple related species in commonly used databases (Ensembl, Flybase, Saccharomyces Genome Database, Wormbase, etc.) has increased dramatically over the last few years. This influx of information has provided a considerable amount of raw material for evaluation of evolutionary relationships. To aid in the process, we have developed JCoDA (Java Codon Delimited Alignment) as a simple-to-use visualization tool for the detection of site specific and regional positive/negative evolutionary selection amongst homologous coding sequences. JCoDA accepts user-inputted unaligned or pre-aligned coding sequences, performs a codon-delimited alignment using ClustalW, and determines the dN/dS calculations using PAML (Phylogenetic Analysis Using Maximum Likelihood, yn00 and codeml) in order to identify regions and sites under evolutionary selection. The JCoDA package includes a graphical interface for Phylip (Phylogeny Inference Package) to generate phylogenetic trees, manages formatting of all required file types, and streamlines passage of information between underlying programs. The raw data are output to user configurable graphs with sliding window options for straightforward visualization of pairwise or gene family comparisons. Additionally, codon-delimited alignments are output in a variety of common formats and all dN/dS calculations can be output in comma-separated value (CSV) format for downstream analysis. To illustrate the types of analyses that are facilitated by JCoDA, we have taken advantage of the well studied sex determination pathway in nematodes as well as the extensive sequence information available to identify genes under positive selection, examples of regional positive selection, and differences in selection based on the role of genes in the sex determination pathway. JCoDA is a configurable, open source, user-friendly visualization tool for performing evolutionary analysis on homologous coding

JCoDA: a tool for detecting evolutionary selection

PubMed Central

2010-01-01

Background The incorporation of annotated sequence information from multiple related species in commonly used databases (Ensembl, Flybase, Saccharomyces Genome Database, Wormbase, etc.) has increased dramatically over the last few years. This influx of information has provided a considerable amount of raw material for evaluation of evolutionary relationships. To aid in the process, we have developed JCoDA (Java Codon Delimited Alignment) as a simple-to-use visualization tool for the detection of site specific and regional positive/negative evolutionary selection amongst homologous coding sequences. Results JCoDA accepts user-inputted unaligned or pre-aligned coding sequences, performs a codon-delimited alignment using ClustalW, and determines the dN/dS calculations using PAML (Phylogenetic Analysis Using Maximum Likelihood, yn00 and codeml) in order to identify regions and sites under evolutionary selection. The JCoDA package includes a graphical interface for Phylip (Phylogeny Inference Package) to generate phylogenetic trees, manages formatting of all required file types, and streamlines passage of information between underlying programs. The raw data are output to user configurable graphs with sliding window options for straightforward visualization of pairwise or gene family comparisons. Additionally, codon-delimited alignments are output in a variety of common formats and all dN/dS calculations can be output in comma-separated value (CSV) format for downstream analysis. To illustrate the types of analyses that are facilitated by JCoDA, we have taken advantage of the well studied sex determination pathway in nematodes as well as the extensive sequence information available to identify genes under positive selection, examples of regional positive selection, and differences in selection based on the role of genes in the sex determination pathway. Conclusions JCoDA is a configurable, open source, user-friendly visualization tool for performing evolutionary

Transoral robotic surgery for the base of tongue squamous cell carcinoma: a preliminary comparison between da Vinci Xi and Si.

PubMed

Alessandrini, Marco; Pavone, Isabella; Micarelli, Alessandro; Caporale, Claudio

2017-09-13

Considering the emerging advantages related to da Vinci Xi robotic platform, the aim of this study is to compare for the first time the operative outcomes of this tool to the previous da Vinci Si during transoral robotic surgery (TORS), both performed for squamous cell carcinomas (SCC) of the base of tongue (BOT). Intra- and peri-operative outcomes of eight patients with early stage (T1-T2) of the BOT carcinoma and undergoing TORS by means of the da Vinci Xi robotic platform (Xi-TORS) are compared with the da Vinci Si group ones (Si-TORS). With respect to Si-TORS group, Xi-TORS group demonstrated a significantly shorter overall operative time, console time, and intraoperative blood loss, as well as peri-operative pain intensity and length of mean hospital stays and nasogastric tube positioning. Considering recent advantages offered by surgical robotic techniques, the da Vinci Xi Surgical System preliminary outcomes could suggest its possible future routine implementation in BOT squamous cell carcinoma procedures.

High resolution structure of cleaved Serpin 42 Da from Drosophila melanogaster.

PubMed

Ellisdon, Andrew M; Zhang, Qingwei; Henstridge, Michelle A; Johnson, Travis K; Warr, Coral G; Law, Ruby Hp; Whisstock, James C

2014-04-24

The Drosophila melanogaster Serpin 42 Da gene (previously Serpin 4) encodes a serine protease inhibitor that is capable of remarkable functional diversity through the alternative splicing of four different reactive centre loop exons. Eight protein isoforms of Serpin 42 Da have been identified to date, targeting the protease inhibitor to both different proteases and cellular locations. Biochemical and genetic studies suggest that Serpin 42 Da inhibits target proteases through the classical serpin 'suicide' inhibition mechanism, however the crystal structure of a representative Serpin 42 Da isoform remains to be determined. We report two high-resolution crystal structures of Serpin 42 Da representing the A/B isoforms in the cleaved conformation, belonging to two different space-groups and diffracting to 1.7 Å and 1.8 Å. Structural analysis reveals the archetypal serpin fold, with the major elements of secondary structure displaying significant homology to the vertebrate serpin, neuroserpin. Key residues known to have central roles in the serpin inhibitory mechanism are conserved in both the hinge and shutter regions of Serpin 42 Da. Furthermore, these structures identify important conserved interactions that appear to be of crucial importance in allowing the Serpin 42 Da fold to act as a versatile template for multiple reactive centre loops that have different sequences and protease specificities. In combination with previous biochemical and genetic studies, these structures confirm for the first time that the Serpin 42 Da isoforms are typical inhibitory serpin family members with the conserved serpin fold and inhibitory mechanism. Additionally, these data reveal the remarkable structural plasticity of serpins, whereby the basic fold is harnessed as a template for inhibition of a large spectrum of proteases by reactive centre loop exon 'switching'. This is the first structure of a Drosophila serpin reported to date, and will provide a platform for future mutational

Pancreatic Islets and Insulinoma Cells Express a Novel Isoform of Group VIA Phospholipase A2 (iPLA2β) that Participates in Glucose-Stimulated Insulin Secretion and Is Not Produced by Alternate Splicing of the iPLA2β Transcript†

PubMed Central

Ramanadham, Sasanka; Song, Haowei; Hsu, Fong-Fu; Zhang, Sheng; Crankshaw, Mark; Grant, Gregory A.; Newgard, Christopher B.; Bao, Shunzhong; Ma, Zhongmin; Turk, John

2013-01-01

Many cells express a group VIA 84 kDa phospholipase A2 (iPLA2β) that is sensitive to inhibition by a bromoenol lactone (BEL) suicide substrate. Inhibition of iPLA2β in pancreatic islets and insulinoma cells suppresses, and overexpression of iPLA2β in INS-1 insulinoma cells amplifies, glucose-stimulated insulin secretion, suggesting that iPLA2β participates in secretion. Western blotting analyses reveal that glucose-responsive 832/13 INS-1 cells express essentially no 84 kDa iPLA2β-immunoreactive protein but predominantly express a previously unrecognized immunoreactive iPLA2β protein in the 70 kDa region that is not generated by a mechanism of alternate splicing of the iPLA2β transcript. To determine if the 70 kDa-immunoreactive protein is a short isoform of iPLA2β, protein from the 70 kDa region was digested with trypsin and analyzed by mass spectrometry. Such analyses reveal several peptides with masses and amino acid sequences that exactly match iPLA2β tryptic peptides. Peptide sequences identified in the 70 kDa tryptic digest include iPLA2β residues 7–53, suggesting that the N-terminus is preserved. We also report here that the 832/13 INS-1 cells express iPLA2β catalytic activity and that BEL inhibits secretagogue-stimulated insulin secretion from these cells but not the incorporation of arachidonic acid into membrane PC pools of these cells. These observations suggest that the catalytic iPLA2β activity expressed in 832/13 INS-1 cells is attributable to a short isoform of iPLA2β and that this isoform participates in insulin secretory but not in membrane phospholipid remodeling pathways. Further, the finding that pancreatic islets also express predominantly a 70 kDa iPLA2β-immunoreactive protein suggests that a signal transduction role of iPLA2β in the native β-cell might be attributable to a 70 kDa isoform of iPLA2β. PMID:14636061

Proof of mechanism study of a novel serotonin transporter blocker, DA-8031, using [11C]DASB positron emission tomography and in vivo microdialysis.

PubMed

Park, Hyun Soo; Jung, In Soon; Lim, Nam Hee; Sung, Ji Hyun; Lee, Sukhyang; Moon, Byung Seok; Lee, Byung Chul; Kang, Kyung Koo; Kim, Sang Eun

2014-07-01

To investigate the efficacy of DA-8031, a novel compound for the treatment of premature ejaculation, we measured serotonin transporter (SERT) occupancy by DA-8031, as well as DA-8031-induced changes in extracellular serotonin levels, in the rat brain using positron emission tomography (PET) and 11C-N,N-dimethyl-2-(2-amino-4-cyanophenylthio) benzylamine ([11C]DASB) and in vivo microdialysis, respectively. [11C]DASB PET scans were performed in rats with graded doses of DA-8031 (vehicle: 10, 30, and 100 mg/kg). SERT occupancy in the midbrain was determined using binding potentials for [11C]DASB calculated by the multilinear reference tissue model. Extracellular serotonin levels were monitored in the dorsal raphe nucleus of rats after the administration of DA-8031 (10-100 mg/kg) using in vivo microdialysis. PET data indicated a reduction of [11C]DASB binding to SERTs in the midbrain as a function of DA-8031 dose. SERT occupancy for each DA-8031 dose (10-100 mg/kg) ranged between 31% and 84%. The drug dose required for 50% occupancy of SERT was 13.5 mg/kg in the midbrain, comparable with previous preclinical behavioral data (∼10-30 mg/kg). In vivo microdialysis showed that DA-8031 produced a dose-dependent increase in extracellular serotonin levels in the dorsal raphe nucleus (33%-81% increase for doses of 10-100 mg/kg). These preclinical data provide a proof of mechanism for DA-8031 as a novel compound of targeting the SERT for the treatment of premature ejaculation, warranting further clinical trials. They also offer insight into the optimal drug dose needed to exert therapeutic effects while minimizing adverse effects in humans. Copyright © 2014 Elsevier Inc. All rights reserved.

Morphology of the D/A interface in vapor deposited bilayer organic photovoltaics

NASA Astrophysics Data System (ADS)

Erwin, Patrick; Dimitriou, Michael; Thompson, Mark E.

2017-08-01

A series of bilayer films were prepared by vacuum deposition onto Silicon substrates. These films consisted of either Si/SiO2/donor/C60 or Si/SiO2/C60/donor, where the organic films were in the 20-40 nm thick range and the donors were 7,7-difluoro-14-phenyl-7H-6l4,7l4-[1,3,2]diazaborinino[4,3-a:6,1-a']diisoindole (bDIP), copper phthalocyanine (CuPC), 3,6,11,14-tetraphenyldiindeno[1,2,3-cd:1',2',3'-lm]perylene (DBP) and 2-(4-(diphenylamino)-2,6- dihydroxyphenyl)-4-(4-(diphenyliminio)-2,6-dihydroxycyclohexa-2,5-dien-1-ylidene)-3-oxocyclobut-1-en-1-olate (DPSQ). The donors chosen here have been reported to give good power efficiencies when incorporated into bilayer photovoltaic cells with a C60 acceptor. These bilayer films were examined by neutron reflectometry to characterize the interface between the donor and C60. In the SiO2/donor/C60 films, DPSQ, CuPC, and DBP show a discrete interface with C60 while bDIP shows substantial spontaneous mixing at the interface, consistent with a donor/(donor + C60)/C60 structure, where the mixed layer is 14 nm.. In the SiO2/C60/donor films, all four donors show negligible mixing at the D/A interface consistent with a discrete D/A junction.

Trombose induzida pelo calor endovenoso: relato de dois casos tratados com rivaroxabana e revisão da literatura

PubMed Central

de Araujo, Walter Junior Boim; Timi, Jorge Rufino Ribas; Erzinger, Fabiano Luiz; Caron, Filipe Carlos

2016-01-01

Resumo Define-se trombose induzida pelo calor endovenoso como a propagação do trombo a partir de uma veia superficial em direção a uma veia mais profunda. Em geral, é considerada clinicamente insignificante quando não há propagação do trombo para o sistema venoso profundo. Essa condição pode ser tratada com terapia anticoagulante, embora a observação pareça ser suficiente, principalmente para graus menores. Neste estudo, relatamos dois casos de trombose induzida pelo calor endovenoso que teriam indicação de heparina de baixo peso molecular até a resolução do quadro. Porém, optou-se pelo uso da rivaroxabana (15 mg de 12 em 12h), com resolução completa do trombo em 4 semanas (caso 1) e em 7 dias (caso 2). A rivaroxabana pode ser uma alternativa promissora no tratamento da trombose induzida pelo calor endovenoso avançada, pela simplicidade da posologia, sem comprometimento da eficácia ou da segurança. São necessários estudos prospectivos, randomizados e controlados que possibilitem melhor entendimento da condição e o desenvolvimento de recomendações mais definitivas sobre opções de prevenção e tratamento.

Monoclonal antibodies against 27.8 kDa protein receptor efficiently block lymphocystis disease virus infection in flounder Paralichthys olivaceus gill cells.

PubMed

Sheng, Xiu-Zhen; Wang, Mu; Xing, Jing; Zhan, Wen-Bin

2012-08-13

In previous research using co-immunoprecipitation, a 27.8 kDa protein in flounder Paralichthys olivaceus gill (FG) cells was found to bind lymphocystis disease virus (LCDV). In this paper, 13 hybridomas secreting monoclonal antibodies (MAbs) against the 27.8 kDa protein were obtained, and 2 MAbs designated as 2G11 and 3D9 were cloned by limiting dilution. Analyzed by indirect enzyme-linked immunosorbent assay (ELISA) and western blotting, the MAbs specifically reacted with the 27.8 kDa protein of FG cells. Confocal fluorescence microscopy and immunogold electron microscopy (IEM) provided evidence that the epitopes recognized by these MAbs were located primarily on the cell membrane and occasionally in the cytoplasm near the cell membrane of FG cells. The MAbs could block LCDV binding after MAbs were pre-incubated with isolated membrane proteins of FG cells in a blocking ELISA, and MAbs also could inhibit LCDV infection of FG cells in culture. Moreover, several target tissues of LCDV in flounder, including gill, stomach, intestine and liver, displayed the presence of the LCDV receptor-27.8 kDa. These results strongly supported the possibility that the 27.8 kDa protein is the putative receptor specific for LCDV infection of FG cells in flounder.

Fibroblast growth factor (FGF)-2 and FGF receptor 3 are required for the development of the substantia nigra, and FGF-2 plays a crucial role for the rescue of dopaminergic neurons after 6-hydroxydopamine lesion.

PubMed

Timmer, Marco; Cesnulevicius, Konstantin; Winkler, Christian; Kolb, Julia; Lipokatic-Takacs, Esther; Jungnickel, Julia; Grothe, Claudia

2007-01-17

Basic fibroblast growth factor (FGF-2) is involved in the development and maintenance of the nervous system. Exogenous administration of FGF-2 increased dopaminergic (DA) graft survival in different animal models of Parkinson's disease. To study the physiological function of the endogenous FGF-2 system, we analyzed the nigrostriatal system of mice lacking FGF-2, mice overexpressing FGF-2, and FGF-receptor-3 (FGFR3)-deficient mice both after development and after 6-hydroxydopamine lesion. FGFR3-deficient mice (+/-) displayed a reduced number of DA neurons compared with the respective wild type. Whereas absence of FGF-2 led to significantly increased numbers of DA neurons, enhanced amount of the growth factor in mice overexpressing FGF-2 resulted in less tyrosine hydroxylase expression and a reduced DA cell density. The volumes of the substantia nigra were enlarged in both FGF-2(-/-) and in FGF-2 transgenic mice, suggesting an important role of FGF-2 for the establishment of the proper number of DA neurons and a normal sized substantia nigra during development. In a second set of experiments, the putative relevance of endogenous FGF-2 after neurotoxin application was investigated regarding the number of rescued DA neurons after partial 6-OHDA lesion. Interestingly, the results after lesion were directly opposed to the results after development: significantly less DA neurons survived in FGF-2(-/-) mice compared with wild-type mice. Together, the results indicate that FGFR3 is crucially involved in regulating the number of DA neurons. The lack of FGF-2 seems to be (over)compensated during development, but, after lesion, compensation mechanisms fail. The transgenic mice showed that endogenous FGF-2 protects DA neurons from 6-OHDA neurotoxicity.

Qual o Papel da Escola e da Mídia na Obtenção dos Conhecimentos Astronômicos?

NASA Astrophysics Data System (ADS)

da Cunha, W. S.; Voelzke, M. R.; Amaral, L. H.

2007-08-01

É amplamente reconhecido que as pessoas em geral têm grande fascínio e interesse pela Astronomia. Por outro lado, o conteúdo dessa área incluído no ensino formal está longe de ser abrangente e suficiente para suprir a demanda. Esse interesse permite aperfeiçoar a divulgação e o ensino não formal de Astronomia através da mídia aliando a adequação do conteúdo à expectativa das pessoas. A reforma do Currículo Básico da Escola Pública da maioria dos Estados brasileiros tem introduzido Astronomia desde a pré-escola até o Ensino Médio. Num estudo realizado com 1180 alunos do Ensino Médio de seis escolas estaduais, revelou-se através da aplicação de um formulário contendo questões que abordavam conhecimentos básicos em Astronomia, como foram adquiridos tais conhecimentos e à infra-estrutura da escola. Para 66,1% dos entrevistados o professor já fez alguma apresentação a respeito de Astronomia. O presente estudo revelou também que 54,4% dos alunos entrevistados adquiriram seus conhecimentos astronômicos na escola, 18,4% através da televisão e 27,1% afirmaram que seus conhecimentos foram obtidos através de outros tipos de mídia (internet, livros didáticos, filmes e revistas). Embora o estudo revele claramente que há certo equilíbrio no meio em que os alunos obtiveram seus conhecimentos astronômicos, a mídia busca não somente sua difusão, mas a disponibilização desse conhecimento de maneira correta, que às vezes, não é atingido, apresentando conceitos sem fundamentação e incorretos. Por outro lado, no dia-a-dia escolar, é comum encontrar professores que vêm para as aulas com concepções prévias, que podem diferir substancialmente das idéias a serem ensinadas, dificultando o aprendizado de futuros conceitos científicos. Uma avaliação criteriosa, avaliando as dificuldades dos professores em determinar o sentido correto dos conceitos e observando a metodologia que utilizam no ensino, poderá proporcionar uma melhor

The Effect of DA-9701 in Opioid-induced Bowel Dysfunction of Guinea Pig.

PubMed

Hussain, Zahid; Rhee, Kwang Won; Lee, Young Ju; Park, Hyojin

2016-07-30

Opioid induced bowel dysfunction (OIBD) is associated with decreased gastrointestinal (GI) propulsive activity due to intake of opioid analgesics. DA-9701, a novel prokinetic agent formulated with Pharbitis Semen and Corydalis Tuber has promising effects on GI motor function. Therefore, we aim to evaluate the prokinetic effects of DA-9701 in an OIBD model of guinea pig. The ileal and distal colon muscle contraction in presence of different doses of DA-9701, morphine, and combination (morphine + DA-9701) was measured by tissue bath study. The prokinetic effect of DA-9701 was assessed by charcoal transit and fecal pellet output assay in an OIBD model of guinea pig. DA-9701 significantly increased the amplitude and area under the curve of ileal muscle contraction, while there was insignificant effect on the distal colon compared to the control. The maximal amplitude of ileal muscle contraction was acquired at a concentration of 10 μg/mL of DA-9701. In contrast, morphine significantly decreased the amplitude of ileal and distal colon muscle contraction compared to the control. Morphine delayed both upper (P < 0.01) and lower (P < 0.05) GI transit, and delayed GI transit was restored by the administration of DA-9701. Morphine induced reduction of contractility was significantly ameliorated by addition of DA-9701 in both ileal and distal colon muscles. DA-9701 significantly increased the amplitude of contraction of the ileal muscle, however the distal colon muscle contraction was insignificant. Additionally, it restored delayed upper and lower GI transit in an OIBD model of guinea pig, and it might prove to be a useful candidate drug in a clinical trial for OIBD.

Extrastriatal dopaminergic abnormalities of DA homeostasis in Parkinson’s patients with medication-induced pathological gambling: A [11C] FLB-457 and PET study

PubMed Central

Ray, Nicola J.; Miyasaki, Janis M.; Zurowski, Mateusz; Ko, Ji Hyun; Cho, Sang Soo; Pellecchia, Giovanna; Antonelli, Francesca; Houle, Sylvain; Lang, Anthony E.; Strafella, Antonio P.

2012-01-01

Impulse control disorders such as pathological gambling (PG) are a serious and common adverse effect of dopamine (DA) replacement medication in Parkinson’s disease (PD). Patients with PG have increased impulsivity and abnormalities in striatal DA, in common with behavioural and substance addictions in the non-PD population. To date, no studies have investigated the role of extrastriatal dopaminergic abnormalities in PD patients with PG. We used the PET radiotracer, [11C] FLB-457, with high-affinity for extrastriatal DA D2/3 receptors. 14 PD patients on DA agonists were imaged while they performed a gambling task involving real monetary reward and a control task. Trait impulsivity was measured with the Barratt Impulsivity Scale (BIS). Seven of the patients had a history of PG that developed subsequent to DA agonist medication. Change in [11C] FLB-457 binding potential (BP) during gambling was reduced in PD with PG patients in the midbrain, where D2/D3 receptors are dominated by autoreceptors. The degree of change in [11C] FLB-457 binding in this region correlated with impulsivity. In the cortex, [11C] FLB-457 BP was significantly greater in the anterior cingulate cortex (ACC) in PD patients with PG during the control task, and binding in this region was also correlated with impulsivity. Our findings provide the first evidence that PD patients with PG have dysfunctional activation of DA autoreceptors in the midbrain and low DA tone in the ACC. Thus, altered striatal and cortical DA homeostasis may incur vulnerability for the development of PG in PD, linked with the impulsive personality trait. PMID:22766031

DA-9701 improves colonic transit time and symptoms in patients with functional constipation: A prospective study.

PubMed

Kim, Su Young; Woo, Hyun Sun; Kim, Kyoung Oh; Choi, Sung Han; Kwon, Kwang An; Chung, Jun-Won; Kim, Yoon Jae; Kim, Jung Ho; Kim, Su Ji; Park, Dong Kyun

2017-12-01

DA-9701, a newly developed prokinetic agent formulated with Pharbitis Semen and Corydalis Tuber, has been shown to effectively treat functional dyspepsia. Recently, it has also been suspected to improve gastrointestinal motor function. The aims of this study were to assess the effect of DA-9701 on colonic transit time (CTT) and symptoms of functional constipation. Thirty-three patients with functional constipation based on the Rome III criteria were prospectively enrolled. The patients received 30-mg DA-9701 three times a day for 24 days. CTT was estimated initially and at the end of treatment. Symptoms such as spontaneous bowel movements, straining, stool form, feeling of incomplete emptying and anorectal blockage, abdominal discomfort and pain, overall defecation satisfaction, and incidence of adverse events were also analyzed. Twenty-seven patients completed the study. DA-9701 was associated with a significantly reduced CTT from 34.9 ± 17.6 to 23.7 ± 19.1 h (P = 0.001). Segmental CTT also significantly decreased after treatment (right CTT: from 16.8 [0.0-28.8] to 6.0 [0.0-25.2] hours, P < 0.001; rectosigmoid transit time: from 13.2 [0.0-38.4] to 6.0 [0.0-33.6] hours, P = 0.021). In addition, all constipation-related subjective symptoms, including spontaneous bowel movement frequency, significantly improved compared with those before treatment. Serious adverse events did not occur. DA-9701 accelerates colonic transit and safely improves symptoms in patients with functional constipation. Therefore, we suggest that this novel agent could help to treat patients with this condition. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Endogenous dopamine (DA) modulates (3H)spiperone binding in vivo in rat brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bischoff, S.; Krauss, J.; Grunenwald, C.

1991-01-01

(3H)spiperone (SPI) binding in vivo, biochemical parameters and behavior were measured after modulating DA levels by various drug treatments. DA releasers and uptake inhibitors increased SPI binding in rat striatum. In other brain areas, the effects were variable, but only the pituitary remained unaffected. Surprisingly, nomifensine decreased SPI binding in frontal cortex. The effects of these drugs were monitored by measuring DA, serotonin (5-HT) and their metabolites in the same rats. The increased SPI binding in striatum was parallel to the locomotor stimulation with the following rank order: amfonelic acid greater than nomifensine greater than D-amphetamine greater than or equalmore » to methylphenidate greater than amineptine greater than bupropion. Decreasing DA levels with reserpine or alpha-methyl-para-tyrosine reduced SPI binding by 45% in striatum only when both drugs were combined. In contrast, reserpine enhanced SPI binding in pituitary. Thus, the amount of releasable DA seems to modulate SPI binding characteristics. It is suggested that in vivo, DA receptors are submitted to dynamic regulation in response to changes in intrasynaptic concentrations of DA.« less

STRESS AND FAILURE ANALYSIS OF RAPIDLY ROTATING ASTEROID (29075) 1950 DA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hirabayashi, Masatoshi; Scheeres, Daniel J., E-mail: masatoshi.hirabayashi@colorado.edu

Rozitis et al. recently reported that near-Earth asteroid (29075) 1950 DA, whose bulk density ranges from 1.0 g cm{sup –3} to 2.4 g cm{sup –3}, is a rubble pile and requires a cohesive strength of at least 44-76 Pa to keep from failing due to its fast spin period. Since their technique for giving failure conditions required the averaged stress over the whole volume, it discarded information about the asteroid's failure mode and internal stress condition. This paper develops a finite element model and revisits the stress and failure analysis of 1950 DA. For the modeling, we do not consider material hardening andmore » softening. Under the assumption of an associated flow rule and uniform material distribution, we identify the deformation process of 1950 DA when its constant cohesion reaches the lowest value that keeps its current shape. The results show that to avoid structural failure the internal core requires a cohesive strength of at least 75-85 Pa. It suggests that for the failure mode of this body, the internal core first fails structurally, followed by the surface region. This implies that if cohesion is constant over the whole volume, the equatorial ridge of 1950 DA results from a material flow going outward along the equatorial plane in the internal core, but not from a landslide as has been hypothesized. This has additional implications for the likely density of the interior of the body.« less

Contribution of DA Signaling to Appetitive Odor Perception in a Drosophila Model.

PubMed

Pu, Yuhan; Palombo, Melissa Megan Masserant; Shen, Ping

2018-04-13

Understanding cognitive processes that translate chemically diverse olfactory stimuli to specific appetitive drives remains challenging. We have shown that food-related odors arouse impulsive-like feeding of food media that are palatable and readily accessible in well-nourished Drosophila larvae. Here we provide evidence that two assemblies of four dopamine (DA) neurons, one per brain hemisphere, contribute to perceptual processing of the qualitative and quantitative attributes of food scents. These DA neurons receive neural representations of chemically diverse food-related odors, and their combined neuronal activities become increasingly important as the chemical complexity of an appetizing odor stimulus increases. Furthermore, in each assembly of DA neurons, integrated odor signals are transformed to one-dimensional DA outputs that have no intrinsic reward values. Finally, a genetic analysis has revealed a D1-type DA receptor (Dop1R1)-gated mechanism in neuropeptide Y-like neurons that assigns appetitive significance to selected DA outputs. Our findings suggest that fly larvae provide a useful platform for elucidation of molecular and circuit mechanisms underlying cognitive processing of olfactory and possibly other sensory cues.

PanDA for COMPASS at JINR

NASA Astrophysics Data System (ADS)

Petrosyan, A. Sh.

2016-09-01

PanDA (Production and Distributed Analysis System) is a workload management system, widely used for data processing at experiments on Large Hadron Collider and others. COMPASS is a high-energy physics experiment at the Super Proton Synchrotron. Data processing for COMPASS runs locally at CERN, on lxbatch, the data itself stored in CASTOR. In 2014 an idea to start running COMPASS production through PanDA arose. Such transformation in experiment's data processing will allow COMPASS community to use not only CERN resources, but also Grid resources worldwide. During the spring and summer of 2015 installation, validation and migration work is being performed at JINR. Details and results of this process are presented in this paper.

Da0324, an inhibitor of nuclear factor-κB activation, demonstrates selective antitumor activity on human gastric cancer cells

PubMed Central

Jin, Rong; Xia, Yiqun; Chen, Qiuxiang; Li, Wulan; Chen, Dahui; Ye, Hui; Zhao, Chengguang; Du, Xiaojing; Shi, Dengjian; Wu, Jianzhang; Liang, Guang

2016-01-01

Background The transcription factor nuclear factor-κB (NF-κB) is constitutively activated in a variety of human cancers, including gastric cancer. NF-κB inhibitors that selectively kill cancer cells are urgently needed for cancer treatment. Curcumin is a potent inhibitor of NF-κB activation. Unfortunately, the therapeutic potential of curcumin is limited by its relatively low potency and poor cellular bioavailability. In this study, we presented a novel NF-κB inhibitor named Da0324, a synthetic asymmetric mono-carbonyl analog of curcumin. The purpose of this study is to research the expression of NF-κB in gastric cancer and the antitumor activity and mechanism of Da0324 on human gastric cancer cells. Methods The expressions between gastric cancer tissues/cells and normal gastric tissues/cells of NF-κB were evaluated by Western blot. The inhibition viability of compounds on human gastric cancer cell lines SGC-7901, BGC-823, MGC-803, and normal gastric mucosa epithelial cell line GES-1 was assessed with the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. Absorption spectrum method and high-performance liquid chromatography method detected the stability of the compound in vitro. The compound-induced changes of inducible NF-κB activation in the SGC-7901 and BGC-823 cells were examined by Western blot analysis and immunofluorescence methods. The antitumor activity of compound was performed by clonogenic assay, matrigel invasion assay, flow cytometric analysis, Western blot analysis, and Hoechst 33258 staining assay. Results High levels of p65 were found in gastric cancer tissues and cells. Da0324 displayed higher growth inhibition against several types of gastric cancer cell lines and showed relatively low toxicity to GES-1. Moreover, Da0324 was more stable than curcumin in vitro. Western blot analysis and immunofluorescence methods showed that Da0324 blocked NF-κB activation. In addition, Da0324 significantly inhibited tumor proliferation

Multiquadrant robotic colorectal surgery: the da Vinci Xi vs Si comparison.

PubMed

Protyniak, Bogdan; Jorden, Jeffrey; Farmer, Russell

2018-03-01

The newly introduced da Vinci Xi Surgical System hopes to address the shortcomings of its predecessor, specifically robotic arm restrictions and difficulty working in multiple quadrants. We compare the two robot platforms in multiquadrant surgery at a major colorectal referral center. Forty-four patients in the da Vinci Si group and 26 patients in the Xi group underwent sigmoidectomy or low anterior resection between 2014 and 2016. Patient demographics, operative variables, and postoperative outcomes were compared using descriptive statistics. Both groups were similar in age, sex, BMI, pelvic surgeries, and ASA class. Splenic flexure was mobilized in more (p = 0.045) da Vinci Xi cases compared to da Vinci Si both for sigmoidectomy (50 vs 15.4%) and low anterior resection (60 vs 29%). There was no significant difference in operative time (219.9 vs 224.7 min; p = 0.640), blood loss (170.0 vs 188.1 mL; p = 0.289), length of stay (5.7 vs 6 days; p = 0.851), or overall complications (26.9 vs 22.7%; p = 0.692) between the da Vinci Xi and Si groups, respectively. Single-dock multiquadrant robotic surgery, measured by splenic flexure mobilization with concomitant pelvic dissection, was more frequently performed using the da Vinci Xi platform with no increase in operative time, bleeding, or postoperative complications. The new platform provides surgeons an easier alternative to the da Vinci Si dual docking or combined robotic/laparoscopic multiquadrant surgery.

MOLECULAR MECHANISM OF HUMAN NRF2 ACTIVATION AND DEGRADATION: ROLE OF SEQUENTIAL PHOSPHORYLATION BY PROTEIN KINASE CK2

PubMed Central

Pi, Jingbo; Bai, Yushi; Reece, Jeffrey M.; Williams, Jason; Liu, Dianxin; Freeman, Michael L.; Fahl, William E.; Shugar, David; Liu, Jie; Qu, Wei; Collins, Sheila; Waalkes, Michael P.

2007-01-01

Nrf2 is a key transcription factor in the cellular response to oxidative stress. In this study we first identify two phosphorylated forms of endogenous human Nrf2 after chemically-induced oxidative stress and provide evidence that protein kinase CK2-mediated sequential phosphorylation plays potential role in Nrf2 activation and degradation. Human Nrf2 has a predicted molecular mass of 66 kDa. However, immunoblots showed that two bands at 98 and 118 kDa, which are identified as phosphorylated forms, are increased in response to Nrf2 inducers. In addition, human Nrf2 was found to be a substrate for CK2 which mediated two steps of phosphorylation, resulting in two forms of Nrf2 migrating with differing Mr at 98 kDa (Nrf2–98) and 118 kDa (Nrf2–118). Our results support a role in which calmodulin binding regulates CK2 activity, in that cold (25 °C) in Ca2+-free media (cold/Ca2+-free) decreased both cellular calcium levels and CK2-calmodulin binding and induced Nrf2–118 formation, the latter of which was prevented by CK2 specific inhibitors. Gel-shift assays showed that the Nrf2–118 generated under cold/Ca2+-free conditions does not bind to the antioxidant response element, indicating that Nrf2–98 has transcriptional activity. In contrast, Nrf2–118 is more susceptible to degradation. These results provide evidence for phosphorylation by CK2 as a critical controlling factor in Nrf2-mediated cellular antioxidant response. PMID:17512459

Output control of da Vinci surgical system's surgical graspers.

PubMed

Johnson, Paul J; Schmidt, David E; Duvvuri, Umamaheswar

2014-01-01

The number of robot-assisted surgeries performed with the da Vinci surgical system has increased significantly over the past decade. The articulating movements of the robotic surgical grasper are controlled by grip controls at the master console. The user interface has been implicated as one contributing factor in surgical grasping errors. The goal of our study was to characterize and evaluate the user interface of the da Vinci surgical system in controlling surgical graspers. An angular manipulator with force sensors was used to increment the grip control angle as grasper output angles were measured. Input force at the grip control was simultaneously measured throughout the range of motion. Pressure film was used to assess the maximum grasping force achievable with the endoscopic grasping tool. The da Vinci robot's grip control angular input has a nonproportional relationship with the grasper instrument output. The grip control mechanism presents an intrinsic resistant force to the surgeon's fingertips and provides no haptic feedback. The da Vinci Maryland graspers are capable of applying up to 5.1 MPa of local pressure. The angular and force input at the grip control of the da Vinci robot's surgical graspers is nonproportional to the grasper instrument's output. Understanding the true relationship of the grip control input to grasper instrument output may help surgeons understand how to better control the surgical graspers and promote fewer grasping errors. Copyright © 2014 Elsevier Inc. All rights reserved.

Purification, crystallization and preliminary X-ray structural studies of a 7.2 kDa cytotoxin isolated from the venom of Daboia russelli russelli of the Viperidae family

PubMed Central

Roy Choudhury, Subhasree; Gomes, Aparna; Gomes, Antony; Dattagupta, Jiban K.; Sen, Udayaditya

2006-01-01

A cytotoxin (MW 7.2 kDa) from Indian Russell’s viper (Daboia russelli russelli) venom possessing antiproliferative activity, cardiotoxicity, neurotoxicity and myotoxicity has been purified, characterized and crystallized. The crystals belong to the tetragonal space group P41, with unit-cell parameters a = b = 47.94, c = 50.2 Å. Larger crystals, which diffracted to 1.5 Å, were found to be twinned; diffraction data were therefore collected to 2.93 Å resolution using a smaller crystal. Molecular-replacement calculations identified two molecules of the protein in the asymmetric unit, which is in accordance with the calculated V M value. PMID:16511326

Common commercial cosmetic products induce arthritis in the DA rat.

PubMed Central

Sverdrup, B; Klareskog, L; Kleinau, S

1998-01-01

Many different agents, including mineral oil and silicone, have the capacity to act as immunological adjuvants, i.e., they can contribute to the activation of the immune system. Some adjuvants, including mineral oil, are known to induce arthritis in certain strains of rats after intradermal injection or percutaneous application. The aim of this study was to determine if common commercial cosmetic products containing mineral oil could induce arthritis in the highly susceptible DA (Dark Agouti) rat. Intradermal injection of five out of eight assayed cosmetic products without further additives resulted in arthritis with synovitis. One of the products induced a very aggressive arthritis, which had declined after 5-9 weeks. When this product was also assayed for arthritogenicity upon percutaneous administration, it induced a mild and transient arthritis in 5 out of 10 DA rats, whereas control animals showed no clinical signs of joint involvement. No arthritic reaction was seen in rats after peroral feeding with the most arthritogenic product or by intravaginal application of Freund's adjuvants. Silicone gel implants in DA rats did not cause arthritis. We conclude that mineral oils included in common commercially available products retain their adjuvant properties and are arthritogenic in the presently investigated arthritis-prone rat strain. There is yet no evidence that mineral oils present in cosmetics may contribute to arthritis in humans, but we suggest that this question should be subject to further investigation. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:9417771

Mevalocidin: a novel, phloem mobile phytotoxin from Fusarium DA056446 and Rosellinia DA092917.

PubMed

Gerwick, B Clifford; Brewster, William K; Deboer, Gerrit J; Fields, Steve C; Graupner, Paul R; Hahn, Donald R; Pearce, Cedric J; Schmitzer, Paul R; Webster, Jeffery D

2013-02-01

A multiyear effort to identify new natural products was built on a hypothesis that both phytotoxins from plant pathogens and antimicrobial compounds might demonstrate herbicidal activity. The discovery of one such compound, mevalocidin, is described in the current report. Mevalocidin was discovered from static cultures of two unrelated fungal isolates designated Rosellinia DA092917 and Fusarium DA056446. The chemical structure was confirmed by independent synthesis. Mevalocidin demonstrated broad spectrum post-emergence activity on grasses and broadleaves and produced a unique set of visual symptoms on treated plants suggesting a novel mode of action. Mevalocidin was rapidly absorbed in a representative grass and broadleaf plant. Translocation occurred from the treated leaf to other plant parts including roots confirming phloem as well as xylem mobility. By 24 hr after application, over 20 % had been redistributed through-out the plant. Mevalocidin is a unique phytotoxin based on its chemistry, with the uncommon attribute of demonstrating both xylem and phloem mobility in grass and broadleaf plants.

Decursinol angelate inhibits PGE2-induced survival of the human leukemia HL-60 cell line via regulation of the EP2 receptor and NFκB pathway

PubMed Central

Shehzad, Adeeb; Islam, Salman Ul; Ahn, Eun-Mi; Lee, You Mie; Lee, Young Sup

2016-01-01

ABSTRACT Decursinol angelate (DA), an active pyranocoumarin compound from the roots of Angelica gigas, has been reported to possess anti-inflammatory and anti-cancer activities. In a previous study, we demonstrated that prostaglandin E2 (PGE2) plays a survival role in HL-60 cells by protecting them from the induction of apoptosis via oxidative stress. Flow cytometry and Hoechst staining revealed that PGE2 suppresses menadione-induced apoptosis, cell shrinkage, and chromatin condensation, by blocking the generation of reactive oxygen species. Treatment of DA was found to reverse the survival effect of PGE2 as well as restoring the menadione-mediated cleavage of caspase-3, lamin B, and PARP. DA blocked PGE2-induced activation of the EP2 receptor signaling pathway, including the activation of PKA and the phosphorylation of CREB. DA also inhibited PGE2-induced expression of cyclooxygenase-2 and the activation of the Ras/Raf/ Erk pathway, which activates downstream targets for cell survival. Finally, DA greatly reduced the PGE2-induced activation of NF-κB p50 and p65 subunits. These results elucidate a novel mechanism for the regulation of cell survival and apoptosis, and open a gateway for further development and combinatory treatments that can inhibit PGE2 in cancer cells. PMID:27414656

Decursinol angelate inhibits PGE2-induced survival of the human leukemia HL-60 cell line via regulation of the EP2 receptor and NFκB pathway.

PubMed

Shehzad, Adeeb; Islam, Salman Ul; Ahn, Eun-Mi; Lee, You Mie; Lee, Young Sup

2016-09-01

Decursinol angelate (DA), an active pyranocoumarin compound from the roots of Angelica gigas, has been reported to possess anti-inflammatory and anti-cancer activities. In a previous study, we demonstrated that prostaglandin E2 (PGE2) plays a survival role in HL-60 cells by protecting them from the induction of apoptosis via oxidative stress. Flow cytometry and Hoechst staining revealed that PGE2 suppresses menadione-induced apoptosis, cell shrinkage, and chromatin condensation, by blocking the generation of reactive oxygen species. Treatment of DA was found to reverse the survival effect of PGE2 as well as restoring the menadione-mediated cleavage of caspase-3, lamin B, and PARP. DA blocked PGE2-induced activation of the EP2 receptor signaling pathway, including the activation of PKA and the phosphorylation of CREB. DA also inhibited PGE2-induced expression of cyclooxygenase-2 and the activation of the Ras/Raf/ Erk pathway, which activates downstream targets for cell survival. Finally, DA greatly reduced the PGE2-induced activation of NF-κB p50 and p65 subunits. These results elucidate a novel mechanism for the regulation of cell survival and apoptosis, and open a gateway for further development and combinatory treatments that can inhibit PGE2 in cancer cells.

An asteroseismic constraint on the mass of the axion from the period drift of the pulsating DA white dwarf star L19-2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Córsico, Alejandro H.; Althaus, Leandro G.; Bertolami, Marcelo M. Miller

We employ an asteroseismic model of L19-2, a relatively massive ( M {sub *} ∼ 0.75 M {sub ⊙}) and hot ( T {sub eff} ∼ 12 100 K) pulsating DA (H-rich atmosphere) white dwarf star (DAV or ZZ Ceti variable), and use the observed values of the temporal rates of period change of its dominant pulsation modes (Π ∼ 113 s and Π ∼ 192 s), to derive a new constraint on the mass of the axion, the hypothetical non-barionic particle considered as a possible component of the dark matter of the Universe. If the asteroseismic model employed ismore » an accurate representation of L19-2, then our results indicate hints of extra cooling in this star, compatible with emission of axions of mass m {sub a} cos{sup 2}β ∼< 25 meV or an axion-electron coupling constant of g {sub ae} ∼< 7 × 10{sup −13}.« less

Sequential recognition of the pre-mRNA branch point by U2AF65 and a novel spliceosome-associated 28-kDa protein.

PubMed Central

Gaur, R K; Valcárcel, J; Green, M R

1995-01-01

Splicing of pre-mRNAs occurs via a lariat intermediate in which an intronic adenosine, embedded within a branch point sequence, forms a 2',5'-phosphodiester bond (RNA branch) with the 5' end of the intron. How the branch point is recognized and activated remains largely unknown. Using site-specific photochemical cross-linking, we have identified two proteins that specifically interact with the branch point during the splicing reaction. U2AF65, an essential splicing factor that binds to the adjacent polypyrimidine tract, crosslinks to the branch point at the earliest stage of spliceosome formation in an ATP-independent manner. A novel 28-kDa protein, which is a constituent of the mature spliceosome, contacts the branch point after the first catalytic step. Our results indicate that the branch point is sequentially recognized by distinct splicing factors in the course of the splicing reaction. Images FIGURE 1 FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 FIGURE 7 FIGURE 8 FIGURE 9 PMID:7493318

Forever Young: The Role of Ubiquitin Receptor DA1 and E3 Ligase BIG BROTHER in Controlling Leaf Growth and Development.

PubMed

Vanhaeren, Hannes; Nam, Youn-Jeong; De Milde, Liesbeth; Chae, Eunyoung; Storme, Veronique; Weigel, Detlef; Gonzalez, Nathalie; Inzé, Dirk

2017-02-01

The final size of plant organs is determined by a combination of cell proliferation and cell expansion. Leaves account for a large part of above-ground biomass and provide energy to complete the plant's life cycle. Although the final size of leaves is remarkably constant under fixed environmental conditions, several genes have been described to enhance leaf growth when their expression is modulated. In Arabidopsis (Arabidopsis thaliana), mutations in DA1 and BB increase leaf size, an effect that is synergistically enhanced in the double mutant. Here, we show that overexpression of a dominant-negative version of DA1 enhances leaf size in a broad range of natural accessions of this species, indicating a highly conserved role of this protein in controlling organ size. We also found that during early stages of development, leaves of da1-1 and bb/eod1-2 mutants were already larger than the isogenic Col-0 wild type, but this phenotype was triggered by different cellular mechanisms. Later during development, da1-1 and bb/eod1-2 leaves showed a prolonged longevity, which was enhanced in the double mutant. Conversely, ectopic expression of DA1 or BB restricted growth and promoted leaf senescence. In concert, shortly upon induction of DA1 and BB expression, several marker genes for the transition from proliferation to expansion were highly up-regulated. Additionally, multiple genes involved in maintaining the mitotic cell cycle were rapidly down-regulated and senescence genes were strongly up-regulated, particularly upon BB induction. With these results, we demonstrate that DA1 and BB restrict leaf size and promote senescence through converging and different mechanisms. © 2017 American Society of Plant Biologists. All Rights Reserved.

Improved cell therapy protocol for Parkinson’s disease based on differentiation efficiency and safety of hESC-, hiPSC and non-human primate iPSC-derived DA neurons

PubMed Central

Maria, Sundberg; Helle, Bogetofte; Tristan, Lawson; Gaynor, Smith; Arnar, Astradsson; Michele, Moore; Teresia, Osborn; Oliver, Cooper; Roger, Spealman; Penelope, Hallett; Ole, Isacson

2013-01-01

The main motor symptoms of Parkinson’s disease are due to the loss of dopaminergic (DA) neurons in the ventral midbrain (VM). For the future treatment of Parkinson’s disease with cell transplantation it is important to develop efficient differentiation methods for production of human iPSCs and hESCs-derived midbrain-type DA neurons. Here we describe an efficient differentiation and sorting strategy for DA-neurons from both human ES/iPS cells and non-human primate iPSCs. The use of non-human primate iPSCs for neuronal differentiation and autologous transplantation is important for pre-clinical evaluation of safety and efficacy of stem cell-derived DA neurons. The aim of this study was to improve the safety of human- and non-human primate-iPSC (PiPSC)-derived DA neurons. According to our results, NCAM+/CD29low sorting enriched VM DA-neurons from pluripotent stem cell-derived neural cell populations. NCAM+/CD29low DA-neurons were positive for FOXA2/TH and EN1/TH and this cell population had increased expression levels of FOXA2, LMX1A, TH, GIRK2, PITX3, EN1, NURR1 mRNA compared to unsorted neural cell populations. PiPSC-derived NCAM+/CD29low DA-neurons were able to restore motor function of 6-OHDA lesioned rats 16 weeks after transplantation. The transplanted sorted cells also integrated in the rodent brain tissue, with robust TH+/hNCAM+ neuritic innervation of the host striatum. One year after autologous transplantation, the primate iPSC-derived neural cells survived in the striatum of one primate without any immunosuppression. These neural cell grafts contained FOXA2/TH-positive neurons in the graft site. This is an important proof of concept for the feasibility and safety of iPSC-derived cell transplantation therapies in the future. PMID:23666606

Environmental benefits and concerns on safety: communicating latest results on nanotechnology safety research-the project DaNa2.0.

PubMed

Kühnel, D; Marquardt, C; Nau, K; Krug, H F; Paul, F; Steinbach, C

2017-04-01

The use of nanotechnology and advanced materials promises to revolutionise many areas of technology and improve our daily life. In that respect, many positive effects on the environment are expected, either directly, by developing new technologies for remediation, filtering techniques or energy generation, or indirectly, by e.g. saving resources due to lower consumption of raw materials, or lower energy and fuel consumption due to reduced weight of vehicles. However, such beneficial effects of new technologies are often confronted by concerns regarding the safety of novel substances or materials. During the past 10 years, great effort has been put into research on potential hazards of nanomaterials towards environmental organisms. As the methodology for reliable assessment of nanomaterials was immature, many studies reporting contradictory results have been published, hindering both risk assessment for nanomaterials, as well as the knowledge communication to all involved stakeholders. Thus, DaNa 2.0 serves as a platform to implement trusted knowledge on nanomaterials for an objective discussion.

Novel botanical drug DA-9803 prevents deficits in Alzheimer's mouse models.

PubMed

Pagnier, Guillaume J; Kastanenka, Ksenia V; Sohn, Miwon; Choi, Sangzin; Choi, Song-Hyen; Soh, HyeYeon; Bacskai, Brian J

2018-01-29

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by deposition of amyloid plaques and disruption of neural circuitry, leading to cognitive decline. Animal models of AD deposit senile plaques and exhibit structural and functional deficits in neurons and neural networks. An effective treatment would prevent or restore these deficits, including calcium dyshomeostasis observed with in-vivo imaging. We examined the effects of DA-9803, a multimodal botanical drug, in 5XFAD and APP/PS1 transgenic mice which underwent daily oral treatment with 30 or 100 mg/kg DA-9803 or vehicle alone. Behavioral testing and longitudinal imaging of amyloid deposits and intracellular calcium in neurons with multiphoton microscopy was performed. Chronic administration of DA-9803 restored behavioral deficits in 5XFAD mice and reduced amyloid-β levels. DA-9803 also prevented progressive amyloid plaque deposition in APP/PS1 mice. Elevated calcium, detected in a subset of neurons before the treatment, was restored and served as a functional indicator of treatment efficacy in addition to the behavioral readout. In contrast, mice treated with vehicle alone continued to progressively accumulate amyloid plaques and calcium overload. In summary, treatment with DA-9803 prevented structural and functional outcome measures in mouse models of AD. Thus, DA-9803 shows promise as a novel therapeutic approach for Alzheimer's disease.

Mechanism of isomers and analogues of resveratrol dimers selectively quenching singlet oxygen by UHPLC-ESI-MS2.

PubMed

Yin, Xuefeng; Yu, Jia; Kong, Qingjun; Ren, Xueyan

2017-12-15

Stilbenoids, in particular, resveratrol and its dimers are abundantly present in Vitis vinifera and proved to be quenchers with selective singlet oxygen. However, only a few mechanisms are reported for their complex molecular architectures. Hence, UHPLC combined with accurate MS is employed to investigate the photo-radiation mechanism of resveratrol dimers systematically. Ⅰ: Resorcinol ring exists in Scirpusin A 1, Trans-ε-viniferin 2 and Trans-σ-viniferin 3. The photochemical products were 14Da or 16Da higher than reagents and underwent an endoperoxide intermediate to quinones; Ⅱ: [2+2] cyclization of intra-molecular trans-double bond. The products were 18Da greater than substrates thereby cycloaddited to oxygen heterocyclic; Ⅲ : [4+1], [4+2] cyclization of oxetane formed products were 28Da and 44Da higher than 3, 2 and 1. Ⅳ : 5-phenol-2,3-dihydrobenzofuran ring exists in 2 been oxidized, causing the products at 16Da, 32Da higher than 2. This is the first to reveal the generally regular mechanism of stilbenoids quenching singlet oxygen. Copyright © 2017 Elsevier Ltd. All rights reserved.

Load evaluation of the da Vinci surgical system for transoral robotic surgery.

PubMed

Fujiwara, Kazunori; Fukuhara, Takahiro; Niimi, Koji; Sato, Takahiro; Kitano, Hiroya

2015-12-01

Transoral robotic surgery, performed with the da Vinci surgical system (da Vinci), is a surgical approach for benign and malignant lesions of the oral cavity and laryngopharynx. It provides several unique advantages, which include a 3-dimensional magnified view and ability to see and work around curves or angles. However, the current da Vinci surgical system does not provide haptic feedback. This is problematic because the potential risks specific to the transoral use of the da Vinci include tooth injury, mucosal laceration, ocular injury and mandibular fracture. To assess the potential for intraoperative injuries, we measured the load of the endoscope and the instrument of the da Vinci Si surgical system. We pressed the endoscope and instrument of the da Vinci Si against Load cell six times each and measured the dynamic load and the time-to-maximum load. We also struck the da Vinci Si endoscope and instrument against the Load cell six times each and measured the impact load. The maximum dynamic load was 7.27 ± 1.31 kg for the endoscope and 1.90 ± 0.72 for the instrument. The corresponding time-to-maximum loads were 1.72 ± 0.22 and 1.29 ± 0.34 s, but the impact loads were significantly lower than the dynamic load. It remains possible that a major load is exerted on adjacent structures by continuous contact with the endoscope and instrument of da Vinci Si. However, there is a minor delay in reaching the maximum load. Careful monitoring by an on-site assistant may, therefore, help prevent contiguous injury.

Operative technique and early experience for robotic-assisted laparoscopic nephroureterectomy (RALNU) using da Vinci Xi.

PubMed

Darwiche, Fadi; Swain, Sanjaya; Kallingal, George; Punnen, Sanoj; Manoharan, Murugesan; Parekh, Dipen J; Gonzalgo, Mark L

2015-01-01

Robotic-assisted laparoscopic nephroureterectomy (RALNU) has been previously utilized for management of upper tract urothelial carcinoma. The da Vinci Xi surgical system was released in April of 2014. We describe our operative technique and early experience for RALNU using the da Vinci Xi system highlighting unique features of this surgical platform. A total of 10 patients with a diagnosis of upper tract urothelial carcinoma underwent RALNU using the da Vinci Xi system between April and November of 2014. A novel, oblique "in line" robotic trocar configuration was utilized to access the upper abdomen (nephrectomy portion) and pelvis (bladder cuff excision) without undocking. The port hopping feature of da Vinci Xi was utilized to facilitate optimal, multi-quadrant visualization during RALNU. Robotic-assisted laparoscopic nephroureterectomy was successfully completed without open conversion in all 10 patients. Mean operative time was 184 min (range 140-300 min), mean estimated blood loss was 121 cc (range 60-300 cc), and mean hospital stay was 2.4 days. Final pathology demonstrated high grade urothelial carcinoma in all patients. Surgical margins were negative in all patients. No intra-operative complications were encountered. One patient developed a pulmonary embolus after being discharged. No patients required a blood transfusion. Mean patient follow-up was 130 days (range 15-210 days). The use of da Vinci Xi with a novel, oblique "in line" port configuration and camera port hopping technique allows for an efficient and reproducible method for RALNU without the need for repositioning the patient or the robot during surgery.

Sobre a largura da última superfície de espalhamento

NASA Astrophysics Data System (ADS)

Nobre, M. A. S.; Pires, N.; Lima, J. A. S.

2003-08-01

De acordo com o modelo do "Big-Bang", no universo primordial a matéria estava em equilíbrio térmico com a radiação. Com a expansão a temperatura da radiação cai. Quando a temperatura chega em torno dos 4.000K, os espalhamentos diminuem, começando a recombinação dos prótons e elétrons em Hidrogênio neutro (era conhecida como da recombinação). Ao final da recombinação, os fótons se propagam livremente sofrendo, em princípio, somente os efeitos do "redshift" cosmológico. Esses fótons nos alcançam hoje como a radiação cósmica de fundo (RCF), e parecem vir de uma superfície esférica ao nosso redor, tal que o raio dela é a distância que ele viajou desde seu último espalhamento na época da recombinação. Naturalmente, esse processo não ocorreu abruptamente, implicando na existência de uma largura no espaço dos "redshifts" que deve depender do modelo cosmológico específico e dos processos físicos considerados. Neste trabalho analisamos os efeitos de diferentes modelos - a saber, aqueles com decaimento do vácuo L(t), criação de matéria, quintessência e gás de Chaplygin - sobre a última superfície de espalhamento da RCF, em particular sua largura e a função visibilidade, que determina a probabilidade de um fóton ter tido seu último espalhamento num "redshift" z. No caso particular dos modelos com decaimento do vácuo, existe uma forte dependência da função visibilidade com L(t). Tais efeitos poderão ser testados através da análise dos resultados de experimentos mais precisos que estão atualmente em andamento, como por exemplo, o WMAP.

A 115 kDa calmodulin-binding protein is located in rat liver endosome fractions.

PubMed Central

Enrich, C; Bachs, O; Evans, W H

1988-01-01

The distribution of calmodulin-binding polypeptides in various rat liver subcellular fractions was investigated. Plasma-membrane, endosome, Golgi and lysosome fractions were prepared by established procedures. The calmodulin-binding polypeptides present in the subcellular fractions were identified by using an overlay technique after transfer from gels to nitrocellulose sheets. Distinctive populations of calmodulin-binding polypeptides were present in all the fractions examined except lysosomes. A major 115 kDa calmodulin-binding polypeptide of pI 4.3 was located to the endosome subfractions, and it emerges as a candidate endosome-specific protein. Partitioning of endosome fractions between aqueous and Triton X-114 phases indicated that the calmodulin-binding polypeptide was hydrophobic. Major calmodulin-binding polypeptides of 140 and 240 kDa and minor polypeptides of 40-60 kDa were present in plasma membranes. The distribution of calmodulin in the various endosome and plasma-membrane fractions was also analysed, and the results indicated that the amounts were high compared with those in the cytosol. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. PMID:3214436

Type I allergy to elderberry (Sambucus nigra) is elicited by a 33.2 kDa allergen with significant homology to ribosomal inactivating proteins.

PubMed

Förster-Waldl, E; Marchetti, M; Schöll, I; Focke, M; Radauer, C; Kinaciyan, T; Nentwich, I; Jäger, S; Schmid, E R; Boltz-Nitulescu, G; Scheiner, O; Jensen-Jarolim, E

2003-12-01

Patients suffering from allergic rhinoconjunctivitis and dyspnoea during summer may exhibit these symptoms after contact with flowers or dietary products of the elderberry tree Sambucus nigra. Patients with a history of summer hayfever were tested in a routine setting for sensitization to elderberry. Nine patients having allergic symptoms due to elderberry and specific sensitization were investigated in detail. We studied the responsible allergens in extracts from elderberry pollen, flowers and berries, and investigated cross-reactivity with allergens from birch, grass and mugwort. Sera from patients were tested for IgE reactivity to elderberry proteins by one-dimensional (1D) and 2D electrophoresis/immunoblotting. Inhibition studies with defined allergens and elderberry-specific antibodies were used to evaluate cross-reactivity. The main elderberry allergen was purified by gel filtration and reversed-phase HPLC, and subjected to mass spectrometry. The in-gel-digested allergen was analysed by the MS/MS sequence analysis and peptide mapping. The N-terminal sequence of the predominant allergen was analysed. 0.6% of 3668 randomly tested patients showed positive skin prick test and/or RAST to elderberry. IgE in patients' sera detected a predominant allergen of 33.2 kDa in extracts from elderberry pollen, flowers and berries, with an isoelectric point at pH 7.0. Pre-incubation of sera with extracts from birch, mugwort or grass pollen rendered insignificant or no inhibition of IgE binding to blotted elderberry proteins. Specific mouse antisera reacted exclusively with proteins from elderberry. N-terminal sequence analysis, as well as MS/MS spectrometry of the purified elderberry allergen, indicated homology with ribosomal inactivating proteins (RIPs). We present evidence that the elderberry plant S. nigra harbours allergenic potency. Independent methodologies argue for a significant homology of the predominant 33.2 kDa elderberry allergen with homology to RIPs. We

Molluscan mega-hemocyanin: an ancient oxygen carrier tuned by a ~550 kDa polypeptide

PubMed Central

2010-01-01

Background The allosteric respiratory protein hemocyanin occurs in gastropods as tubular di-, tri- and multimers of a 35 × 18 nm, ring-like decamer with a collar complex at one opening. The decamer comprises five subunit dimers. The subunit, a 400 kDa polypeptide, is a concatenation of eight paralogous functional units. Their exact topology within the quaternary structure has recently been solved by 3D electron microscopy, providing a molecular model of an entire didecamer (two conjoined decamers). Here we study keyhole limpet hemocyanin (KLH2) tridecamers to unravel the exact association mode of the third decamer. Moreover, we introduce and describe a more complex type of hemocyanin tridecamer discovered in fresh/brackish-water cerithioid snails (Leptoxis, Melanoides, Terebralia). Results The "typical" KLH2 tridecamer is partially hollow, whereas the cerithioid tridecamer is almost completely filled with material; it was therefore termed "mega-hemocyanin". In both types, the staggering angle between adjoining decamers is 36°. The cerithioid tridecamer comprises two typical decamers based on the canonical 400 kDa subunit, flanking a central "mega-decamer" composed of ten unique ~550 kDa subunits. The additional ~150 kDa per subunit substantially enlarge the internal collar complex. Preliminary oxygen binding measurements indicate a moderate hemocyanin oxygen affinity in Leptoxis (p50 ~9 mmHg), and a very high affinity in Melanoides (~3 mmHg) and Terebralia (~2 mmHg). Species-specific and individual variation in the proportions of the two subunit types was also observed, leading to differences in the oligomeric states found in the hemolymph. Conclusions In cerithioid hemocyanin tridecamers ("mega-hemocyanin") the collar complex of the central decamer is substantially enlarged and modified. The preliminary O2 binding curves indicate that there are species-specific functional differences in the cerithioid mega-hemocyanins which might reflect different physiological

A estabilidade dos PAHS em função da energia da radiação interestelar nas faixas UV e raios-X

NASA Astrophysics Data System (ADS)

Pinotti, R.; Costa, R. K.; Boechat-Roberty, H. M.; Lago, A.; Souza, G. B.

2003-08-01

A nebulosa CRL 618, uma proto-nebulosa planetária cuja nuvem molecular espessa envolve uma estrela B0, contém uma grande quantidade de C2H2 e CH4. Estas moléculas são consideradas os tijolos da criação de grandes moléculas carbonadas como os Hidrocarbonetos Policíclicos Aromáticos (PAHs). Esta nebulosa, por estar exposta a intensos campos de UV e Raios-X, é uma região de fotodissociação molecular que propicia a formação de novas moléculas, confirmada pela presença de C4H2 e C6H6 (Benzeno), que é a unidade básica dos PAHs. Atribui-se a esta família de moléculas orgânicas duas propriedades fundamentais, a resistência para sobreviver ao campo de radiação UV interestelar e a geração das bandas de emissão não identificadas (UIR) observadas no infravermelho. No entanto, alguns autores questionam a resistência dos PAHs ao campo de radiação UV interestelar. Empregando a técnica de Espectrometria de Massas por Tempo de Vôo, no modo de coincidência fotoelétron-fotoíon, estudamos a ionização e fragmentação das seguintes moléculas: Benzeno, Benzeno deuterado, Naftaleno, Antraceno e Fenantreno. Utilizamos uma fonte de Hélio monocromática em 21,21 eV (584,5 Å) e a radiação Síncroton do Laboratório Nacional de Luz Síncroton (LNLS) em diferentes energias nas proximidades da borda do C 1s ( 290 eV). Comprovamos a estabilidade dos PAHs sob ação de UV (21,21 eV), onde eles apresentam um baixo nível de fotodissociação, produzindo fragmentos ionizados com rendimento total na ordem de 5 por cento em relação ao íon molecular pai. Entretanto, em altas energias, na faixa de Raios-X, a quebra destas moléculas torna-se mais intensa, com a produção de muitos fragmentos. Como uma das rotas de fragmentação do Naftaleno é [(C10H8) = > (C6H6+) + (C4H2) + (e-)], e como temos as evidências observacionais da existência do C4H2 e C6H6 na nebulosa CRL 618, sugerimos que este ambiente também possui o Naftaleno.

Tão perto de casa, tão longe de nós: etnografia das novas margens no centro da urbe

PubMed Central

Fernandes, Por Luís

2011-01-01

Philippe Bourgois é, desde 2007, “Richard Perry University professor” no Departamento de Antropologia e de Medicina Familiar e de Práticas Comunitárias na Universidade da Pensilvânia. Esteve durante largos anos ligado ao Departamento de Antropologia, História e Medicina Social da Universidade da Califórnia, São Francisco. A publicação, em 1995, de In Search of Respect: Selling Crack in El Barrio1 projectaria o seu nome muito para além dos Estados Unidos: uma etnografia no coração porto-riquenho do Harlem, em torno dos actores e dos ambientes da venda de crack. Seguir-se-ia um longo trabalho de terreno em acampamentos de dependentes de heroína em São Francisco, orientando o seu trabalho para as formas mais radicais da pobreza e da marginalidade nos EUA. É deste trabalho de terreno que sai o seu último livro, Righteous Dopefiend2. Em Junho de 2007 esteve em Lisboa para participar na 3.a edição do “Ethnografeast”. Foi então que aproveitámos a oportunidade para ouvir um percurso invulgar contado pelo próprio: uma longa conversa no Hotel Zurique, cujo nome só vem ao caso por evocar o país onde passou uma parte da infância. PMID:22013286

Regulation of Dab2 expression in intestinal and renal epithelia by development.

PubMed

Vázquez-Carretero, María D; García-Miranda, Pablo; Calonge, María L; Peral, María J; Ilundáin, Anunciación A

2011-01-01

Disabled-2 (Dab2) is an intracellular adaptor protein proposed to function in endocytosis. Here, we investigate the intestinal and renal Dab2 expression versus maturation. Dab2 mRNA levels measured by RT-PCR are greater in the small than in the large intestine. Immunological studies localize Dab2 to the terminal web domain of the enterocytes and reveal the presence of a 96-kDa Dab2 isoform in the apical membrane of the jejunum, ileum, and renal cortex of the suckling and adult rat. A 69-kDa Dab2 isoform is only observed in the apical membranes of the suckling ileum. During the suckling period, the Dab2 mRNA levels measured in the enterocytes and crypts and those of the 96-kDa Dab2 isoform are greater in the ileum than in the jejunum. No segmental differences are observed in the adult intestine. In the intestine, the levels of Dab2 mRNA and those of the 96-kDa Dab2 isoform decrease to adult values at weaning, whereas in the kidney they increase with development. Weaning the pups on a commercial milk diet slows the periweaning decline in the levels of Dab2 mRNA in the crypts and of those of the 96-kDa isoform. This is the first report showing that the 96-kDa Dab2 isoform is expressed at the apical domain of rat small intestine, that ontogeny regulates Dab2 gene expression in intestine and kidney and that retarding weaning affects intestinal Dab2 gene expression.

Preparation of Cu2O-Reduced Graphene Nanocomposite Modified Electrodes towards Ultrasensitive Dopamine Detection

PubMed Central

He, Quanguo; Liu, Jun; Liu, Xiaopeng; Li, Guangli; Deng, Peihong; Liang, Jing

2018-01-01

Cu2O-reduced graphene oxide nanocomposite (Cu2O-RGO) was used to modify glassy carbon electrodes (GCE), and applied for the determination of dopamine (DA). The microstructure of Cu2O-RGO nanocomposite material was characterized by scanning electron microscope. Then the electrochemical reduction condition for preparing Cu2O-RGO/GCE and experimental conditions for determining DA were further optimized. The electrochemical behaviors of DA on the bare electrode, RGO- and Cu2O-RGO-modified electrodes were also investigated using cyclic voltammetry in phosphate-buffered saline solution (PBS, pH 3.5). The results show that the oxidation peaks of ascorbic acid (AA), dopamine (DA), and uric acid (UA) could be well separated and the peak-to-peak separations are 204 mV (AA-DA) and 144 mV (DA-UA), respectively. Moreover, the linear response ranges for the determination of 1 × 10−8 mol/L~1 × 10−6 mol/L and 1 × 10−6 mol/L~8 × 10−5 mol/L with the detection limit 6.0 × 10−9 mol/L (S/N = 3). The proposed Cu2O-RGO/GCE was further applied to the determination of DA in dopamine hydrochloride injections with satisfactory results. PMID:29329206

Pesticides, Microglial NOX2, and Parkinson's disease

PubMed Central

Taetzsch, Thomas; Block, Michelle L.

2013-01-01

Accumulating evidence indicates that pesticide exposure is associated with an increased risk for developing Parkinson's disease (PD). Several pesticides known to damage dopaminergic (DA) neurons, such as paraquat, rotenone, lindane, and dieldrin also demonstrate the ability to activate microglia, the resident innate immune cell in the brain. While each of these environmental toxicants may impact microglia through unique mechanisms, they all appear to converge on a common final pathway of microglial activation: NADPH oxidase 2 (NOX2) activation. This review will detail the role of microglia in selective DA neurotoxicity, highlight what is currently known about the mechanism of microglial NOX2 activation in these key pesticides, and describe the importance for DA neuron survival and PD etiology. PMID:23349115

Caffeine increases striatal dopamine D2/D3 receptor availability in the human brain.

PubMed

Volkow, N D; Wang, G-J; Logan, J; Alexoff, D; Fowler, J S; Thanos, P K; Wong, C; Casado, V; Ferre, S; Tomasi, D

2015-04-14

Caffeine, the most widely consumed psychoactive substance in the world, is used to promote wakefulness and enhance alertness. Like other wake-promoting drugs (stimulants and modafinil), caffeine enhances dopamine (DA) signaling in the brain, which it does predominantly by antagonizing adenosine A2A receptors (A2AR). However, it is unclear if caffeine, at the doses consumed by humans, increases DA release or whether it modulates the functions of postsynaptic DA receptors through its interaction with adenosine receptors, which modulate them. We used positron emission tomography and [(11)C]raclopride (DA D2/D3 receptor radioligand sensitive to endogenous DA) to assess if caffeine increased DA release in striatum in 20 healthy controls. Caffeine (300 mg p.o.) significantly increased the availability of D2/D3 receptors in putamen and ventral striatum, but not in caudate, when compared with placebo. In addition, caffeine-induced increases in D2/D3 receptor availability in the ventral striatum were associated with caffeine-induced increases in alertness. Our findings indicate that in the human brain, caffeine, at doses typically consumed, increases the availability of DA D2/D3 receptors, which indicates that caffeine does not increase DA in the striatum for this would have decreased D2/D3 receptor availability. Instead, we interpret our findings to reflect an increase in D2/D3 receptor levels in striatum with caffeine (or changes in affinity). The association between increases in D2/D3 receptor availability in ventral striatum and alertness suggests that caffeine might enhance arousal, in part, by upregulating D2/D3 receptors.

Caffeine increases striatal dopamine D2/D3 receptor availability in the human brain

PubMed Central

Volkow, N D; Wang, G-J; Logan, J; Alexoff, D; Fowler, J S; Thanos, P K; Wong, C; Casado, V; Ferre, S; Tomasi, D

2015-01-01

Caffeine, the most widely consumed psychoactive substance in the world, is used to promote wakefulness and enhance alertness. Like other wake-promoting drugs (stimulants and modafinil), caffeine enhances dopamine (DA) signaling in the brain, which it does predominantly by antagonizing adenosine A2A receptors (A2AR). However, it is unclear if caffeine, at the doses consumed by humans, increases DA release or whether it modulates the functions of postsynaptic DA receptors through its interaction with adenosine receptors, which modulate them. We used positron emission tomography and [11C]raclopride (DA D2/D3 receptor radioligand sensitive to endogenous DA) to assess if caffeine increased DA release in striatum in 20 healthy controls. Caffeine (300 mg p.o.) significantly increased the availability of D2/D3 receptors in putamen and ventral striatum, but not in caudate, when compared with placebo. In addition, caffeine-induced increases in D2/D3 receptor availability in the ventral striatum were associated with caffeine-induced increases in alertness. Our findings indicate that in the human brain, caffeine, at doses typically consumed, increases the availability of DA D2/D3 receptors, which indicates that caffeine does not increase DA in the striatum for this would have decreased D2/D3 receptor availability. Instead, we interpret our findings to reflect an increase in D2/D3 receptor levels in striatum with caffeine (or changes in affinity). The association between increases in D2/D3 receptor availability in ventral striatum and alertness suggests that caffeine might enhance arousal, in part, by upregulating D2/D3 receptors. PMID:25871974

Caffeine increases striatal dopamine D 2/D 3 receptor availability in the human brain

DOE PAGES

Volkow, N. D.; Wang, G. -J.; Logan, J.; ...

2015-04-14

Caffeine, the most widely consumed psychoactive substance in the world, is used to promote wakefulness and enhance alertness. Like other wake-promoting drugs (stimulants and modafinil), caffeine enhances dopamine (DA) signaling in the brain, which it does predominantly by antagonizing adenosine A 2A receptors (A 2AR). However, it is unclear if caffeine, at the doses consumed by humans, increases DA release or whether it modulates the functions of postsynaptic DA receptors through its interaction with adenosine receptors, which modulate them. We used positron emission tomography and [ 11C]raclopride (DA D 2/D 3 receptor radioligand sensitive to endogenous DA) to assess ifmore » caffeine increased DA release in striatum in 20 healthy controls. Caffeine (300mg p.o.) significantly increased the availability of D 2/D 3 receptors in putamen and ventral striatum, but not in caudate, when compared with placebo. In addition, caffeine-induced increases in D 2/D 3 receptor availability in the ventral striatum were associated with caffeine-induced increases in alertness. Our findings indicate that in the human brain, caffeine, at doses typically consumed, increases the availability of DA D 2/D 3 receptors, which indicates that caffeine does not increase DA in the striatum for this would have decreased D 2/D 3 receptor availability. Instead, we interpret our findings to reflect an increase in D 2/D 3 receptor levels in striatum with caffeine (or changes in affinity). Furthermore, the association between increases in D 2/D 3 receptor availability in ventral striatum and alertness suggests that caffeine might enhance arousal, in part, by upregulating D 2/D 3 receptors.« less

Caffeine increases striatal dopamine D 2/D 3 receptor availability in the human brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Volkow, N. D.; Wang, G. -J.; Logan, J.

Caffeine, the most widely consumed psychoactive substance in the world, is used to promote wakefulness and enhance alertness. Like other wake-promoting drugs (stimulants and modafinil), caffeine enhances dopamine (DA) signaling in the brain, which it does predominantly by antagonizing adenosine A 2A receptors (A 2AR). However, it is unclear if caffeine, at the doses consumed by humans, increases DA release or whether it modulates the functions of postsynaptic DA receptors through its interaction with adenosine receptors, which modulate them. We used positron emission tomography and [ 11C]raclopride (DA D 2/D 3 receptor radioligand sensitive to endogenous DA) to assess ifmore » caffeine increased DA release in striatum in 20 healthy controls. Caffeine (300mg p.o.) significantly increased the availability of D 2/D 3 receptors in putamen and ventral striatum, but not in caudate, when compared with placebo. In addition, caffeine-induced increases in D 2/D 3 receptor availability in the ventral striatum were associated with caffeine-induced increases in alertness. Our findings indicate that in the human brain, caffeine, at doses typically consumed, increases the availability of DA D 2/D 3 receptors, which indicates that caffeine does not increase DA in the striatum for this would have decreased D 2/D 3 receptor availability. Instead, we interpret our findings to reflect an increase in D 2/D 3 receptor levels in striatum with caffeine (or changes in affinity). Furthermore, the association between increases in D 2/D 3 receptor availability in ventral striatum and alertness suggests that caffeine might enhance arousal, in part, by upregulating D 2/D 3 receptors.« less

Influence of Culture Conditions on Expression of the 40-Kilodalton Porin Protein of Vibrio anguillarum Serotype O2

PubMed Central

Davey, Michelle L.; Hancock, Robert E. W.; Mutharia, Lucy M.

1998-01-01

Vibrio anguillarum serotype O2 strains express a 40-kDa outer membrane porin protein. Immunoblot analysis revealed that antigenic determinants of the V. anguillarum O2 40-kDa porin were conserved within bacterial species of the genus Vibrio. The relative amounts of the V. anguillarum O2 40-kDa porin were enhanced by growth of V. anguillarum O2 in CM9 medium containing 5 to 10% sucrose or 0.1 to 0.5 M NaCl. In contrast, the levels of the porin were significantly reduced when cells were grown at 37°C, and a novel 60-kDa protein was also observed. However, the osmolarity or ionic concentration of the growth medium did not influence expression of the 60-kDa protein. Growth in medium containing greater than 0.6 mM EDTA reduced production of the V. anguillarum O2 40-kDa porin and enhanced levels of a novel 19-kDa protein. Thus, expression of the V. anguillarum O2 40-kDa porin was osmoregulated and possibly coregulated by temperature. The N-terminal amino acid sequence of the V. anguillarum O2 40-kDa protein and the effect of environmental factors on the cellular levels of the porin suggested that the V. anguillarum O2 40-kDa porin was functionally similar to the OmpC porin of Escherichia coli. However, pore conductance assays revealed that the V. anguillarum O2 40-kDa porin was a general diffusion porin with a pore size in the range of that of the OmpF porin of E. coli. PMID:9435071

The Da Vinci European BioBank: A Metabolomics-Driven Infrastructure

PubMed Central

Carotenuto, Dario; Luchinat, Claudio; Marcon, Giordana; Rosato, Antonio; Turano, Paola

2015-01-01

We present here the organization of the recently-constituted da Vinci European BioBank (daVEB, https://www.davincieuropeanbiobank.org/it). The biobank was created as an infrastructure to support the activities of the Fiorgen Foundation (http://www.fiorgen.net/), a nonprofit organization that promotes research in the field of pharmacogenomics and personalized medicine. The way operating procedures concerning samples and data have been developed at daVEB largely stems from the strong metabolomics connotation of Fiorgen and from the involvement of the scientific collaborators of the foundation in international/European projects aimed to tackle the standardization of pre-analytical procedures and the promotion of data standards in metabolomics. PMID:25913579

Device-Associated Healthcare-Associated Infections (DA-HAI) and the caveat of multiresistance in a multidisciplinary intensive care unit.

PubMed

Khan, Inam Danish; Basu, Atoshi; Kiran, Sheshadri; Trivedi, Shaleen; Pandit, Priyanka; Chattoraj, Anupam

2017-07-01

Device-Associated Healthcare-Associated Infections (DA-HAI), including Ventilator-Associated Pneumonia (VAP), Central-Line-Associated Blood Stream Infection (CLABSI), and Catheter-Related Urinary Tract Infection (CAUTI), are considered as principal contributors to healthcare hazard and threat to patient safety as they can cause prolonged hospital stay, sepsis, and mortality in the ICU. The study intends to characterize DA-HAI in a tertiary care multidisciplinary ICU of a teaching hospital in eastern India. This prospective outcome-surveillance study was conducted among 2157 ICU patients of a 760-bedded teaching hospital in Eastern India. Clinical, laboratory and environmental surveillance, and screening of HCPs were conducted using the US Centers for Disease Control and Prevention (CDC)'s National Healthcare Safety Network (NHSN) definitions and methods. With 8824 patient/bed/ICU days and 14,676 device days, pooled average device utilization ratio was 1.66, total episodes of DA-HAI were 114, and mean monthly rates of DA-HAI, VAP, CLABSI, and CAUTI were 4.75, 2, 1.4, and 1.25/1000 device days. Most common pathogens isolated from DA-HAI patients were Klebsiella pneumoniae (24.6%), Escherichia coli (21.9%), and Pseudomonas aeruginosa (20.2%). All Acinetobacter baumanii , >80% K. pneumoniae and E. coli , and >70% P. aeruginosa were susceptible only to colistin and tigecycline. One P. aeruginosa isolate was panresistant. Mean rates of VAP, CLABSI, and CAUTI were 14.4, 8.1, and 4.5 per 1000 device days, which are comparable with Indian and global ICUs. Patients and HCPs form important reservoirs of infection. Resolute conviction and sustained momentum in Infection Control Initiatives are an essential step toward patient safety.

Comparing the da Vinci si single console and dual console in teaching novice surgeons suturing techniques.

PubMed

Crusco, Salvatore; Jackson, Tiffany; Advincula, Arnold

2014-01-01

Robot-assisted laparoscopic surgery is often taught with the surgical mentor at the surgeon console and the trainee at the patient's bedside. The da Vinci dual console (Intuitive Surgical, Sunnyvale, California) allows a surgical mentor to teach with both the mentor and the trainee working at a surgeon console simultaneously. The purpose of this study is to evaluate the effectiveness of the dual console versus the single console for teaching medical students robotic tasks. Forty novice medical students were randomized to either the da Vinci single-console or dual-console group and were taught 4 knot-tying techniques by a surgical mentor. The students were timed while performing the tasks. No statistically significant differences in mean task times were observed between the single- and dual-console groups: interrupted stitch with a 2-handed knot (300 seconds for single vs 294 seconds for dual, P=.59), interrupted stitch with a 1-handed knot (198 seconds for single vs 212 seconds for dual, P=.88), figure-of-8 stitch with a 2-handed knot (261 seconds for single vs 219 seconds for dual, P=.20), and figure-of-8 stitch with a 1-handed knot (200 seconds for single vs 199 seconds for dual, P=.53). No significant difference was observed in performance time when teaching knot-tying techniques to medical students using the da Vinci dual console compared with the single console. More research needs to be performed on the utility of the da Vinci dual console in surgical training.

Comparing the da Vinci Si Single Console and Dual Console in Teaching Novice Surgeons Suturing Techniques

PubMed Central

Jackson, Tiffany; Advincula, Arnold

2014-01-01

Background and Objectives: Robot-assisted laparoscopic surgery is often taught with the surgical mentor at the surgeon console and the trainee at the patient's bedside. The da Vinci dual console (Intuitive Surgical, Sunnyvale, California) allows a surgical mentor to teach with both the mentor and the trainee working at a surgeon console simultaneously. The purpose of this study is to evaluate the effectiveness of the dual console versus the single console for teaching medical students robotic tasks. Methods: Forty novice medical students were randomized to either the da Vinci single-console or dual-console group and were taught 4 knot-tying techniques by a surgical mentor. The students were timed while performing the tasks. Results: No statistically significant differences in mean task times were observed between the single- and dual-console groups: interrupted stitch with a 2-handed knot (300 seconds for single vs 294 seconds for dual, P = .59), interrupted stitch with a 1-handed knot (198 seconds for single vs 212 seconds for dual, P = .88), figure-of-8 stitch with a 2-handed knot (261 seconds for single vs 219 seconds for dual, P = .20), and figure-of-8 stitch with a 1-handed knot (200 seconds for single vs 199 seconds for dual, P = .53). Conclusion: No significant difference was observed in performance time when teaching knot-tying techniques to medical students using the da Vinci dual console compared with the single console. More research needs to be performed on the utility of the da Vinci dual console in surgical training. PMID:25392618

Interaction of human platelets with laminin and identification of the 67 kDa laminin receptor on platelets.

PubMed Central

Tandon, N N; Holland, E A; Kralisz, U; Kleinman, H K; Robey, F A; Jamieson, G A

1991-01-01

A microtitre adhesion assay has been developed to define parameters affecting the adherence of washed platelets to laminin. Adherence was optimally supported by Mg2+ and was inhibited by Ca2+ and by anti-laminin Fab fragments, but significant adhesion (75-90% of control) was found both in heparinized plasma containing physiological levels of bivalent cations and in plasma anti-coagulated with EGTA. Adherence was unaffected by platelet activation with ADP but was decreased by 50% by treatment with alpha-thrombin (1 unit/ml, 5 min). Adherence was unaffected by monospecific polyclonal antibodies to glycoprotein (GP) Ib and GPIV, and was normal with platelets from two patients with Glanzmann's thrombasthaenia, indicating that GPIb, the GPIIb/IIIa complex and GPIV are not involved in platelet-laminin interaction. Affinity chromatography of Triton-solubilized membranes on laminin-Sepharose followed by elution with 0.2 M-glycine/HCl (pH 2.85) identified a major band with a molecular mass of 67 kDa in the reduced and of 53 kDa in the unreduced form. This protein gave a positive reaction on Western blotting with a monospecific polyclonal antibody raised against the high-affinity laminin receptor isolated from human breast carcinoma tissue. The adhesion of platelets to laminin was inhibited by two monoclonal IgM antibodies specific to the LR-1 domain of the 67 kDa receptor. The binding protein was surface-oriented, as shown by flow cytofluorimetry and by the fact that it could be iodinated in intact platelets, but it was not labelled by the periodate-borotritide procedure, suggesting that it did not contain terminal sialic acid. The laminin-derived peptides Tyr-Ile-Gly-Ser-Arg and Cys-Asp-Pro-Gly-Tyr-Ile-Gly-Ser-Arg-NH2, which constitute a complementary binding domain in laminin for the 67 kDa receptor, themselves supported platelet adhesion, bound to the receptor and inhibited the adhesion of platelets to laminin. In addition, Fab fragments of anti

Concentration change of DA, DOPAC, Glu and GABA in brain tissues in schizophrenia developmental model rats induced by MK-801.

PubMed

Liu, Yong; Tang, Yamei; Pu, Weidan; Zhang, Xianghui; Zhao, Jingping

2011-08-01

To explore the related neurobiochemical mechanism by comparing the concentration change of dopamine (DA), dihydroxy-phenyl acetic acid (DOPAC), glutamate (Glu), and γ-aminobutyric acid (GABA) in the brain tissues in schizophrenia (SZ) developmental model rats and chronic medication model rats. A total of 60 neonatal male Spragur-Dawley (SD) rats were randomly assigned to 3 groups at the postnatal day 6: an SZ developmental rat model group (subcutaneous injection with MK-801 at the postnatal day 7-10, 0.1 mg/kg, Bid), a chronic medication model group (intraperitoneal injection at the postnatal day 47-60, 0.2 mg/kg,Qd), and a normal control group (injection with 0.9% normal saline during the corresponding periods). DA, DOPAC, Glu, and GABA of the tissue homogenate from the medial prefrontal cortex (mPFC) and hippocampus were examined with Coularray electrochemic detection by high performance liquid chromatogram technique. The utilization rate of DA and Glu was calculated. Compared with the normal control group, the concentration of DA and DOPAC in the mPFC and the hippocampus in the SZ developmental model group significantly decreased (P<0.05), and the GABA concentration and Glu utilization rate in the mPFC also decreased (P<0.05). Compared with the chronic medication model group, the DA concentration of the mPFC in the SZ developmental group decreased (P<0.05), and the DOPAC concentration and the utility rate of DA in the hippocampus also decreased (P<0.01, P<0.05, respectively). The activities of DA, Glu and GABA system decrease in the mPFC and the DA system function reduces in the hippocampus of SZ developmental rats.

Performances on simulator and da Vinci robot on subjects with and without surgical background.

PubMed

Moglia, Andrea; Ferrari, Vincenzo; Melfi, Franca; Ferrari, Mauro; Mosca, Franco; Cuschieri, Alfred; Morelli, Luca

2017-08-17

To assess whether previous training in surgery influences performance on da Vinci Skills Simulator and da Vinci robot. In this prospective study, thirty-seven participants (11 medical students, 17 residents, and 9 attending surgeons) without previous experience in laparoscopy and robotic surgery performed 26 exercises at da Vinci Skills Simulator. Thirty-five then executed a suture using a da Vinci robot. The overall scores on the exercises at the da Vinci Skills Simulator show a similar performance among the groups with no statistically significant pair-wise differences (p < .05). The quality of the suturing based on the unedited videos of the test run was similar for the intermediate (7 (4, 10)) and expert group (6.5 (4.5, 10)), and poor for the untrained groups (5 (3.5, 9)), without statistically significant difference (p < .05). This study showed, for subjects new to laparoscopy and robotic surgery, insignificant differences in the scores at the da Vinci Skills Simulator and at the da Vinci robot on inanimate models.

Dopamine induces growth inhibition and vascular normalization through reprogramming M2-polarized macrophages in rat C6 glioma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qin, Tian; Wang, Chenlong; Chen, Xuewei

Dopamine (DA), a monoamine catecholamine neurotransmitter with antiangiogenic activity, stabilizes tumor vessels in colon, prostate and ovarian cancers, thus increases chemotherapeutic efficacy. Here, in the rat C6 glioma models, we investigated the vascular normalization effects of DA and its mechanisms of action. DA (25, 50 mg/kg) inhibited tumor growth, while a precursor of DA (levodopa) prolonged the survival time of rats bearing orthotopic C6 glioma. DA improved tumor perfusion, with significant effects from day 3, and a higher level at days 5 to 7. In addition, DA decreased microvessel density and hypoxia-inducible factor-1α expression in tumor tissues, while increasing themore » coverage of pericyte. Conversely, an antagonist of dopamine receptor 2 (DR2) (eticlopride) but not DR1 (butaclamol) abrogated DA-induced tumor regression and vascular normalization. Furthermore, DA improved the delivery and efficacy of temozolomide therapy. Importantly, DA increased representative M1 markers (iNOS, CXCL9, etc.), while decreasing M2 markers (CD206, arginase-1, etc.). Depletion of macrophages by clodronate or zoledronic acid attenuated the effects of DA. Notably, DA treatment induced M2-to-M1 polarization in RAW264.7 cells and mouse peritoneal macrophages, and enhanced the migration of pericyte-like cells (10T1/2), which was reversed by eticlopride or DR2-siRNA. Such changes were accompanied by the downregulation of VEGF/VEGFR2 signaling. In summary, DA induces growth inhibition and vascular normalization through reprogramming M2-polarized macrophages. Thus, targeting the tumor microvasculature by DA represents a promising strategy for human glioma therapy. - Highlights: • Dopamine induces tumor growth inhibition and vascular normalization in rat C6 glioma. • Dopamine switches macrophage phenotype from M2 to M1. • Dopamine-induced vascular normalization is mediated by macrophage polarization. • Dopamine is a promising agent targeting the microvasculature in

Subcellular localization and expression pattern of the neurofibromatosis type 2 protein merlin/schwannomin.

PubMed

Schmucker, B; Ballhausen, W G; Kressel, M

1997-01-01

To elucidate the physiological function of the neurofibromatosis type 2 (NF2) tumor suppressor protein merlin/schwannomin, we studied the expression pattern and subcellular localization in human fibroblasts by Western blot analyses and immunofluorescence using a polyclonal antibody raised against the C-terminus of merlin. Three of the six merlin isoforms identified in this study (75 kDa, 58 kDa, 45 kDa) have been reported earlier and can be explained by alternative splicing. In addition, we detected higher molecular weight bands of about 110 kDa, 100 kDa and 84 kDa. Although the merlin bands of 100 kDa and 110 kDa may represent homo- or heterodimers, oligomerization due to formation of disulfide bonds was excluded. Furthermore, the isoforms of 84 kDa and 58 kDa were quantitatively extractable in Lubrol WX, indicating a localization in or close to the plasma membrane. The 45 kDa band, however, was not soluble in Lubrol WX compatible with a localization of this NF2 isoform in the endoplasmic reticulum. Applying confocal laser scanning microscopy, merlin was shown to be located in four subcellular compartments: (i) perinuclear in a compartment resembling endoplasmic reticulum, (ii) in ruffling membranes and at the leading edges, (iii) in filopodia, and (iv) at cell/substrate adhesion points. Codistribution of merlin and F-actin filaments was found in filopodia, ruffling membranes and at the insertion points of stress fibers at cell/substrate adhesion junctions as shown by phalloidin-rhodamine staining. Double immunofluorescence analyses of merlin and moesin revealed a colocalization in filopodia and ruffling membranes. The localization of merlin in the actin-rich cortical cytoskeleton corresponds to the ezrin-radixin-moesin family of proteins suggesting the NF2 protein to contribute to the regulation of cell growth by interaction with cytoskeleton-associated proteins.

Ecological Carrying Capacity of Land Use Changes in Da'an City

NASA Astrophysics Data System (ADS)

Wang, H.; Zhang, J.; Li, B.

2018-04-01

Based on GIS and RS technology, this paper analyzed the land use change in Da'an city from 1995 to 2010. land-use ecological evaluation index was constructed to evaluate the land-use ecological risk of Da 'an city dynamically, and the land-use ecological risk level map was made, and then the distribution and change of the land-use ecological carrying capacity pattern of Da'an city were analyzed qualitatively. According to the evaluation results of ecological carrying capacity, the ecological environment of Da'an city has deteriorated in fifteen years. in 1995, the poor ecological environment area is mainly distributed in the northeast area of Da'an city, and the area is small, while the area of the central and southern areas is large; In 2010, the western region also appeared environmental degradation, the northeast environment deterioration is serious, the dominant area is reduced, and a small amount of deterioration in the central and southern regions. According to the study of this paper, in the future, we should strengthen the comprehensive management of this part of the area, strengthen vegetation coverage, reduce soil erosion, ensure the effective improvement of ecological environment.

The real code of leonardo da vinci.

PubMed

Ose, Leiv

2008-02-01

Leonardo da Vinci was born in Italy. Among the researchers and scientists, he is favourably known for his remarkable efforts in scientific work. His investigations of atherosclerosis judiciously combine three separate fields of research. In 1506, he finished his masterpiece, painting of Mona Lisa. A careful clinical examination of the famous painting reveals a yellow irregular leather-like spot at the inner end of the left upper eyelid and a soft bumpy well-defined swelling of the dorsum of the right hand beneath the index finger about 3 cm long. This is probably the first case of familial hypercholesterolemia (FH). The FH code of Leonardo da Vinci was given immense consideration by scientists like Carl Muller, who described the xanthomas tuberosum and angina pectoris. On the contrary, Akira Endo searched for microbial metabolites that would inhibit HMG-CoA reductase, the rate-limiting enzyme in the synthesis of cholesterol and finally, Michael Brown and Joseph Goldstein published a remarkable series of elegant and insightful papers in the 70s and 80s. They established that the cellular uptake of low-density lipoprotein (LDL) essentially requires the LDL receptor. this was the real Code of Leonardo da Vinci.

Leonardo da Vinci's studies of the heart.

PubMed

Shoja, Mohammadali M; Agutter, Paul S; Loukas, Marios; Benninger, Brion; Shokouhi, Ghaffar; Namdar, Husain; Ghabili, Kamyar; Khalili, Majid; Tubbs, R Shane

2013-08-20

Leonardo da Vinci's detailed drawings are justly celebrated; however, less well known are his accounts of the structures and functions of the organs. In this paper, we focus on his illustrations of the heart, his conjectures about heart and blood vessel function, his experiments on model systems to test those conjectures, and his unprecedented conclusions about the way in which the cardiovascular system operates. In particular, da Vinci seems to have been the first to recognize that the heart is a muscle and that systole is the active phase of the pump. He also seems to have understood the functions of the auricles and pulmonary veins, identified the relationship between the cardiac cycle and the pulse, and explained the hemodynamic mechanism of valve opening and closure. He also described anatomical variations and changes in structure and function that occurred with age. We outline da Vinci's varied career and suggest ways in which his personality, experience, skills and intellectual heritage contributed to these advances in understanding. We also consider his influence on later studies in anatomy and physiology. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

[RESEARCH PROGRESS OF PERIPHERAL NERVE SURGERY ASSISTED BY Da Vinci ROBOTIC SYSTEM].

PubMed

Shen, Jie; Song, Diyu; Wang, Xiaoyu; Wang, Changjiang; Zhang, Shuming

2016-02-01

To summarize the research progress of peripheral nerve surgery assisted by Da Vinci robotic system. The recent domestic and international articles about peripheral nerve surgery assisted by Da Vinci robotic system were reviewed and summarized. Compared with conventional microsurgery, peripheral nerve surgery assisted by Da Vinci robotic system has distinctive advantages, such as elimination of physiological tremors and three-dimensional high-resolution vision. It is possible to perform robot assisted limb nerve surgery using either the traditional brachial plexus approach or the mini-invasive approach. The development of Da Vinci robotic system has revealed new perspectives in peripheral nerve surgery. But it has still been at the initial stage, more basic and clinical researches are still needed.

Pharmacokinetics of chlorogenic acid and corydaline in DA-9701, a new botanical gastroprokinetic agent, in rats.

PubMed

Jung, Ji Won; Kim, Ju Myung; Jeong, Jin Seok; Son, Miwon; Lee, Hye Suk; Lee, Myung Gull; Kang, Hee Eun

2014-07-01

1.Few studies describing the pharmacokinetic properties of chlorogenic acid (CA) and corydaline (CRD) which are marker compounds of a new prokinetic botanical agent, DA-9701, have been reported. The aim of the present study is to evaluate the pharmacokinetic properties CA and CRD following intravenous and oral administration of pure CA (1-8 mg/kg) or CRD (1.1-4.5 mg/kg) and their equivalent dose of DA-9701 to rats. 2.  Dose-proportional AUC and dose-independent clearance (10.3-12.1 ml/min/kg) of CA were observed following its administration. Oral administration of CA as DA-9701 did not influence the oral pharmacokinetic parameters of CA. Incomplete absorption of CA, its decomposition in the gastrointestinal tract, and/or pre-systemic metabolism resulted in extremely low oral bioavailability (F) of CA (0.478-0.899%). 3.  CRD showed greater dose-normalized AUC in the higher dose group than that in lower dose group(s) after its administration due to saturation of its metabolism via decreased non-renal clearance (by 51.3%) and first-pass extraction. As a result, the F of CRD following 4.5 mg/kg oral CRD (21.1%) was considerably greater than those of the lower dose groups (9.10 and 13.8%). However, oral administration of CRD as DA-9701 showed linear pharmacokinetics as a result of increased AUC and F in lower-dose groups (by 182% and 78.5%, respectively) compared to those of pure CRD. The greater oral AUC of CRD for DA-9701 than for pure CRD could be due to decreased hepatic and/or GI first-pass extraction of CRD by other components in DA-9701.

Plant-originated glycoprotein (24 kDa) has an inhibitory effect on proliferation of BNL CL.2 cells in response to di(2-ethylhexyl)phthalate.

PubMed

Lee, Jin; Lim, Kye-Taek

2011-08-01

Di(2-ethylhexyl)phthalate (DEHP) is one of the many environmental chemicals that are widely used in polyvinyl chloride products, vinyl flooring, food packaging and infant toys. They cause cell proliferation or dysfunction of human liver. The purpose of this study is to investigate the inhibitory effect of a glycoprotein (24 kDa) isolated from Zanthoxylum piperitum DC (ZPDC) on proliferation of liver cell in the DEHP-induced BNL CL. 2 cells. [³H]-thymidine incorporation, intracellular reactive oxygen species (ROS), intracellular Ca²⁺ mobilization and activity of protein kinase C (PKC) were measured using radioactivity and fluorescence method respectively. The expression of mitogen-activated protein kinases [extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK)], activator protein (AP)-1 (c-Jun and c-Fos), proliferating cell nuclear antigen (PCNA) and cell cycle-related factors (cyclin D1/cyclin-dependent kinase [CDK] 4) were evaluated using Western blotting or electrophoretic mobility shift assay. The results in this study showed that the levels of [³H]-thymidine incorporation, intracellular ROS, intracellular Ca²⁺ mobilization and activity of PKCα were inhibited by ZPDC glycoprotein (100 µg/ml) in the DEHP-induced BNL CL. 2 cells. Also, activities of ERK, JNK and AP-1 were reduced by ZPDC glycoprotein (100 µg/ml). With regard to cell proliferation, activities of PCNA and cyclin D1/CDK4 were significantly suppressed at treatment with ZPDC glycoprotein (100 µg/ml) in the presence of DEHP. Taken together, these findings suggest that ZPDC glycoprotein significantly normalized activities of PCNA and cyclin D1/CDK4, which relate to cell proliferation factors. Thus, ZPDC glycoprotein appears to be one of the compounds derived from natural products that are able to inhibit cell proliferation in the phthalate-induced BNL CL. 2 cells. Copyright © 2011 John Wiley & Sons, Ltd.

Dopamine D2-Like Receptors and Behavioral Economics of Food Reinforcement

PubMed Central

Soto, Paul L; Hiranita, Takato; Xu, Ming; Hursh, Steven R; Grandy, David K; Katz, Jonathan L

2016-01-01

Previous studies suggest dopamine (DA) D2-like receptor involvement in the reinforcing effects of food. To determine contributions of the three D2-like receptor subtypes, knockout (KO) mice completely lacking DA D2, D3, or D4 receptors (D2R, D3R, or D4R KO mice) and their wild-type (WT) littermates were exposed to a series of fixed-ratio (FR) food-reinforcement schedules in two contexts: an open economy with additional food provided outside the experimental setting and a closed economy with all food earned within the experimental setting. A behavioral economic model was used to quantify reinforcer effectiveness with food pellets obtained as a function of price (FR schedule value) plotted to assess elasticity of demand. Under both economies, as price increased, food pellets obtained decreased more rapidly (ie, food demand was more elastic) in DA D2R KO mice compared with WT littermates. Extinction of responding was studied in two contexts: by eliminating food deliveries and by delivering food independently of responding. A hyperbolic model quantified rates of extinction. Extinction in DA D2R KO mice occurred less rapidly compared with WT mice in both contexts. Elasticity of food demand was higher in DA D4R KO than WT mice in the open, but not closed, economy. Extinction of responding in DA D4R KO mice was not different from that in WT littermates in either context. No differences in elasticity of food demand or extinction rate were obtained in D3R KO mice and WT littermates. These results indicate that the D2R is the primary DA D2-like receptor subtype mediating the reinforcing effectiveness of food. PMID:26205210

Forever Young: The Role of Ubiquitin Receptor DA1 and E3 Ligase BIG BROTHER in Controlling Leaf Growth and Development1[OPEN

PubMed Central

Vanhaeren, Hannes; De Milde, Liesbeth

2017-01-01

The final size of plant organs is determined by a combination of cell proliferation and cell expansion. Leaves account for a large part of above-ground biomass and provide energy to complete the plant’s life cycle. Although the final size of leaves is remarkably constant under fixed environmental conditions, several genes have been described to enhance leaf growth when their expression is modulated. In Arabidopsis (Arabidopsis thaliana), mutations in DA1 and BB increase leaf size, an effect that is synergistically enhanced in the double mutant. Here, we show that overexpression of a dominant-negative version of DA1 enhances leaf size in a broad range of natural accessions of this species, indicating a highly conserved role of this protein in controlling organ size. We also found that during early stages of development, leaves of da1-1 and bb/eod1-2 mutants were already larger than the isogenic Col-0 wild type, but this phenotype was triggered by different cellular mechanisms. Later during development, da1-1 and bb/eod1-2 leaves showed a prolonged longevity, which was enhanced in the double mutant. Conversely, ectopic expression of DA1 or BB restricted growth and promoted leaf senescence. In concert, shortly upon induction of DA1 and BB expression, several marker genes for the transition from proliferation to expansion were highly up-regulated. Additionally, multiple genes involved in maintaining the mitotic cell cycle were rapidly down-regulated and senescence genes were strongly up-regulated, particularly upon BB induction. With these results, we demonstrate that DA1 and BB restrict leaf size and promote senescence through converging and different mechanisms. PMID:28003326

Automatic localization of the da Vinci surgical instrument tips in 3-D transrectal ultrasound.

PubMed

Mohareri, Omid; Ramezani, Mahdi; Adebar, Troy K; Abolmaesumi, Purang; Salcudean, Septimiu E

2013-09-01

Robot-assisted laparoscopic radical prostatectomy (RALRP) using the da Vinci surgical system is the current state-of-the-art treatment option for clinically confined prostate cancer. Given the limited field of view of the surgical site in RALRP, several groups have proposed the integration of transrectal ultrasound (TRUS) imaging in the surgical workflow to assist with accurate resection of the prostate and the sparing of the neurovascular bundles (NVBs). We previously introduced a robotic TRUS manipulator and a method for automatically tracking da Vinci surgical instruments with the TRUS imaging plane, in order to facilitate the integration of intraoperative TRUS in RALRP. Rapid and automatic registration of the kinematic frames of the da Vinci surgical system and the robotic TRUS probe manipulator is a critical component of the instrument tracking system. In this paper, we propose a fully automatic registration technique based on automatic 3-D TRUS localization of robot instrument tips pressed against the air-tissue boundary anterior to the prostate. The detection approach uses a multiscale filtering technique to identify and localize surgical instrument tips in the TRUS volume, and could also be used to detect other surface fiducials in 3-D ultrasound. Experiments have been performed using a tissue phantom and two ex vivo tissue samples to show the feasibility of the proposed methods. Also, an initial in vivo evaluation of the system has been carried out on a live anaesthetized dog with a da Vinci Si surgical system and a target registration error (defined as the root mean square distance of corresponding points after registration) of 2.68 mm has been achieved. Results show this method's accuracy and consistency for automatic registration of TRUS images to the da Vinci surgical system.

OpenDA-WFLOW framework for improving hydrologic predictions using distributed hydrologic models

NASA Astrophysics Data System (ADS)

Weerts, Albrecht; Schellekens, Jaap; Kockx, Arno; Hummel, Stef

2017-04-01

Data assimilation (DA) holds considerable potential for improving hydrologic predictions (Liu et al., 2012) and increase the potential for early warning and/or smart water management. However, advances in hydrologic DA research have not yet been adequately or timely implemented in operational forecast systems to improve the skill of forecasts for better informed real-world decision making. The objective of this work is to highlight the development of a generic linkage of the open source OpenDA package and the open source community hydrologic modeling framework Openstreams/WFLOW and its application in operational hydrological forecasting on various spatial scales. The coupling between OpenDA and Openstreams/wflow framework is based on the emerging standard Basic Model Interface (BMI) as advocated by CSDMS using cross-platform webservices (i.e. Apache Thrift) developed by Hut et al. (2016). The potential application of the OpenDA-WFLOW for operational hydrologic forecasting including its integration with Delft-FEWS (used by more than 40 operational forecast centers around the world (Werner et al., 2013)) is demonstrated by the presented case studies. We will also highlight the possibility to give real-time insight into the working of the DA methods applied for supporting the forecaster as mentioned as one of the burning issues by Liu et al., (2012).

Novas determinações dos parâmetros atmosféricos das estrelas anãs brancas DA

NASA Astrophysics Data System (ADS)

Giovannini, O.; Costa, A. F. M.; Kepler, S. O.

2003-08-01

Nós temos selecionado uma amostra de estrelas anãs brancas DA (atmosfera de hidrogênio) a partir dos índices de Strömgren cujos valores estão próximos a região de instabilidade das estrelas anãs brancas DA variáveis, as chamadas estrelas DAV ou ZZ Ceti. O objetivo é determinar os parâmetros fundamentais (temperatura efetiva, Teff, aceleração da gravidade, log g, e massa) destas estrelas para verificar quais os parâmetros estelares estão envolvidos com o mecanismo de pulsação das estrelas DAV. Nós obtemos, até agora, mais de 120 espectros óticos de estrelas DA. Entre as estrelas selecionadas há 20 estrelas variáveis (DAV). Assim, podemos verificar se existem ou não estrelas não variáveis dentro da faixa de instabilidade das estrelas ZZ Ceti. Neste trabalho nós apresentamos a determinação dos parâmetros atmosféricos (temperatura efetiva, Teff, e aceleração da gravidade, log g) das estrelas anãs brancas DA usando os novos modelos de atmosfera ML2/a = 0.6. Estes modelos têm sido utilizados recentemente por fornecerem uma excelente consistência interna na determinação das temperaturas nas regiões do ultra-violeta e ótico. Os parâmetros atmosféricos são determinados espectroscopicamente através da comparação do fluxo de energia das linhas de Balmer (Hb à H9) entre os espectros observados e sintéticos (gerados pelos modelos de atmosfera). As temperaturas obtidas com os novos modelos são, em geral, menores (~ 1000 K menos) que as temperaturas determinadas anteriormente, com modelos ML1. Os valores de log g não mudaram significativamente (menos de 10%). A faixa de instabilidade das DAVs está entre 11000 e 13000 K, consistente com dados de outros autores.

Comparison of standard laparoscopic distal pancreatectomy with minimally invasive distal pancreatectomy using the da Vinci S system.

PubMed

Ito, Masahiro; Asano, Yukio; Shimizu, Tomohiro; Uyama, Ichiro; Horiguchi, Akihiko

2014-01-01

Minimally invasive procedures for pancreatic pathologies are increasingly being used, including distal pancreatectomy. This study aimed to assess the indications for and outcomes of the da Vinci distal pancreatectomy procedure. We reviewed the medical records of patients who underwent pancreatic head resection from April 2009 to September 2013. Four patients (mean age, 52.7 years) underwent da Vinci distal pancreatectomy and 10 (mean age, 68.0 +/- 12.1 years) underwent laparoscopic distal pancreatectomy. The mean surgical duration was 292 +/- 153 min and 306 +/- 29 min, the mean blood loss was 153 +/- 71 mL and 61.7 +/- 72 mL, and the mean postoperative length of stay was 24 +/- 11 days and 14 +/- 3 days in the da Vinci distal pancreatectomy and laparoscopic distal pancreatectomy groups, respectively. One patient who underwent da Vinci distal pancreatectomy developed a pancreatic fistula, while 2 patients in the laparoscopic distal pancreatectomy group developed splenic ischemia and gastric torsion, respectively. Laparoscopic and robotic pancreatic resection were both safe and feasible in selected patients with distal pancreatic pathologies. Further studies are necessary to clarify the role of robotic surgery in the advanced laparoscopic era.

DA white dwarfs in Sloan Digital Sky Survey Data Release 7 and a search for infrared excess emission

NASA Astrophysics Data System (ADS)

Girven, J.; Gänsicke, B. T.; Steeghs, D.; Koester, D.

2011-10-01

We present a method which uses colour-colour cuts on the Sloan Digital Sky Survey (SDSS) photometry to select white dwarfs with hydrogen-rich (DA) atmospheres without the recourse to spectroscopy. This method results in a sample of DA white dwarfs that is 95 per cent complete at an efficiency of returning a true DA white dwarf of 62 per cent. The approach was applied to SDSS Data Release 7 for objects with and without SDSS spectroscopy. This led to 4636 spectroscopicially confirmed DA white dwarfs with g≤ 19; a ˜70 per cent increase compared to Eisenstein et al.'s 2006 sample. Including the photometric-only objects, we estimate a factor of 3 increase in DA white dwarfs. We find that the SDSS spectroscopic follow-up is 44 per cent complete for DA white dwarfs with Teff≳ 8000 K. We further cross-correlated the SDSS sample with Data Release 8 of the UKIRT (United Kingdom Infrared Telescope) Infrared Deep Sky Survey (UKIDSS) Large Area Survey. The spectral energy distributions (SED) of both subsets, with and without SDSS spectroscopy, were fitted with white dwarf models to determine the fraction of DA white dwarfs with low-mass stellar companions or dusty debris discs via the detection of excess near-infrared emission. From the spectroscopic sample we find that 2.0 per cent of white dwarfs have an excess consistent with a brown dwarf type companion, with a firm lower limit of 0.8 per cent. From the white dwarfs with photometry only, we find that 1.8 per cent are candidates for having brown dwarf companions. Similarly, both samples show that ˜1 per cent of white dwarfs are candidates for having a dusty debris disc.

32 CFR 644.512 - DA-SBA joint set-aside determination.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 4 2010-07-01 2010-07-01 true DA-SBA joint set-aside determination. 644.512 Section 644.512 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL... Stone § 644.512 DA-SBA joint set-aside determination. Section 15 of the Small Business Act (15 U.S.C...

Leonardo da Vinci's foot: historical evidence of concept.

PubMed

Jastifer, James R; Toledo-Pereyra, Luis H

2012-10-01

Leonardo da Vinci (1452-1519), world-renowned Italian renaissance master, is known for his contributions to, and broad interests in science and art. The objective of this work is to demonstrate the extent of his science by applying the use of his concepts to current models of foot and ankle mechanics. The art and science of Leonardo Da Vinci were extensively analyzed by reviewing his original drawings and hand written notebooks as well as their English translation. Current medical journals including the topics of foot, ankle, and biomechanics were reviewed for modern evidence and application of his concepts. The library of Michigan State University and the electronic library of the Royal Library at Windsor Castle were extensively utilized. From the depths of Santa Maria Nuova Hospital in Florence and Santo Spirito Hospital in Rome, through his commentary and anatomical drawings of around 30 cadaver dissections he performed, Leonardo da Vinci expressed his concept of foot and ankle anatomy and mechanics. He laid forth concepts, which vary little from current theories including those of proportion, statics and joint stability, sesamoid biomechanics, and structural support of the foot. Leonardo da Vinci, by combining an interest in anatomy and a gift of genius and artistic ability laid a foundation of foot and ankle anatomy and mechanics that have been applied in modern clinical sciences. Leonardo in this way made important contributions to the practice of foot and ankle orthopedics.

Evaluation of the diuretic activity in two Mexican medicinal species: Selaginella nothohybrida and Selaginella lepidophylla and its effects with ciclooxigenases inhibitors.

PubMed

Aguilar, María I; Benítez, Wendy V; Colín, Arturo; Bye, Robert; Ríos-Gómez, Ramiro; Calzada, Fernando

2015-04-02

Doradilla is a plant that has a long history in the Mexican traditional system of medicine for gall and renal stones, diuresis, stomach and liver inflammation among other diseases. Major components isolated from these plants include biflavonoids as amentoflavone (1), robustaflavone (2) and (S)-2,3-dihydrorobustaflavone (3) and the carbohydrate trehalose (4). The aim of this study was to evaluate the diuretic effect of the decoction of Selaginella nothohybrida Valdespino and Selaginella lepidophylla (Hook & Grev) Spring (Selaginellaceae), and compounds 1-4. We also explored the probable mode of action comparing the effects when using nonspecific and specific COX׳s inhibitors. Three biflavonoids (1-3) were isolated from the ethyl acetate extraction of the aqueous decoction and the carbohydrate trehalose (4) from the aqueous phase. The structures of all compounds were elucidated by spectroscopic methods and comparisons were made against published data. The diuretic activity was assessed in mice by oral administration of the decoctions in doses of 1000 and 2000mg/kg and biflavonoids 1-3 and trehalose (4) in a dose range of 10mg/kg using furosemide as a standard drug. Inhibitors of COX׳s such as acetyl salicylic acid, sodium naproxen, indomethacin and Celebrex were also assayed to analyze the involvement of renal prostaglandins in diuresis. Water excretion rate, pH, density, conductivity, and contents of Na(+) and K(+) were measured in the urine of mice. Decoction of Selaginella lepidophylla showed lower effect in the urine output at doses of 1000 and 2000mg/kg, while decoction of Selaginella nothohybrida produced an increase at 2000mg/kg (P<0.05). Urinary electrolytes excretion was also affected by this last extract and pure compounds: decoction diminished urinary excretion of sodium and potassium ions, so as compounds 1 and 4; compounds 2 and 3 observed just a natriuretic effect. Pretreated mice with COX׳s inhibitors and then with test compounds 1, 2, 4 and

Nucleotide sequence and phylogenetic analysis of Cucurbit yellow stunting disorder virus RNA 2.

PubMed

Livieratos, Ioannis C; Coutts, Robert H A

2002-06-01

The complete nucleotide sequence of Cucurbit yellow stunting disorder virus (CYSDV) RNA 2, a whitefly (Bemisia tabaci)-transmitted closterovirus with a bi-partite genome, is reported. CYSDV RNA 2 is 7,281 nucleotides long and contains the closterovirus hallmark gene array with a similar arrangement to the prototype member of the genus Crinivirus, Lettuce infectious yellows virus (LIYV). CYSDV RNA 2 contains open reading frames (ORFs) potentially encoding in a 5' to 3' direction for proteins of 5 kDa (ORF 1; hydrophobic protein), 62 kDa (ORF 2; heat shock protein 70 homolog, HSP70h), 59 kDa (ORF 3; protein of unknown function), 9 kDa (ORF 4; protein of unknown function), 28.5 kDa (ORF 5; coat protein, CP), 53 kDa (ORF 6; coat protein minor, CPm), and 26.5 kDa (ORF 7; protein of unknown function). Pairwise comparisons of CYSDV RNA 2-encoded proteins (HSP70h, p59 and CPm) among the closteroviruses showed that CYSDV is closely related to LIYV. Phylogenetic analysis based on the amino acid sequence of the HSP70h, indicated that CYSDV clusters with other members of the genus Crinivirus, and it is related to Little cherry virus-1 (LChV-1), but is distinct from the aphid- or mealybug-transmitted closteroviruses.

Effect of DA-9701 on Colorectal Distension-Induced Visceral Hypersensitivity in a Rat Model

PubMed Central

Kim, Eun Ran; Min, Byung-Hoon; Lee, Tae Ho; Son, Miwon; Rhee, Poong-Lyul

2014-01-01

Background/Aims DA-9701 is a newly developed drug made from the vegetal extracts of Pharbitidis semen and Co-rydalis tuber. The aim of this study was to evaluate the effect of DA-9701 on colorectal distension (CRD)-induced visceral hypersensitivity in a rat model. Methods Male Sprague-Dawley rats were subjected to neonatal colon irritation (CI) using CRD at 1 week after birth (CI group). At 6 weeks after birth, CRD was applied to these rats with a pressure of 20 to 90 mm Hg, and changes in the mean arterial pressure (MAP) were measured at baseline (i.e., without any drug administration) and after the administration of different doses of DA-9701. Results In the absence of DA-9701, the MAP changes after CRD were significantly higher in the CI group than in the control group at all applied pressures. In the control group, MAP changes after CRD were not significantly affected by the administration of DA-9701. In the CI group, however, the administration of DA-9701 resulted in a significant decrease in MAP changes after CRD. The administration of DA-9701 at a dose of 1.0 mg/kg produced a more significant decrease in MAP changes than the 0.3 mg/kg dose. Conclusions The administration of DA-9701 resulted in a significant increase in pain threshold in rats with CRD-induced visceral hypersensitivity. PMID:25071903

Effect of DA-9701 on colorectal distension-induced visceral hypersensitivity in a rat model.

PubMed

Kim, Eun Ran; Min, Byung-Hoon; Lee, Tae Ho; Son, Miwon; Rhee, Poong-Lyul

2014-07-01

DA-9701 is a newly developed drug made from the vegetal extracts of Pharbitidis semen and Co-rydalis tuber. The aim of this study was to evaluate the effect of DA-9701 on colorectal distension (CRD)-induced visceral hypersensitivity in a rat model. Male Sprague-Dawley rats were subjected to neonatal colon irritation (CI) using CRD at 1 week after birth (CI group). At 6 weeks after birth, CRD was applied to these rats with a pressure of 20 to 90 mm Hg, and changes in the mean arterial pressure (MAP) were measured at baseline (i.e., without any drug administration) and after the administration of different doses of DA-9701. In the absence of DA-9701, the MAP changes after CRD were significantly higher in the CI group than in the control group at all applied pressures. In the control group, MAP changes after CRD were not significantly affected by the administration of DA-9701. In the CI group, however, the administration of DA-9701 resulted in a significant decrease in MAP changes after CRD. The administration of DA-9701 at a dose of 1.0 mg/kg produced a more significant decrease in MAP changes than the 0.3 mg/kg dose. The administration of DA-9701 resulted in a significant increase in pain threshold in rats with CRD-induced visceral hypersensitivity.

Thinking like Leonardo da Vinci and its implications for the modern doctor.

PubMed

Baum, Neil

2013-01-01

Most people when asked to name the most creative, innovative, and multidimensional people in history would agree that Leonardo da Vinci is either at the top or very close to the number one position on that list. Wouldn't it be nice to think like da Vinci? This article shares the seven unique principles of thinking that da Vinci used that enabled him to be the greatest painter, sculptor, architect, musician, mathematician, engineer, inventor, anatomist, geologist, cartographer, botanist, and writer of his (if not of all) time. This article will take you deep into the notebooks and codices of da Vinci, and suggest ways his ideas can be used by anyone in the healthcare profession to make them a better healthcare provider.

76 FR 31457 - Airworthiness Directives; Diamond Aircraft Industries GmbH Model DA 42 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-01

... Airworthiness Directives; Diamond Aircraft Industries GmbH Model DA 42 Airplanes AGENCY: Federal Aviation... reportedly found on DA 42 Main Landing Gear (MLG) Damper-to-Trailing Arm joints during standard maintenance... DA 42 Main Landing Gear (MLG) Damper-to-Trailing Arm joints during standard maintenance. Depending on...

Role of D2 dopamine receptors of the ventral pallidum in inhibitory avoidance learning.

PubMed

Lénárd, László; Ollmann, Tamás; László, Kristóf; Kovács, Anita; Gálosi, Rita; Kállai, Veronika; Attila, Tóth; Kertes, Erika; Zagoracz, Olga; Karádi, Zoltán; Péczely, László

2017-03-15

In our present experiments, the role of D2 dopamine (DA) receptors of the ventral pallidum (VP) was investigated in one trial step-through inhibitory avoidance paradigm. Animals were shocked 3 times in the conditioning trial, with 0.5mA current for 1s. Subsequently bilateral microinjection of the D2 DA receptor agonist quinpirole was administered into the VP in three doses (0.1μg, 1.0μg or 5.0μg in 0.4μl saline). We also applied the D2 DA receptor antagonist sulpiride (0.4μg in 0.4μl saline) alone or 15min prior to the agonist treatment to elucidate whether the agonist effect was specific for the D2 DA receptors. Control animals received saline. In a supplementary experiment, it was also investigated whether application of the same conditioning method leads to the formation of short-term memory in the experimental animals. In the experiment with the D2 DA receptor agonist, only the 0.1μg quinpirole increased significantly the step-through latency during the test trials: retention was significant compared to the controls even 2 weeks after conditioning. The D2 DA receptor antagonist sulpiride pretreatment proved that the effect was due to the agonist induced activation of the D2 DA receptors of the VP. The supplementary experiment demonstrated that short-term memory is formed after conditioning in the experimental animals, supporting that the agonist enhanced memory consolidation in the first two experiments. Our results show that the activation of the D2 DA receptors in the VP facilitates memory consolidation as well as memory-retention in inhibitory avoidance paradigm. Copyright © 2017 Elsevier B.V. All rights reserved.

Oleosins (24 and 18 kDa) are hydrolyzed not only in extracted soybean oil bodies but also in soybean germination.

PubMed

Chen, Yeming; Zhao, Luping; Cao, Yanyun; Kong, Xiangzhen; Hua, Yufei

2014-01-29

After oil bodies (OBs) were extracted from ungerminated soybean by pH 6.8 extraction, it was found that 24 and 18 kDa oleosins were hydrolyzed in the extracted OBs, which contained many OB extrinsic proteins (i.e., lipoxygenase, β-conglycinin, γ-conglycinin, β-amylase, glycinin, Gly m Bd 30K (Bd 30K), and P34 probable thiol protease (P34)) as well as OB intrinsic proteins. In this study, some properties (specificity, optimal pH and temperature) of the proteases of 24 and 18 kDa oleosins and the oleosin hydrolysis in soybean germination were examined, and the high relationship between Bd 30K/P34 and the proteases was also discussed. The results showed (1) the proteases were OB extrinsic proteins, which had high specificity to hydrolyze 24 and 18 kDa oleosins, and cleaved the specific peptide bonds to form limited hydrolyzed products; (2) 24 and 18 kDa oleosins were not hydrolyzed in the absence of Bd 30K and P34 (or some Tricine-SDS-PAGE undetectable proteins); (3) the protease of 24 kDa oleosin had strong resistance to alkaline pH while that of 18 kDa oleosin had weak resistance to alkaline pH, and Bd 30K and P34, resolved into two spots on two-dimensional electrophoresis gel, also showed the same trend; (4) 16 kDa oleosin as well as 24 and 18 kDa oleosins were hydrolyzed in soybean germination, and Bd 30K and P34 were always contained in the extracted OBs from germinated soybean even when all oleosins were hydrolyzed; (5) the optimal temperature and pH of the proteases were respectively determined as in the ranges of 35-50 °C and pH 6.0-6.5, while 60 °C or pH 11.0 could denature them.

Impact of disruption of secondary binding site S2 on dopamine transporter function.

PubMed

Zhen, Juan; Reith, Maarten E A

2016-09-01

The structures of the leucine transporter, drosophila dopamine transporter, and human serotonin transporter show a secondary binding site (designated S2 ) for drugs and substrate in the extracellular vestibule toward the membrane exterior in relation to the primary substrate recognition site (S1 ). The present experiments are aimed at disrupting S2 by mutating Asp476 and Ile159 to Ala. Both mutants displayed a profound decrease in [(3) H]DA uptake compared with wild-type associated with a reduced turnover rate kcat . This was not caused by a conformational bias as the mutants responded to Zn(2+) (10 μM) similarly as WT. The dopamine transporters with either the D476A or I159A mutation both displayed a higher Ki for dopamine for the inhibition of [3H](-)-2-β-carbomethoxy-3-β-(4-fluorophenyl)tropane binding than did the WT transporter, in accordance with an allosteric interaction between the S1 and S2 sites. The results provide evidence in favor of a general applicability of the two-site allosteric model of the Javitch/Weinstein group from LeuT to dopamine transporter and possibly other monoamine transporters. X-ray structures of transporters closely related to the dopamine (DA) transporter show a secondary binding site S2 in the extracellular vestibule proximal to the primary binding site S1 which is closely linked to one of the Na(+) binding sites. This work examines the relationship between S2 and S1 sites. We found that S2 site impairment severely reduced DA transport and allosterically reduced S1 site affinity for the cocaine analog [(3) H]CFT. Our results are the first to lend direct support for the application of the two-site allosteric model, advanced for bacterial LeuT, to the human DA transporter. The model states that, after binding of the first DA molecule (DA1 ) to the primary S1 site (along with Na(+) ), binding of a second DA (DA2 ) to the S2 site triggers, through an allosteric interaction, the release of DA1 and Na(+) into the cytoplasm. © 2016

Early clinical experience with the da Vinci Xi Surgical System in general surgery.

PubMed

Hagen, Monika E; Jung, Minoa K; Ris, Frederic; Fakhro, Jassim; Buchs, Nicolas C; Buehler, Leo; Morel, Philippe

2017-09-01

The da Vinci Xi Surgical System (Intuitive Surgical Inc., Sunnyvale, CA, USA) has been released in 2014 to facilitate minimally invasive surgery. Novel features are targeted towards facilitating complex multi-quadrant procedures, but data is scarce so far. Perioperative data of patients who underwent robotic general surgery with the da Vinci Xi system within the first 6 month after installation were collected and analyzed. The gastric bypass procedures performed with the da Vinci Xi Surgical System were compared to an equal amount of the last procedures with the da Vinci Si Surgical System. Thirty-one foregut (28 Roux-en-Y gastric bypasses), 6 colorectal procedures and 1 revisional biliary procedure were performed. The mean operating room (OR) time was 221.8 (±69.0) minutes for gastric bypasses and 306.5 (±48.8) for colorectal procedures with mean docking time of 9.4 (±3.8) minutes. The gastric bypass procedure was transitioned from a hybrid to a fully robotic approach. In comparison to the last 28 gastric bypass procedures performed with the da Vinci Si Surgical System, the OR time was comparable (226.9 versus 230.6 min, p = 0.8094), but the docking time significantly longer with the da Vinci Xi Surgical System (8.5 versus 6.1 min, p = 0.0415). All colorectal procedures were performed with a single robotic docking. No intraoperative and two postoperative complications occurred. The da Vinci Xi might facilitate single-setups of totally robotic gastric bypass and colorectal surgeries. However, further comparable research is needed to clearly determine the significance of this latest version of the da Vinci Surgical System.

76 FR 14346 - Airworthiness Directives; Diamond Aircraft Industries GmbH Model DA 42 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-16

... Industries GmbH Model DA 42 Airplanes AGENCY: Federal Aviation Administration (FAA), Department of... been reportedly found on DA 42 Main Landing Gear (MLG) Damper-to-Trailing Arm joints during standard... condition for the specified products. The MCAI states: Cracks have been reportedly found on DA 42 Main...

Prevention of Oxidized Low Density Lipoprotein-Induced Endothelial Cell Injury by DA-PLGA-PEG-cRGD Nanoparticles Combined with Ultrasound

PubMed Central

Li, Zhaojun; Huang, Hui; Huang, Lili; Du, Lianfang; Sun, Ying; Duan, Yourong

2017-01-01

In general, atherosclerosis is considered to be a form of chronic inflammation. Dexamethasone has anti-inflammatory effects in atherosclerosis, but it was not considered for long-term administration on account of a poor pharmacokinetic profile and adverse side effects. Nanoparticles in which drugs can be dissolved, encapsulated, entrapped or chemically attached to the particle surface have abilities to incorporate dexamethasone and to be used as controlled or targeted drug delivery system. Long circulatory polymeric nanoparticles present as an assisting approach for controlled and targeted release of the encapsulated drug at the atherosclerotic site. Polymeric nanoparticles combined with ultrasound (US) are widely applied in cancer treatment due to their time applications, low cost, simplicity, and safety. However, there are few studies on atherosclerosis treatment using polymeric nanoparticles combined with US. In this study, targeted dexamethasone acetate (DA)-loaded poly (lactide-glycolide)-polyethylene glycol-cRGD (PLGA-PEG-cRGD) nanoparticles (DA-PLGA-PEG-cRGD NPs) were prepared by the emulsion-evaporation method using cRGD modified PLGA-PEG polymeric materials (PLGA-PEG-cRGD) prepared as the carrier. The average particle size of DA-PLGA-PEG-cRGD NPs was 221.6 ± 0.9 nm. Morphology of the nanoparticles was spherical and uniformly dispersed. In addition, the DA released profiles suggested that ultrasound could promote drug release from the nanocarriers and accelerate the rate of release. In vitro, the cellular uptake process of fluorescein isothiocyanate (FITC)@DA-PLGA-PEG-cRGD NPs combined with US into the damaged human umbilical vein endothelial cells (HUVECs) indicated that US promoted rapid intracellular uptake of FITC@DA- PLGA-PEG-cRGD NPs. The cell viability of DA-PLGA-PEG-cRGD NPs combined with US reached 91.9% ± 0.2%, which demonstrated that DA-PLGA-PEG-cRGD NPs combined with US had a positive therapeutic effect on damaged HUVECs. Overall, DA

Prevention of Oxidized Low Density Lipoprotein-Induced Endothelial Cell Injury by DA-PLGA-PEG-cRGD Nanoparticles Combined with Ultrasound.

PubMed

Li, Zhaojun; Huang, Hui; Huang, Lili; Du, Lianfang; Sun, Ying; Duan, Yourong

2017-04-13

In general, atherosclerosis is considered to be a form of chronic inflammation. Dexamethasone has anti-inflammatory effects in atherosclerosis, but it was not considered for long-term administration on account of a poor pharmacokinetic profile and adverse side effects. Nanoparticles in which drugs can be dissolved, encapsulated, entrapped or chemically attached to the particle surface have abilities to incorporate dexamethasone and to be used as controlled or targeted drug delivery system. Long circulatory polymeric nanoparticles present as an assisting approach for controlled and targeted release of the encapsulated drug at the atherosclerotic site. Polymeric nanoparticles combined with ultrasound (US) are widely applied in cancer treatment due to their time applications, low cost, simplicity, and safety. However, there are few studies on atherosclerosis treatment using polymeric nanoparticles combined with US. In this study, targeted dexamethasone acetate (DA)-loaded poly (lactide-glycolide)-polyethylene glycol-cRGD (PLGA-PEG-cRGD) nanoparticles (DA-PLGA-PEG-cRGD NPs) were prepared by the emulsion-evaporation method using cRGD modified PLGA-PEG polymeric materials (PLGA-PEG-cRGD) prepared as the carrier. The average particle size of DA-PLGA-PEG-cRGD NPs was 221.6 ± 0.9 nm. Morphology of the nanoparticles was spherical and uniformly dispersed. In addition, the DA released profiles suggested that ultrasound could promote drug release from the nanocarriers and accelerate the rate of release. In vitro, the cellular uptake process of fluorescein isothiocyanate (FITC)@DA-PLGA-PEG-cRGD NPs combined with US into the damaged human umbilical vein endothelial cells (HUVECs) indicated that US promoted rapid intracellular uptake of FITC@DA- PLGA-PEG-cRGD NPs. The cell viability of DA-PLGA-PEG-cRGD NPs combined with US reached 91.9% ± 0.2%, which demonstrated that DA-PLGA-PEG-cRGD NPs combined with US had a positive therapeutic effect on damaged HUVECs. Overall, DA

The 1.17 Day Orbit of the Double-degenerate (DA+DQ) NLTT 16249

NASA Astrophysics Data System (ADS)

Vennes, S.; Kawka, A.; O'Toole, S. J.; Thorstensen, J. R.

2012-09-01

New spectroscopic observations show that the double-degenerate system NLTT 16249 is in a close orbit (a = 5.6 ± 0.3 R ⊙) with a period of 1.17 days. The total mass of the system is estimated between 1.47 and 2.04 M ⊙ but it is not expected to merge within a Hubble timescale (t merge ≈ 1011 yr). Vennes & Kawka originally identified the system because of the peculiar composite hydrogen (DA class) and molecular (C2-DQ class and CN) spectra and the new observations establish this system as the first DA plus DQ close double degenerate. Also, the DQ component was the first of its class to show nitrogen dredged up from the core in its atmosphere. The star may be viewed as the first known DQ descendant of the born-again PG1159 stars. Alternatively, the presence of nitrogen may be the result of past interactions and truncated evolution in a close binary system. Based on observations made with ESO telescopes at the La Silla Paranal Observatory under program ID 86.D-0562.

[Diagnostic Accuracy of the LiSe-DaZ for Children with Specific Language Impairment].

PubMed

Stephan, T; Keilmann, A

2015-12-01

Currently, only few tests for the development of speech and language exist for bi- or multilingual children in Germany. One of those, the LiSe-DaZ (Linguistic performance measurement - German as a second language), was examined in a prospective study regarding its practicability and the sensitivity to detect children with specific language impairment in a group of children aged 5 to 7 who suffered from a severe language impairment according to clinical tests. 74 children (mean age: 60 months; 46% monolingual German-speaking; 54% bi- or multilingual) with severe specific language impairment were examined with the LiSe-DaZ in addition to the clinical established diagnostic during their in-patient stay in the hospital. The children, on average, showed in the receptive language abilities (LiSe-DaZ vs. TROG-D), the expressive vocabulary (LiSe-DaZ vs. AWST-R or WWT) and in the use of prepositions (LiSe-DaZ vs. Ravensburger Dysgrammatical clinical trial) significantly (p<0,0005) better results in the LiSe-DaZ. Thus, the majority of children were diagnosed as language impaired by clinically established tests whereas the LiSe-DaZ considered the children's language development to be normal. This difference was consistently more prominent for children with German as a second language. Compared with the clinically established tests, the informative value of the LiSe-DaZ turned out to be insufficient. The LiSe-DaZ does not detect children with the need of language therapy. Nevertheless, a norming of the established speech tests for bi- or multilingual children would be desirable to avoid unfounded judgements. © Georg Thieme Verlag KG Stuttgart · New York.

Effect of DA-9701 on Gastric Motor Function Assessed by Magnetic Resonance Imaging in Healthy Volunteers: A Randomized, Double-Blind, Placebo-Controlled Trial.

PubMed

Min, Yang Won; Min, Byung-Hoon; Kim, Seonwoo; Choi, Dongil; Rhee, Poong-Lyul

2015-01-01

Improving gastric accommodation and gastric emptying is an attractive physiological treatment target in patients with functional dyspepsia (FD). We evaluated the effect of DA-9701, a new drug for FD, on gastric motor function after a meal in healthy volunteers using magnetic resonance imaging (MRI). Forty healthy volunteers were randomly allocated to receive either DA-9701 or placebo. After 5 days of treatment, subjects underwent gastric MRI (60 min before and 15, 30, 45, 60, 90, and 120 min after a liquid test meal). Gastric volume was measured through 3-dimensional reconstruction from MRI data. We analyzed 4 outcome variables including changes in total gastric volume (TGV), proximal TGV, and proximal to distal TGV ratio after a meal and gastric emptying rates after adjusting values at the pre-test meal. Changes in TGV and proximal TGV after a meal did not differ between the DA-9701 and placebo groups (difference between groups -25.9 mL, 95% confidence interval [CI] -54.0 to 2.3 mL, P = 0.070 and -2.9 mL, 95% CI -30.3 to 24.5 mL, P = 0.832, respectively). However, pre-treatment with DA-9701 increased postprandial proximal to distal TGV ratio more than placebo (difference between groups 0.93, 95% CI 0.08 to 1.79, P = 0.034). In addition, pre-treatment with DA-9701 significantly increased gastric emptying as compared with placebo (mean difference between groups 3.41%, 95% CI 0.54% to 6.29%, P = 0.021, by mixed model for repeated measures). Our results suggested that DA-9701 enhances gastric emptying and does not significantly affect gastric accommodation in healthy volunteers. Further studies to confirm whether DA-9701 enhances these gastric motor functions in patients with FD are warranted. ClinicalTrials.gov NCT02091635.

Multiple D2 heteroreceptor complexes: new targets for treatment of schizophrenia

PubMed Central

Borroto-Escuela, Dasiel O.; Pintsuk, Julia; Schäfer, Thorsten; Friedland, Kristina; Ferraro, Luca; Tanganelli, Sergio; Liu, Fang; Fuxe, Kjell

2016-01-01

The dopamine (DA) neuron system most relevant for schizophrenia is the meso-limbic-cortical DA system inter alia densely innervating subcortical limbic regions. The field of dopamine D2 receptors and schizophrenia changed markedly with the discovery of many types of D2 heteroreceptor complexes in subcortical limbic areas as well as the dorsal striatum. The results indicate that the D2 is a hub receptor which interacts not only with many other G protein-coupled receptors (GPCRs) including DA isoreceptors but also with ion-channel receptors, receptor tyrosine kinases, scaffolding proteins and DA transporters. Disturbances in several of these D2 heteroreceptor complexes may contribute to the development of schizophrenia through changes in the balance of diverse D2 homo- and heteroreceptor complexes mediating the DA signal, especially to the ventral striato-pallidal γ-aminobutyric acid (GABA) pathway. This will have consequences for the control of this pathway of the glutamate drive to the prefrontal cortex via the mediodorsal thalamic nucleus which can contribute to psychotic processes. Agonist activation of the A2A protomer in the A2A–D2 heteroreceptor complex inhibits D2 Gi/o mediated signaling but increases the D2 β-arrestin2 mediated signaling. Through this allosteric receptor–receptor interaction, the A2A agonist becomes a biased inhibitory modulator of the Gi/o mediated D2 signaling, which may the main mechanism for its atypical antipsychotic properties especially linked to the limbic A2A–D2 heterocomplexes. The DA and glutamate hypotheses of schizophrenia come together in the signal integration in D2–N-methyl-d-aspartate (NMDA) and A2A–D2–metabotropic glutamate receptor 5 (mGlu5) heteroreceptor complexes, especially in the ventral striatum. 5-Hydroxytryptamine 2A (5-HT2A)–D2 heteroreceptor complexes are special targets for atypical antipsychotics with high potency to block their 5-HT2A protomer signaling in view of the potential development of

Leonardo da Vinci (1452-1519) and his depictions of the human spine.

PubMed

Bowen, Garvin; Gonzales, Jocelyn; Iwanaga, Joe; Fisahn, Christian; Loukas, Marios; Oskouian, Rod J; Tubbs, R Shane

2017-12-01

Few individuals in history have exerted so great an influence and made such extensive contributions to so many disciplines as Leonardo da Vinci. Da Vinci's inquisitive, experimental mentality led him to many discoveries, such as spinal cord function and the proper anatomy of several organ systems. Respected not only as an artist but also as an anatomist, he made many significant contributions to the field. This article explores da Vinci's drawings, in relation to the anatomy of the human spine.

Tryptic digestion of human GPIIIa. Isolation and biochemical characterization of the 23 kDa N-terminal glycopeptide carrying the antigenic determinant for a monoclonal antibody (P37) which inhibits platelet aggregation.

PubMed Central

Calvete, J J; Rivas, G; Maruri, M; Alvarez, M V; McGregor, J L; Hew, C L; Gonzalez-Rodriguez, J

1988-01-01

Early digestion of pure human platelet glycoprotein IIIa (GPIIIa) leads to a single cleavage of the molecule at 23 kDa far from one of the terminal amino acids. Automated Edman degradation demonstrates that GPIIIa and the smaller (23 kDa) tryptic fragment share the same N-terminal amino acid sequence. A further cleavage occurs in the larger fragment (80 kDa), reducing its apparent molecular mass by 10 kDa. The 23 kDa fragment remains attached to the larger ones in unreduced samples. Stepwise reduction of early digested GPIIIa with dithioerythritol selectively reduces the single disulphide bond joining the smaller (23 kDa) to the larger (80/70 kDa) fragments. Two fractions were obtained by size-exclusion chromatography of early digested GPIIIa after partial or full reduction and alkylation. The larger-size fraction contains the 80/70 kDa fragments, while the 23 kDa fragment is isolated in the smaller. The amino acid compositions of these fractions do not differ very significantly from the composition of GPIIIa; however the 23 kDa fragment contains only 10.2% by weight of sugars and is richer in neuraminic acid. Disulphide bonds are distributed four in the 23 kDa glycopeptide and 20-21 in the 80/70 kDa glycopeptide. The epitope for P37, a monoclonal antibody which inhibits platelet aggregation [Melero & González-Rodríguez (1984) Eur. J. Biochem. 141, 421-427] is situated within the first 17 kDa of the N-terminal region of GPIIIa, which gives a special functional interest to this extracellular region of GPIIIa. On the other hand, the epitopes for GPIIIa-specific monoclonal antibodies, P6, P35, P40 and P97, which do not interfere with platelet aggregation, are located within the larger tryptic fragment (80/70 kDa). Thus, the antigenic areas available in the extracellular surface of GPIIIa for these five monoclonal antibodies are now more precisely delineated. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. PMID:2455507

Regolith grain size and cohesive strength of near-Earth Asteroid (29075) 1950 DA

NASA Astrophysics Data System (ADS)

Gundlach, B.; Blum, J.

2015-09-01

Due to its fast rotation period of 2.12 h, about half of the surface of near-Earth Asteroid (29075) 1950 DA experiences negative (i.e., outward directed) acceleration levels (Rozitis, B., Maclennan, E., Emery, J.P. [2014]. Nature 512, 174-176). Thus, cohesion of the surface material is mandatory to prevent rotational breakup of the asteroid. Rozitis et al. (Rozitis, B., Maclennan, E., Emery, J.P. [2014]. Nature 512, 174-176) concluded that a grain size of ∼6 cm or lower is needed to explain the required cohesive strength of 64-20+12Pa . Here, we present another approach to determine the grain size of near-Earth Asteroid (29075) 1950 DA by using the thermal inertia value from Rozitis et al. (Rozitis, B., Maclennan, E., Emery, J.P. [2014]. Nature 512, 174-176) and a model of the heat conductivity of the surface regolith (Gundlach, B., Blum, J. [2013]. Icarus 223, 479-492). This method yields a mean particle radius ranging from 32 μm to 117 μm. The derived grain sizes are then used to infer the cohesive strength of the surface material of Asteroid (29075) 1950 DA (ranging from 24 Pa to 88 Pa), by using laboratory measurements of the tensile strength of powders.

The Real Code of Leonardo da Vinci

PubMed Central

Ose, Leiv

2008-01-01

Leonardo da Vinci was born in Italy. Among the researchers and scientists, he is favourably known for his remarkable efforts in scientific work. His investigations of atherosclerosis judiciously combine three separate fields of research. In 1506, he finished his masterpiece, painting of Mona Lisa. A careful clinical examination of the famous painting reveals a yellow irregular leather-like spot at the inner end of the left upper eyelid and a soft bumpy well-defined swelling of the dorsum of the right hand beneath the index finger about 3 cm long. This is probably the first case of familial hypercholesterolemia (FH). The FH code of Leonardo da Vinci was given immense consideration by scientists like Carl Muller, who described the xanthomas tuberosum and angina pectoris. On the contrary, Akira Endo searched for microbial metabolites that would inhibit HMG-CoA reductase, the rate-limiting enzyme in the synthesis of cholesterol and finally, Michael Brown and Joseph Goldstein published a remarkable series of elegant and insightful papers in the 70s and 80s. They established that the cellular uptake of low-density lipoprotein (LDL) essentially requires the LDL receptor. In conclusion: this was the real Code of Leonardo da Vinci. PMID:19924278

[The rational application of Da Vinci surgical system in thyroidectomy].

PubMed

He, Q Q

2017-08-01

Da Vinci surgical system is the most advanced minimally invasive surgical platform in the world, and this system has been widely used in cardiac surgery, urology surgery, gynecologic surgery and general surgery. Although the application of this system was relatively late in thyroid surgery, the number of thyroidectomy with Da Vinci surgical system is increasing quickly. Having reviewed recent studies and summarized clinical experience, compared with traditional open operation, the robotic thyroidectomy has the same surgical safety and effectiveness in selective patients with thyroid cancer. In this paper, several aspects on this novel operation were demonstrated, including surgical indications and contraindications, the approaches, surgical procedures and postoperative complications, in order to promote the rational application of Da Vinci surgical system in thyroidectomy.

32 CFR 635.23 - DA Form 4833 (Commander's Report of Disciplinary or Administrative Action).

Code of Federal Regulations, 2014 CFR

2014-07-01

... the PMO. The Battalion Commander or the first Lieutenant Colonel in the chain of command is... DA Form 4833 within 45 days of receipt. (1) Appropriate blocks will be checked and blanks annotated... the disposition on DA Form 4833 as appropriate. That portion of the signature block of DA Form 4833...

32 CFR 635.23 - DA Form 4833 (Commander's Report of Disciplinary or Administrative Action).

Code of Federal Regulations, 2010 CFR

2010-07-01

... the PMO. The Battalion Commander or the first Lieutenant Colonel in the chain of command is... DA Form 4833 within 45 days of receipt. (1) Appropriate blocks will be checked and blanks annotated... the disposition on DA Form 4833 as appropriate. That portion of the signature block of DA Form 4833...

32 CFR 635.23 - DA Form 4833 (Commander's Report of Disciplinary or Administrative Action).

Code of Federal Regulations, 2011 CFR

2011-07-01

... the PMO. The Battalion Commander or the first Lieutenant Colonel in the chain of command is... DA Form 4833 within 45 days of receipt. (1) Appropriate blocks will be checked and blanks annotated... the disposition on DA Form 4833 as appropriate. That portion of the signature block of DA Form 4833...

32 CFR 635.23 - DA Form 4833 (Commander's Report of Disciplinary or Administrative Action).

Code of Federal Regulations, 2013 CFR

2013-07-01

... the PMO. The Battalion Commander or the first Lieutenant Colonel in the chain of command is... DA Form 4833 within 45 days of receipt. (1) Appropriate blocks will be checked and blanks annotated... the disposition on DA Form 4833 as appropriate. That portion of the signature block of DA Form 4833...

32 CFR 635.23 - DA Form 4833 (Commander's Report of Disciplinary or Administrative Action).

Code of Federal Regulations, 2012 CFR

2012-07-01

... the PMO. The Battalion Commander or the first Lieutenant Colonel in the chain of command is... DA Form 4833 within 45 days of receipt. (1) Appropriate blocks will be checked and blanks annotated... the disposition on DA Form 4833 as appropriate. That portion of the signature block of DA Form 4833...

Do two current canine parvovirus type 2 and 2b vaccines provide protection against the new type 2c variant?

PubMed

Larson, Laurie J; Schultz, R D

2008-01-01

Three groups (n=9 or 10) of 12-week-old canine parvovirus type 2 (CPV-2) antibody-negative puppies were vaccinated: one group with a product containing modified-live CPV-2b (Galaxy DA2PPv; Schering-Plough Animal Health), one group with a product containing modified-live CPV-2 (Continuum DAP, Intervet), and one group (controls) with sterile saline. All puppies receiving CPV-2 and CPV-2b vaccines developed antibody as determined by the hemagglutination inhibition assay. All groups of puppies were challenged with a combination of virulent CPV-2b and CPV-2c 5 weeks after vaccination. All puppies in the CPV-2 and CPV-2b vaccinated groups were protected from disease, whereas all control group puppies developed disease and 50% died or were euthanized. This study demonstrated that the CPV-2 and CPV-2b vaccine components of the Continuum DAP and Galaxy DA2PPv products, respectively, provided protection against the CPV-2b virus and also provided complete protection against the new CPV-2c variant.

Identification of Rice Genes Associated With Enhanced Cold Tolerance by Comparative Transcriptome Analysis With Two Transgenic Rice Plants Overexpressing DaCBF4 or DaCBF7, Isolated From Antarctic Flowering Plant Deschampsia antarctica

PubMed Central

Byun, Mi Young; Cui, Li Hua; Lee, Jungeun; Park, Hyun; Lee, Andosung; Kim, Woo Taek; Lee, Hyoungseok

2018-01-01

Few plant species can survive in Antarctica, the harshest environment for living organisms. Deschampsia antarctica is the only natural grass species to have adapted to and colonized the maritime Antarctic. To investigate the molecular mechanism of the Antarctic adaptation of this plant, we identified and characterized D. antarctica C-repeat binding factor 4 (DaCBF4), which belongs to monocot CBF group IV. The transcript level of DaCBF4 in D. antarctica was markedly increased by cold and dehydration stress. To assess the roles of DaCBF4 in plants, we generated a DaCBF4-overexpressing transgenic rice plant (Ubi:DaCBF4) and analyzed its abiotic stress response phenotype. Ubi:DaCBF4 displayed enhanced tolerance to cold stress without growth retardation under any condition compared to wild-type plants. Because the cold-specific phenotype of Ubi:DaCBF4 was similar to that of Ubi:DaCBF7 (Byun et al., 2015), we screened for the genes responsible for the improved cold tolerance in rice by selecting differentially regulated genes in both transgenic rice lines. By comparative transcriptome analysis using RNA-seq, we identified 9 and 15 genes under normal and cold-stress conditions, respectively, as putative downstream targets of the two D. antarctica CBFs. Overall, our results suggest that Antarctic hairgrass DaCBF4 mediates the cold-stress response of transgenic rice plants by adjusting the expression levels of a set of stress-responsive genes in transgenic rice plants. Moreover, selected downstream target genes will be useful for genetic engineering to enhance the cold tolerance of cereal plants, including rice. PMID:29774046

Identification of Rice Genes Associated With Enhanced Cold Tolerance by Comparative Transcriptome Analysis With Two Transgenic Rice Plants Overexpressing DaCBF4 or DaCBF7, Isolated From Antarctic Flowering Plant Deschampsia antarctica.

PubMed

Byun, Mi Young; Cui, Li Hua; Lee, Jungeun; Park, Hyun; Lee, Andosung; Kim, Woo Taek; Lee, Hyoungseok

2018-01-01

Few plant species can survive in Antarctica, the harshest environment for living organisms. Deschampsia antarctica is the only natural grass species to have adapted to and colonized the maritime Antarctic. To investigate the molecular mechanism of the Antarctic adaptation of this plant, we identified and characterized D. antarctica C-repeat binding factor 4 ( DaCBF4 ), which belongs to monocot CBF group IV. The transcript level of DaCBF4 in D. antarctica was markedly increased by cold and dehydration stress. To assess the roles of DaCBF4 in plants, we generated a DaCBF4 -overexpressing transgenic rice plant ( Ubi:DaCBF4 ) and analyzed its abiotic stress response phenotype. Ubi:DaCBF4 displayed enhanced tolerance to cold stress without growth retardation under any condition compared to wild-type plants. Because the cold-specific phenotype of Ubi:DaCBF4 was similar to that of Ubi:DaCBF7 (Byun et al., 2015), we screened for the genes responsible for the improved cold tolerance in rice by selecting differentially regulated genes in both transgenic rice lines. By comparative transcriptome analysis using RNA-seq, we identified 9 and 15 genes under normal and cold-stress conditions, respectively, as putative downstream targets of the two D. antarctica CBFs. Overall, our results suggest that Antarctic hairgrass DaCBF4 mediates the cold-stress response of transgenic rice plants by adjusting the expression levels of a set of stress-responsive genes in transgenic rice plants. Moreover, selected downstream target genes will be useful for genetic engineering to enhance the cold tolerance of cereal plants, including rice.

Biofortification of soybean meal: immunological properties of the 27 kDa γ-zein.

PubMed

Krishnan, Hari B; Jang, Sungchan; Kim, Won-Seok; Kerley, Monty S; Oliver, Melvin J; Trick, Harold N

2011-02-23

Legumes, including soybeans ( Glycine max ), are deficient in sulfur-containing amino acids, which are required for the optimal growth of monogastric animals. This deficiency can be overcome by expressing heterologous proteins rich in sulfur-containing amino acids in soybean seeds. A maize 27 kDa γ-zein, a cysteine-rich protein, has been successfully expressed in several crops including soybean, barley, and alfalfa with the intent to biofortify these crops for animal feed. Previous work has shown that the maize 27 kDa zein can withstand digestion by pepsin and elicit an immunogenic response in young pigs. By use of sera from patients who tested positive by ImmunoCAP assay for elevated IgE to maize proteins, specific IgE binding to the 27 kDa γ-zein is demonstrated. Bioinformatic analysis using the full-length and 80 amino acid sliding window FASTA searches identified significant sequence homology of the 27 kDa γ-zein with several known allergens. Immunoblot analysis using human serum that cross-reacts with maize seed proteins also revealed specific IgE-binding to the 27 kDa γ-zein in soybean seed protein extracts containing the 27 kDa zein. This study demonstrates for the first time the allergenicity potential of the 27 kDa γ-zein and the potential that this protein has to limit livestock performance when used in soybeans that serve as a biofortified feed supplement.

[The Da Vinci Medical-mental motivation program for supporting lifestyle changes in patients with type 2 diabetes].

PubMed

Kempf, K; Dirk, M; Kolb, H; Hebestreit, A; Bittner, G; Martin, S

2012-02-01

Healthy diet and physical activity can improve metabolic control in patients with type 2 diabetes mellitus. However, lifestyle change without external help is difficult: an alteration of mental attitude is necessary to achieve long-term success. A computer-based motivational program ("Da Vinci") has been developed to help patients to change their mental attitudes and beliefs. Patients with type 2 diabetes were supervised by psychological trainers in four sessions at ten study centers. The interactive computer program allowed for identification of motivation restraints and overcoming them. Parameters of carbohydrate metabolism were measured at the beginning and end of the three-months program as well as three and six months after end of program. All participants (n = 61) developed a positive attitude towards the range of their action and by themselves changed their lifestyle. After three months their weight (-4.6 kg; p < 0.0001), body mass index (-1.1 kg/m2; p < 0.0001), waist circumference (-3.5 cm; p < 0.0001), HbA1c (-0.6 %; p < 0.0001), triglycerides (-31.1 mg/dl; p = 0.033), systolic (-4.0 mmHg; p = 0.005) and diastolic blood pressure (-3.0 mmHg; p = 0.006) had been reduced. Short duration of diabetes and high baseline HbA1c values were predictive for successful HbA1c reduction. Three and six months after end of the program participants were able to maintain or even augment achieved improvements. During the motivational program, which is intended to alter mental attitude and beliefs, but not to teach knowledge about diabetes, participants were able to significantly improve their metabolic control. As these improvements were maintained long-term, this points to sustainable lifestyle change. © Georg Thieme Verlag KG Stuttgart · New York.

Assessment of in vivo organ-uptake and in silico prediction of CYP mediated metabolism of DA-Phen, a new dopaminergic agent.

PubMed

Sutera, Flavia Maria; Giannola, Libero Italo; Murgia, Denise; De Caro, Viviana

2017-12-01

The drug development process strives to predict metabolic fate of a drug candidate, together with its uptake in major organs, whether they act as target, deposit or metabolism sites, to the aim of establish a relationship between the pharmacodynamics and the pharmacokinetics and highlight the potential toxicity of the drug candidate. The present study was aimed at evaluating the in vivo uptake of 2-Amino-N-[2-(3,4-dihydroxy-phenyl)-ethyl]-3-phenyl-propionamide (DA-Phen) - a new dopaminergic neurotransmission modulator, in target and non-target organs of animal subjects and integrating these data with SMARTCyp results, an in silico method that predicts the sites of cytochrome P450-mediated metabolism of drug-like molecules. Wistar rats, subjected to two different behavioural studies in which DA-Phen was intraperitoneally administrated at a dose equal to 0.03mmol/kg, were sacrificed after the experimental protocols and their major organs were analysed to quantify the drug uptake. The data obtained were integrated with in silico prediction of potential metabolites of DA-Phen using the SmartCYP predictive tool. DA-Phen reached quantitatively the Central Nervous System and the results showed that the amide bond of the DA-Phen is scarcely hydrolysed as it was found intact in analyzed organs. As a consequence, it is possible to assume that DA-Phen acts as dopaminergic modulator per se and not as a Dopamine prodrug, thus avoiding peripheral release and toxic side effects due to the endogenous neurotransmitter. Furthermore the identification of potential metabolites related to biotransformation of the drug candidate leads to a more careful evaluation of the appropriate route of administration for future intended therapeutic aims and potential translation into clinical studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Virtual Observatory Service TheoSSA: Establishing a Database of Synthetic Stellar Flux Standards I. NLTE Spectral Analysis of the DA-Type White Dwarf G191-B2B *,**,***,****

NASA Technical Reports Server (NTRS)

Rauch, T.; Werner, K.; Bohlin, R.; Kruk, J. W.

2013-01-01

Hydrogen-rich, DA-type white dwarfs are particularly suited as primary standard stars for flux calibration. State-of-the-art NLTE models consider opacities of species up to trans-iron elements and provide reliable synthetic stellar-atmosphere spectra to compare with observations. Aims. We will establish a database of theoretical spectra of stellar flux standards that are easily accessible via a web interface. Methods. In the framework of the Virtual Observatory, the German Astrophysical Virtual Observatory developed the registered service TheoSSA. It provides easy access to stellar spectral energy distributions (SEDs) and is intended to ingest SEDs calculated by any model-atmosphere code. In case of the DA white dwarf G191-B2B, we demonstrate that the model reproduces not only its overall continuum shape but also the numerous metal lines exhibited in its ultraviolet spectrum. Results. TheoSSA is in operation and contains presently a variety of SEDs for DA-type white dwarfs. It will be extended in the near future and can host SEDs of all primary and secondary flux standards. The spectral analysis of G191-B2B has shown that our hydrostatic models reproduce the observations best at Teff =60 000 +/- 2000K and log g=7.60 +/- 0.05.We newly identified Fe vi, Ni vi, and Zn iv lines. For the first time, we determined the photospheric zinc abundance with a logarithmic mass fraction of -4.89 (7.5 × solar). The abundances of He (upper limit), C, N, O, Al, Si, O, P, S, Fe, Ni, Ge, and Sn were precisely determined. Upper abundance limits of about 10% solar were derived for Ti, Cr, Mn, and Co. Conclusions. The TheoSSA database of theoretical SEDs of stellar flux standards guarantees that the flux calibration of all astronomical data and cross-calibration between different instruments can be based on the same models and SEDs calculated with different model-atmosphere codes and are easy to compare.

Early experience using the da Vinci Surgical System for the treatment of mediastinal tumors.

PubMed

Kajiwara, Naohiro; Taira, Masahiro; Yoshida, Koichi; Hagiwara, Masaru; Kakihana, Masatoshi; Usuda, Jitsuo; Uchida, Osamu; Ohira, Tatsuo; Kawate, Norihiko; Ikeda, Norihiko

2011-10-01

The da Vinci Surgical System has been used in only a few cases for treating mediastinal tumors in Japan. Recently, we used the da Vinci Surgical System for various types of anterior and middle mediastinal tumors in clinical practice. We report our early experience using the da Vinci Surgical System. Seven patients gave written informed consent to undergo robotic surgery for mediastinal tumor dissection using the da Vinci Surgical System. We evaluated the safety and feasibility of this system for the surgical treatment of mediastinal tumors. Two specialists in thoracic surgery who are certified to use the da Vinci S Surgical System and another specialist acted as an assistant performed the tumor dissection. We were able to access difficult-to-reach areas, such as the mediastinum, safely. All the resected tumors were classified as benign tumors histologically. The average da Vinci setting time was 14.0 min, the average working time was 55.7 min, and the average overall operating time was 125.9 min. The learning curve for the da Vinci setup and manipulation time was short. Robotic surgery enables mediastinal tumor dissection in certain cases more safely and easily than conventional video-assisted thoracoscopic surgery and less invasively than open thoracotomy.

DA-9701: A New Multi-Acting Drug for the Treatment of Functional Dyspepsia

PubMed Central

Kwon, Yong Sam; Son, Miwon

2013-01-01

Motilitone® (DA-9701) is a new herbal drug that was launched for the treatment of functional dyspepsia in December 2011 in Korea. The heterogeneous symptom pattern and multiple causes of functional dyspepsia have resulted in multiple drug target strategies for its treatment. DA-9701, a compound consisting of a combination of Corydalis Tuber and Pharbitidis Semen, has being developed for treatment of functional dyspepsia. It has multiple mechanisms of action such as fundus relaxation, visceral analgesia, and prokinetic effects. Furthermore, it was found to significantly enhance meal-induced gastric accommodation and increase gastric compliance in dogs. DA-9701 also showed an analgesic effect in rats with colorectal distension induced visceral hypersensitivity and an antinociceptive effect in beagle dogs with gastric distension-induced nociception. The pharmacological effects of DA-9701 also include conventional effects, such as enhanced gastric emptying and gastrointestinal transit. The safety profi le of DA-9701 is also preferable to that of other treatments. PMID:24265862

Synergetic effects of DA-6/GA₃ with EDTA on plant growth, extraction and detoxification of Cd by Lolium perenne.

PubMed

He, Shanying; Wu, Qiuling; He, Zhenli

2014-12-01

Research is needed to improve efficiency of phytoextraction of heavy metals from contaminated soils. A pot experiment was carried out to study the effects of plant growth regulators (PGRs) (diethyl aminoethyl hexanoate (C18H33NO8, DA-6) and gibberellic acid 3 (C19H22O6, GA3)) and/or EDTA on Cd extraction, subcellular distribution and chemical forms in Lolium perenne. The addition of EDTA or PGRs significantly enhanced Cd extraction efficiency (P<0.05), with the decreasing order of: 1 μM DA-6>10 μM DA-6>10 μM GA3>2.5 mmol kg(-1) EDTA>other treatments of PGR alone. PGRs+EDTA resulted in a further increase in Cd extraction efficiency, with EDTA+1 μM DA-6 being the most efficient. At the subcellular level, about 44-57% of Cd was soluble fraction, 18-44% in cell walls, and 12-25% in cellular organelles fraction. Chemical speciation analysis showed that 40-54% of Cd was NaCl extractable, 7-23% HAc extractable, followed by other fractions. EDTA increased the proportions of Cd in soluble and cellular organelles fraction, as well as the metal migration in shoot; therefore, the toxicity to plant increased and plant growth was inhibited. Conversely, PGRs fixed more Cd in cell walls and reduced Cd migration in shoot; thus, metal toxicity was reduced. In addition, PGRs promoted plant biomass growth significantly (P<0.05), with 1 μM DA-6 being the most effective. A combination of DA-6/GA3 with EDTA can alleviate the adverse effect of EDTA on plant growth, and the treatment of EDTA+1 μM DA-6 appears to be optimal for improving the remediation efficiency of L. perenne for Cd contaminated soil. Copyright © 2014 Elsevier Ltd. All rights reserved.

Endoplasmic reticulum stress (ER-stress) by 2-deoxy-D-glucose (2DG) reduces cyclooxygenase-2 (COX-2) expression and N-glycosylation and induces a loss of COX-2 activity via a Src kinase-dependent pathway in rabbit articular chondrocytes.

PubMed

Yu, Seon-Mi; Kim, Song-Ja

2010-11-30

Endoplasmic reticulum (ER) stress regulates a wide range of cellular responses including apoptosis, proliferation, inflammation, and differentiation in mammalian cells. In this study, we observed the role of 2-deoxy-D-glucose (2DG) on inflammation of chondrocytes. 2DG is well known as an inducer of ER stress, via inhibition of glycolysis and glycosylation. Treatment of 2DG in chondrocytes considerably induced ER stress in a dose- and time-dependent manner, which was demonstrated by a reduction of glucose regulated protein of 94 kDa (grp94), an ER stress-inducible protein, as determined by a Western blot analysis. In addition, induction of ER stress by 2DG led to the expression of COX-2 protein with an apparent molecular mass of 66-70kDa as compared with the normally expressed 72-74 kDa protein. The suppression of ER stress with salubrinal (Salub), a selective inhibitor of eif2-alpha dephosphorylation, successfully prevented grp94 induction and efficiently recovered 2DG- modified COX-2 molecular mass and COX-2 activity might be associated with COX-2 N-glycosylation. Also, treatment of 2DG increased phosphorylation of Src in chondrocytes. The inhibition of the Src signaling pathway with PP2 (Src tyrosine kinase inhibitor) suppressed grp94 expression and restored COX-2 expression, N-glycosylation, and PGE2 production, as determined by a Western blot analysis and PGE2 assay. Taken together, our results indicate that the ER stress induced by 2DG results in a decrease of the transcription level, the molecular mass, and the activity of COX-2 in rabbit articular chondrocytes via a Src kinase-dependent pathway.

Spectroscopic Classification of ASASSN-15cz and ASASSN-15da as Type Ia Supernovae

NASA Astrophysics Data System (ADS)

Porter, A.; Wagner, R. M.; Miller, C. J.; Koff, R. A.; Kiyota, S.; Brimacombe, J.; Holoien, T. W.-S.; Stanek, K. Z.; Kochanek, C. S.; Danilet, A. B.; Simonian, G.; Basu, U.; Goss, N.; Beacom, J. F.; Shappee, B. J.; Prieto, J. L.; Bersier, D.; Dong, Subo; Wozniak, P. R.; Falco, E.; Szczygiel, D.; Pojmanski, G.; Nicholls, B.

2015-02-01

We obtained optical spectroscopy (range 398-685 nm; resolution 0.3 nm) of ASASSN-15cz (ATEL #7058) and ASASSN-15da (ATEL #7061) on 2015 February 13.18 and 13.35 UT respectively using the Hiltner 2.4 m telescope (+OSMOS) of the MDM Observatory on Kitt Peak, Arizona.

PanDA Pilot Submission using Condor-G: Experience and Improvements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao X.; Hover John; Wlodek Tomasz

2011-01-01

PanDA (Production and Distributed Analysis) is the workload management system of the ATLAS experiment, used to run managed production and user analysis jobs on the grid. As a late-binding, pilot-based system, the maintenance of a smooth and steady stream of pilot jobs to all grid sites is critical for PanDA operation. The ATLAS Computing Facility (ACF) at BNL, as the ATLAS Tier1 center in the US, operates the pilot submission systems for the US. This is done using the PanDA 'AutoPilot' scheduler component which submits pilot jobs via Condor-G, a grid job scheduling system developed at the University of Wisconsin-Madison.more » In this paper, we discuss the operation and performance of the Condor-G pilot submission at BNL, with emphasis on the challenges and issues encountered in the real grid production environment. With the close collaboration of Condor and PanDA teams, the scalability and stability of the overall system has been greatly improved over the last year. We review improvements made to Condor-G resulting from this collaboration, including isolation of site-based issues by running a separate Gridmanager for each remote site, introduction of the 'Nonessential' job attribute to allow Condor to optimize its behavior for the specific character of pilot jobs, better understanding and handling of the Gridmonitor process, as well as better scheduling in the PanDA pilot scheduler component. We will also cover the monitoring of the health of the system.« less

Effect of DA-8031, a novel oral compound for premature ejaculation, on male rat sexual behavior.

PubMed

Kang, Kyung Koo; Sung, Ji Hyun; Kim, Soon Hoe; Lee, Sukhyang

2014-03-01

DA-8031 is a potent and selective serotonin transporter inhibitor developed for the treatment of premature ejaculation. The aim of the present study was to investigate the effects of DA-8031 on male sexual behavior in a rat model. Sexual behavior was examined after an acute oral administration of 10, 30 or 100 mg/kg of DA-8031 in copulation studies with female rats. Pharmacokinetic parameters were calculated after oral administration of DA-8031 at a dose level of 30 mg/kg. DA-8031 treatment produced a dose-dependent increase in ejaculation latency time and showed statistical significance at 30 and 100 mg/kg dosage levels compared with the vehicle (P < 0.05). In addition, DA-8031 treatment reduced the mean number of ejaculations in a dose-dependent manner. No changes in post-ejaculatory interval, numbers of mounts, intromissions or ejaculations were observed at any dose. In pharmacokinetic study, the blood concentration of DA-8031 peaked at 0.38 ± 0.14 h after oral administration, and then rapidly declined with a half-life of 1.79 ± 0.32 h. Treatment with DA-8031 delays the ejaculation latency time without affecting the initiation of mounting behavior or post-ejaculatory interval in rats. Furthermore, DA-8031 is rapidly absorbed and eliminated after oral administration in rats. These preclinical findings provide a clue for the clinical testing of DA-8031 as an "on-demand" agent for premature ejaculation. © 2013 The Japanese Urological Association.

Draft Genome Sequences of Two Bacillus thuringiensis Strains and Characterization of a Putative 41.9-kDa Insecticidal Toxin

PubMed Central

Palma, Leopoldo; Muñoz, Delia; Berry, Colin; Murillo, Jesús; Caballero, Primitivo

2014-01-01

In this work, we report the genome sequencing of two Bacillus thuringiensis strains using Illumina next-generation sequencing technology (NGS). Strain Hu4-2, toxic to many lepidopteran pest species and to some mosquitoes, encoded genes for two insecticidal crystal (Cry) proteins, cry1Ia and cry9Ea, and a vegetative insecticidal protein (Vip) gene, vip3Ca2. Strain Leapi01 contained genes coding for seven Cry proteins (cry1Aa, cry1Ca, cry1Da, cry2Ab, cry9Ea and two cry1Ia gene variants) and a vip3 gene (vip3Aa10). A putative novel insecticidal protein gene 1143 bp long was found in both strains, whose sequences exhibited 100% nucleotide identity. The predicted protein showed 57 and 100% pairwise identity to protein sequence 72 from a patented Bt strain (US8318900) and to a putative 41.9-kDa insecticidal toxin from Bacillus cereus, respectively. The 41.9-kDa protein, containing a C-terminal 6× HisTag fusion, was expressed in Escherichia coli and tested for the first time against four lepidopteran species (Mamestra brassicae, Ostrinia nubilalis, Spodoptera frugiperda and S. littoralis) and the green-peach aphid Myzus persicae at doses as high as 4.8 µg/cm2 and 1.5 mg/mL, respectively. At these protein concentrations, the recombinant 41.9-kDa protein caused no mortality or symptoms of impaired growth against any of the insects tested, suggesting that these species are outside the protein’s target range or that the protein may not, in fact, be toxic. While the use of the polymerase chain reaction has allowed a significant increase in the number of Bt insecticidal genes characterized to date, novel NGS technologies promise a much faster, cheaper and efficient screening of Bt pesticidal proteins. PMID:24784323

Morphogenetic Studies of the Drosophila DA1 Ventral Olfactory Projection Neuron

PubMed Central

Yu, Hung-Hsiang

2016-01-01

In the Drosophila olfactory system, odorant information is sensed by olfactory sensory neurons and relayed from the primary olfactory center, the antennal lobe (AL), to higher olfactory centers via olfactory projection neurons (PNs). A major portion of the AL is constituted with dendrites of four groups of PNs, anterodorsal PNs (adPNs), lateral PNs (lPNs), lateroventral PNs (lvPNs) and ventral PNs (vPNs). Previous studies have been focused on the development and function of adPNs and lPNs, while the investigation on those of lvPNs and vPNs received less attention. Here, we study the molecular and cellular mechanisms underlying the morphogenesis of a putative male-pheromone responding vPN, the DA1 vPN. Using an intersection strategy to remove background neurons labeled within a DA1 vPN-containing GAL4 line, we depicted morphological changes of the DA1 vPN that occurs at the pupal stage. We then conducted a pilot screen using RNA interference knock-down approach to identify cell surface molecules, including Down syndrome cell adhesion molecule 1 and Semaphorin-1a, that might play essential roles for the DA1 vPN morphogenesis. Taken together, by revealing molecular and cellular basis of the DA1 vPN morphogenesis, we should provide insights into future comprehension of how vPNs are assembled into the olfactory neural circuitry. PMID:27163287

Morphogenetic Studies of the Drosophila DA1 Ventral Olfactory Projection Neuron.

PubMed

Shen, Hung-Chang; Wei, Jia-Yi; Chu, Sao-Yu; Chung, Pei-Chi; Hsu, Tsai-Chi; Yu, Hung-Hsiang

2016-01-01

In the Drosophila olfactory system, odorant information is sensed by olfactory sensory neurons and relayed from the primary olfactory center, the antennal lobe (AL), to higher olfactory centers via olfactory projection neurons (PNs). A major portion of the AL is constituted with dendrites of four groups of PNs, anterodorsal PNs (adPNs), lateral PNs (lPNs), lateroventral PNs (lvPNs) and ventral PNs (vPNs). Previous studies have been focused on the development and function of adPNs and lPNs, while the investigation on those of lvPNs and vPNs received less attention. Here, we study the molecular and cellular mechanisms underlying the morphogenesis of a putative male-pheromone responding vPN, the DA1 vPN. Using an intersection strategy to remove background neurons labeled within a DA1 vPN-containing GAL4 line, we depicted morphological changes of the DA1 vPN that occurs at the pupal stage. We then conducted a pilot screen using RNA interference knock-down approach to identify cell surface molecules, including Down syndrome cell adhesion molecule 1 and Semaphorin-1a, that might play essential roles for the DA1 vPN morphogenesis. Taken together, by revealing molecular and cellular basis of the DA1 vPN morphogenesis, we should provide insights into future comprehension of how vPNs are assembled into the olfactory neural circuitry.

Modified Da Chengqi granules improvement in immune function in early severe acute pancreatitis patients.

PubMed

Jiang, D-L; Yang, J; Jiang, S-Y; Yuan, F-L; Gu, Y-L; Li, J-P; Pei, Z-J

2016-06-24

We investigated the role of modified Da Chengqi granules in improving immune function in early severe acute pancreatitis patients. Early severe acute pancreatitis patients who agreed to receive combined treatment of traditional Chinese and Western medicine were randomly assigned to the experimental or control group. All subjects received conventional therapy to support organ function. The experimental group also received modified Da Chengqi granules. Cytokine (interleukin-6, interleukin-10, and tumor necrosis factor-α) levels, immunological markers (HLA-DR, Treg, and Th1/Th2), urinary lactulose/mannitol ratio, and endotoxin levels were measured at 1, 3, 7, and 14 days after hospital admission. The total mortality rate was 11.69% (9/77), which was significantly lower in the experimental group [4.88% (2/41)] than in the control group [19.44% (7/36); χ(2) = 3.940, P < 0.05]. Serum interleukin-6, interleukin-10, tumor necrosis factor-α and endotoxin levels and the lactulose/mannitol ratio were significantly lower on day 7 and day 14 than on day 1 in experimental and control groups (P < 0.01). Immunological indices were significantly lower in the experimental group than in the control group on day 14 (all P < 0.01 or 0.05). HLA-DR-positive cell ratio gradually increased over 14 days in experimental and control groups (P < 0.01 vs day 1), but was higher in the experimental group than in the control group by day 14 (P < 0.05). Notably, Treg cell prevalence and Th1/Th2 cell ratio deteriorated within 7 days in both groups (P < 0.01 vs day 1), but then returned to day 1 levels (P < 0.01 or 0.05 vs day 1). Significant differences in Treg levels and Th1/Th2 cell ratio between experimental and control groups were observed on day 14 (P < 0.01). These results show that modified Da Chengqi granules can improve immune function in early severe acute pancreatitis patients.

Ebf2 is required for development of dopamine neurons in the midbrain periaqueductal gray matter of mouse.

PubMed

Yang, Qiaoqiao; Liu, Shuxi; Yin, Min; Yin, Yanqing; Zhou, Guomin; Zhou, Jiawei

2015-11-01

Dopaminergic (DA) neurons in the midbrain ventral periaqueductal gray matter (PAG) play critical roles in various physiological and pathophysiological processes including sleep-wake rhyme, antinociception, and drug addiction. However, the molecular mechanisms underlying their development are poorly understood. Here, we showed that PAG DA neurons arose as early as E15.5 in mouse embryos. During the prenatal period, the majority of PAG DA neurons was distributed in the intermediate and caudal regions of the PAG. In the postnatal brain, ∼50% of PAG DA neurons were preferentially located in the caudal portion of the PAG. Moreover, transcription factor early B-cell factor 2 (Ebf2) was transiently expressed in a subset of DA neurons in embryonic ventral mesencephalon. Functional analysis revealed that loss of Ebf2 in vivo caused a marked reduction in the number of DA neurons in the midbrain PAG but not in the substantia nigra and ventral tegmental area. Thus, Ebf2 is identified as a novel and important regulator selectively required for midbrain PAG DA neuron development. © 2015 Wiley Periodicals, Inc.

Determinação de regiões de órbitas diretas estáveis ao redor da Lua

NASA Astrophysics Data System (ADS)

de Melo, C. F.; Winter, O. C.; Vieira Neto, E.

2003-08-01

Neste Trabalho estamos investigando regiões do sistema Terra-Lua que contêm órbitas diretas estáveis ao redor da Lua visando a utilização destas órbitas em futuras missões de veículos espaciais como alternativas de trajetórias com baixo custo de manutenção. Adotando-se o problema restrito de três corpos, Terra-Lua-partícula, a localização e a extensão destas regiões de estabilidade foram investigadas numericamente considerando como estável toda órbita que permanece ao redor a Lua por, no mínimo, 1000 dias com energia de dois corpos da partícula em relação à Lua negativa. A estabilidade de tais regiões está associada a duas famílias de órbitas periódicas simples H1 e H2 e a órbitas quase-periódicas associadas a elas. Uma vez identificadas as regiões de estabilidade passamos a analisá-las introduzindo, paulatinamente, outras interações relevantes ao sistema como as perturbações do Sol (via problema restrito de quatro corpos), das marés, da pressão de radiação e do achatamento terrestre. Os resultados encontrados até o momento mostram que a perturbação do Sol é a única que reduz significativamente o tamanho das regiões de estabilidade. Também estamos investigando o comportamento de tais regiões quando características intrínsecas do sistema como as excentricidades das órbitas da Terra e da Lua e a inclinação da órbita Lua são consideradas. Com este estudo estamos reunindo informações que nos permitirão compreender a evolução das regiões de estabilidade no sistema Terra-Lua, bem como estabelecer parâmetros adequados para a utilização das trajetórias estáveis em futuras missões espaciais. Agradecimentos: Este projeto conta com o apoio do CNPq, da Capes e da Fapesp.

RISING FROM THE ASHES: MID-INFRARED RE-BRIGHTENING OF THE IMPOSTOR SN 2010da IN NGC 300

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lau, Ryan M.; Ressler, Michael E.; Kasliwal, Mansi M.

2016-10-20

We present multi-epoch mid-infrared (IR) photometry and the optical discovery observations of the “impostor” supernova (SN) 2010da in NGC 300 using new and archival Spitzer Space Telescope images and ground-based observatories. The mid-infrared counterpart of SN 2010da was detected as Spitzer Infrared Intensive Transient Survey (SPIRITS) 14bme in the SPIRITS, an ongoing systematic search for IR transients. Before erupting on 2010 May 24, the SN 2010da progenitor exhibited a constant mid-IR flux at 3.6 and only a slight ∼10% decrease at 4.5 μ m between 2003 November and 2007 December. A sharp increase in the 3.6 μ m flux followedmore » by a rapid decrease measured ∼150 days before and ∼80 days after the initial outburst, respectively, reveal a mid-IR counterpart to the coincident optical and high luminosity X-ray outbursts. At late times, after the outburst (∼2000 days), the 3.6 and 4.5 μ m emission increased to over a factor of two times the progenitor flux and is currently observed (as of 2016 Feb) to be fading, but still above the progenitor flux. We attribute the re-brightening mid-IR emission to continued dust production and increasing luminosity of the surviving system associated with SN 2010da. We analyze the evolution of the dust temperature ( T {sub d} ∼ 700–1000 K), mass ( M {sub d} ∼ 0.5–3.8 × 10{sup −7} M {sub ⊙}), luminosity ( L {sub IR} ∼ 1.3–3.5 × 10{sup 4} L {sub ⊙}), and the equilibrium temperature radius ( R {sub eq} ∼ 6.4–12.2 au) in order to resolve the nature of SN 2010da. We address the leading interpretation of SN 2010da as an eruption from a luminous blue variable high-mass X-ray binary (HMXB) system. We propose that SN 2010da is instead a supergiant (sg)B[e]-HMXB based on similar luminosities and dust masses exhibited by two other known sgB[e]-HMXB systems. Additionally, the SN 2010da progenitor occupies a similar region on a mid-IR color–magnitude diagram (CMD) with known sgB[e] stars in the Large

Activation of serotonin 2C receptors in dopamine neurons inhibits binge-like eating in mice

PubMed Central

Xu, Pingwen; He, Yanlin; Cao, Xuehong; Valencia-Torres, Lourdes; Yan, Xiaofeng; Saito, Kenji; Wang, Chunmei; Yang, Yongjie; Hinton, Antentor; Zhu, Liangru; Shu, Gang; Myers, Martin G.; Wu, Qi; Tong, Qingchun; Heisler, Lora K.; Xu, Yong

2016-01-01

Background Neural networks that regulate binge eating remain to be identified, and effective treatments for binge eating are limited. Methods We combined neuroanatomical, pharmacological, electrophysiological, Cre-lox, and chemogenetic approaches to investigate the functions of 5-HT 2C receptor (5-HT2CR) expressed by dopamine (DA) neurons in the regulation of binge-like eating behavior in mice. Results We showed that 5-HT stimulates DA neural activity through a 5-HT2CR-mediated mechansim, and activation of this midbrain 5-HT-DA neural circuit effectively inhibits binge-like eating behavior in mice. Notably, 5-HT medications, including fluoxetine, d-Fenfluramine, and lorcaserin (a selective 5-HT2CR agonist), act upon 5-HT2CRs expressed by DA neurons to inhibit binge-like eating in mice. Conclusions We identified the 5-HT2CR population in DA neurons as one potential target for anti-binge therapies, and provided pre-clinical evidence that 5-HT2CR agonists could be used to treat binge eating. PMID:27516377

Dopamine inhibits somatolactin gene expression in tilapia pituitary cells through the dopamine D2 receptors.

PubMed

Jiang, Quan; Lian, Anji; He, Qi

2016-07-01

Dopamine (DA) is an important neurotransmitter in the central nervous system of vertebrates and possesses key hypophysiotropic functions. Early studies have shown that DA has a potent inhibitory effect on somatolactin (SL) release in fish. However, the mechanisms responsible for DA inhibition of SL gene expression are largely unknown. To this end, tilapia DA type-1 (D1) and type-2 (D2) receptor transcripts were examined in the neurointermediate lobe (NIL) of the tilapia pituitary by real-time PCR. In tilapia, DA not only was effective in inhibiting SL mRNA levels in vivo and in vitro, but also could abolish pituitary adenylate cyclase-activating polypeptide (PACAP)- and salmon gonadotropin-releasing hormone (sGnRH)-stimulated SL gene expression at the pituitary level. In parallel studies, the specific D2 receptor agonists quinpirole and bromocriptine could mimic the DA-inhibited SL gene expression. Furthermore, the D2 receptor antagonists domperidone and (-)-sulpiride could abolish the SL response to DA or the D2 agonist quinpirole, whereas D1 receptor antagonists SCH23390 and SKF83566 were not effective in this respect. In primary cultures of tilapia NIL cells, D2 agonist quinpirole-inhibited cAMP production could be blocked by co-treatment with the D2 antagonist domperidone and the ability of forskolin to increase cAMP production was also inhibited by quinpirole. Using a pharmacological approach, the AC/cAMP pathway was shown to be involved in quinpirole-inhibited SL mRNA expression. These results provide evidence that DA can directly inhibit SL gene expression at the tilapia pituitary level via D2 receptor through the AC/cAMP-dependent mechanism. Copyright © 2016 Elsevier Inc. All rights reserved.

Seeking 'energy' vs. pain relief in spas in Brazil (Caldas da Imperatriz) and Portugal (Termas da Sulfurea).

PubMed

Quintela, Maria Manuel

2011-04-01

This paper is a comparative ethnography of the therapeutic practices at two different spa locations: Caldas da Imperatriz, SC, Brazil, and Termas da Sulfurea in Cabeco de Vide, Portugal. The comparison reveals the existence of contrasting 'explanatory models' held by the spa-goers as well as by the official medical systems. In the Portuguese context this model is highly medicalized; in the Brazilian case, spa treatments are viewed as 'alternative' or 'complementary' therapy and are also related to religious philosophies. Each model corresponds to a different idiom expressing certain experiences and world views, one focusing on 'pains' (dores) and the other on 'energy' (energia), the former leading to the rationale of 'curing', the latter to the notion of 'energizing'. In this paper the author intends to analyze and contrast the categories found in these models, which originate from different conceptions of health, illness and healing for Brazilian and Portuguese spa-goers.

OpenDA Open Source Generic Data Assimilation Environment and its Application in Process Models

NASA Astrophysics Data System (ADS)

El Serafy, Ghada; Verlaan, Martin; Hummel, Stef; Weerts, Albrecht; Dhondia, Juzer

2010-05-01

Data Assimilation techniques are essential elements in state-of-the-art development of models and their optimization with data in the field of groundwater, surface water and soil systems. They are essential tools in calibration of complex modelling systems and improvement of model forecasts. The OpenDA is a new and generic open source data assimilation environment for application to a choice of physical process models, applied to case dependent domains. OpenDA was introduced recently when the developers of Costa, an open-source TU Delft project [http://www.costapse.org; Van Velzen and Verlaan; 2007] and those of the DATools from the former WL|Delft Hydraulics [El Serafy et al 2007; Weerts et al. 2009] decided to join forces. OpenDA makes use of a set of interfaces that describe the interaction between models, observations and data assimilation algorithms. It focuses on flexible applications in portable systems for modelling geophysical processes. It provides a generic interfacing protocol that allows combination of the implemented data assimilation techniques with, in principle, any time-stepping model duscribing a process(atmospheric processes, 3D circulation, 2D water level, sea surface temperature, soil systems, groundwater etc.). Presently, OpenDA features filtering techniques and calibration techniques. The presentation will give an overview of the OpenDA and the results of some of its practical applications. Application of data assimilation in portable operational forecasting systems—the DATools assimilation environment, El Serafy G.Y., H. Gerritsen, S. Hummel, A. H. Weerts, A.E. Mynett and M. Tanaka (2007), Journal of Ocean Dynamics, DOI 10.1007/s10236-007-0124-3, pp.485-499. COSTA a problem solving environment for data assimilation applied for hydrodynamical modelling, Van Velzen and Verlaan (2007), Meteorologische Zeitschrift, Volume 16, Number 6, December 2007 , pp. 777-793(17). Application of generic data assimilation tools (DATools) for flood

Cav1.3 channels control D2-autoreceptor responses via NCS-1 in substantia nigra dopamine neurons

PubMed Central

Dragicevic, Elena; Poetschke, Christina; Duda, Johanna; Schlaudraff, Falk; Lammel, Stephan; Schiemann, Julia; Fauler, Michael; Hetzel, Andrea; Watanabe, Masahiko; Lujan, Rafael; Malenka, Robert C.; Striessnig, Joerg

2014-01-01

Dopamine midbrain neurons within the substantia nigra are particularly prone to degeneration in Parkinson’s disease. Their selective loss causes the major motor symptoms of Parkinson’s disease, but the causes for the high vulnerability of SN DA neurons, compared to neighbouring, more resistant ventral tegmental area dopamine neurons, are still unclear. Consequently, there is still no cure available for Parkinson’s disease. Current therapies compensate the progressive loss of dopamine by administering its precursor l-DOPA and/or dopamine D2-receptor agonists. D2-autoreceptors and Cav1.3-containing L-type Ca2+ channels both contribute to Parkinson’s disease pathology. L-type Ca2+ channel blockers protect SN DA neurons from degeneration in Parkinson’s disease and its mouse models, and they are in clinical trials for neuroprotective Parkinson’s disease therapy. However, their physiological functions in SN DA neurons remain unclear. D2-autoreceptors tune firing rates and dopamine release of SN DA neurons in a negative feedback loop through activation of G-protein coupled potassium channels (GIRK2, or KCNJ6). Mature SN DA neurons display prominent, non-desensitizing somatodendritic D2-autoreceptor responses that show pronounced desensitization in PARK-gene Parkinson’s disease mouse models. We analysed surviving human SN DA neurons from patients with Parkinson’s disease and from controls, and detected elevated messenger RNA levels of D2-autoreceptors and GIRK2 in Parkinson’s disease. By electrophysiological analysis of postnatal juvenile and adult mouse SN DA neurons in in vitro brain-slices, we observed that D2-autoreceptor desensitization is reduced with postnatal maturation. Furthermore, a transient high-dopamine state in vivo, caused by one injection of either l-DOPA or cocaine, induced adult-like, non-desensitizing D2-autoreceptor responses, selectively in juvenile SN DA neurons, but not ventral tegmental area dopamine neurons. With pharmacological

Cav1.3 channels control D2-autoreceptor responses via NCS-1 in substantia nigra dopamine neurons.

PubMed

Dragicevic, Elena; Poetschke, Christina; Duda, Johanna; Schlaudraff, Falk; Lammel, Stephan; Schiemann, Julia; Fauler, Michael; Hetzel, Andrea; Watanabe, Masahiko; Lujan, Rafael; Malenka, Robert C; Striessnig, Joerg; Liss, Birgit

2014-08-01

Dopamine midbrain neurons within the substantia nigra are particularly prone to degeneration in Parkinson's disease. Their selective loss causes the major motor symptoms of Parkinson's disease, but the causes for the high vulnerability of SN DA neurons, compared to neighbouring, more resistant ventral tegmental area dopamine neurons, are still unclear. Consequently, there is still no cure available for Parkinson's disease. Current therapies compensate the progressive loss of dopamine by administering its precursor l-DOPA and/or dopamine D2-receptor agonists. D2-autoreceptors and Cav1.3-containing L-type Ca(2+) channels both contribute to Parkinson's disease pathology. L-type Ca(2+) channel blockers protect SN DA neurons from degeneration in Parkinson's disease and its mouse models, and they are in clinical trials for neuroprotective Parkinson's disease therapy. However, their physiological functions in SN DA neurons remain unclear. D2-autoreceptors tune firing rates and dopamine release of SN DA neurons in a negative feedback loop through activation of G-protein coupled potassium channels (GIRK2, or KCNJ6). Mature SN DA neurons display prominent, non-desensitizing somatodendritic D2-autoreceptor responses that show pronounced desensitization in PARK-gene Parkinson's disease mouse models. We analysed surviving human SN DA neurons from patients with Parkinson's disease and from controls, and detected elevated messenger RNA levels of D2-autoreceptors and GIRK2 in Parkinson's disease. By electrophysiological analysis of postnatal juvenile and adult mouse SN DA neurons in in vitro brain-slices, we observed that D2-autoreceptor desensitization is reduced with postnatal maturation. Furthermore, a transient high-dopamine state in vivo, caused by one injection of either l-DOPA or cocaine, induced adult-like, non-desensitizing D2-autoreceptor responses, selectively in juvenile SN DA neurons, but not ventral tegmental area dopamine neurons. With pharmacological and genetic

An intron-containing glycoside hydrolase family 9 cellulase gene encodes the dominant 90 kDa component of the cellulosome of the anaerobic fungus Piromyces sp. strain E2.

PubMed Central

Steenbakkers, Peter J M; Ubhayasekera, Wimal; Goossen, Harry J A M; van Lierop, Erik M H M; van der Drift, Chris; Vogels, Godfried D; Mowbray, Sherry L; Op den Camp, Huub J M

2002-01-01

The cellulosome produced by Piromyces sp. strain E2 during growth on filter paper was purified by using an optimized cellulose-affinity method consisting of steps of EDTA washing of the cellulose-bound protein followed by elution with water. Three dominant proteins were identified in the cellulosome preparation, with molecular masses of 55, 80 and 90 kDa. Treatment of cellulose-bound cellulosome with a number of denaturing agents was also tested. Incubation with 0.5% (w/v) SDS or 8 M urea released most cellulosomal proteins, while leaving the greater fraction of the 80, 90 and 170 kDa components. To investigate the major 90 kDa cellulosome protein further, the corresponding gene, cel9A, was isolated, using immunoscreening and N-terminal sequencing. Inspection of the cel9A genomic organization revealed the presence of four introns, allowing the construction of a consensus for introns in anaerobic fungi. The 2800 bp cDNA clone contained an open reading frame of 2334 bp encoding a 757-residue extracellular protein. Cel9A includes a 445-residue glycoside hydrolase family 9 catalytic domain, and so is the first fungal representative of this large family. Both modelling of the catalytic domain as well as the activity measured with low level expression in Escherichia coli indicated that Cel9A is an endoglucanase. The catalytic domain is succeeded by a putative beta-sheet module of 160 amino acids with unknown function, followed by a threonine-rich linker and three fungal docking domains. Homology modelling of the Cel9A dockerins suggested that the cysteine residues present are all involved in disulphide bridges. The results presented here are used to discuss evolution of glycoside hydrolase family 9 enzymes. PMID:12071852

Microparticles prepared with 50-190kDa chitosan as promising non-toxic carriers for pulmonary delivery of isoniazid.

PubMed

Oliveira, Paula M; Matos, Breno N; Pereira, Priscilla A T; Gratieri, Taís; Faccioli, Lucia H; Cunha-Filho, Marcílio S S; Gelfuso, Guilherme M

2017-10-15

Chitosan biocompatibility and mucoadhesiveness make it an ideal polymer for antituberculotic drugs microcapsulation for pulmonary delivery. Yet, previous study indicated toxicity problems to J-774.1-cells treated with some medium molecular weight (190-310kDa) chitosan microparticles. As polymer molecular weight is a crucial factor to be considered, this paper describes the preparation and characterization of chitosan (50-190kDa) microparticles containing isoniazid (INH). Cytotoxicity assays were also performed on murine peritoneal (J-774.1) and alveolar (AMJ2-C11) macrophages cell lines, followed by cytokines detection from AMJ2-C11 cells. Spray-drying process produced mucoadhesive microparticles from 3.2μm to 3.9μm, entrapping more than 89% of the drug and preserving their chemical stability. Drug release behavior could be controlled by the use of cross-linked or uncross-linked chitosan, the latter leading to a rapid drug release. Mucoadhesive potential of the microparticles was characterized following in vitro and ex vivo assays. Finally, a significant reduction on toxicity against peritoneal macrophages and no toxic effect on alveolar macrophages with use of such microparticles were observed. In conclusion, 50-190kDa chitosan microparticles may act as promising non-cytotoxic carriers for pulmonary delivery of INH showing marked alveoli macrophage activation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Influence of 120 kDa Pyruvate:Ferredoxin Oxidoreductase on Pathogenicity of Trichomonas vaginalis.

PubMed

Song, Hyun-Ouk

2016-02-01

Trichomonas vaginalis is a flagellate protozoan parasite and commonly infected the lower genital tract in women and men. Iron is a known nutrient for growth of various pathogens, and also reported to be involved in establishment of trichomoniasis. However, the exact mechanism was not clarified. In this study, the author investigated whether the 120 kDa protein of T. vaginalis may be involved in pathogenicity of trichomonads. Antibodies against 120 kDa protein of T. vaginalis, which was identified as pyruvate:ferredoxin oxidoreductase (PFOR) by peptide analysis of MALDI-TOF-MS, were prepared in rabbits. Pretreatment of T. vaginalis with anti-120 kDa Ab decreased the proliferation and adherence to vaginal epithelial cells (MS74) of T. vaginalis. Subcutaneous tissue abscess in anti-120 kDa Ab-treated T. vaginalis-injected mice was smaller in size than that of untreated T. vaginalis-infected mice. Collectively, the 120 kDa protein expressed by iron may be involved in proliferation, adhesion to host cells, and abscess formation, thereby may influence on the pathogenicity of T. vaginalis.

Nicotine- and methamphetamine-induced dopamine release evaluated with in-vivo binding of radiolabelled raclopride to dopamine D2 receptors: comparison with in-vivo microdialysis data.

PubMed

Kim, Sang Eun; Han, Seung-Moo

2009-07-01

The effect of substances which alter extracellular dopamine (DA) concentration has been studied by measuring changes in the binding of radiolabelled raclopride, a DA D2 receptor ligand that is sensitive to endogenous DA. To better characterize the relationship between extracellular DA concentration and DA D2 receptor binding of raclopride, we compared the changes of extracellular DA concentration (measured using in-vivo microdialysis) and in-vivo [3H]raclopride binding induced by different doses of methamphetamine (Meth) and nicotine, drugs that enhance DA release with and without blocking DA transporters (DATs), respectively, in rat striatum. Nicotine elicited a modest increase of striatal extrasynaptic extracellular DA, while Meth produced a marked increase of striatal extrasynaptic DA in a dose-dependent manner. There was a close correlation between the decrease in [3H]raclopride in-vivo binding and the increase in extrasynaptic DA concentration induced by both nicotine (r2=0.95, p<0.001) and Meth (r2=0.98, p=0.001), supporting the usefulness of the radiolabelled raclopride-binding measurement for the non-invasive assessment of DA release following interventions in the living brain. However, the linear regression analysis revealed that the ratio of percent DA increase to percent [3H]raclopride binding reduction was 25-fold higher for Meth (34.8:1) than for nicotine (1.4:1). The apparent discrepancy in the extrasynaptic DA-[3H]raclopride binding relationship between the DA-enhancing drugs with and without DAT-blocking property indicates that the competition between endogenous DA and radiolabelled raclopride takes place at the intrasynaptic rather than extrasynaptic DA D2 receptors and reflects synaptic concentration of DA.

Identification of an abundant 56 kDa protein implicated in food allergy as granule-bound starch synthase

USDA-ARS?s Scientific Manuscript database

Rice, the staple food of South and East Asian counties, is considered to be hypoallergenic. However, several clinical studies have documented rice-induced allergy in sensitive patients. Rice proteins with molecular weights of 14-16 kDa, 26 kDa, 33 kDa and 56 kDa have been identified as allergens. Re...

DaRT: A CALL System to Help Students Practice and Develop Reasoning Skills in Choosing English Articles.

ERIC Educational Resources Information Center

Yoshii, Rika; Milne, Alastair

1998-01-01

Describes DaRT, a computer assisted language-learning system for helping English-as-a-Second-Language students master English articles. DaRT uses a diagrammatic reasoning tool to present communicative contexts for exercises in choosing appropriate articles. This paper describes the development of DaRT and DaRT's system components and concludes…

DA 5505: a novel topical formulation of terbinafine that enhances skin penetration and retention.

PubMed

Thapa, Raj Kumar; Han, Sang-Duk; Park, Hyoung Geun; Son, Miwon; Jun, Joon Ho; Kim, Jong Oh

2015-01-01

Topical fungal infections can become severe if left untreated. Efficient treatment modalities for topical fungal infections aid the penetration of antifungal agents deep into viable skin layers. Terbinafine is a fungicidal agent that inhibits ergosterol, an essential fungal component. The main objective of this study was to evaluate skin permeation and retention of a terbinafine-loaded solution containing chitosan as a film former. Comparative assessment of skin permeation and retention was performed using a prepared formulation (DA 5505) and marketed formulations of terbinafine in murine and porcine skin. To mimic fungal infection of skin, keratinized skin was induced in NC/Nga mice. In comparison with the marketed formulations, DA 5505 exhibited significantly better skin permeation. The flux, permeation coefficient, and enhancement ratio of terbinafine were remarkably increased by DA 5505 in comparison with the marketed formulations, and lag time was dramatically reduced. DA 5505 significantly increased cumulative terbinafine retention in viable skin layers in comparison with the marketed solution, suggesting enhanced efficacy. Furthermore, DA 5505 exhibited superior skin permeation in normal skin and keratinized skin. Thus, the DA 5505 formulation has the potential to effectively deliver terbinafine to superficial and deep cutaneous fungal infections.

A randomized, multi-center, open-label, phase III study of once-per-cycle DA-3031, a pegylated G-CSF, in comparison with daily filgrastim in patients receiving TAC chemotherapy for breast cancer.

PubMed

Park, K H; Lee, S; Park, J H; Kang, S Y; Kim, H Y; Park, I H; Park, Y H; Im, Y H; Lee, H J; Park, S; Lee, S I; Jung, K H; Kim, Y S; Seo, Jae Hong

2017-02-01

This multi-center, randomized, phase III study was conducted to demonstrate the non-inferiority of DA-3031 compared with daily filgrastim in patients during the first cycle of chemotherapy for breast cancer in terms of the duration of severe neutropenia (DSN). Seventy-four patients with breast cancer who were receiving combination chemotherapy with docetaxel, doxorubicin, and cyclophosphamide (TAC) were enrolled. All participants were randomized to receive either daily subcutaneous injections of filgrastim 100 μg/m 2 /day for up to 10 days or a single subcutaneous injection of DA-3031 at fixed doses of 6 mg on day 2 of each chemotherapy cycle. The mean duration of grade 4 (G4) neutropenia in cycle 1 was 2.08 ± 0.85 days for the filgrastim group and 2.28 ± 1.14 days for the DA-3031 group. The difference between groups was 0.2 ± 1.10 days (95 % confidence interval (CI) = -0.26, 0.66), which supported non-inferiority. No statistically significant differences were observed in nadir absolute neutrophil count (ANC) (154.34/mm 3 and 161.75/mm 3 for the filgrastim and DA-3031 groups, respectively; P = 0.8414) or in time to ANC recovery (10.03 ± 0.75 and 9.83 ± 1.56 days in the filgrastim and DA-3031 groups, respectively; P = 0.0611) during cycle 1. Serious AEs occurred in six (15.8 %) patients receiving filgrastim and in ten (27.8 %) patients receiving DA-3031; however, none was determined to be related to the study drug. DA-3031 and daily filgrastim are similar in regard to DSN and safety in breast cancer patients receiving TAC chemotherapy.

Implantable microencapsulated dopamine (DA): prolonged functional release of DA in denervated striatal tissue.

PubMed

McRae, A; Hjorth, S; Mason, D; Dillon, L; Tice, T

1990-01-01

Biodegradable controlled-release microcapsule systems made with the biocompatible biodegradable polyester excipient poly [DL-lactide-co-gly-colide] constitute an exciting new technology for drug delivery to the central nervous system (CNS). The present study describes functional observations indicating that implantation of dopamine (DA) microcapsules encapsulated within two different polymer excipients into denervated striatal tissue assures a prolonged release of the transmitter in vivo. This technology has a considerable potential for basic and possibly clinical research.

Fabrications of some kinds of 2-D frameworks consisting of nanosized polyoxomolybdate anion [Mo 36O 112(H 2O) 16] 8- via condensation processes

NASA Astrophysics Data System (ADS)

Eda, Kazuo; Iriki, Yuichi; Kawamura, Kenjiro; Ikuki, Takeshi; Hayashi, Masahiko

2007-12-01

We succeeded to prepare novel [Mo 36O 112(H 2O) 16] 8- ({Mo 36}) compounds by using 1,3-diamino-2-propanol ( βOHC 3-DA) and 1,3,5-tris(aminomethyl)benzene (MES-TA)+1,3-diaminopropane (C 3-DA) as linkers, and determined their crystal structures. We have confirmed they have unique two-dimensional (2-D) molybdenum oxide frameworks, which are formed by condensation of {Mo 36}s. Side-staggered arrays of {Mo 36}s, connected in lying position by eight bridges per a {Mo 36}, are formed in the compound with βOHC 3-DA, while herringbone arrays of {Mo 36}s, connected in standing position by four bridges per a {Mo 36}, are built in the compound with MES-TA+C 3-DA. The latter compound exhibited non-stoichiometric property, and its composition and cell parameters varied depending on the relative concentration of MES-TA in the mother solution.

Color constrains depth in da Vinci stereopsis for camouflage but not occlusion.

PubMed

Wardle, Susan G; Gillam, Barbara J

2013-12-01

Monocular regions that occur with binocular viewing of natural scenes can produce a strong perception of depth--"da Vinci stereopsis." They occur either when part of the background is occluded in one eye, or when a nearer object is camouflaged against a background surface in one eye's view. There has been some controversy over whether da Vinci depth is constrained by geometric or ecological factors. Here we show that the color of the monocular region constrains the depth perceived from camouflage, but not occlusion, as predicted by ecological considerations. Quantitative depth was found in both cases, but for camouflage only when the color of the monocular region matched the binocular background. Unlike previous reports, depth failed even when nonmatching colors satisfied conditions for perceptual transparency. We show that placing a colored line at the boundary between the binocular and monocular regions is sufficient to eliminate depth from camouflage. When both the background and the monocular region contained vertical contours that could be fused, some observers appeared to use fusion, and others da Vinci constraints, supporting the existence of a separate da Vinci mechanism. The results show that da Vinci stereopsis incorporates color constraints and is more complex than previously assumed.

[A comparative study of Da Vinci robot system with video-assisted thoracoscopy in the surgical treatment of mediastinal lesions].

PubMed

Ding, Renquan; Tong, Xiangdong; Xu, Shiguang; Zhang, Dakun; Gao, Xin; Teng, Hong; Qu, Jiaqi; Wang, Shumin

2014-07-20

In recent years, Da Vinci robot system applied in the treatment of intrathoracic surgery mediastinal diseases become more mature. The aim of this study is to summarize the clinical data about mediastinal lesions of General Hospital of Shenyang Military Region in the past 4 years, then to analyze the treatment effect and promising applications of da Vinci robot system in the surgical treatment of mediastinal lesions. 203 cases of mediastinal lesions were collected from General Hospital of Shenyang Military Region between 2010 and 2013. These patients were divided into two groups da Vinci and video-assisted thoracoscopic surgery (VATS) according to the selection of the treatments. The time in surgery, intraoperative blood loss, postoperative drainage amount within three days after surgery, the period of bearing drainage tubes, hospital stays and hospitalization expense were then compared. All patients were successfully operated, the postoperative recovery is good and there is no perioperative death. The different of the time in surgery between two groups is Robots group 82 (20-320) min and thoracoscopic group 89 (35-360) min (P>0.05). The intraoperative blood loss between two groups is robot group 10 (1-100) mL and thoracoscopic group 50 (3-1,500) mL. The postoperative drainage amount within three days after surgery between two groups is robot group 215 (0-2,220) mL and thoracoscopic group 350 (50-1,810) mL. The period of bearing drainage tubes after surgery between two groups is robot group 3 (0-10) d and thoracoscopic group: 5 (1-18) d. The difference of hospital stays between two groups is robot group 7 (2-15) d and thoracoscopic group 9 (2-50) d. The hospitalization expense between two groups is robot group (18,983.6±4,461.2) RMB and thoracoscopic group (9,351.9±2,076.3) RMB (All P<0.001). The da Vinci robot system is safe and efficient in the treatment of mediastinal lesions compared with video-assisted thoracoscopic approach, even though its expense is higher.

Papain cleavage of the 38,000-dalton fragment inhibits the binding of 4, 4'-diisothiocyanostilbene-2, 2'-disulfonate to lys-539 on the 60,000-dalton fragment in human band 3.

PubMed

Yamaguchi, Takeo; Kojima, Hideaki; Kawaguchi, Shiori; Shimada, Maiko; Aso, Haruka

2017-08-01

Human band 3 is a 98-kDa transmembrane (TM) protein comprising 14 TM segments. Papain cleavages band 3 into 38- and 60-kDa fragments. Under vigorous conditions, the cleavage of the loop region between the TM 7 of gate domain and the TM 8 of core domain in the 38-kDa fragment produces 7- and 31-kDa fragments. Conformational changes of the TM 5 segment containing Lys-539 by cleavage of the 38-kDa fragment remain unclear. Pressure-induced haemolysis of erythrocytes was suppressed by binding of 4, 4'-diisothiocyanostilbene-2, 2'-disulfonate (DIDS) to Lys-539. Such effect of DIDS was not observed upon cleavage of the 38-kDa fragment, because of inhibition of DIDS binding to Lys-539. Using fluorescence of DIDS labelled to Lys-539, conformational changes of band 3 were examined. Fluorescence spectra demonstrated that the molecular motion of DIDS is more restricted upon digestion of the 38-kDa fragment. Interestingly, the quenching of DIDS fluorescence showed that Hg2+ is less accessible to DIDS upon digestion of the 38-kDa fragment. Taken together, we propose that the conformational changes of the TM 5 segment characterized by the sequestration and restricted motion of Lys-539 are induced by the cleavage of the loop region between the TM 7 and the TM 8. © The Authors 2017. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

Ultrasonic irradiation enhanced the ability of Fluorescein-DA-Fe(III) on sonodynamic and sonocatalytic damages of DNA molecules.

PubMed

Wu, Qiong; Chen, Xia; Jia, Lizhen; Wang, Yi; Sun, Ying; Huang, Xingjun; Shen, Yuxiang; Wang, Jun

2017-11-01

The interaction of DNA with Bis [N,N-bis (carboxymethyl) aminomethyl] fluorescein-Ferrous(III) (Fluorescein-DA-Fe(III)) with dual functional (sonodynamic and sonocatalytic) activity was studied by UV-vis spectroscopy, fluorescence spectroscopy, FT-IR spectroscopy, circular dichroism (CD) spectroscopy and viscosity measurements. And then, the damage of DNA caused by Fluorescein-DA-Fe(III) under ultrasonic irradiation (US) was researched by agarose gel electrophoresis and cytotoxicity assay. Meanwhile, some influenced factors such as ultrasonic irradiation time and Fluorescein-DA-Fe(III) concentration on the damage degree of DNA molecules were also examined. As a control, for Bis [N,N-bis (carboxymethyl) aminomethyl] fluorescein (Fluorescein-DA), the same experiments were carried out. The results showed that both Fluorescein-DA-Fe(III) and Fluorescein-DA can interact with DNA molecules. Under ultrasonic irradiation, Fluorescein-DA shows sonodynamic activity, which can damage DNA molecules. While, in the presence of Fe(III) ion, the Fluorescein-DA-Fe(III) displays not only sonodynamic activity but also sonocatalytic activity under ultrasonic irradiation, which injures DNA more serious than Fluorescein-DA. The researches confirmed the dual function (sonodynamic activity and sonocatalytic activity) of Fluorescein-DA-Fe(III) and expanded the usage of Fluorescein-DA-Fe(III) as a sonosensitizer in sonodynamic therapy (SDT). Copyright © 2017 Elsevier B.V. All rights reserved.

Tonic 5nM DA Stabilizes Neuronal Output by Enabling Bidirectional Activity-Dependent Regulation of the Hyperpolarization Activated Current via PKA and Calcineurin

PubMed Central

Krenz, Wulf-Dieter C.; Rodgers, Edmund W.; Baro, Deborah J.

2015-01-01

Volume transmission results in phasic and tonic modulatory signals. The actions of tonic dopamine (DA) at type 1 DA receptors (D1Rs) are largely undefined. Here we show that tonic 5nM DA acts at D1Rs to stabilize neuronal output over minutes by enabling activity-dependent regulation of the hyperpolarization activated current (I h). In the presence but not absence of 5nM DA, I h maximal conductance (G max) was adjusted according to changes in slow wave activity in order to maintain spike timing. Our study on the lateral pyloric neuron (LP), which undergoes rhythmic oscillations in membrane potential with depolarized plateaus, demonstrated that incremental, bi-directional changes in plateau duration produced corresponding alterations in LP I hG max when preparations were superfused with saline containing 5nM DA. However, when preparations were superfused with saline alone there was no linear correlation between LP I hGmax and duty cycle. Thus, tonic nM DA modulated the capacity for activity to modulate LP I h G max; this exemplifies metamodulation (modulation of modulation). Pretreatment with the Ca2+-chelator, BAPTA, or the specific PKA inhibitor, PKI, prevented all changes in LP I h in 5nM DA. Calcineurin inhibitors blocked activity-dependent changes enabled by DA and revealed a PKA-mediated, activity-independent enhancement of LP I hG max. These data suggested that tonic 5nM DA produced two simultaneous, PKA-dependent effects: a direct increase in LP I h G max and a priming event that permitted calcineurin regulation of LP I h. The latter produced graded reductions in LP I hG max with increasing duty cycles. We also demonstrated that this metamodulation preserved the timing of LP’s first spike when network output was perturbed with bath-applied 4AP. In sum, 5nM DA permits slow wave activity to provide feedback that maintains spike timing, suggesting that one function of low-level, tonic modulation is to stabilize specific features of a dynamic output. PMID

Tonic 5nM DA stabilizes neuronal output by enabling bidirectional activity-dependent regulation of the hyperpolarization activated current via PKA and calcineurin.

PubMed

Krenz, Wulf-Dieter C; Rodgers, Edmund W; Baro, Deborah J

2015-01-01

Volume transmission results in phasic and tonic modulatory signals. The actions of tonic dopamine (DA) at type 1 DA receptors (D1Rs) are largely undefined. Here we show that tonic 5nM DA acts at D1Rs to stabilize neuronal output over minutes by enabling activity-dependent regulation of the hyperpolarization activated current (I h). In the presence but not absence of 5nM DA, I h maximal conductance (G max) was adjusted according to changes in slow wave activity in order to maintain spike timing. Our study on the lateral pyloric neuron (LP), which undergoes rhythmic oscillations in membrane potential with depolarized plateaus, demonstrated that incremental, bi-directional changes in plateau duration produced corresponding alterations in LP I hG max when preparations were superfused with saline containing 5nM DA. However, when preparations were superfused with saline alone there was no linear correlation between LP I hGmax and duty cycle. Thus, tonic nM DA modulated the capacity for activity to modulate LP I h G max; this exemplifies metamodulation (modulation of modulation). Pretreatment with the Ca2+-chelator, BAPTA, or the specific PKA inhibitor, PKI, prevented all changes in LP I h in 5nM DA. Calcineurin inhibitors blocked activity-dependent changes enabled by DA and revealed a PKA-mediated, activity-independent enhancement of LP I hG max. These data suggested that tonic 5nM DA produced two simultaneous, PKA-dependent effects: a direct increase in LP I h G max and a priming event that permitted calcineurin regulation of LP I h. The latter produced graded reductions in LP I hG max with increasing duty cycles. We also demonstrated that this metamodulation preserved the timing of LP's first spike when network output was perturbed with bath-applied 4AP. In sum, 5nM DA permits slow wave activity to provide feedback that maintains spike timing, suggesting that one function of low-level, tonic modulation is to stabilize specific features of a dynamic output.

Modulation of the Senescence-Associated Inflammatory Phenotype in Human Fibroblasts by Olive Phenols

PubMed Central

Menicacci, Beatrice; Cipriani, Caterina; Margheri, Francesca

2017-01-01

Senescent cells display an increase in the secretion of growth factors, inflammatory cytokines and proteolytic enzymes, termed the “senescence-associated-secretory-phenotype” (SASP), playing a major role in many age-related diseases. The phenolic compounds present in extra-virgin olive oil are inhibitors of oxidative damage and have been reported to play a protective role in inflammation-related diseases. Particularly, hydroxytyrosol and oleuropein are the most abundant and more extensively studied. Pre-senescent human lung (MRC5) and neonatal human dermal (NHDF) fibroblasts were used as cellular model to evaluate the effect of chronic (4–6 weeks) treatment with 1 μM hydroxytyrosol (HT) or 10 μM oleuropein aglycone (OLE) on senescence/inflammation markers. Both phenols were effective in reducing β-galactosidase-positive cell number and p16 protein expression. In addition, senescence/inflammation markers such as IL-6 and metalloprotease secretion, and Ciclooxigenase type 2 (COX-2) and α-smooth-actin levels were reduced by phenol treatments. In NHDF, COX-2 expression, Nuclear Factor κ-light-chain-enhancer of activated B cells (NFκB) protein level and nuclear localization were augmented with culture senescence and decreased by OLE and HT treatment. Furthermore, the inflammatory effect of Tumor Necrosis Factor α (TNFα) exposure was almost completely abolished in OLE- and HT-pre-treated NHDF. Thus, the modulation of the senescence-associated inflammatory phenotype might be an important mechanism underlying the beneficial effects of olive oil phenols. PMID:29084133

The Indicative and Subjunctive "da"-complements in Serbian A Syntactic-Semantic Approach

ERIC Educational Resources Information Center

Todorovic, Natasa

2012-01-01

A syntactic-semantic investigation of subjunctive and indicative "da"-complements in Serbian is conducted in this project. After a careful comparison of Serbian sentence constructions with "da"-complements to the equivalent sentence structures in languages of the Balkans as well as other Slavic languages, it is clearly…

Simplifying and expanding the screening for peptides <2 kDa by direct urine injection, liquid chromatography, and ion mobility mass spectrometry.

PubMed

Thomas, Andreas; Görgens, Christian; Guddat, Sven; Thieme, Detlef; Dellanna, Frank; Schänzer, Wilhelm; Thevis, Mario

2016-01-01

The analysis of low-molecular-mass peptides in doping controls has become a mandatory aspect in sports drug testing and, thus, the number of samples that has to be tested for these analytes has been steadily increasing. Several peptides <2 kDa with performance-enhancing properties are covered by the list of prohibited substances of the World Anti-Doping Agency including Desmopressin, LH-RH, Buserelin, Triptorelin, Leuprolide, GHRP-1, GHRP-2, GHRP-3, GHRP-4, GHRP-5,GHRP-6, Alexamorelin, Ipamorelin, Hexarelin, ARA-290, AOD-9604, TB-500 and Anamorelin. With the presented method employing direct urine injection into a liquid chromatograph followed by ion-mobility time-of-flight mass spectrometry, a facile, specific and sensitive assay for the aforementioned peptidic compounds is provided. The accomplished sensitivity allows for limits of detection between 50 and 500 pg/mL and thus covers the minimum required performance level of 2 ng/mL accordingly. The method is precise (imprecision <20%) and linear in the estimated working range between 0 and 10 ng/mL. The stability of the peptides in urine was tested, and -20°C was found to be the appropriate storage temperature for sports drug testing. Finally, proof-of-concept was shown by analysing elimination study urine samples collected from individuals having administered GHRP-6, GHRP-2, or LHRH. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The coolest DA white dwarfs detected at soft X-ray wavelengths

NASA Technical Reports Server (NTRS)

Kidder, K. M.; Holberg, J. B.; Barstow, M. A.; Tweedy, R. W.; Wesemael, F.

1992-01-01

New soft X-ray/EUV photometric observations of the DA white dwarfs KPD 0631 + 1043 = WD 0631 + 107 and PG 1113 + 413 = WD 1113 + 413 are analyzed. Previously reported soft X-ray detections of three other DAs and the failure to detect a fourth DA in deep Exosat observations are investigated. New ground-based spectra are presented for all of the objects, with IUE Ly-alpha spectra for some. These data are used to constrain the effective temperatures and surface gravities. The improved estimates of these parameters are employed to refer a photospheric He abundance for the hotter objects and to elucidate an effective observational low-temperature threshold for the detection of pure hydrogen DA white dwarfs at soft X-ray wavelengths.

Purification, crystallization and preliminary X-ray structural studies of a 7.2 kDa cytotoxin isolated from the venom of Daboia russelli russelli of the Viperidae family

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roy Choudhury, Subhasree; Gomes, Aparna; Gomes, Antony

2006-03-01

A cytotoxin from Indian Russell’s viper (D. russelli russelli) venom having multifunctional activity has been crystallized in space group P4{sub 1}. Larger crystals diffracted to 1.5 Å but were found to be twinned; preliminary data were therefore collected (2.93 Å) from a smaller crystal. A cytotoxin (MW 7.2 kDa) from Indian Russell’s viper (Daboia russelli russelli) venom possessing antiproliferative activity, cardiotoxicity, neurotoxicity and myotoxicity has been purified, characterized and crystallized. The crystals belong to the tetragonal space group P4{sub 1}, with unit-cell parameters a = b = 47.94, c = 50.2 Å. Larger crystals, which diffracted to 1.5 Å, weremore » found to be twinned; diffraction data were therefore collected to 2.93 Å resolution using a smaller crystal. Molecular-replacement calculations identified two molecules of the protein in the asymmetric unit, which is in accordance with the calculated V{sub M} value.« less

dK/da effects on the SCC growth rates of nickel base alloys in high-temperature water

NASA Astrophysics Data System (ADS)

Chen, Kai; Wang, Jiamei; Du, Donghai; Andresen, Peter L.; Zhang, Lefu

2018-05-01

The effect of dK/da on crack growth behavior of nickel base alloys has been studied by conducting stress corrosion cracking tests under positive and negative dK/da loading conditions on Alloys 690, 600 and X-750 in high temperature water. Results indicate that positive dK/da accelerates the SCC growth rates, and the accelerating effect increases with dK/da and the initial CGR. The FRI model was found to underestimate the dK/da effect by ∼100X, especially for strain hardening materials, and this underscores the need for improved insight and models for crack tip strain rate. The effect of crack tip strain rate and dK/dt in particular can explain the dK/da accelerating effect.

[Trattamento farmacologico del disturbo da uso di alcol. Evidenze scientifiche].

PubMed

Attilia, Fabio; Perciballi, Roberta; Rotondo, Claudia; Capriglione, Ida; Iannuzzi, Silvia; Attilia, Maria Luisa; Vitali, Mario; Alessandrini, Giovanni; Scamporrino, Maria Concetta Marcella; Fiore, Marco; Ceccanti, Mauro

2018-01-01

RIASSUNTO. La terapia farmacologica nei pazienti con disturbo da uso di alcol riveste un ruolo centrale nel progetto terapeutico, altamente contestualizzato in un approccio multidisciplinare. Sebbene i trattamenti non farmacologici per la dipendenza da alcol risultino ben strutturati e in continua evoluzione, dal punto di vista medico le possibilità di intervento sono realmente ristrette, con poche molecole a disposizione approvate per il disturbo da uso di alcol: nello specifico, l'acamprostato, il naltrexone e, più recentemente, il nalmefene tra gli anticraving; il disulfiram tra gli avversivanti. Nuovi approcci sperimentali stanno cercando di ampliare tale gamma attraverso l'utilizzo di farmaci off-label. Evidenze scientifiche devono supportare l'indicazione terapeutica, quest'ultima deve dimostrarsi "cucita" sulle esigenze del paziente e sulle comorbilità presenti tenendo conto del profilo bio-psico-sociale individuale. Fondamentale risulta il follow-up per valutare la ritenzione in trattamento e il monitoraggio degli outcome alcologici.

Independent mediation of unconditioned motor behavior by striatal D1 and D2 receptors in rats depleted of dopamine as neonates.

PubMed

Bruno, J P; Byrnes, E M; Johnson, B J

1995-11-01

The effects of systemic administration of DA receptor antagonists suggest that unconditioned motor behavior in rats depleted of DA as neonates continues to be dependent upon dopaminergic transmission, yet the specific contribution of D1 and D2 receptors to these behaviors has been altered. The purpose of the present study was to determine whether these depletion-induced receptor changes are occurring at the level of striatal DA terminals and their targets. The ability of bilateral intrastriatal injections (0.5 microliter) of DA receptor antagonists to induce motoric deficits was determined in adult rats treated with vehicle or 6-OHDA (100 micrograms, intraventricular) on postnatal day 3. Administration of the D1-like antagonist SCH 23390 (0.5-2.0 micrograms) or the D2-like antagonist clebopride (1.0-4.0 micrograms) induced dose-dependent akinesia, catalepsy, and somatosensory neglect in vehicle-treated controls. In contrast, neither antagonist produced deficits in rats depleted of forebrain DA as neonates. However, combined administration of SCH 23390 + clebopride induced similar akinesia, catalepsy, and somatosensory neglect in both controls and DA depleted animals. Animals depleted of DA were more sensitive than controls to the low doses of this combined D1 + D2 antagonism. These results demonstrate that activation of striatal DA receptors remains necessary for unconditioned motor behavior in rats depleted of DA as neonates. However, the specific contributions of D1- and D2-like receptors to these behaviors differ between intact animals and those depleted of DA as neonates. The ability of endogenous DA acting at either D1 or D2 receptors to support spontaneous motor behavior in rats depleted of DA as neonates may contribute to their relative sparing from parkinsonian deficits.

The 21.5-kDa isoform of myelin basic protein has a non-traditional PY-nuclear-localization signal

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, Graham S.T.; Seymour, Lauren V.; Boggs, Joan M.

2012-06-15

Highlights: Black-Right-Pointing-Pointer Full-length 21.5-kDa MBP isoform is translocated to the nucleus. Black-Right-Pointing-Pointer We hypothesized that the exon-II-encoded sequence contained the NLS. Black-Right-Pointing-Pointer We mutated this sequence in RFP-tagged constructs and transfected N19-cells. Black-Right-Pointing-Pointer Abolition of two key positively-charged residues resulted in loss of nuclear-trafficking. Black-Right-Pointing-Pointer The 21.5-kDa isoform of classic MBP contains a non-traditional PY-NLS. -- Abstract: The predominant 18.5-kDa classic myelin basic protein (MBP) is mainly responsible for compaction of the myelin sheath in the central nervous system, but is multifunctional, having numerous interactions with Ca{sup 2+}-calmodulin, actin, tubulin, and SH3-domains, and can tether these proteins to a lipidmore » membrane in vitro. The full-length 21.5-kDa MBP isoform has an additional 26 residues encoded by exon-II of the classic gene, which causes it to be trafficked to the nucleus of oligodendrocytes (OLGs). We have performed site-directed mutagenesis of selected residues within this segment in red fluorescent protein (RFP)-tagged constructs, which were then transfected into the immortalized N19-OLG cell line to view protein localization using epifluorescence microscopy. We found that 21.5-kDa MBP contains two non-traditional PY-nuclear-localization signals, and that arginine and lysine residues within these motifs were involved in subcellular trafficking of this protein to the nucleus, where it may have functional roles during myelinogenesis.« less

The hyperthermic and neurotoxic effects of 'Ecstasy' (MDMA) and 3,4 methylenedioxyamphetamine (MDA) in the Dark Agouti (DA) rat, a model of the CYP2D6 poor metabolizer phenotype.

PubMed Central

Colado, M. I.; Williams, J. L.; Green, A. R.

1995-01-01

1. The effect of administration of 3,4-methylenedioxymethamphetamine (MDMA or 'Ecstasy') and its N-demethylated product, 3,4-methylenedioxyamphetamine (MDA) on both rectal temperature and long term neurotoxic loss of cerebral 5-hydroxytryptamine (5-HT) has been studied in male and female Dark Agouti (DA) rats. The female metabolizes debrisoquine more slowly than the male and its use has been suggested as a model of the human debrisoquine 4-hydroxylase poor metabolizer phenotype. 2. A novel h.p.l.c. method was developed and used to measure plasma MDMA and MDA concentrations in the DA rats. 3. The hyperthermic response following MDMA was enhanced in female rats. Plasma MDMA concentrations were also 57% higher than in males 45 min post-injection, while plasma concentrations of MDA were 48% lower. 4. Plasma concentrations of MDMA and MDA in male rats were unaffected by pretreatment with proadifen (15 mg kg-1) or quinidine (60 mg kg-1), but the hyperthermic response to MDMA (10 mg kg-1, i.p.) was enhanced by quinidine pretreatment. 5. The hyperthermic response following MDA was greater in male DA rats, despite plasma drug concentrations being 40% higher in females 60 min after injection. 6. Seven days after a single dose of MDMA (10 mg kg-1, i.p.) there was a substantial loss in the concentration of 5-HT and 5-hydroxyindoleacetic acid (5-HIA) in cortex and hippocampus. [3H]-paroxetine binding was also decreased by 27% in the cortex, indicating that the amine loss reflected a neurodegenerative change. MDMA (5 mg kg-1, i.p.) was without effect on brain 5-HT content.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7582557

Activation of the EBV/C3d receptor (CR2, CD21) on human B lymphocyte surface triggers tyrosine phosphorylation of the 95-kDa nucleolin and its interaction with phosphatidylinositol 3 kinase.

PubMed

Barel, M; Le Romancer, M; Frade, R

2001-03-01

We previously demonstrated that CR2 activation on human B lymphocyte surface triggered tyrosine phosphorylation of a p95 component and its interaction with p85 subunit of phosphatidylinositol 3' (PI 3) kinase. Despite identical molecular mass of 95 kDa, this tyrosine phosphorylated p95 molecule was not CD19, the proto-oncogene Vav, or the adaptator Gab1. To identify this tyrosine phosphorylated p95 component, we first purified it by affinity chromatography on anti-phosphotyrosine mAb covalently linked to Sepharose 4B, followed by polyacrylamide gel electrophoresis. Then, the isolated 95-kDa tyrosine phosphorylated band was submitted to amino acid analysis by mass spectrometry; the two different isolated peptides were characterized by amino acid sequences 100% identical with two different domains of nucleolin, localized between aa 411--420 and 611--624. Anti-nucleolin mAb was used to confirm the antigenic properties of this p95 component. Functional studies demonstrated that CR2 activation induced, within a brief span of 2 min, tyrosine phosphorylation of nucleolin and its interaction with Src homology 2 domains of the p85 subunit of PI 3 kinase and of 3BP2 and Grb2, but not with Src homology 2 domains of Fyn and Gap. These properties of nucleolin were identical with those of the p95 previously described and induced by CR2 activation. Furthermore, tyrosine phosphorylation of nucleolin was also induced in normal B lymphocytes by CR2 activation but neither by CD19 nor BCR activation. These data support that tyrosine phosphorylation of nucleolin and its interaction with PI 3 kinase p85 subunit constitute one of the earlier steps in the specific intracellular signaling pathway of CR2.

An isoform of myosin XI is responsible for the translocation of endoplasmic reticulum in tobacco cultured BY-2 cells.

PubMed

Yokota, Etsuo; Ueda, Shunpei; Tamura, Kentaro; Orii, Hidefumi; Uchi, Satoko; Sonobe, Seiji; Hara-Nishimura, Ikuko; Shimmen, Teruo

2009-01-01

The involvement of myosin XI in generating the motive force for cytoplasmic streaming in plant cells is becoming evident. For a comprehensive understanding of the physiological roles of myosin XI isoforms, it is necessary to elucidate the properties and functions of each isoform individually. In tobacco cultured BY-2 cells, two types of myosins, one composed of 175 kDa heavy chain (175 kDa myosin) and the other of 170 kDa heavy chain (170 kDa myosin), have been identified biochemically and immunocytochemically. From sequence analyses of cDNA clones encoding heavy chains of 175 kDa and 170 kDa myosin, both myosins have been classified as myosin XI. Immunocytochemical studies using a polyclonal antibody against purified 175 kDa myosin heavy chain showed that the 175 kDa myosin is distributed throughout the cytoplasm as fine dots in interphase BY-2 cells. During mitosis, some parts of 175 kDa myosin were found to accumulate in the pre-prophase band (PPB), spindle, the equatorial plane of a phragmoplast and on the circumference of daughter nuclei. In transgenic BY-2 cells, in which an endoplasmic reticulum (ER)-specific retention signal, HDEL, tagged with green fluorescent protein (GFP) was stably expressed, ER showed a similar behaviour to that of 175 kDa myosin. Furthermore, this myosin was co-fractionated with GFP-ER by sucrose density gradient centrifugation. From these findings, it was suggested that the 175 kDa myosin is a molecular motor responsible for translocating ER in BY-2 cells.

The adenosine A2A antagonist MSX-3 reverses the effort-related effects of dopamine blockade: differential interaction with D1 and D2 family antagonists.

PubMed

Worden, Lila T; Shahriari, Mona; Farrar, Andrew M; Sink, Kelly S; Hockemeyer, Jörg; Müller, Christa E; Salamone, John D

2009-04-01

Brain dopamine (DA) participates in the modulation of instrumental behavior, including aspects of behavioral activation and effort-related choice behavior. Rats with impaired DA transmission reallocate their behavior away from food-seeking behaviors that have high response requirements, and instead select less effortful alternatives. Although accumbens DA is considered a critical component of the brain circuitry regulating effort-related choice behavior, emerging evidence demonstrates a role for adenosine A(2A) receptors. Adenosine A(2A) receptor antagonism has been shown to reverse the effects of DA antagonism. The present experiments were conducted to determine if this effect was dependent upon the subtype of DA receptor that was antagonized to produce the changes in effort-related choice. The adenosine A(2A) receptor antagonist MSX-3 (0.5-2.0 mg/kg IP) was assessed for its ability to reverse the effects of the D1 family antagonist SCH39166 (ecopipam; 0.2 mg/kg IP) and the D2 family antagonist eticlopride (0.08 mg/kg IP), using a concurrent lever pressing/chow feeding procedure. MSX-3 produced a substantial dose-related reversal of the effects of eticlopride on lever pressing and chow intake. At the highest dose of MSX-3, there was a complete reversal of the effects of eticlopride on lever pressing. In contrast, MSX-3 produced only a minimal attenuation of the effects of SCH39166, as measured by regression and effect size analyses. The greater ability of MSX-3 to reverse the effects of D2 vs. D1 blockade may be related to the colocalization of D2 and adenosine A(2A) receptors on the same population of striatal neurons.

Análise da aplicação e dos resultados do modelo OPM3® para a área da saúde

PubMed Central

Augusto dos Santos, Luis; de Fátima Marin, Heimar

2015-01-01

Esta pesquisa procurou analisar se um modelo de questionário criado por uma comunidade internacional de gerenciamento de projetos e se é aplicavél a organizações voltadas a área de saúde. O modelo OPM3® (Organizational Project Management Maturity Model) foi criado para que organizações de qualquer área ou porte pudessem identificar a presença, ou ausência, de boas práticas de gerenciamento. O objetivo da aplicação desse modelo é avaliar sempre a organização e não o entrevistado. No presente artigo, são apresentados os resultados da aplicação desse modelo em uma organização que possuía produtos e serviços de tecnologia da informação aplicados à área de saúde. Este estudo verificou que o modelo é aplicável de forma rápida e que a organização analisada possuía um número expressivo de boas práticas. PMID:26924862

Vectra DA for the objective measurement of disease activity in patients with rheumatoid arthritis.

PubMed

Segurado, O G; Sasso, E H

2014-01-01

Quantitative and regular assessment of disease activity in rheumatoid arthritis (RA) is required to achieve treatment targets such as remission and to optimize clinical outcomes. To assess inflammation accurately, predict joint damage and monitor treatment response, a measure of disease activity in RA should reflect the pathological processes resulting in irreversible joint damage and functional disability. The Vectra DA blood test is an objective measure of disease activity for patients with RA. Vectra DA provides an accurate, reproducible score on a scale of 1 to 100 based on the concentrations of 12 biomarkers that reflect the pathophysiologic diversity of RA. The analytical validity, clinical validity, and clinical utility of Vectra DA have been evaluated for patients with RA in registries and prospective and retrospective clinical studies. As a biomarker-based instrument for assessing disease activity in RA, the Vectra DA test can help monitor therapeutic response to methotrexate and biologic agents and assess clinically challenging situations, such as when clinical measures are confounded by non-inflammatory pain from fibromyalgia. Vectra DA scores correlate with imaging of joint inflammation and are predictive for radiographic progression, with high Vectra DA scores being associated with more frequent and severe progression and low scores being predictive for non-progression. In summary, the Vectra DA score is an objective measure of RA disease activity that quantifies inflammatory status. By predicting risk for joint damage more effectively than conventional clinical and laboratory measures, it has the potential to complement these measures and optimise clinical decision making.

Maize 27 kDa gamma-zein is a potential allergen for early weaned pigs.

PubMed

Krishnan, Hari B; Kerley, Monty S; Allee, Gary L; Jang, Sungchan; Kim, Won-Seok; Fu, Chunjiang J

2010-06-23

Soybean and maize are extensively used in animal feed, primarily in poultry, swine, and cattle diets. Soybean meal can affect pig performance in the first few weeks following weaning and elicit specific antibodies in weaned piglets. Though maize is a major component of pig feed, it is not known if any of the maize proteins can elicit immunological response in young pigs. In this study, we have identified a prominent 27 kDa protein from maize as an immunodominant protein in young pigs. This protein, like some known allergens, exhibited resistance to pepsin digestion in vitro. Several lines of evidence identify the immunodominant 27 kDa protein as a gamma-zein, a maize seed storage protein. First, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis of different solubility classes of maize seed proteins revealed the presence of an abundant 27 kDa protein in the prolamin (zein) fraction. Antibodies raised against the purified maize 27 kDa gamma-zein also reacted against the same protein recognized by the young pig serum. Additionally, matrix-assisted laser desorption ionization time-of-flight mass spectrometry analysis of the peptides generated by trypsin digestion of the immunodominant 27 kDa protein showed significant homology to the maize 27 kDa gamma-zein. Since eliminating the allergenic protein will have a great impact on the nutritive value of the maize meal and expand its use in the livestock industry, it will be highly desirable to develop maize cultivars completely lacking the 27 kDa allergenic protein.

The sandfly fauna (Diptera: Psychodidae: Phlebotominae) of the Parque Estadual da Serra da Tiririca, Rio de Janeiro, Brazil.

PubMed

Rodrigues, Andressa Alencastre Fuzari; Barbosa, Vanessa de Araújo; Andrade Filho, José Dilermando; Brazil, Reginaldo Peçanha

2013-11-01

Cutaneous leishmaniasis (CL) in the state of Rio de Janeiro is sporadic and can be characterised as a peridomestic transmission that occurs in modified natural environments. The aim of this work was to study the fauna and ecological characteristics of sandflies in an environmentally protected area (the State Park of Serra da Tiririca) within the remnants of the Atlantic Forest in the municipalities of Niterói and Maricá and their possible relationship with leishmaniasis. Captures were performed using light traps during the night once a month for one year in both sylvatic environments and areas surrounding homes near the park. A total of 1,037 sandflies were captured, belonging to nine genera and 12 species: Evandromyia tupynambai (34.1%), Migonemyia migonei (20.6%), Brumptomyia cunhai (13.8%), Micropygomyia schreiberi (9.7%), Psathyromyia lanei (6.5%), Brumptomyia nitzulescui (5.7%), Evandromyia edwardsi (5.4%), Nyssomyia intermedia (2.8%), Evandromyia cortelezzii (0.6%), Pintomyia bianchigalatiae (0.5%), Lutzomyia longipalpis (0.2%) and Sciopemyia microps (0.1%). Both Mg. migonei and Ny. intermedia may be acting as vectors of CL in this area.

Variation in tumor response to fluosol-DA (20%)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sasai, K.; Ono, K.; Nishidai, T.

1989-05-01

The effects of Fluosol-DA 20% (FDA) and carbogen (95% O2/5% CO/sub 2/) on radiosensitivity of the three experimental tumors, SCC VII tumor, RIF-I tumor, and transplanted mammary tumor of C/sub 3/H/He mouse, subcutaneously inoculated in the leg were examined. The effect of FDA plus carbogen, and carbogen alone on radiosensitivity of SCC VII and RIF-I tumors was tested using the in vivo-in vitro assay. The growth curves were obtained for both SCC VII tumor and transplanted mammary tumor. The effect of the combination of FDA and carbogen was only observed in the transplanted mammary tumor. In the other two tumors,more » only the effect of inspiring carbogen was observed. We concluded that the effect of FDA on the radiosensitivity of experimental tumors varies with the kind of tumor systems.« less

Robotic Colorectal Resection With and Without the Use of the New Da Vinci Table Motion: A Case-Matched Study.

PubMed

Palmeri, Matteo; Gianardi, Desirée; Guadagni, Simone; Di Franco, Gregorio; Bastiani, Luca; Furbetta, Niccolò; Simoncini, Tommaso; Zirafa, Cristina; Melfi, Franca; Buccianti, Piero; Moglia, Andrea; Cuschieri, Alfred; Mosca, Franco; Morelli, Luca

2018-06-01

The da Vinci Table Motion (dVTM) is a new device that enables patients to be repositioned with instruments in place within the abdomen, and without undocking the robot. The present study was designed to compare operative and short-term outcomes of patients undergoing colorectal cancer surgery with the da Vinci Xi system, with or without use of the dVTM. Ten patients underwent robotic colorectal resection for cancer with the use of dVTM (Xi-dVTM group) between May 2015 and October 2015 at our center. The intraoperative and short-term clinical outcome were compared, using a case-control methodology (propensity scores approach to create 1:2 matched pairs), with a similar group of patients who underwent robotic colorectal surgery for cancer without the use of the dVTM device (Xi-only group). Overall robotic operative time was shorter in the Xi-dVTM group ( P = .04). Operations were executed fully robotic in all Xi-dVTM cases, while 2 cases of the Xi-only group required conversion to open surgery because of bulky tumors and difficult exposure. Postoperative medical complications were higher in the Xi-only group ( P = .024). In this preliminary experience, the use of the new dVTM with the da Vinci Xi in colorectal surgery, by overcoming the limitations of the fixed positions of the patient, enhanced the workflow and resulted in improved exposure of the operative field. Further studies with a greater number of patients are needed to confirm these benefits of the dVTM-da Vinci Xi robotically assisted colorectal surgery.

The da Vinci robotic surgical assisted anterior lumbar interbody fusion: technical development and case report.

PubMed

Beutler, William J; Peppelman, Walter C; DiMarco, Luciano A

2013-02-15

Technique development to use the da Vince Robotic Surgical System for anterior lumbar interbody fusion at L5-S1 is detailed. A case report is also presented. To evaluate and develop the da Vinci robotic assisted laparoscopic anterior lumbar stand-alone interbody fusion procedure. Anterior lumbar interbody fusion is a common procedure associated with potential morbidity related to the surgical approach. The da Vinci robot provides intra-abdominal dissection and visualization advantages compared with the traditional open and laparoscopic approach. The surgical techniques for approach to the anterior lumbar spine using the da Vinci robot were developed and modified progressively beginning with operative models followed by placement of an interbody fusion cage in the living porcine model. Development continued to progress with placement of fusion cage in a human cadaver, completed first in the laboratory setting and then in the operating room. Finally, the first patient with fusion completed using the da Vinci robot-assisted approach is presented. The anterior transperitoneal approach to the lumbar spine is accomplished with enhanced visualization and dissection capability, with maintenance of pneumoperitoneum using the da Vinci robot. Blood loss is minimal. The visualization inside the disc space and surrounding structures was considered better than current open and laparoscopic techniques. The da Vinci robot Surgical System technique continues to develop and is now described for the transperitoneal approach to the anterior lumbar spine. 4.

The Unfairness of Equal Treatment: Objectivity in L2 Testing and Dynamic Assessment

ERIC Educational Resources Information Center

Lantolf, James P.; Poehner, Matthew E.

2013-01-01

This paper considers dynamic assessment (DA) as it relates to second language (L2) development. DA is grounded in Vygotsky's (1987) sociocultural theory of mind, which holds that human consciousness emerges as a result of participation in culturally organized social activities where mediation plays a key role in guiding development. In DA, the…

Analysis of 45-years of Eclipse Timings of the Hyades (K2 V+ DA) Eclipsing Binary V471 Tauri

NASA Astrophysics Data System (ADS)

Marchioni, Lucas; Guinan, Edward; Engle, Scott

2018-01-01

V471 Tau is an important detached 0.521-day eclipsing binary composed of a K2 V and a hot DA white dwarf star. This system resides in the Hyades star cluster located approximately 153 Ly from us. V471 Tau is considered to be the end-product of common-envelope binary star evolution and is currently a pre-CV system. V471 Tau serves as a valuable astrophysical laboratory for studying stellar evolution, white dwarfs, stellar magnetic dynamos, and possible detection of low mass companions using the Light Travel Time (LTT) Effects. Since its discovery as an eclipsing binary in 1970, photometry has been carried out and many eclipse timings have been determined. We have performed an analysis of the available photometric data available on V471 Tauri. The binary system has been the subject of analyses regarding the orbital period. From this analysis several have postulated the existence of a third body in the form of a brown dwarf that is causing periodic variations in the system’s apparent period. In this study we combine ground based data with photometry secured recently from the Kepler K2 mission. After detrending and phasing the available data, we are able to compare the changing period of the eclipsing binary system against predictions on the existence of this third body. The results of the analysis will be presented. This research is sponsored by grants from NASA and NSF for which we are very grateful.

The virtual observatory service TheoSSA: Establishing a database of synthetic stellar flux standards. I. NLTE spectral analysis of the DA-type white dwarf G191-B2B

NASA Astrophysics Data System (ADS)

Rauch, T.; Werner, K.; Bohlin, R.; Kruk, J. W.

2013-12-01

Context. Hydrogen-rich, DA-type white dwarfs are particularly suited as primary standard stars for flux calibration. State-of-the-art NLTE models consider opacities of species up to trans-iron elements and provide reliable synthetic stellar-atmosphere spectra to compare with observations. Aims: We will establish a database of theoretical spectra of stellar flux standards that are easily accessible via a web interface. Methods: In the framework of the Virtual Observatory, the German Astrophysical Virtual Observatory developed the registered service TheoSSA. It provides easy access to stellar spectral energy distributions (SEDs) and is intended to ingest SEDs calculated by any model-atmosphere code. In case of the DA white dwarf G191-B2B, we demonstrate that the model reproduces not only its overall continuum shape but also the numerous metal lines exhibited in its ultraviolet spectrum. Results: TheoSSA is in operation and contains presently a variety of SEDs for DA-type white dwarfs. It will be extended in the near future and can host SEDs of all primary and secondary flux standards. The spectral analysis of G191-B2B has shown that our hydrostatic models reproduce the observations best at and log g = 7.60 ± 0.05. We newly identified Fe vi, Ni vi, and Zn iv lines. For the first time, we determined the photospheric zinc abundance with a logarithmic mass fraction of -4.89 (7.5 × solar). The abundances of He (upper limit), C, N, O, Al, Si, O, P, S, Fe, Ni, Ge, and Sn were precisely determined. Upper abundance limits of about 10% solar were derived for Ti, Cr, Mn, and Co. Conclusions: The TheoSSA database of theoretical SEDs of stellar flux standards guarantees that the flux calibration of all astronomical data and cross-calibration between different instruments can be based on the same models and SEDs calculated with different model-atmosphere codes and are easy to compare. Based on observations with the NASA/ESA Hubble Space Telescope, obtained at the Space Telescope

36 kDa glycoprotein isolated from Rhus verniciflua stokes inhibits G/GO-induced mitochondrial apoptotic signal pathways in BNL CL.2 cells.

PubMed

Lee, Sei-Jung; Oh, Phil-Sun; Lim, Kwang; Lim, Kye-Taek

2005-12-01

Rhus verniciflua Stokes is one of the medicinal plants traditionally used to heal and treat hepatic and inflammatory diseases. We found that a glycoprotein isolated from the fruit has a molecular weight of 36 kDa and consists of a carbohydrate component (38.75%) and a protein (61.25%), and that the glycoprotein has a strong scavenging activity against hydroxyl radicals without any pro-oxidant activity in the cell-free system. In glucose/glucose oxidase (G/GO)-induced BNL CL.2 cells, the results showed that Rhus verniciflua Stokes glycoprotein has dose-dependent blocking activities against G/GO-induced cytotoxicity and apoptosis, increasing the glutathione (GSH) peroxidase activity. In the activity of the mitochondrial apoptotic mediators (cytochrome c, caspases and poly(ADP-ribose)polymerase (PARP)), the glycoprotein (100 microg/ml) showed an inhibitory effect on cytochrome c release, caspase-9/3 activation, and PARP cleavage. Moreover, Rhus verniciflua Stokes glycoprotein has a stimulating effect on the nitric oxide production. Here, we speculate that this glycoprotein is one of the natural antioxidants and of the modulators of apoptotic signal pathways in BNL CL.2 cells.

The glyoxysomal and plastid molecular chaperones (70-kDa heat shock protein) of watermelon cotyledons are encoded by a single gene

PubMed Central

Wimmer, Bernhard; Lottspeich, Friedrich; van der Klei, Ida; Veenhuis, Marten; Gietl, Christine

1997-01-01

The monoclonal a-70-kDa heat shock protein (hsp70) antibody recognizes in crude extracts from watermelon (Citrullus vulgaris) cotyledons two hsps with molecular masses of 70 and 72 kDa. Immunocytochemistry on watermelon cotyledon tissue and on isolated glyoxysomes identified hsp70s in the matrix of glyoxysomes and plastids. Affinity purification and partial amino acid determination revealed the 70-kDa protein to share high sequence identity with cytosolic hsp70s from a number of plant species, while the 72 kDa protein was very similar to plastid hsp70s from pea and cucumber. A full-length cDNA clone encoding the 72-kDa hsp70 was isolated and identified two start methionines in frame within the N-terminal presequence leading either to an N-terminal extension of 67 amino acids or to a shorter one of 47 amino acids. The longer presequence was necessary and sufficient to target a reporter protein into watermelon proplastids in vitro. The shorter extension starting from the second methionine within the long version harbored a consensus peroxisomal targeting signal (RT-X5-KL) that directed in vivo a reporter protein into peroxisomes of the yeast Hansenula polymorpha. Peroxisomal targeting was however prevented, when the 67-residue presequence was fused to the reporter protein, indicating that the peroxisomal targeting signal 2 information is hidden in this context. We propose that the 72-kDa hsp70 is encoded by a single gene, but targeted alternatively into two organelles by the modulated use of its presequence. PMID:9391076

Opportunity cost in the economic evaluation of da Vinci robotic assisted surgery.

PubMed

Fuertes-Guiró, Fernando; Girabent-Farrés, Montserrat; Viteri-Velasco, Eduardo

2016-04-01

This study aims to demonstrate the importance of the opportunity cost in using da Vinci robotic surgery, assisted by a comprehensive review of the literature to determine the differences in the total cost of surgery and operative time in traditional laparoscopic surgery and da Vinci robotic surgery. We identified the studies comparing the use of traditional laparoscopic surgery with robotics during the period 2002-2012 in the electronic economic evaluation databases, and another electronic search was performed for publications by Spanish hospitals in the same period to calculate the opportunity cost. A meta-analysis of response variables considering the total cost of the intervention and surgical time was completed using the items selected in the first revision, and their differences were analyzed. We then calculated the opportunity cost represented by these time differences using the data obtained from the studies in the second review of the literature. Nine items were selected in the first review and three in the second. Traditional laparoscopic surgery has a lower cost than the da Vinci (p < 0.00001). Robotic surgery takes longer (8.0-65.5 min) than traditional surgery (p < 0.00001), and this difference represents an average opportunity cost for robot use of € 489.98, with a unit cost factor/time which varies according to the pathology dealt with, from € 8.2 to 18.7/min. The opportunity cost is a quantity that must be included in the total cost of using a surgical technology within an economic cost analysis in the context of an economic evaluation.

An Exploratory Study on DRD2 and Creative Potential

ERIC Educational Resources Information Center

Zhang, Shun; Zhang, Muzi; Zhang, Jinghuan

2014-01-01

One critical step toward to a better understanding of creativity is to unveil its underlying genetic architectures. Recently, several studies have been conducted to investigate the effects of dopamine (DA) and 5-hydroxytryptamine (5-HT) related genetic polymorphisms on creativity. Among DA related genes, dopamine D2 receptor gene…

Estudo de não gaussianidade nas anisotropias da RCF medidas Wmap

NASA Astrophysics Data System (ADS)

Andrade, A. P. A.; Wuensche, C. A.; Ribeiro, A. L. B.

2003-08-01

A investigação do campo de flutuações da Radiação Cósmica de Fundo (RCF) pode oferecer um importante teste para os modelos cosmológicos que descrevem a origem e a evolução das flutuações primordiais. De um lado, apresenta-se o modelo inflacionário que prevê um espectro de flutuações adiabáticas distribuídas segundo uma gaussiana e, de outro, os modelos de defeitos topológicos (dentre outros) que descrevem um mecanismo para a geração de flutuações de isocurvatura que obedecem a uma distribuição não gaussiana. Este trabalho tem como objetivo caracterizar traços do modelo não gaussiano de campo misto (entre flutuações adiabáticas e de isocurvatura) nos mapas do Wilkinson Microwave Anisotropy Probe (WMAP). Simulações das anisotropias da RCF no contexto de mistura indicam traços marcantes na distribuição das flutuações de temperatura, mesmo quando consideradas pequenas contribuições do campo de isocurvatura (da ordem de 0.001). O efeito da mistura entre os campos resulta na transferência de potência de flutuações em escalas angulares intermediárias para flutuações em pequenas escalas angulares. Este efeito pode ser caracterizado pela relação entre as amplitudes dos primeiros picos acústicos no espectro de potência da RCF. Neste trabalho, investigamos a contribuição do campo de isocurvatura, no contexto de mistura, sobre as observações recentes da RCF realizadas pelo WMAP. As previsões do modelo de campo misto, uma vez confrontadas com as observações em pequenas escalas angulares, podem ajudar a revelar a natureza das flutuações primordiais.

Integration of PanDA workload management system with Titan supercomputer at OLCF

NASA Astrophysics Data System (ADS)

De, K.; Klimentov, A.; Oleynik, D.; Panitkin, S.; Petrosyan, A.; Schovancova, J.; Vaniachine, A.; Wenaus, T.

2015-12-01

The PanDA (Production and Distributed Analysis) workload management system (WMS) was developed to meet the scale and complexity of LHC distributed computing for the ATLAS experiment. While PanDA currently distributes jobs to more than 100,000 cores at well over 100 Grid sites, the future LHC data taking runs will require more resources than Grid computing can possibly provide. To alleviate these challenges, ATLAS is engaged in an ambitious program to expand the current computing model to include additional resources such as the opportunistic use of supercomputers. We will describe a project aimed at integration of PanDA WMS with Titan supercomputer at Oak Ridge Leadership Computing Facility (OLCF). The current approach utilizes a modified PanDA pilot framework for job submission to Titan's batch queues and local data management, with light-weight MPI wrappers to run single threaded workloads in parallel on Titan's multicore worker nodes. It also gives PanDA new capability to collect, in real time, information about unused worker nodes on Titan, which allows precise definition of the size and duration of jobs submitted to Titan according to available free resources. This capability significantly reduces PanDA job wait time while improving Titan's utilization efficiency. This implementation was tested with a variety of Monte-Carlo workloads on Titan and is being tested on several other supercomputing platforms. Notice: This manuscript has been authored, by employees of Brookhaven Science Associates, LLC under Contract No. DE-AC02-98CH10886 with the U.S. Department of Energy. The publisher by accepting the manuscript for publication acknowledges that the United States Government retains a non-exclusive, paid-up, irrevocable, world-wide license to publish or reproduce the published form of this manuscript, or allow others to do so, for United States Government purposes.

A Creative Approach to the Common Core Standards: The Da Vinci Curriculum

ERIC Educational Resources Information Center

Chaucer, Harry

2012-01-01

"A Creative Approach to the Common Core Standards: The Da Vinci Curriculum" challenges educators to design programs that boldly embrace the Common Core State Standards by imaginatively drawing from the genius of great men and women such as Leonardo da Vinci. A central figure in the High Renaissance, Leonardo made extraordinary contributions as a…

Initial experience with the new da Vinci single-port robot-assisted platform.

PubMed

Ballestero Diego, R; Zubillaga Guerrero, S; Truan Cacho, D; Carrion Ballardo, C; Velilla Diez, G; Calleja Hermosa, P; Gutiérrez Baños, J L

2017-06-01

To describe our experience in the first cases of urological surgeries performed with the da Vinci single-port robot-assisted platform. We performed 5 single-port robot-assisted surgeries (R-LESS) between May and October 2014. We performed 3 ureteral reimplant surgeries, one ureteropyeloplasty in an inverted kidney and 1 partial nephrectomy. The perioperative and postoperative results were collected, as well as a report of the complications according to the Clavien classification system. Of the 5 procedures, 4 were performed completely by LESS, while 1 procedure was reconverted to multiport robot-assisted surgery. There were no intraoperative complications. We observed perioperative complications in 4 patients, all of which were grade 1 or 2. The mean surgical time was 262minutes (range, 230-300). In our initial experience with the da Vinci device, R-LESS surgery was feasible and safe. There are still a number of limitations in its use, which require new and improved R-LESS platforms. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.