[2015 updated position statement of the management of hyperglycaemia in type 2 diabetes].

PubMed

Scheen, A J; Paquot, N

2015-08-26

The strategy for the management ot type 2 diabetes, summarized by a group of European and American experts, has been updated early 2015. A patient-centered approach is recommended and the first drug choice is metformin combined with lifestyle improvement. After failure of metformin monotherapy, the selection of a second drug should be based on the efficacy, safety and cost of each pharmacological class. When compared to the position statement of 2012, the most important changes are the possible addition of a gliptin to a dual oral therapy or even to insulin, the commercialization of sodium-glucose cotransporters type 2 (SGLT2) inhibitors (gliflozins, to be used in dual or triple therapy, even in combination with insulin) and the possible combination of a glucagon-like peptide-I receptor agonist together with a basal insulin.

Selection of the NIR region for a regression model of the ethanol concentration in fermentation process by an online NIR and mid-IR dual-region spectrometer and 2D heterospectral correlation spectroscopy.

PubMed

Nishii, Takashi; Genkawa, Takuma; Watari, Masahiro; Ozaki, Yukihiro

2012-01-01

A new selection procedure of an informative near-infrared (NIR) region for regression model building is proposed that uses an online NIR/mid-infrared (mid-IR) dual-region spectrometer in conjunction with two-dimensional (2D) NIR/mid-IR heterospectral correlation spectroscopy. In this procedure, both NIR and mid-IR spectra of a liquid sample are acquired sequentially during a reaction process using the NIR/mid-IR dual-region spectrometer; the 2D NIR/mid-IR heterospectral correlation spectrum is subsequently calculated from the obtained spectral data set. From the calculated 2D spectrum, a NIR region is selected that includes bands of high positive correlation intensity with mid-IR bands assigned to the analyte, and used for the construction of a regression model. To evaluate the performance of this procedure, a partial least-squares (PLS) regression model of the ethanol concentration in a fermentation process was constructed. During fermentation, NIR/mid-IR spectra in the 10000 - 1200 cm(-1) region were acquired every 3 min, and a 2D NIR/mid-IR heterospectral correlation spectrum was calculated to investigate the correlation intensity between the NIR and mid-IR bands. NIR regions that include bands at 4343, 4416, 5778, 5904, and 5955 cm(-1), which result from the combinations and overtones of the C-H group of ethanol, were selected for use in the PLS regression models, by taking the correlation intensity of a mid-IR band at 2985 cm(-1) arising from the CH(3) asymmetric stretching vibration mode of ethanol as a reference. The predicted results indicate that the ethanol concentrations calculated from the PLS regression models fit well to those obtained by high-performance liquid chromatography. Thus, it can be concluded that the selection procedure using the NIR/mid-IR dual-region spectrometer combined with 2D NIR/mid-IR heterospectral correlation spectroscopy is a powerful method for the construction of a reliable regression model.

Dual-wavelength quantum cascade laser for trace gas spectroscopy

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

Jágerská, J.; Tuzson, B.; Mangold, M.

2014-10-20

We demonstrate a sequentially operating dual-wavelength quantum cascade laser with electrically separated laser sections, emitting single-mode at 5.25 and 6.25 μm. Based on a single waveguide ridge, this laser represents a considerable asset to optical sensing and trace gas spectroscopy, as it allows probing multiple gas species with spectrally distant absorption features using conventional optical setups without any beam combining optics. The laser capability was demonstrated in simultaneous NO and NO{sub 2} detection, reaching sub-ppb detection limits and selectivity comparable to conventional high-end spectroscopic systems.

Percutaneous Dual-valve Intervention in a High-risk Patient with Severe Aortic and Mitral Stenosis

PubMed Central

Mrevlje, Blaz; Aboukura, Mohamad; Nienaber, Christoph A.

2016-01-01

Aortic stenosis is the most frequent and mitral stenosis is the least frequent native single-sided valve disease in Europe. Patients with the combination of severe symptomatic degenerative aortic and mitral stenosis are very rare. Guidelines for the treatment of heart valve diseases are clear for single-valve situations. However, there is no common agreement or recommendation for the best treatment strategy in patients with multiple valve disease and severe concomitant comorbidities. A 76-year-old female patient with the combination of severe degenerative symptomatic aortic and mitral stenosis and several comorbidities including severe obesity, who was found unsuitable surgical candidate by the heart team and unsuitable for two-time general anesthesia in the case of two-step single-valve percutaneous approach by anesthesiologists, underwent successful percutaneous dual-valve single-intervention (transcatheter aortic valve implantation and percutaneous mitral balloon commissurotomy). Percutaneous dual-valve single-intervention is feasible in selected symptomatic high-risk patients. PMID:27867460

Hydrophobic interaction chromatography in dual salt system increases protein binding capacity.

PubMed

Senczuk, Anna M; Klinke, Ralph; Arakawa, Tsutomu; Vedantham, Ganesh; Yigzaw, Yinges

2009-08-01

Hydrophobic interaction chromatography (HIC) uses weakly hydrophobic resins and requires a salting-out salt to promote protein-resin interaction. The salting-out effects increase with protein and salt concentration. Dynamic binding capacity (DBC) is dependent on the binding constant, as well as on the flow characteristics during sample loading. DBC increases with the salt concentration but decreases with increasing flow rate. Dynamic and operational binding capacity have a major raw material cost/processing time impact on commercial scale production of monoclonal antibodies. In order to maximize DBC the highest salt concentration without causing precipitation is used. We report here a novel method to maintain protein solubility while increasing the DBC by using a combination of two salting-out salts (referred to as dual salt). In a series of experiments, we explored the dynamic capacity of a HIC resin (TosoBioscience Butyl 650M) with combinations of salts. Using a model antibody, we developed a system allowing us to increase the dynamic capacity up to twofold using the dual salt system over traditional, single salt system. We also investigated the application of this novel approach to several other proteins and salt combinations, and noted a similar protein solubility and DBC increase. The observed increase in DBC in the dual salt system was maintained at different linear flow rates and did not impact selectivity.

Dual gold catalysis: σ,π-propyne acetylide and hydroxyl-bridged digold complexes as easy-to-prepare and easy-to-handle precatalysts.

PubMed

Hashmi, A Stephen K; Lauterbach, Tobias; Nösel, Pascal; Vilhelmsen, Mie Højer; Rudolph, Matthias; Rominger, Frank

2013-01-14

A series of dinuclear gold σ,π-propyne acetylide complexes were prepared and tested for their catalytic ability in dual gold catalysis that was based on the reaction of an electrophilic π-complex of gold with a gold acetylide. The air-stable and storable catalysts can be isolated as silver-free catalysts in their activated form. These dual catalysts allow a fast initiation phase for the dual catalytic cycles without the need for additional additives for acetylide formation. Because propyne serves as a throw-away ligand, no traces of the precatalyst are generated. Based on the fast initiation process, side products are minimized and reaction rates are higher for these catalysts. A series of test reactions were used to demonstrate the general applicability of these catalysts. Lower catalyst loadings, faster reaction rates, and better selectivity, combined with the practicability of these catalysts, make them ideal catalysts for dual gold catalysis. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Reduced VEGF production, angiogenesis, and vascular regrowth contribute to the antitumor properties of dual mTORC1/mTORC2 inhibitors

PubMed Central

Falcon, Beverly L.; Barr, Sharon; Gokhale, Prafulla C.; Chou, Jeyling; Fogarty, Jennifer; Depeille, Philippe; Miglarese, Mark; Epstein, David M.; McDonald, Donald M.

2011-01-01

The mammalian target of rapamycin (mTOR) pathway is implicated widely in cancer pathophysiology. Dual inhibition of the mTOR kinase complexes mTORC1 and mTORC2 decreases tumor xenograft growth in vivo and VEGF secretion in vitro, but the relationship between these two effects are unclear. In this study, we examined the effects of mTORC1/2 dual inhibition on VEGF production, tumor angiogenesis, vascular regression, and vascular regrowth, and we compared the effects of dual inhibition to mTORC1 inhibition alone. ATP-competitive inhibitors OSI-027 and OXA-01 targeted both mTORC1 and mTORC2 signaling in vitro and in vivo, unlike rapamycin which only inhibited mTORC1 signaling. OXA-01 reduced VEGF production in tumors in a manner associated with decreased vessel sprouting but little vascular regression. In contrast, rapamycin exerted less effect on tumoral production of VEGF. Treatment with the selective VEGFR inhibitor OSI-930 reduced vessel sprouting and caused substantial vascular regression in tumors. However, following discontinuation of OSI-930 administration tumor regrowth could be slowed by OXA-01 treatment. Combining dual inhibitors of mTORC1 and mTORC2 with a VEGFR2 inhibitor decreased tumor growth more than either inhibitor alone. Together, these results indicate that dual inhibition of mTORC1/2 exerts anti-angiogenic and anti-tumoral effects that are even more efficacious when combined with a VEGFR antagonist. PMID:21363918

Evaluation of innovative rocket engines for single-stage earth-to-orbit vehicles

NASA Astrophysics Data System (ADS)

Manski, Detlef; Martin, James A.

1988-07-01

Computer models of rocket engines and single-stage-to-orbit vehicles that were developed by the authors at DFVLR and NASA have been combined. The resulting code consists of engine mass, performance, trajectory and vehicle sizing models. The engine mass model includes equations for each subsystem and describes their dependences on various propulsion parameters. The engine performance model consists of multidimensional sets of theoretical propulsion properties and a complete thermodynamic analysis of the engine cycle. The vehicle analyses include an optimized trajectory analysis, mass estimation, and vehicle sizing. A vertical-takeoff, horizontal-landing, single-stage, winged, manned, fully reusable vehicle with a payload capability of 13.6 Mg (30,000 lb) to low earth orbit was selected. Hydrogen, methane, propane, and dual-fuel engines were studied with staged-combustion, gas-generator, dual bell, and the dual-expander cycles. Mixture ratio, chamber pressure, nozzle exit pressure liftoff acceleration, and dual fuel propulsive parameters were optimized.

Evaluation of innovative rocket engines for single-stage earth-to-orbit vehicles

NASA Technical Reports Server (NTRS)

Manski, Detlef; Martin, James A.

1988-01-01

Computer models of rocket engines and single-stage-to-orbit vehicles that were developed by the authors at DFVLR and NASA have been combined. The resulting code consists of engine mass, performance, trajectory and vehicle sizing models. The engine mass model includes equations for each subsystem and describes their dependences on various propulsion parameters. The engine performance model consists of multidimensional sets of theoretical propulsion properties and a complete thermodynamic analysis of the engine cycle. The vehicle analyses include an optimized trajectory analysis, mass estimation, and vehicle sizing. A vertical-takeoff, horizontal-landing, single-stage, winged, manned, fully reusable vehicle with a payload capability of 13.6 Mg (30,000 lb) to low earth orbit was selected. Hydrogen, methane, propane, and dual-fuel engines were studied with staged-combustion, gas-generator, dual bell, and the dual-expander cycles. Mixture ratio, chamber pressure, nozzle exit pressure liftoff acceleration, and dual fuel propulsive parameters were optimized.

Discovery of Indazoles as Potent, Orally Active Dual Neurokinin 1 Receptor Antagonists and Serotonin Transporter Inhibitors for the Treatment of Depression.

PubMed

Degnan, Andrew P; Tora, George O; Huang, Hong; Conlon, David A; Davis, Carl D; Hanumegowda, Umesh M; Hou, Xiaoping; Hsiao, Yi; Hu, Joanna; Krause, Rudolph; Li, Yu-Wen; Newton, Amy E; Pieschl, Rick L; Raybon, Joseph; Rosner, Thorsten; Sun, Jung-Hui; Taber, Matthew T; Taylor, Sarah J; Wong, Michael K; Zhang, Huiping; Lodge, Nicholas J; Bronson, Joanne J; Macor, John E; Gillman, Kevin W

2016-12-21

Combination studies of neurokinin 1 (NK1) receptor antagonists and serotonin-selective reuptake inhibitors (SSRIs) have shown promise in preclinical models of depression. Such a combination may offer important advantages over the current standard of care. Herein we describe the discovery and optimization of an indazole-based chemotype to provide a series of potent dual NK1 receptor antagonists/serotonin transporter (SERT) inhibitors to overcome issues of ion channel blockade. This effort culminated in the identification of compound 9, an analogue that demonstrated favorable oral bioavailability, excellent brain uptake, and robust in vivo efficacy in a validated depression model. Over the course of this work, a novel heterocycle-directed asymmetric hydrogenation was developed to facilitate installation of the key stereogenic center.

Boolean Logic Tree of Label-Free Dual-Signal Electrochemical Aptasensor System for Biosensing, Three-State Logic Computation, and Keypad Lock Security Operation.

PubMed

Lu, Jiao Yang; Zhang, Xin Xing; Huang, Wei Tao; Zhu, Qiu Yan; Ding, Xue Zhi; Xia, Li Qiu; Luo, Hong Qun; Li, Nian Bing

2017-09-19

The most serious and yet unsolved problems of molecular logic computing consist in how to connect molecular events in complex systems into a usable device with specific functions and how to selectively control branchy logic processes from the cascading logic systems. This report demonstrates that a Boolean logic tree is utilized to organize and connect "plug and play" chemical events DNA, nanomaterials, organic dye, biomolecule, and denaturant for developing the dual-signal electrochemical evolution aptasensor system with good resettability for amplification detection of thrombin, controllable and selectable three-state logic computation, and keypad lock security operation. The aptasensor system combines the merits of DNA-functionalized nanoamplification architecture and simple dual-signal electroactive dye brilliant cresyl blue for sensitive and selective detection of thrombin with a wide linear response range of 0.02-100 nM and a detection limit of 1.92 pM. By using these aforementioned chemical events as inputs and the differential pulse voltammetry current changes at different voltages as dual outputs, a resettable three-input biomolecular keypad lock based on sequential logic is established. Moreover, the first example of controllable and selectable three-state molecular logic computation with active-high and active-low logic functions can be implemented and allows the output ports to assume a high impediment or nothing (Z) state in addition to the 0 and 1 logic levels, effectively controlling subsequent branchy logic computation processes. Our approach is helpful in developing the advanced controllable and selectable logic computing and sensing system in large-scale integration circuits for application in biomedical engineering, intelligent sensing, and control.

Blockade of Cocaine or σ Receptor Agonist Self Administration by Subtype-Selective σ Receptor Antagonists

PubMed Central

Hiranita, Takato; Kopajtic, Theresa A.; Rice, Kenner C.; Mesangeau, Christophe; Narayanan, Sanju; Abdelazeem, Ahmed H.; McCurdy, Christopher R.

2016-01-01

The identification of sigma receptor (σR) subtypes has been based on radioligand binding and, despite progress with σ1R cellular function, less is known about σR subtype functions in vivo. Recent findings that cocaine self administration experience will trigger σR agonist self administration was used in this study to assess the in vivo receptor subtype specificity of the agonists (+)-pentazocine, PRE-084 [2-(4-morpholinethyl) 1-phenylcyclohexanecarboxylate hydrochloride], and 1,3-di-o-tolylguanidine (DTG) and several novel putative σR antagonists. Radioligand binding studies determined in vitro σR selectivity of the novel compounds, which were subsequently studied for self administration and antagonism of cocaine, (+)-pentazocine, PRE-084, or DTG self administration. Across the dose ranges studied, none of the novel compounds were self administered, nor did they alter cocaine self administration. All compounds blocked DTG self administration, with a subset also blocking (+)-pentazocine and PRE-084 self administration. The most selective of the compounds in binding σ1Rs blocked cocaine self administration when combined with a dopamine transport inhibitor, either methylphenidate or nomifensine. These drug combinations did not decrease rates of responding maintained by food reinforcement. In contrast, the most selective of the compounds in binding σ2Rs had no effect on cocaine self administration in combination with either dopamine transport inhibitor. Thus, these results identify subtype-specific in vivo antagonists, and the utility of σR agonist substitution for cocaine self administration as an assay capable of distinguishing σR subtype selectivity in vivo. These results further suggest that effectiveness of dual σR antagonism and dopamine transport inhibition in blocking cocaine self administration is specific for σ1Rs and further support this dual targeting approach to development of cocaine antagonists. PMID:27189970

Simultaneous Dual Selective Targeted Delivery of Two Covalent Gemcitabine Immunochemotherapeutics and Complementary Anti-Neoplastic Potency of [Se]-Methylselenocysteine

PubMed Central

Coyne, C. P.; Jones, Toni; Bear, Ryan

2015-01-01

The anti-metabolite chemotherapeutic, gemcitabine is relatively effective for a spectrum of neoplastic conditions that include various forms of leukemia and adenocarcinoma/carcinoma. Rapid systemic deamination of gemcitabine accounts for a brief plasma half-life but its sustained administration is often curtailed by sequelae and chemotherapeutic-resistance. A molecular strategy that diminishes these limitations is the molecular design and synthetic production of covalent gemcitabine immunochemotherapeutics that possess properties of selective “targeted” delivery. The simultaneous dual selective “targeted” delivery of gemcitabine at two separate sites on the external surface membrane of a single cancer cell types represents a therapeutic approach that can increase cytosol chemotherapeutic deposition; prolong chemotherapeutic plasma half-life (reduces administration frequency); minimize innocent exposure of normal tissues and healthy organ systems; and ultimately enhance more rapid and thorough resolution of neoplastic cell populations. Materials and Methods: A light-reactive gemcitabine intermediate synthesized utilizing succinimidyl 4,4-azipentanoate was covalently bound to anti-EGFR or anti-HER2/neu IgG by exposure to UV light (354-nm) resulting in the synthesis of covalent immunochemotherapeutics, gemcitabine-(C4-amide)-[anti-EGFR] and gemcitabine-(C4-amide)-[anti-HER2/neu]. Cytotoxic anti-neoplastic potency of gemcitabine-(C4-amide)-[anti-EGFR] and gemcitabine-(C4-amide)-[anti-HER2/neu] between gemcitabine-equivalent concentrations of 10−12 M and 10−6 M was determined utilizing chemotherapeutic-resistant mammary adenocarcinoma (SKRr-3). The organoselenium compound, [Se]-methylselenocysteine was evaluated to determine if it complemented the anti-neoplastic potency of the covalent gemcitabine immunochemotherapeutics. Results: Gemcitabine-(C4-amide)-[anti-EGFR], gemcitabine-(C4-amide)-[anti-HER2/neu] and the dual simultaneous combination of gemcitabine-(C4-amide)-[anti-EGFR] with gemcitabine-(C4-amide)-[anti-HER2/neu] all had anti-neoplastic cytotoxic potency against mammary adenocarcinoma. Gemcitabine-(C4-amide)-[anti-EGFR] and gemcitabine-(C4-amide)-[anti-HER2/neu] produced progressive increases in anti-neoplastic cytotoxicity that were greatest between gemcitabine-equivalent concentrations of 10−9 M and 10−6 M. Dual simultaneous combinations of gemcitabine-(C4-amide)-[anti-EGFR] with gemcitabine-(C4-amide)-[anti-HER2/neu] produced levels of anti-neoplastic cytotoxicity intermediate between each of the individual covalent gemcitabine immunochemotherapeutics. Total anti-neoplastic cytotoxicity of the dual simultaneous combination of gemcitabine-(C4-amide)-[anti-EGFR] and gemcitabine-(C4-amide)-[anti-HER2/neu] against chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3) was substantially higher when formulated with [Se]-methylsele-nocysteine. PMID:25821636

Preparation of a novel dual-function strong cation exchange/hydrophobic interaction chromatography stationary phase for protein separation.

PubMed

Zhao, Kailou; Yang, Li; Wang, Xuejiao; Bai, Quan; Yang, Fan; Wang, Fei

2012-08-30

We have explored a novel dual-function stationary phase which combines both strong cation exchange (SCX) and hydrophobic interaction chromatography (HIC) characteristics. The novel dual-function stationary phase is based on porous and spherical silica gel functionalized with ligand containing sulfonic and benzyl groups capable of electrostatic and hydrophobic interaction functionalities, which displays HIC character in a high salt concentration, and IEC character in a low salt concentration in mobile phase employed. As a result, it can be employed to separate proteins with SCX and HIC modes, respectively. The resolution and selectivity of the dual-function stationary phase were evaluated under both HIC and SCX modes with standard proteins and can be comparable to that of conventional IEC and HIC columns. More than 96% of mass and bioactivity recoveries of proteins can be achieved in both HIC and SCX modes, respectively. The results indicated that the novel dual-function column could replace two individual SCX and HIC columns for protein separation. Mixed retention mechanism of proteins on this dual-function column based on stoichiometric displacement theory (SDT) in LC was investigated to find the optimal balance of the magnitude of electrostatic and hydrophobic interactions between protein and the ligand on the silica surface in order to obtain high resolution and selectivity for protein separation. In addition, the effects of the hydrophobicity of the ligand of the dual-function packings and pH of the mobile phase used on protein separation were also investigated in detail. The results show that the ligand with suitable hydrophobicity to match the electrostatic interaction is very important to prepare the dual-function stationary phase, and a better resolution and selectivity can be obtained at pH 6.5 in SCX mode. Therefore, the dual-function column can replace two individual SCX and HIC columns for protein separation and be used to set up two-dimensional liquid chromatography with a single column (2DLC-1C), which can also be employed to separate three kinds of active proteins completely, such as lysozyme, ovotransferrin and ovalbumin from egg white. The result is very important not only to the development of new 2DLC technology with a single column for proteomics, but also to recombinant protein drug production for saving column expense and simplifying the process in biotechnology. Copyright © 2012 Elsevier B.V. All rights reserved.

Fat suppression with short inversion time inversion-recovery and chemical-shift selective saturation: a dual STIR-CHESS combination prepulse for turbo spin echo pulse sequences.

PubMed

Tanabe, Koji; Nishikawa, Keiichi; Sano, Tsukasa; Sakai, Osamu; Jara, Hernán

2010-05-01

To test a newly developed fat suppression magnetic resonance imaging (MRI) prepulse that synergistically uses the principles of fat suppression via inversion recovery (STIR) and spectral fat saturation (CHESS), relative to pure CHESS and STIR. This new technique is termed dual fat suppression (Dual-FS). To determine if Dual-FS could be chemically specific for fat, the phantom consisted of the fat-mimicking NiCl(2) aqueous solution, porcine fat, porcine muscle, and water was imaged with the three fat-suppression techniques. For Dual-FS and STIR, several inversion times were used. Signal intensities of each image obtained with each technique were compared. To determine if Dual-FS could be robust to magnetic field inhomogeneities, the phantom consisting of different NiCl(2) aqueous solutions, porcine fat, porcine muscle, and water was imaged with Dual-FS and CHESS at the several off-resonance frequencies. To compare fat suppression efficiency in vivo, 10 volunteer subjects were also imaged with the three fat-suppression techniques. Dual-FS could suppress fat sufficiently within the inversion time of 110-140 msec, thus enabling differentiation between fat and fat-mimicking aqueous structures. Dual-FS was as robust to magnetic field inhomogeneities as STIR and less vulnerable than CHESS. The same results for fat suppression were obtained in volunteers. The Dual-FS-STIR-CHESS is an alternative and promising fat suppression technique for turbo spin echo MRI. Copyright 2010 Wiley-Liss, Inc.

Metal artifact correction for x-ray computed tomography using kV and selective MV imaging.

PubMed

Wu, Meng; Keil, Andreas; Constantin, Dragos; Star-Lack, Josh; Zhu, Lei; Fahrig, Rebecca

2014-12-01

The overall goal of this work is to improve the computed tomography (CT) image quality for patients with metal implants or fillings by completing the missing kilovoltage (kV) projection data with selectively acquired megavoltage (MV) data that do not suffer from photon starvation. When both of these imaging systems, which are available on current radiotherapy devices, are used, metal streak artifacts are avoided, and the soft-tissue contrast is restored, even for regions in which the kV data cannot contribute any information. Three image-reconstruction methods, including two filtered back-projection (FBP)-based analytic methods and one iterative method, for combining kV and MV projection data from the two on-board imaging systems of a radiotherapy device are presented in this work. The analytic reconstruction methods modify the MV data based on the information in the projection or image domains and then patch the data onto the kV projections for a FBP reconstruction. In the iterative reconstruction, the authors used dual-energy (DE) penalized weighted least-squares (PWLS) methods to simultaneously combine the kV/MV data and perform the reconstruction. The authors compared kV/MV reconstructions to kV-only reconstructions using a dental phantom with fillings and a hip-implant numerical phantom. Simulation results indicated that dual-energy sinogram patch FBP and the modified dual-energy PWLS method can successfully suppress metal streak artifacts and restore information lost due to photon starvation in the kV projections. The root-mean-square errors of soft-tissue patterns obtained using combined kV/MV data are 10-15 Hounsfield units smaller than those of the kV-only images, and the structural similarity index measure also indicates a 5%-10% improvement in the image quality. The added dose from the MV scan is much less than the dose from the kV scan if a high efficiency MV detector is assumed. The authors have shown that it is possible to improve the image quality of kV CTs for patients with metal implants or fillings by completing the missing kV projection data with selectively acquired MV data that do not suffer from photon starvation. Numerical simulations demonstrated that dual-energy sinogram patch FBP and a modified kV/MV PWLS method can successfully suppress metal streak artifacts and restore information lost due to photon starvation in kV projections. Combined kV/MV images may permit the improved delineation of structures of interest in CT images for patients with metal implants or fillings.

Design of a highly selective quenched activity-based probe and its application in dual color imaging studies of cathepsin S activity localization.

PubMed

Oresic Bender, Kristina; Ofori, Leslie; van der Linden, Wouter A; Mock, Elliot D; Datta, Gopal K; Chowdhury, Somenath; Li, Hao; Segal, Ehud; Sanchez Lopez, Mateo; Ellman, Jonathan A; Figdor, Carl G; Bogyo, Matthew; Verdoes, Martijn

2015-04-15

The cysteine cathepsins are a group of 11 proteases whose function was originally believed to be the degradation of endocytosed material with a high degree of redundancy. However, it has become clear that these enzymes are also important regulators of both health and disease. Thus, selective tools that can discriminate between members of this highly related class of enzymes will be critical to further delineate the unique biological functions of individual cathepsins. Here we present the design and synthesis of a near-infrared quenched activity-based probe (qABP) that selectively targets cathepsin S which is highly expressed in immune cells. Importantly, this high degree of selectivity is retained both in vitro and in vivo. In combination with a new green-fluorescent pan-reactive cysteine cathepsin qABP we performed dual color labeling studies in bone marrow-derived immune cells and identified vesicles containing exclusively cathepsin S activity. This observation demonstrates the value of our complementary cathepsin probes and provides evidence for the existence of specific localization of cathepsin S activity in dendritic cells.

Ni-Nanocluster Modified Black TiO2 with Dual Active Sites for Selective Photocatalytic CO2 Reduction.

PubMed

Billo, Tadesse; Fu, Fang-Yu; Raghunath, Putikam; Shown, Indrajit; Chen, Wei-Fu; Lien, Hsiang-Ting; Shen, Tzu-Hsien; Lee, Jyh-Fu; Chan, Ting-Shan; Huang, Kuo-You; Wu, Chih-I; Lin, M C; Hwang, Jih-Shang; Lee, Chih-Hao; Chen, Li-Chyong; Chen, Kuei-Hsien

2018-01-01

One of the key challenges in artificial photosynthesis is to design a photocatalyst that can bind and activate the CO 2 molecule with the smallest possible activation energy and produce selective hydrocarbon products. In this contribution, a combined experimental and computational study on Ni-nanocluster loaded black TiO 2 (Ni/TiO 2[Vo] ) with built-in dual active sites for selective photocatalytic CO 2 conversion is reported. The findings reveal that the synergistic effects of deliberately induced Ni nanoclusters and oxygen vacancies provide (1) energetically stable CO 2 binding sites with the lowest activation energy (0.08 eV), (2) highly reactive sites, (3) a fast electron transfer pathway, and (4) enhanced light harvesting by lowering the bandgap. The Ni/TiO 2[Vo] photocatalyst has demonstrated highly selective and enhanced photocatalytic activity of more than 18 times higher solar fuel production than the commercial TiO 2 (P-25). An insight into the mechanisms of interfacial charge transfer and product formation is explored. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Development of Strategy Use in Elementary School Children: Working Memory and Individual Differences

ERIC Educational Resources Information Center

Imbo, Ineke; Vandierendonck, Andre

2007-01-01

The current study tested the development of working memory involvement in children's arithmetic strategy selection and strategy efficiency. To this end, an experiment in which the dual-task method and the choice/no-choice method were combined was administered to 10- to 12-year-olds. Working memory was needed in retrieval, transformation, and…

Integrated process and dual-function catalyst for olefin epoxidation

DOEpatents

Zhou, Bing; Rueter, Michael

2003-01-01

The invention discloses a dual-functional catalyst composition and an integrated process for production of olefin epoxides including propylene oxide by catalytic reaction of hydrogen peroxide from hydrogen and oxygen with olefin feeds such as propylene. The epoxides and hydrogen peroxide are preferably produced simultaneously in situ. The dual-functional catalyst comprises noble metal crystallites with dimensions on the nanometer scale (on the order of <1 nm to 10 nm), specially dispersed on titanium silicalite substrate particles. The dual functional catalyst catalyzes both the direct reaction of hydrogen and oxygen to generate hydrogen peroxide intermediate on the noble metal catalyst surface and the reaction of the hydrogen peroxide intermediate with the propylene feed to generate propylene oxide product. Combining both these functions in a single catalyst provides a very efficient integrated process operable below the flammability limits of hydrogen and highly selective for the production of hydrogen peroxide to produce olefin oxides such as propylene oxide without formation of undesired co-products.

Two-stage earth-to-orbit vehicles with dual-fuel propulsion in the Orbiter

NASA Technical Reports Server (NTRS)

Martin, J. A.

1982-01-01

Earth-to-orbit vehicle studies of future replacements for the Space Shuttle are needed to guide technology development. Previous studies that have examined single-stage vehicles have shown advantages for dual-fuel propulsion. Previous two-stage system studies have assumed all-hydrogen fuel for the Orbiters. The present study examined dual-fuel Orbiters and found that the system dry mass could be reduced with this concept. The possibility of staging the booster at a staging velocity low enough to allow coast-back to the launch site is shown to be beneficial, particularly in combination with a dual-fuel Orbiter. An engine evaluation indicated the same ranking of engines as did a previous single-stage study. Propane and RP-1 fuels result in lower vehicle dry mass than methane, and staged-combustion engines are preferred over gas-generator engines. The sensitivity to the engine selection is less for two-stage systems than for single-stage systems.

Preparation and Reinforcement of Dual-Porous Biocompatible Cellulose Scaffolds for Tissue Engineering.

PubMed

Pircher, Nicole; Fischhuber, David; Carbajal, Leticia; Strauß, Christine; Nedelec, Jean-Marie; Kasper, Cornelia; Rosenau, Thomas; Liebner, Falk

2015-09-01

1Biocompatible cellulose-based aerogels composed of nanoporous struts, which embed interconnected voids of controlled micron-size, have been prepared employing temporary templates of fused porogens, reinforcement by interpenetrating PMMA networks and supercritical carbon dioxide drying. Different combinations of cellulose solvent (Ca(SCN) 2 /H 2 O/LiCl or [EMIm][OAc]/DMSO) and anti-solvent (EtOH), porogen type (paraffin wax or PMMA spheres) and porogen size (various fractions in the range of 100-500 μm) as well as intensity of PMMA reinforcement have been investigated to tailor the materials for cell scaffolding applications. All aerogels exhibited an open and dual porosity (micronporosity >100 μm and nanoporosity extending to the low micrometer range). Mechanical properties of the dual-porous aerogels under compressive stress were considerably improved by introduction of interpenetrating PMMA networks. The effect of the reinforcing polymer on attachment, spreading, and proliferation of NIH 3T3 fibroblast cells, cultivated on selected dual-porous aerogels to pre-evaluate their biocompatibility was similarly positive.

Developing a weighting strategy to include mobile phone numbers into an ongoing population health survey using an overlapping dual-frame design with limited benchmark information

PubMed Central

2014-01-01

Background In 2012 mobile phone numbers were included into the ongoing New South Wales Population Health Survey (NSWPHS) using an overlapping dual-frame design. Previously in the NSWPHS the sample was selected using random digit dialing (RDD) of landline phone numbers. The survey was undertaken using computer assisted telephone interviewing (CATI). The weighting strategy needed to be significantly expanded to manage the differing probabilities of selection by frame, including that of children of mobile-only phone users, and to adjust for the increased chance of selection of dual-phone users. This paper describes the development of the final weighting strategy to properly combine the data from two overlapping sample frames accounting for the fact that population benchmarks for the different sampling frames were not available at the state or regional level. Methods Estimates of the number of phone numbers for the landline and mobile phone frames used to calculate the differing probabilities of selection by frame, for New South Wales (NSW) and by stratum, were obtained by apportioning Australian estimates as none were available for NSW. The weighting strategy was then developed by calculating person selection probabilities, selection weights, applying a constant composite factor to the dual-phone users sample weights, and benchmarking to the latest NSW population by age group, sex and stratum. Results Data from the NSWPHS for the first quarter of 2012 was used to test the weighting strategy. This consisted of data on 3395 respondents with 2171 (64%) from the landline frame and 1224 (36%) from the mobile frame. However, in order to calculate the weights, data needed to be available for all core weighting variables and so 3378 respondents, 2933 adults and 445 children, had sufficient data to be included. Average person weights were 3.3 times higher for the mobile-only respondents, 1.3 times higher for the landline-only respondents and 1.7 times higher for dual-phone users in the mobile frame compared to the dual-phone users in the landline frame. The overall weight effect for the first quarter of 2012 was 1.93 and the coefficient of variation of the weights was 0.96. The weight effects for 2012 were similar to, and in many cases less than, the effects found in the corresponding quarter of the 2011 NSWPHS when only a landline based sample was used. Conclusions The inclusion of mobile phone numbers, through an overlapping dual-frame design, improved the coverage of the survey and an appropriate weighing procedure is feasible, although it added substantially to the complexity of the weighting strategy. Access to accurate Australian, State and Territory estimates of the number of landline and mobile phone numbers and type of phone use by at least age group and sex would greatly assist in the weighting of dual-frame surveys in Australia. PMID:25189826

Developing a weighting strategy to include mobile phone numbers into an ongoing population health survey using an overlapping dual-frame design with limited benchmark information.

PubMed

Barr, Margo L; Ferguson, Raymond A; Hughes, Phil J; Steel, David G

2014-09-04

In 2012 mobile phone numbers were included into the ongoing New South Wales Population Health Survey (NSWPHS) using an overlapping dual-frame design. Previously in the NSWPHS the sample was selected using random digit dialing (RDD) of landline phone numbers. The survey was undertaken using computer assisted telephone interviewing (CATI). The weighting strategy needed to be significantly expanded to manage the differing probabilities of selection by frame, including that of children of mobile-only phone users, and to adjust for the increased chance of selection of dual-phone users. This paper describes the development of the final weighting strategy to properly combine the data from two overlapping sample frames accounting for the fact that population benchmarks for the different sampling frames were not available at the state or regional level. Estimates of the number of phone numbers for the landline and mobile phone frames used to calculate the differing probabilities of selection by frame, for New South Wales (NSW) and by stratum, were obtained by apportioning Australian estimates as none were available for NSW. The weighting strategy was then developed by calculating person selection probabilities, selection weights, applying a constant composite factor to the dual-phone users sample weights, and benchmarking to the latest NSW population by age group, sex and stratum. Data from the NSWPHS for the first quarter of 2012 was used to test the weighting strategy. This consisted of data on 3395 respondents with 2171 (64%) from the landline frame and 1224 (36%) from the mobile frame. However, in order to calculate the weights, data needed to be available for all core weighting variables and so 3378 respondents, 2933 adults and 445 children, had sufficient data to be included. Average person weights were 3.3 times higher for the mobile-only respondents, 1.3 times higher for the landline-only respondents and 1.7 times higher for dual-phone users in the mobile frame compared to the dual-phone users in the landline frame. The overall weight effect for the first quarter of 2012 was 1.93 and the coefficient of variation of the weights was 0.96. The weight effects for 2012 were similar to, and in many cases less than, the effects found in the corresponding quarter of the 2011 NSWPHS when only a landline based sample was used. The inclusion of mobile phone numbers, through an overlapping dual-frame design, improved the coverage of the survey and an appropriate weighing procedure is feasible, although it added substantially to the complexity of the weighting strategy. Access to accurate Australian, State and Territory estimates of the number of landline and mobile phone numbers and type of phone use by at least age group and sex would greatly assist in the weighting of dual-frame surveys in Australia.

An easy prepared dual-channel chemosensor for selective and instant detection of fluoride based on double Schiff-base

NASA Astrophysics Data System (ADS)

Leng, Yan-Li; Zhang, Jian-Hui; Li, Qiao; Zhang, You-Ming; Lin, Qi; Yao, Hong; Wei, Tai-Bao

2016-10-01

A colorimetric and fluorescent dual-channel fluoride chemosensor N,N‧-bis (4-diethylaminosalicylidene) hydrazine (sensor S) bearing two imine groups has been designed and synthesized. This structurally simple probe displays rapid response and high selectivity for fluoride over other common anions (Cl-, Br-, I-, AcO-, H2PO4-, HSO4-, ClO4-, CN- and SCN-) in a highly polar aqueous DMSO solution. Mechanism studies suggested that the sensor firstly combined with F- through hydrogen bonds and then experienced the deprotonation process at higher concentrations of F- anion to the two Ar-OH groups. The detection limit was 5.78 × 10- 7 M of F-, which points to the high detection sensitivity. Test strips based on sensor S were fabricated, which could act as a convenient and efficient F- test kit to detect F- for ;in-the-field; measurement.

Merging gold and organocatalysis: a facile asymmetric synthesis of annulated pyrroles.

PubMed

Hack, Daniel; Loh, Charles C J; Hartmann, Jan M; Raabe, Gerhard; Enders, Dieter

2014-04-01

The combination of cinchona-alkaloid-derived primary amine and Au(I) -phosphine catalysts allowed the selective C-H functionalization of two adjacent carbon atoms of pyrroles under mild reaction conditions. This sequential dual activation provides seven-membered-ring-annulated pyrrole derivatives in excellent yields and enantioselectivities. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Genetic algorithm based feature selection combined with dual classification for the automated detection of proliferative diabetic retinopathy.

PubMed

Welikala, R A; Fraz, M M; Dehmeshki, J; Hoppe, A; Tah, V; Mann, S; Williamson, T H; Barman, S A

2015-07-01

Proliferative diabetic retinopathy (PDR) is a condition that carries a high risk of severe visual impairment. The hallmark of PDR is the growth of abnormal new vessels. In this paper, an automated method for the detection of new vessels from retinal images is presented. This method is based on a dual classification approach. Two vessel segmentation approaches are applied to create two separate binary vessel map which each hold vital information. Local morphology features are measured from each binary vessel map to produce two separate 4-D feature vectors. Independent classification is performed for each feature vector using a support vector machine (SVM) classifier. The system then combines these individual outcomes to produce a final decision. This is followed by the creation of additional features to generate 21-D feature vectors, which feed into a genetic algorithm based feature selection approach with the objective of finding feature subsets that improve the performance of the classification. Sensitivity and specificity results using a dataset of 60 images are 0.9138 and 0.9600, respectively, on a per patch basis and 1.000 and 0.975, respectively, on a per image basis. Copyright © 2015 Elsevier Ltd. All rights reserved.

The case against specialized visual-spatial short-term memory.

PubMed

Morey, Candice C

2018-05-24

The dominant paradigm for understanding working memory, or the combination of the perceptual, attentional, and mnemonic processes needed for thinking, subdivides short-term memory (STM) according to whether memoranda are encoded in aural-verbal or visual formats. This traditional dissociation has been supported by examples of neuropsychological patients who seem to selectively lack STM for either aural-verbal, visual, or spatial memoranda, and by experimental research using dual-task methods. Though this evidence is the foundation of assumptions of modular STM systems, the case it makes for a specialized visual STM system is surprisingly weak. I identify the key evidence supporting a distinct verbal STM system-patients with apparent selective damage to verbal STM and the resilience of verbal short-term memories to general dual-task interference-and apply these benchmarks to neuropsychological and experimental investigations of visual-spatial STM. Contrary to the evidence on verbal STM, patients with apparent visual or spatial STM deficits tend to experience a wide range of additional deficits, making it difficult to conclude that a distinct short-term store was damaged. Consistently with this, a meta-analysis of dual-task visual-spatial STM research shows that robust dual-task costs are consistently observed regardless of the domain or sensory code of the secondary task. Together, this evidence suggests that positing a specialized visual STM system is not necessary. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Activity of dual SRC-ABL inhibitors highlights the role of BCR/ABL kinase dynamics in drug resistance

PubMed Central

Azam, Mohammad; Nardi, Valentina; Shakespeare, William C.; Metcalf, Chester A.; Bohacek, Regine S.; Wang, Yihan; Sundaramoorthi, Raji; Sliz, Piotr; Veach, Darren R.; Bornmann, William G.; Clarkson, Bayard; Dalgarno, David C.; Sawyer, Tomi K.; Daley, George Q.

2006-01-01

Mutation in the ABL kinase domain is the principal mechanism of imatinib resistance in patients with chronic myelogenous leukemia. Many mutations favor active kinase conformations that preclude imatinib binding. Because the active forms of ABL and SRC resemble one another, we tested two dual SRC-ABL kinase inhibitors, AP23464 and PD166326, against 58 imatinib-resistant (IMR) BCR/ABL kinase variants. Both compounds potently inhibit most IMR variants, and in vitro drug selection demonstrates that active (AP23464) and open (PD166326) conformation-specific compounds are less susceptible to resistance than imatinib. Combinations of inhibitors suppressed essentially all resistance mutations, with the notable exception of T315I. Guided by mutagenesis studies and molecular modeling, we designed a series of AP23464 analogues to target T315I. The analogue AP23846 inhibited both native and T315I variants of BCR/ABL with submicromolar potency but showed nonspecific cellular toxicity. Our data illustrate how conformational dynamics of the ABL kinase accounts for the activity of dual SRC-ABL inhibitors against IMR-mutants and provides a rationale for combining conformation specific inhibitors to suppress resistance. PMID:16754879

Prediction of selectivity for enantiomeric separations of uncharged compounds by capillary electrophoresis involving dual cyclodextrin systems.

PubMed

Abushoffa, Adel M; Fillet, Marianne; Hubert, Phillipe; Crommen, Jacques

2002-03-01

The single-isomer polyanionic cyclodextrin (CD) derivative heptakis-6-sulfato-beta-cyclodextrin (HSbetaCD) has been tested as chiral additive for the enantioseparation of non-steroidal anti-inflammatory drugs, such as fenoprofen, flurbiprofen, ibuprofen and ketoprofen, in capillary electrophoresis, using a pH 2.5 phosphoric acid-triethanolamine buffer in the reversed polarity mode. In most cases, the enantiomers of these acidic compounds, present in uncharged form at that pH, were only poorly resolved with HSbetaCD alone. However, the use of HSbetaCD in combination with the neutral CD derivative, heptakis-(2,3,6-tri-O-methyl)-beta-cyclodextrin (TMbetaCD), which has a particularly high enantioselectivity towards these compounds, has led to complete enantioresolution in reasonably low migration times in most cases. Affinity constants for the enantiomers with the two cyclodextrins were determined, using linear regression in a two-step approach. Affinity constants with the charged HSbetaCD were first calculated in single systems while those with the neutral TMbetaCD were determined in dual systems. Selectivity for the enantiomeric separation of these compounds in dual CD systems could be predicted using recently developed mathematical models.

The Design of Dual-Emissive Composite Material [Zn2(HL)3]+@MOF-5 as Self-Calibrating Luminescent Sensors of Al3+ Ions and Monoethanolamine.

PubMed

Wu, Meng-Meng; Wang, Jiao-Yang; Sun, Rui; Zhao, Cui; Zhao, Jiong-Peng; Che, Guang-Bo; Liu, Fu-Chen

2017-08-21

Introducing another chromophore into a luminescent MOF is a potential way to assembling novel dual-emissive luminescent materials. Putting the chromophore, for which luminescence can be enhanced by Zn 2+ ion, into MOF-5 by the "bottle around ship" strategy is a simple but efficient synthesis method to realize such dual-emissive materials. According to this strategy, a novel dual-emissive luminescent composite material [Zn 2 (HL) 3 ] + @MOF-5 was constructed by loading the [La 3 (HL) 2 L 2 (NO 3 ) 3 H 2 O] (1) (H 2 L = 7,7'-(ethane-1,1'-diyl)8-hydro-quinoline) into MOF-5, in which the [Zn 2 (HL) 3 ] + anions were transformed from 1 with the existence of Zn 2+ . The dual-emissive composite materials show excellent luminescence with two emissions of MOF-5 at 410 nm and [Zn 2 (HL) 3 ] + at 524 nm. Furthermore, by combining characteristics of MOF-5 and the guest chromophore, the composite material is highly selectively sensitive toward Al 3+ and monoethanolamine, which makes [Zn 2 (HL) 3 ] + @MOF-5 a potential self-calibrated fluorescence sensor.

Blockade of Cocaine or σ Receptor Agonist Self Administration by Subtype-Selective σ Receptor Antagonists.

PubMed

Katz, Jonathan L; Hiranita, Takato; Kopajtic, Theresa A; Rice, Kenner C; Mesangeau, Christophe; Narayanan, Sanju; Abdelazeem, Ahmed H; McCurdy, Christopher R

2016-07-01

The identification of sigma receptor (σR) subtypes has been based on radioligand binding and, despite progress with σ1R cellular function, less is known about σR subtype functions in vivo. Recent findings that cocaine self administration experience will trigger σR agonist self administration was used in this study to assess the in vivo receptor subtype specificity of the agonists (+)-pentazocine, PRE-084 [2-(4-morpholinethyl) 1-phenylcyclohexanecarboxylate hydrochloride], and 1,3-di-o-tolylguanidine (DTG) and several novel putative σR antagonists. Radioligand binding studies determined in vitro σR selectivity of the novel compounds, which were subsequently studied for self administration and antagonism of cocaine, (+)-pentazocine, PRE-084, or DTG self administration. Across the dose ranges studied, none of the novel compounds were self administered, nor did they alter cocaine self administration. All compounds blocked DTG self administration, with a subset also blocking (+)-pentazocine and PRE-084 self administration. The most selective of the compounds in binding σ1Rs blocked cocaine self administration when combined with a dopamine transport inhibitor, either methylphenidate or nomifensine. These drug combinations did not decrease rates of responding maintained by food reinforcement. In contrast, the most selective of the compounds in binding σ2Rs had no effect on cocaine self administration in combination with either dopamine transport inhibitor. Thus, these results identify subtype-specific in vivo antagonists, and the utility of σR agonist substitution for cocaine self administration as an assay capable of distinguishing σR subtype selectivity in vivo. These results further suggest that effectiveness of dual σR antagonism and dopamine transport inhibition in blocking cocaine self administration is specific for σ1Rs and further support this dual targeting approach to development of cocaine antagonists. U.S. Government work not protected by U.S. copyright.

Combined experimental and theoretical studies on selective sensing of zinc and pyrophosphate ions by rational design of compartmental chemosensor probe: Dual sensing behaviour via secondary recognition approach and cell imaging studies.

PubMed

Mawai, Kiran; Nathani, Sandip; Roy, Partha; Singh, U P; Ghosh, Kaushik

2018-05-08

A compartmental chemosensor probe HL has been designed and synthesized for the selective recognition of zinc ions over other transition metal ions via fluorescence "ON" strategy. The chemosensing behaviour of HL was demonstrated through fluorescence, absorption and NMR spectroscopic techniques. The molecular structure of the zinc complex derived from HL was determined by X-ray crystallography. A probable mechanism of this selective sensing behavior was described on the basis of spectroscopic results and theoretical studies by density functional theory (DFT). The biological applicability of the chemosensor HL was examined via cell imaging on HeLa cells. The HL-zinc complex served as a secondary fluorescent probe responding to the pyrophosphate anion specifically over other anions. The fluorescence enhancement of HL in association with Zn2+ ions was quenched in the presence of pyrophosphate (PPi). Thus, a dual response was established based on "OFF-ON-OFF" strategy for detection of both cation and anion. This phenomenon was utilized in the construction of a "INHIBIT" logic gate.

Metal artifact correction for x-ray computed tomography using kV and selective MV imaging

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

Wu, Meng, E-mail: mengwu@stanford.edu; Keil, Andreas; Constantin, Dragos

Purpose: The overall goal of this work is to improve the computed tomography (CT) image quality for patients with metal implants or fillings by completing the missing kilovoltage (kV) projection data with selectively acquired megavoltage (MV) data that do not suffer from photon starvation. When both of these imaging systems, which are available on current radiotherapy devices, are used, metal streak artifacts are avoided, and the soft-tissue contrast is restored, even for regions in which the kV data cannot contribute any information. Methods: Three image-reconstruction methods, including two filtered back-projection (FBP)-based analytic methods and one iterative method, for combining kVmore » and MV projection data from the two on-board imaging systems of a radiotherapy device are presented in this work. The analytic reconstruction methods modify the MV data based on the information in the projection or image domains and then patch the data onto the kV projections for a FBP reconstruction. In the iterative reconstruction, the authors used dual-energy (DE) penalized weighted least-squares (PWLS) methods to simultaneously combine the kV/MV data and perform the reconstruction. Results: The authors compared kV/MV reconstructions to kV-only reconstructions using a dental phantom with fillings and a hip-implant numerical phantom. Simulation results indicated that dual-energy sinogram patch FBP and the modified dual-energy PWLS method can successfully suppress metal streak artifacts and restore information lost due to photon starvation in the kV projections. The root-mean-square errors of soft-tissue patterns obtained using combined kV/MV data are 10–15 Hounsfield units smaller than those of the kV-only images, and the structural similarity index measure also indicates a 5%–10% improvement in the image quality. The added dose from the MV scan is much less than the dose from the kV scan if a high efficiency MV detector is assumed. Conclusions: The authors have shown that it is possible to improve the image quality of kV CTs for patients with metal implants or fillings by completing the missing kV projection data with selectively acquired MV data that do not suffer from photon starvation. Numerical simulations demonstrated that dual-energy sinogram patch FBP and a modified kV/MV PWLS method can successfully suppress metal streak artifacts and restore information lost due to photon starvation in kV projections. Combined kV/MV images may permit the improved delineation of structures of interest in CT images for patients with metal implants or fillings.« less

Dual-mode acoustic wave biosensors microarrays

NASA Astrophysics Data System (ADS)

Auner, Gregory W.; Shreve, Gina; Ying, Hao; Newaz, Golam; Hughes, Chantelle; Xu, Jianzeng

2003-04-01

We have develop highly sensitive and selective acoustic wave biosensor arrays with signal analysis systems to provide a fingerprint for the real-time identification and quantification of a wide array of bacterial pathogens and environmental health hazards. We have developed an unique highly sensitive dual mode acoustic wave platform prototype that, when combined with phage based selective detection elements, form a durable bacteria sensor. Arrays of these new real-time biosensors are integrated to form a biosensor array on a chip. This research and development program optimizes advanced piezoelectric aluminum nitride wide bandgap semiconductors, novel micromachining processes, advanced device structures, selective phage displays development and immobilization techniques, and system integration and signal analysis technology to develop the biosensor arrays. The dual sensor platform can be programmed to sense in a gas, vapor or liquid environment by switching between acoustic wave resonate modes. Such a dual mode sensor has tremendous implications for applications involving monitoring of pathogenic microorganisms in the clinical setting due to their ability to detect airborne pathogens. This provides a number of applications including hospital settings such as intensive care or other in-patient wards for the reduction of nosocomial infections and maintenance of sterile environments in surgical suites. Monitoring for airborn pathogen transmission in public transportation areas such as airplanes may be useful for implementation of strategies for redution of airborn transmission routes. The ability to use the same sensor in the liquid sensing mode is important for tracing the source of airborn pathogens to local liquid sources. Sensing of pathogens in saliva will be useful for sensing oral pathogens and support of decision-making strategies regarding prevention of transmission and support of treatment strategies.

Center for Hypersonic Combined Cycle Flow Physics

DTIC Science & Technology

2015-03-24

team of expert experimentalists and numerical and chemical kinetic modelers. Flowfields were examined in the turbine /ramjet dual inlet mode transition...using data from the NASA Glenn IMX facility and RANS calculations. In the ramjet/scramjet mode regime a dual-mode combustion wind tunnel was developed...SUBJECT TERMS Hypersonic combined cycle propulsion, turbine /ram dual-inlet transition, ram/scram dual-mode transition, hypervelocity regime, RANS, Hybrid

Dual-band frequency selective surface with large band separation and stable performance

NASA Astrophysics Data System (ADS)

Zhou, Hang; Qu, Shao-Bo; Peng, Wei-Dong; Lin, Bao-Qin; Wang, Jia-Fu; Ma, Hua; Zhang, Jie-Qiu; Bai, Peng; Wang, Xu-Hua; Xu, Zhuo

2012-05-01

A new technique of designing a dual-band frequency selective surface with large band separation is presented. This technique is based on a delicately designed topology of L- and Ku-band microwave filters. The two band-pass responses are generated by a capacitively-loaded square-loop frequency selective surface and an aperture-coupled frequency selective surface, respectively. A Faraday cage is located between the two frequency selective surface structures to eliminate undesired couplings. Based on this technique, a dual-band frequency selective surface with large band separation is designed, which possesses large band separation, high selectivity, and stable performance under various incident angles and different polarizations.

Dynamic, continuous multitasking training leads to task-specific improvements but does not transfer across action selection tasks

NASA Astrophysics Data System (ADS)

Bender, Angela D.; Filmer, Hannah L.; Naughtin, Claire K.; Dux, Paul E.

2017-12-01

The ability to perform multiple tasks concurrently is an ever-increasing requirement in our information-rich world. Despite this, multitasking typically compromises performance due to the processing limitations associated with cognitive control and decision-making. While intensive dual-task training is known to improve multitasking performance, only limited evidence suggests that training-related performance benefits can transfer to untrained tasks that share overlapping processes. In the real world, however, coordinating and selecting several responses within close temporal proximity will often occur in high-interference environments. Over the last decade, there have been notable reports that training on video action games that require dynamic multitasking in a demanding environment can lead to transfer effects on aspects of cognition such as attention and working memory. Here, we asked whether continuous and dynamic multitasking training extends benefits to tasks that are theoretically related to the trained tasks. To examine this issue, we asked a group of participants to train on a combined continuous visuomotor tracking task and a perceptual discrimination task for six sessions, while an active control group practiced the component tasks in isolation. A battery of tests measuring response selection, response inhibition, and spatial attention was administered before and immediately after training to investigate transfer. Multitasking training resulted in substantial, task-specific gains in dual-task ability, but there was no evidence that these benefits generalized to other action control tasks. The findings suggest that training on a combined visuomotor tracking and discrimination task results in task-specific benefits but provides no additional value for untrained action selection tasks.

Combination use of medicines from two classes of renin-angiotensin system blocking agents: risk of hyperkalemia, hypotension, and impaired renal function.

PubMed

Esteras, Raquel; Perez-Gomez, Maria Vanessa; Rodriguez-Osorio, Laura; Ortiz, Alberto; Fernandez-Fernandez, Beatriz

2015-08-01

European and United States regulatory agencies recently issued warnings against the use of dual renin-angiotensin system (RAS) blockade therapy through the combined use of angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs) or aliskiren in any patient, based on absence of benefit for most patients and increased risk of hyperkalemia, hypotension, and renal failure. Special emphasis was made not to use these combinations in patients with diabetic nephropathy. The door was left open to therapy individualization, especially for patients with heart failure, when the combined use of an ARB and ACEI is considered absolutely essential, although renal function, electrolytes and blood pressure should be closely monitored. Mineralocorticoid receptor antagonists were not affected by this warning despite increased risk of hyperkalemia. We now critically review the risks associated with dual RAS blockade and answer the following questions: What safety issues are associated with dual RAS blockade? Can the safety record of dual RAS blockade be improved? Is it worth trying to improve the safety record of dual RAS blockade based on the potential benefits of the combination? Is dual RAS blockade dead? What is the role of mineralocorticoid antagonists in combination with other RAS blocking agents: RAAS blockade?

In Vitro Comparison of a Novel Single Probe Dual-Energy Lithotripter to Current Devices.

PubMed

Carlos, Evan C; Wollin, Daniel A; Winship, Brenton B; Jiang, Ruiyang; Radvak, Daniela; Chew, Ben H; Gustafson, Michael R; Simmons, W Neal; Zhong, Pei; Preminger, Glenn M; Lipkin, Michael E

2018-06-01

The LithoClast Trilogy is a novel single probe, dual-energy lithotripter with ultrasonic (US) vibration and electromagnetic impact forces. ShockPulse and LithoClast Select are existing lithotripters that also use a combination of US and mechanical impact energies. We compared the efficacy and tip motion of these devices in an in vitro setting. Begostones, in the ratio 15:3, were used in all trials. Test groups were Trilogy, ShockPulse, Select ultrasound (US) only, and Select ultrasound with pneumatic (USP). For clearance testing, a single investigator facile with each lithotripter fragmented 10 stones per device. For drill testing, a hands-free apparatus with a submerged balance was used to apply 1 or 2 lbs of pressure on a stone in contact with the device tip. High-speed photography was used to assess Trilogy and ShockPulse's probe tip motion. Select-USP was slowest and Trilogy fastest on clearance testing (p < 0.01). On 1 lbs drill testing, Select-US was slowest (p = 0.001). At 2 lbs, ShockPulse was faster than Select US (p = 0.027), but did not significantly outpace Trilogy nor Select-USP. At either weight, there was no significant difference between Trilogy and ShockPulse. During its US function, Trilogy's maximum downward tip displacement was 0.041 mm relative to 0.0025 mm with ShockPulse. Trilogy had 0.25 mm of maximum downward displacement during its impactor function while ShockPulse had 0.01 mm. Single probe dual-energy devices, such as Trilogy and ShockPulse, represent the next generation of lithotripters. Trilogy more efficiently cleared stone than currently available devices, which could be explained by its larger probe diameter and greater downward tip displacement during both US and impactor functions.

Independently tunable dual-band perfect absorber based on graphene at mid-infrared frequencies

DOE PAGES

Zhang, Yuping; Li, Tongtong; Chen, Qi; ...

2015-12-22

We design a dual-band absorber formed by combining two cross-shaped metallic resonators of different sizes within a super-unit-cell arranged in mirror symmetry. Simulations indicate that absorption efficiencies greater than 99% can be achieved at two different frequencies under normal incidence. We also employ a design scheme with graphene integration, which allows independent tuning of individual absorption frequencies by electrostatically changing the Fermi energy of the graphene layer. High absorbance is maintained over a wide incident angle range up to 50 degrees for both TE and TM polarizations. Thus, it enables a promising way to design electrically tunable absorbers, which maymore » contribute toward the realization of frequency selective detectors for sensing applications.« less

A Dual-Stage Two-Phase Model of Selective Attention

ERIC Educational Resources Information Center

Hubner, Ronald; Steinhauser, Marco; Lehle, Carola

2010-01-01

The dual-stage two-phase (DSTP) model is introduced as a formal and general model of selective attention that includes both an early and a late stage of stimulus selection. Whereas at the early stage information is selected by perceptual filters whose selectivity is relatively limited, at the late stage stimuli are selected more efficiently on a…

A liquid-phase microextraction method, combining a dual gauge microsyringe with a hollow fiber membrane, for the determination of organochlorine pesticides in aqueous solution by gas chromatography/ion trap mass spectrometry.

PubMed

Yan, Chih-Hao; Wu, Hui-Fen

2004-01-01

A liquid-phase microextraction (LPME) method has been demonstrated for the extraction and determination of organochlorine pesticides (OCPs) in aqueous solution. The method combines a dual gauge microsyringe with a hollow fiber membrane (LPME/DGM-HF) followed by detection by gas chromatography/ion trap mass spectrometry (GC/ITMS). The advantages include speed, low solvent and sample consumption, simplicity and ease of use. The extraction time, solvent selection, salt concentration and sample stirring rate have been investigated in order to optimize extraction efficiency. The viability is evaluated by measuring the linearity and detection limit of the five OCPs in aqueous solution. Detection linearity for the OCPs has been achieved over a range of concentrations between 1 and 500 microg/L (r2 > 0.930), with a detection limit of 0.1 microg/L for each OCP. Copyright 2004 John Wiley & Sons, Ltd.

Modulated-alignment dual-axis (MAD) confocal microscopy for deep optical sectioning in tissues

PubMed Central

Leigh, Steven Y.; Chen, Ye; Liu, Jonathan T.C.

2014-01-01

A strategy is presented to enable optical-sectioning microscopy with improved contrast and imaging depth using low-power (0.5 - 1 mW) diode laser illumination. This technology combines the inherent strengths of focal-modulation microscopy and dual-axis confocal (DAC) microscopy for rejecting out-of-focus and multiply scattered background light in tissues. The DAC architecture is unique in that it utilizes an intersecting pair of illumination and collection beams to improve the spatial-filtering and optical-sectioning performance of confocal microscopy while focal modulation selectively ‘labels’ in-focus signals via amplitude modulation. Simulations indicate that modulating the spatial alignment of dual-axis beams at a frequency f generates signals from the focal volume of the microscope that are modulated at 2f with minimal modulation of background signals, thus providing nearly an order-of-magnitude improvement in optical-sectioning contrast compared to DAC microscopy alone. Experiments show that 2f lock-in detection enhances contrast and imaging depth within scattering phantoms and fresh tissues. PMID:24940534

Optical and photoacoustic dual-modality imaging guided synergistic photodynamic/photothermal therapies

NASA Astrophysics Data System (ADS)

Yan, Xuefeng; Hu, Hao; Lin, Jing; Jin, Albert J.; Niu, Gang; Zhang, Shaoliang; Huang, Peng; Shen, Baozhong; Chen, Xiaoyuan

2015-01-01

Phototherapies such as photodynamic therapy (PDT) and photothermal therapy (PTT), due to their specific spatiotemporal selectivity and minimal invasiveness, have been widely investigated as alternative treatments of malignant diseases. Graphene and its derivatives not only have been used as carriers to deliver photosensitizers for PDT, but also as photothermal conversion agents (PTCAs) for PTT. Herein, we strategically designed and produced a novel photo-theranostic platform based on sinoporphyrin sodium (DVDMS) photosensitizer-loaded PEGylated graphene oxide (GO-PEG-DVDMS) for enhanced fluorescence/photoacoustic (PA) dual-modal imaging and combined PDT and PTT. The GO-PEG carrier drastically improves the fluorescence of loaded DVDMS via intramolecular charge transfer. Concurrently, DVDMS significantly enhances the near-infrared (NIR) absorption of GO for improved PA imaging and PTT. The cancer theranostic capability of the as-prepared GO-PEG-DVDMS was carefully investigated both in vitro and in vivo. This novel theranostics is well suited for fluorescence/PA dual-modal imaging and synergistic PDT/PTT.

Hepatic MR imaging for in vivo differentiation of steatosis, iron deposition and combined storage disorder: single-ratio in/opposed phase analysis vs. dual-ratio Dixon discrimination.

PubMed

Bashir, Mustafa R; Merkle, Elmar M; Smith, Alastair D; Boll, Daniel T

2012-02-01

To assess whether in vivo dual-ratio Dixon discrimination can improve detection of diffuse liver disease, specifically steatosis, iron deposition and combined disease over traditional single-ratio in/opposed phase analysis. Seventy-one patients with biopsy-proven (17.7 ± 17.0 days) hepatic steatosis (n = 16), iron deposition (n = 11), combined deposition (n = 3) and neither disease (n = 41) underwent MR examinations. Dual-echo in/opposed-phase MR with Dixon water/fat reconstructions were acquired. Analysis consisted of: (a) single-ratio hepatic region-of-interest (ROI)-based assessment of in/opposed ratios; (b) dual-ratio hepatic ROI assessment of in/opposed and fat/water ratios; (c) computer-aided dual-ratio assessment evaluating all hepatic voxels. Disease-specific thresholds were determined; statistical analyses assessed disease-dependent voxel ratios, based on single-ratio (a) and dual-ratio (b and c) techniques. Single-ratio discrimination succeeded in identifying iron deposition (I/O(Ironthreshold)<0.88) and steatosis (I/O(Fatthreshold>1.15)) from normal parenchyma, sensitivity 70.0%; it failed to detect combined disease. Dual-ratio discrimination succeeded in identifying abnormal hepatic parenchyma (F/W(Normalthreshold)>0.05), sensitivity 96.7%; logarithmic functions for iron deposition (I/O(Irondiscriminator)e((F/W(Fat)-0.01)/0.48)) differentiated combined from isolated diseases, sensitivity 100.0%; computer-aided dual-ratio analysis was comparably sensitive but less specific, 90.2% vs. 97.6%. MR two-point-Dixon imaging using dual-ratio post-processing based on in/opposed and fat/water ratios improved in vivo detection of hepatic steatosis, iron deposition, and combined storage disease beyond traditional in/opposed analysis. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

The NETPET Score: Combining FDG and Somatostatin Receptor Imaging for Optimal Management of Patients with Metastatic Well-Differentiated Neuroendocrine Tumors.

PubMed

Hindié, Elif

2017-01-01

Neuroendocrine tumors (NET) are often metastatic at the time of diagnosis. Metastatic well-differentiated (G1/G2) NET may display a wide range of behaviors, ranging from indolent to aggressive, even within apparently homogeneous categories. Thus, selecting the optimal treatment strategy is a challenging task. Somatostatin receptor imaging (SRI) is the standard molecular imaging technique for well-differentiated NET. When performed with 68 Ga-labeled somatostatin analogs (SRI-PET), it offers exquisite sensitivity for disease staging. SRI is also a prerequisite for using targeted radionuclide therapy (e.g. 177 Lu-DOTATATE). 18F-FDG imaging has traditionally been reserved for staging poorly-differentiated G3 neuroendocrine carcinomas. However, recent data showed that FDG imaging has prognostic value in patients with well-differentiated NET: high uptake was associated with an increased risk of early progression while low uptake suggested an indolent tumor. In this issue of the Journal, Chan and colleagues propose a grading system where the results from the combined reading of SRI-PET and FDG-PET are reported as a single parameter, the "NETPET" score. While the scoring system still needs validation, it is clear that time has come to think about FDG and SRI in metastatic NET not as competitors but as complementary imaging modalities. Dual-tracer imaging can be viewed as a way to characterize disease phenotype in the whole-body. Moving from the prognostic value of dual-tracer imaging to a tool that allows for individualized management would require prospective trials. This editorial will argue that dual-tracer FDG-PET and SRI-PET might influence management of patients with well-differentiated metastatic NET and help selecting between different therapy options.

Enhancement of selectivity and resolution in the enantioseparation of uncharged compounds using mixtures of oppositely charged cyclodextrins in capillary electrophoresis.

PubMed

Abushoffa, Adel M; Fillet, Marianne; Servais, Anne-Catherine; Hubert, Philippe; Crommen, Jacques

2003-01-01

The enantiomeric separation of some nonsteroidal anti-inflammatory drugs (NSAIDs) was investigated in capillary electrophoresis (CE) using dual systems with mixtures of charged cyclodextrin (CD) derivatives. A significant enhancement of selectivity and resolution could be achieved in the enantioseparation of these analytes in their uncharged form by the simultaneous addition of two oppositely charged CD derivatives to the background electrolyte. The combination of the single-isomer cationic CD, permethyl-6-monoamino-6-monodeoxy-beta-CD (PMMAbetaCD) and the single-isomer polyanionic CD, heptakis-6-sulfato-beta-cyclodextrin (HSbetaCD) in a pH 2.5 phosphoric acid-triethanolamine buffer, was designed and employed for the enantioseparation of profens. The improvement in selectivity and resolution can be attributed to the fact that the two CDs, which lead to independent and enantioselective complexation with the analyte enantiomers, have not only opposite effects on the electrophoretic mobility of these compounds but also opposite affinity patterns towards the enantiomers of these compounds. Binding constants for these enantiomers with each CD were determined using linear regression approach, in order to be able to predict the effect of the concentrations of the two CDs on enantiomeric selectivity and resolution in such dual systems.

Photocatalytic Hydrogen-Evolution Cross-Couplings: Benzene C-H Amination and Hydroxylation.

PubMed

Zheng, Yi-Wen; Chen, Bin; Ye, Pan; Feng, Ke; Wang, Wenguang; Meng, Qing-Yuan; Wu, Li-Zhu; Tung, Chen-Ho

2016-08-17

We present a blueprint for aromatic C-H functionalization via a combination of photocatalysis and cobalt catalysis and describe the utility of this strategy for benzene amination and hydroxylation. Without any sacrificial oxidant, we could use the dual catalyst system to produce aniline directly from benzene and ammonia, and phenol from benzene and water, both with evolution of hydrogen gas under unusually mild conditions in excellent yields and selectivities.

Cost-effectiveness of vildagliptin for people with type 2 diabetes mellitus in Brazil; findings and implications.

PubMed

De Oliveira, Gustavo Laine Araujo; Guerra Júnior, Augusto Afonso; Godman, Brian; Acurcio, Francisco de Assis

2017-04-01

Vildagliptin is an inhibitor of the enzyme dipeptidyl peptidase 4, indicated for the treatment of type 2 diabetes mellitus, combined or not with metformin. This study aims to evaluate the cost-effectiveness of vildagliptin in the Brazilian context. Areas covered: Using MEDLINE, Cochrane Library, Lilacs and CRD, six studies were selected for the economic models. This study utilised cost data in the Brazilian health system to provide the context. Expert commentary: Type 2 diabetes mellitus is an epidemic disease and represents a challenge for all health care systems. Although guidelines clearly define first-line treatment, there are several other promising treatments. Vildagliptin is one of them, resulting in a mean lifetime increase of 0.31 years compared to metformin alone and 1.19 more life years compared to other metformin combinations. Considering observational data, life years with dual vildagliptin-containing treatments were 0.37 more compared to other dual treatments. However, its high cost versus generic metformin and its unclear safety profile weakens its subsequent cost-effectiveness. Consequently, the incorporation of vildagliptin or its combination with metformin is currently not recommended for the Brazilian Health Care System. This may change as more data becomes available.

Improved Cognition While Cycling in Parkinson’s Disease Patients and Healthy Adults

PubMed Central

Hazamy, Audrey A.; Altmann, Lori J. P.; Stegemöller, Elizabeth; Bowers, Dawn; Lee, Hyo Keun; Wilson, Jonathan; Okun, Michael S.; Hass, Chris J.

2017-01-01

Persons with Parkinson’s disease (PD) are typically more susceptible than healthy adults to impaired performance when two tasks (dual task interference) are performed simultaneously. This limitation has by many experts been attributed to limitations in cognitive resources. Nearly all studies of dual task performance in PD employ walking or balance-based motor tasks, which are commonly impaired in PD. These tasks can be performed using a combination of one or two executive function tasks. The current study examined whether persons with PD would demonstrate greater dual task effects on cognition compared to healthy older adults (HOAs) during a concurrent cycling task. Participants with and without PD completed a battery of 12 cognitive tasks assessing visual and verbal processing in the following cognitive domains: speed of processing, controlled processing, working memory and executive function. Persons with PD exhibited impairments compared to healthy participants in select tasks (i.e., 0-Back, 2-Back and operation span). Further, both groups unexpectedly exhibited dual task facilitation of response times in visual tasks across cognitive domains, and improved verbal recall during an executive function task. Only one measure, 2-back, showed a speed-accuracy trade-off in the dual task. These results demonstrate that, when paired with a motor task in which they are not impaired, people with PD exhibit similar dual task effects on cognitive tasks as HOAs, even when these dual task effects are facilitative. More generally, these findings demonstrate that pairing cognitive tasks with cycling may actually improve cognitive performance which may have therapeutic relevance to cognitive decline associated with aging and PD pathology. PMID:28088064

Neurofeedback training improves the dual-task performance ability in stroke patients.

PubMed

Lee, Young-Shin; Bae, Sea-Hyun; Lee, Sung-Hee; Kim, Kyung-Yoon

2015-05-01

Owing to the reduced capacity for information processing following a stroke, patients commonly present with difficulties in performing activities of daily living that combine two or more tasks. To address this problem, in the present study, we investigated the effects of neurofeedback training on the abilities of stroke patients to perform dual motor tasks. We randomly assigned 20 patients who had sustained a stroke within the preceding 6 months to either a pseudo-neurofeedback (n = 10) or neurofeedback (n = 10) group. Both groups participated in a general exercise intervention for 8 weeks, three times a week for 30 min per session, under the same conditions. An electrode was secured to the scalp over the region of the central lobe (Cz), in compliance with the International 10-20 System. The electrode was inactive for the pseudo-training group. Participants in the neurofeedback training group received the 30-min neurofeedback training per session for reinforcing the sensorimotor rhythm. Electroencephalographic activity of the two groups was compared. In addition, selected parameters of gait (velocity, cadence [step/min], stance phase [%], and foot pressure) were analyzed using a 10-m walk test, attention-demanding task, walk task and quantified by the SmartStep system. The neurofeedback group showed significantly improved the regulation of the sensorimotor rhythm (p < 0.001) and ability to execute dual tasks (p < 0.01). Significant improvements on selected gait parameters (velocity and cadence; p < 0.05) were also observed. We thus propose that the neurofeedback training is effective to improve the dual-task performance in stroke patients.

Clinging to the Past: The Air Force’s War on Dual-Career Families

DTIC Science & Technology

2014-06-01

combines existing research on stress and work-family conflict with new primary research on current USAF dual-career families in the form of a case...incompatibilities between the Air Force family schema (conceptions of, and practices relating to, USAF families). The study combines existing research on stress ... Stress Pathways ..................................................... 74 Figure 5, Civilian Dual-Career Stress Pathways

Effect of variation of impression material combinations, dual arch tray types, and sequence of pour on the accuracy of working dies: "An in vitro study".

PubMed

Reddy, Nagam Raja; Reddy, Jakranpally Sathya; Padmaja, Bramha Josyula Indira; Reddy, Budigi Madan Mohan; Sunil, Motupalli; Reddy, Bommireddy Tejeswar

2016-01-01

To evaluate the accuracy of dies made from dual arch impressions using different sectional dual arch trays, combinations of elastomeric impression materials, and the sequence of pour of dies. The dual arch impression materials were grouped into three groups depending on the combination of impression materials used and each group is subdivided into four subgroups. A sample size of 8 in each subgroup yielding a total 96 impressions will be made into three groups of 32 each (Group I, II, and III). Group I constitute impressions made using monophase (M) impression material, Group II constitute impressions made using combination of heavy body and light body (HL), and Group III constitute impressions made using combination of putty and light body (PL). Dies obtained were evaluated with a travelling microscope to measure the buccolingual width of the tooth at the margin by using the sharp corners of the notches as reference points. Descriptive analysis namely mean and standard deviation, one-way analysis of variance test. The results obtained in this study indicate that though not statistically significant, the metal dual arch trays performed better when compared to the plastic trays in reproducing die dimensions. From the results obtained, dies poured from combination of heavy body and light body impressions using plastic or metal dual arch trays showed least variation in bucco-lingual dimension from master model.

Effect of variation of impression material combinations, dual arch tray types, and sequence of pour on the accuracy of working dies: “An in vitro study”

PubMed Central

Reddy, Nagam Raja; Reddy, Jakranpally Sathya; Padmaja, Bramha Josyula Indira; Reddy, Budigi Madan Mohan; Sunil, Motupalli; Reddy, Bommireddy Tejeswar

2016-01-01

Aims: To evaluate the accuracy of dies made from dual arch impressions using different sectional dual arch trays, combinations of elastomeric impression materials, and the sequence of pour of dies. Subjects and Methods: The dual arch impression materials were grouped into three groups depending on the combination of impression materials used and each group is subdivided into four subgroups. A sample size of 8 in each subgroup yielding a total 96 impressions will be made into three groups of 32 each (Group I, II, and III). Group I constitute impressions made using monophase (M) impression material, Group II constitute impressions made using combination of heavy body and light body (HL), and Group III constitute impressions made using combination of putty and light body (PL). Dies obtained were evaluated with a travelling microscope to measure the buccolingual width of the tooth at the margin by using the sharp corners of the notches as reference points. Statistical Analysis Used: Descriptive analysis namely mean and standard deviation, one-way analysis of variance test. Results: The results obtained in this study indicate that though not statistically significant, the metal dual arch trays performed better when compared to the plastic trays in reproducing die dimensions. Conclusions: From the results obtained, dies poured from combination of heavy body and light body impressions using plastic or metal dual arch trays showed least variation in bucco-lingual dimension from master model. PMID:27141172

Selective endothelin ETA and dual ET(A)/ET(B) receptor blockade improve endothelium-dependent vasodilatation in patients with type 2 diabetes and coronary artery disease.

PubMed

Rafnsson, Arnar; Shemyakin, Alexey; Pernow, John

2014-11-24

Endothelin-1 contributes to endothelial dysfunction in patients with atherosclerosis and type 2 diabetes. In healthy arteries the ETA receptor mediates the main part of the vasoconstriction induced by endothelin-1 whilst the ETB receptor mediates vasodilatation. The ETB receptor expression is upregulated on vascular smooth muscle cells in atherosclerosis and may contribute to the increased vasoconstrictor tone and endothelial dysfunction observed in this condition. Due to these opposing effects of the ETB receptor it remains unclear whether ETB blockade together with ETA blockade may be detrimental or beneficial. The aim was therefore to compare the effects of selective ETA and dual ETA/ETB blockade on endothelial function in patients with type 2 diabetes and coronary artery disease. Forearm endothelium-dependent and endothelium-independent vasodilatation was assessed by venous occlusion plethysmography in 12 patients before and after selective ETA or dual ETA/ETB receptor blockade. Dual ETA/ETB receptor blockade increased baseline forearm blood flow by 30±14% (P<0.01) whereas selective ETA blockade did not (14±8%). Both selective ETA blockade and dual ETA/ETB blockade significantly improved endothelium-dependent vasodilatation. The improvement did not differ between the two treatments. There was also an increase in endothelium-independent vasodilatation with both treatments. Dual ETA/ETB blockade did not significantly increase microvascular flow but improved transcutaneous pO2. Both selective ETA and dual ETA/ETB improve endothelium-dependent vasodilatation in patients with type 2 diabetes and coronary artery disease. ETB blockade increases basal blood flow but does not additionally improve endothelium-dependent vasodilatation. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Sensitive determination of cholesterol and its metabolic steroid hormones by UHPLC-MS/MS via derivatization coupled with dual ultrasonic-assisted dispersive liquid-liquid microextraction.

PubMed

Zhao, Xian-En; Yan, Ping; Wang, Renjun; Zhu, Shuyun; You, Jinmao; Bai, Yu; Liu, Huwei

2016-08-01

Quantitative analysis of cholesterol and its metabolic steroid hormones plays a vital role in diagnosing endocrine disorders and understanding disease progression, as well as in clinical medicine studies. Because of their extremely low abundance in body fluids, it remains a challenging task to develop a sensitive detection method. A hyphenated technique of dual ultrasonic-assisted dispersive liquid-liquid microextraction (dual-UADLLME) coupled with microwave-assisted derivatization (MAD) was proposed for cleansing, enrichment and sensitivity enhancement. 4'-Carboxy-substituted rosamine (CSR) was synthesized and used as derivatization reagent. An ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method was developed for determination of cholesterol and its metabolic steroid hormones in the multiple reaction monitoring mode. Parameters of dual-UADLLME, MAD and UHPLC-MS/MS were all optimized. Satisfactory linearity, recovery, repeatability, accuracy and precision, absence of matrix effect and extremely low limits of detection (LODs, 0.08-0.15 pg mL(-1) ) were achieved. Through the combination of dual-UADLLME and MAD, a determination method for cholesterol and its metabolic steroid hormones in human plasma, serum and urine samples was developed and validated with high sensitivity, selectivity, accuracy and perfect matrix effect results. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Innovative spectrophotometric methods for simultaneous estimation of the novel two-drug combination: Sacubitril/Valsartan through two manipulation approaches and a comparative statistical study

NASA Astrophysics Data System (ADS)

Eissa, Maya S.; Abou Al Alamein, Amal M.

2018-03-01

Different innovative spectrophotometric methods were introduced for the first time for simultaneous quantification of sacubitril/valsartan in their binary mixture and in their combined dosage form without prior separation through two manipulation approaches. These approaches were developed and based either on two wavelength selection in zero-order absorption spectra namely; dual wavelength method (DWL) at 226 nm and 275 nm for valsartan, induced dual wavelength method (IDW) at 226 nm and 254 nm for sacubitril and advanced absorbance subtraction (AAS) based on their iso-absorptive point at 246 nm (λiso) and 261 nm (sacubitril shows equal absorbance values at the two selected wavelengths) or on ratio spectra using their normalized spectra namely; ratio difference spectrophotometric method (RD) at 225 nm and 264 nm for both of them in their ratio spectra, first derivative of ratio spectra (DR1) at 232 nm for valsartan and 239 nm for sacubitril and mean centering of ratio spectra (MCR) at 260 nm for both of them. Both sacubitril and valsartan showed linearity upon application of these methods in the range of 2.5-25.0 μg/mL. The developed spectrophotmetric methods were successfully applied to the analysis of their combined tablet dosage form ENTRESTO™. The adopted spectrophotometric methods were also validated according to ICH guidelines. The results obtained from the proposed methods were statistically compared to a reported HPLC method using Student t-test, F-test and a comparative study was also developed with one-way ANOVA, showing no statistical difference in accordance to precision and accuracy.

Dual-Reactable Fluorescent Probes for Highly Selective and Sensitive Detection of Biological H2 S.

PubMed

Wei, Chao; Wang, Runyu; Zhang, Changyu; Xu, Guoce; Li, Yanyan; Zhang, Qiang-Zhe; Li, Lu-Yuan; Yi, Long; Xi, Zhen

2016-05-06

Hydrogen sulfide (H2 S) is an important endogenous signaling molecule with a variety of biological functions. Development of fluorescent probes for highly selective and sensitive detection of H2 S is necessary. We show here that dual-reactable fluorescent H2 S probes could react with higher selectivity than single-reactable probes. One of the dual-reactable probes gives more than 4000-fold turn-on response when reacting with H2 S, the largest response among fluorescent H2 S probes reported thus far. In addition, the probe could be used for high-throughput enzymatic assays and for the detection of Cys-induced H2 S in cells and in zebrafish. These dual-reactable probes hold potential for highly selective and sensitive detection of H2 S in biological systems. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A multi writable thiophene-based selective and reversible chromogenic fluoride probe with dual -NH functionality

NASA Astrophysics Data System (ADS)

Vishwakarma, Siddharth; Kumar, Ajit; Pandey, Abha; Upadhyay, K. K.

2017-01-01

A chromogenic fluoride probe bearing bis imine groups having dual -NH functionality (BSB) has been designed, synthesised and structurally characterized by its single crystal X-ray diffraction studies. The BSB could visually and spectroscopically recognise F- with high selectivity over other anions by exhibiting intense chromogenic response (from colourless to red) for F- in acetonitrile solution. The UV-visible titration and 1H NMR titration experiments indicated that the observed changes occur via a combined process including hydrogen bonding and deprotonation between the BSB and F-. Moreover theoretical calculations at the Density Functional Theory (DFT) level shed further light upon probe design strategy and the nature of interactions between BSB and F-. The limit of detection and binding constant of BSB towards F- were found to be 6.9 × 10- 7 M and 1.42 ± 0.069 × 108 M- 2 respectively. Finally, by using F- and H+ as chemical inputs and the absorbance as output, a INHIBIT logic gate was constructed, which exhibits "Multi-write" ability without obvious degradation in its optical output.

Dual ant colony operational modal analysis parameter estimation method

NASA Astrophysics Data System (ADS)

Sitarz, Piotr; Powałka, Bartosz

2018-01-01

Operational Modal Analysis (OMA) is a common technique used to examine the dynamic properties of a system. Contrary to experimental modal analysis, the input signal is generated in object ambient environment. Operational modal analysis mainly aims at determining the number of pole pairs and at estimating modal parameters. Many methods are used for parameter identification. Some methods operate in time while others in frequency domain. The former use correlation functions, the latter - spectral density functions. However, while some methods require the user to select poles from a stabilisation diagram, others try to automate the selection process. Dual ant colony operational modal analysis parameter estimation method (DAC-OMA) presents a new approach to the problem, avoiding issues involved in the stabilisation diagram. The presented algorithm is fully automated. It uses deterministic methods to define the interval of estimated parameters, thus reducing the problem to optimisation task which is conducted with dedicated software based on ant colony optimisation algorithm. The combination of deterministic methods restricting parameter intervals and artificial intelligence yields very good results, also for closely spaced modes and significantly varied mode shapes within one measurement point.

Thermodynamic Study of Multi Pressure HRSG in Gas/Steam Combined Cycle Power Plant

NASA Astrophysics Data System (ADS)

Sharma, Meeta; Singh, Onkar

2018-01-01

Combined cycle power plants have a combination of gas based topping cycle and steam based bottoming cycle through the use of Heat Recovery Steam Generator (HRSG). These HRSG may be either of single pressure (SP) or dual pressure (DP) or multiple pressure type. Here in this study thermodynamic analysis is carried out for optimal performance of HRSG using different types of HRSG layout for combined cycle efficiency improvement. Performance of single pressure HRSG and dual pressure HRSG, utilized in gas/steam combined cycle is analyzed and presented here. In comparison to single pressure, dual pressure HRSG offers 10 to 15% higher reduction in stack temperature due to greater heat recovery and thus improved plant efficiency.

Dual-wavelength multifrequency photothermal wave imaging combined with optical coherence tomography for macrophage and lipid detection in atherosclerotic plaques using gold nanoparticles

PubMed Central

Wang, Tianyi; Jacob Mancuso, J.; Sapozhnikova, Veronika; Dwelle, Jordan; Ma, Li L.; Willsey, Brian; Shams Kazmi, S. M.; Qiu, Jinze; Li, Xiankai; Asmis, Reto; Johnston, Keith P.; Feldman, Marc D.

2012-01-01

Abstract. The objective of this study was to assess the ability of combined photothermal wave (PTW) imaging and optical coherence tomography (OCT) to detect, and further characterize the distribution of macrophages (having taken up plasmonic gold nanorose as a contrast agent) and lipid deposits in atherosclerotic plaques. Aortas with atherosclerotic plaques were harvested from nine male New Zealand white rabbits divided into nanorose- and saline-injected groups and were imaged by dual-wavelength (800 and 1210 nm) multifrequency (0.1, 1 and 4 Hz) PTW imaging in combination with OCT. Amplitude PTW images suggest that lateral and depth distribution of nanorose-loaded macrophages (confirmed by two-photon luminescence microscopy and RAM-11 macrophage stain) and lipid deposits can be identified at selected modulation frequencies. Radiometric temperature increase and modulation amplitude of superficial nanoroses in response to 4 Hz laser irradiation (800 nm) were significantly higher than native plaque (P<0.001). Amplitude PTW images (4 Hz) were merged into a coregistered OCT image, suggesting that superficial nanorose-loaded macrophages are distributed at shoulders on the upstream side of atherosclerotic plaques (P<0.001) at edges of lipid deposits. Results suggest that combined PTW-OCT imaging can simultaneously reveal plaque structure and composition, permitting characterization of nanorose-loaded macrophages and lipid deposits in atherosclerotic plaques. PMID:22502567

Evaluation of the dual differential radiometer for remote sensing of sediment and chlorophyll in turbid waters

NASA Technical Reports Server (NTRS)

Witte, W. G.

1975-01-01

The dual differential radiometer (DDR) was tested to determine its capability for measuring suspended sediment and chlorophyll in turbid waters. Measurements were obtained from a boat dock and from a helicopter with combinations of sample and reference filters with peak transmissions at various wavelengths. Water samples were taken concurrently and were analyzed for light scattering, particle count, and total chlorophyll. Least-squares estimates of the linear relationship between DDR output and the water parameters yielded correlation coefficients of less than 0.7. Under the turbid water conditions of the present tests, the DDR did not accurately measure either suspended sediment or chlorophyll. A precise knowledge of the spectral signatures of various pollutants might enable appropriate filters to be selected for tuning the DDR to monitor a particular pollutant.

Experimental investigation of shock-cell noise reduction for dual-stream nozzles in simulated flight comprehensive data report. Volume 2: Laser velocimeter data, static pressures and shadowgraph photos

NASA Technical Reports Server (NTRS)

Yamamoto, K.; Janardan, B. A.; Brausch, J. F.; Hoerst, D. J.; Price, A. O.

1984-01-01

Parameters which contribute to supersonic jet shock noise were investigated for the purpose of determining means to reduce such noise generation to acceptable levels. Six dual-stream test nozzles with varying flow passage and plug closure designs were evaluated under simulated flight conditions in an anechoic chamber. All nozzles had combined convergent-divergent or convergent flow passages. Mean velocity and turbulence velocity measurements of 25 selected flow conditions were performed employing a laser Doppler velocimeter. Static pressure measurements were made to define the actual convergence-divergence condition. Test point definition, tabulation of aerodynamic test conditions, velocity histograms, and shadowgraph photographs are presented. Flow visualization through shadowgraph photography can contribute to the development of an analytical prediction model for shock noise from coannular plug nozzles.

A Dual-Specific Targeting Approach Based on the Simultaneous Recognition of Duplex and Quadruplex Motifs.

PubMed

Nguyen, Thi Quynh Ngoc; Lim, Kah Wai; Phan, Anh Tuân

2017-09-20

Small-molecule ligands targeting nucleic acids have been explored as potential therapeutic agents. Duplex groove-binding ligands have been shown to recognize DNA in a sequence-specific manner. On the other hand, quadruplex-binding ligands exhibit high selectivity between quadruplex and duplex, but show limited discrimination between different quadruplex structures. Here we propose a dual-specific approach through the simultaneous application of duplex- and quadruplex-binders. We demonstrated that a quadruplex-specific ligand and a duplex-specific ligand can simultaneously interact at two separate binding sites of a quadruplex-duplex hybrid harbouring both quadruplex and duplex structural elements. Such a dual-specific targeting strategy would combine the sequence specificity of duplex-binders and the strong binding affinity of quadruplex-binders, potentially allowing the specific targeting of unique quadruplex structures. Future research can be directed towards the development of conjugated compounds targeting specific genomic quadruplex-duplex sites, for which the linker would be highly context-dependent in terms of length and flexibility, as well as the attachment points onto both ligands.

Decreases in cocaine self-administration with dual inhibition of the dopamine transporter and σ receptors.

PubMed

Hiranita, Takato; Soto, Paul L; Kohut, Stephen J; Kopajtic, Theresa; Cao, Jianjing; Newman, Amy H; Tanda, Gianluigi; Katz, Jonathan L

2011-11-01

Sigma receptor (σR) antagonists attenuate many behavioral effects of cocaine but typically not its reinforcing effects in self-administration procedures. However, the σR antagonist rimcazole and its N-propylphenyl analogs, [3-(cis-3,5-dimethyl-4-[3-phenylpropyl]-1-piperazinyl)-propyl]diphenylamine hydrochloride (SH 3-24) and 9-[3-(cis-3,5-dimethyl-4-[3-phenylpropyl]-1-piperazinyl)-propyl]carbazole hydrobromide (SH 3-28), dose-dependently decreased the maximal rates of cocaine self-administration without affecting comparable responding maintained by food reinforcement. In contrast, a variety of σR antagonists [N-phenethylpiperidine oxalate (AC927), N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine dihydrobromide (BD 1008), N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino) ethylamine dihydrobromide (BD 1047), N-[2-(3,4-dichlorophenyl) ethyl]-4-methylpiperazine dihydrochloride (BD 1063), and N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine monohydrochloride (NE-100)] had no effect on cocaine self-administration across the range of doses that decreased rates of food-maintained responding. Rimcazole analogs differed from selective σR antagonists in their dual affinities for σRs and the dopamine transporter (DAT) assessed with radioligand binding. Selective DAT inhibitors and σR antagonists were studied alone and in combination on cocaine self-administration to determine whether actions at both σRs and the DAT were sufficient to reproduce the effects of rimcazole analogs. Typical DAT inhibitors [2β-carbomethoxy-3β-(4-fluorophenyl)tropane (WIN 35,428), methylphenidate, and nomifensine] dose-dependently shifted the cocaine dose-effect curve leftward. Combinations of DAT inhibitor and σR antagonist doses that were behaviorally inactive alone decreased cocaine self-administration without effects on food-maintained responding. In addition, whereas the DAT inhibitors were self-administered at rates similar to those of cocaine, neither rimcazole analogs nor typical σR antagonists (NE-100 and AC927) maintained responding above control levels across a wide range of doses. These findings suggest that the unique effects of rimcazole analogs are due to dual actions at the DAT and σRs and that a combined target approach may have utility in development of medical treatments for cocaine abuse.

Genetic characterization of a core collection of flax (Linum usitatissimum L.) suitable for association mapping studies and evidence of divergent selection between fiber and linseed types

PubMed Central

2013-01-01

Background Flax is valued for its fiber, seed oil and nutraceuticals. Recently, the fiber industry has invested in the development of products made from linseed stems, making it a dual purpose crop. Simultaneous targeting of genomic regions controlling stem fiber and seed quality traits could enable the development of dual purpose cultivars. However, the genetic diversity, population structure and linkage disequilibrium (LD) patterns necessary for association mapping (AM) have not yet been assessed in flax because genomic resources have only recently been developed. We characterized 407 globally distributed flax accessions using 448 microsatellite markers. The data was analyzed to assess the suitability of this core collection for AM. Genomic scans to identify candidate genes selected during the divergent breeding process of fiber flax and linseed were conducted using the whole genome shotgun sequence of flax. Results Combined genetic structure analysis assigned all accessions to two major groups with six sub-groups. Population differentiation was weak between the major groups (FST = 0.094) and for most of the pairwise comparisons among sub-groups. The molecular coancestry analysis indicated weak relatedness (mean = 0.287) for most individual pairs. Abundant genetic diversity was observed in the total panel (5.32 alleles per locus), and some sub-groups showed a high proportion of private alleles. The average genome-wide LD (r2) was 0.036, with a relatively fast decay of 1.5 cM. Genomic scans between fiber flax and linseed identified candidate genes involved in cell-wall biogenesis/modification, xylem identity and fatty acid biosynthesis congruent with genes previously identified in flax and other plant species. Conclusions Based on the abundant genetic diversity, weak population structure and relatedness and relatively fast LD decay, we concluded that this core collection is suitable for AM studies targeting multiple agronomic and quality traits aiming at the improvement of flax as a true dual purpose crop. Our genomic scans provide the first insights into candidate regions affected by divergent selection in flax. In combination with AM, genomic scans have the ability to increase the power to detect loci influencing complex traits. PMID:23647851

Genetic characterization of a core collection of flax (Linum usitatissimum L.) suitable for association mapping studies and evidence of divergent selection between fiber and linseed types.

PubMed

Soto-Cerda, Braulio J; Diederichsen, Axel; Ragupathy, Raja; Cloutier, Sylvie

2013-05-06

Flax is valued for its fiber, seed oil and nutraceuticals. Recently, the fiber industry has invested in the development of products made from linseed stems, making it a dual purpose crop. Simultaneous targeting of genomic regions controlling stem fiber and seed quality traits could enable the development of dual purpose cultivars. However, the genetic diversity, population structure and linkage disequilibrium (LD) patterns necessary for association mapping (AM) have not yet been assessed in flax because genomic resources have only recently been developed. We characterized 407 globally distributed flax accessions using 448 microsatellite markers. The data was analyzed to assess the suitability of this core collection for AM. Genomic scans to identify candidate genes selected during the divergent breeding process of fiber flax and linseed were conducted using the whole genome shotgun sequence of flax. Combined genetic structure analysis assigned all accessions to two major groups with six sub-groups. Population differentiation was weak between the major groups (F(ST) = 0.094) and for most of the pairwise comparisons among sub-groups. The molecular coancestry analysis indicated weak relatedness (mean = 0.287) for most individual pairs. Abundant genetic diversity was observed in the total panel (5.32 alleles per locus), and some sub-groups showed a high proportion of private alleles. The average genome-wide LD (r²) was 0.036, with a relatively fast decay of 1.5 cM. Genomic scans between fiber flax and linseed identified candidate genes involved in cell-wall biogenesis/modification, xylem identity and fatty acid biosynthesis congruent with genes previously identified in flax and other plant species. Based on the abundant genetic diversity, weak population structure and relatedness and relatively fast LD decay, we concluded that this core collection is suitable for AM studies targeting multiple agronomic and quality traits aiming at the improvement of flax as a true dual purpose crop. Our genomic scans provide the first insights into candidate regions affected by divergent selection in flax. In combination with AM, genomic scans have the ability to increase the power to detect loci influencing complex traits.

Discovery of Dual ETA/ETB Receptor Antagonists from Traditional Chinese Herbs through in Silico and in Vitro Screening

PubMed Central

Wang, Xing; Zhang, Yuxin; Liu, Qing; Ai, Zhixin; Zhang, Yanling; Xiang, Yuhong; Qiao, Yanjiang

2016-01-01

Endothelin-1 receptors (ETAR and ETBR) act as a pivotal regulator in the biological effects of ET-1 and represent a potential drug target for the treatment of multiple cardiovascular diseases. The purpose of the study is to discover dual ETA/ETB receptor antagonists from traditional Chinese herbs. Ligand- and structure-based virtual screening was performed to screen an in-house database of traditional Chinese herbs, followed by a series of in vitro bioassay evaluation. Aristolochic acid A (AAA) was first confirmed to be a dual ETA/ETB receptor antagonist based intracellular calcium influx assay and impedance-based assay. Dose-response curves showed that AAA can block both ETAR and ETBR with IC50 of 7.91 and 7.40 μM, respectively. Target specificity and cytotoxicity bioassay proved that AAA is a selective dual ETA/ETB receptor antagonist and has no significant cytotoxicity on HEK293/ETAR and HEK293/ETBR cells within 24 h. It is a feasible and effective approach to discover bioactive compounds from traditional Chinese herbs using in silico screening combined with in vitro bioassay evaluation. The structural characteristic of AAA for its activity was especially interpreted, which could provide valuable reference for the further structural modification of AAA. PMID:26999111

Novel selective and potent 5-HT reuptake inhibitors with 5-HT1D antagonist activity: chemistry and pharmacological evaluation of a series of thienopyran derivatives.

PubMed

Torrado, Alicia; Lamas, Carlos; Agejas, Javier; Jiménez, Alma; Diaz, Nuria; Gilmore, Jeremy; Boot, John; Findlay, Jeremy; Hayhurst, Lorna; Wallace, Louise; Broadmore, Richard; Tomlinson, Rosemarie

2004-10-15

A series of compounds combining the naphthylpiperazine and thienopyran scaffolds has been prepared and evaluated for 5-HT reuptake inhibition with 5-HT1D antagonist activity. The design of these compounds has been based on the 'overlapping type' strategy where two pharmacophores are linked in a single molecule. The resultant dual pharmacological profile has the potential to deliver a more efficient treatment for depression.

Comparison of image quality and radiation dose between split-filter dual-energy images and single-energy images in single-source abdominal CT.

PubMed

Euler, André; Obmann, Markus M; Szucs-Farkas, Zsolt; Mileto, Achille; Zaehringer, Caroline; Falkowski, Anna L; Winkel, David J; Marin, Daniele; Stieltjes, Bram; Krauss, Bernhard; Schindera, Sebastian T

2018-02-19

To compare image quality and radiation dose of abdominal split-filter dual-energy CT (SF-DECT) combined with monoenergetic imaging to single-energy CT (SECT) with automatic tube voltage selection (ATVS). Two-hundred single-source abdominal CT scans were performed as SECT with ATVS (n = 100) and SF-DECT (n = 100). SF-DECT scans were reconstructed and subdivided into composed images (SF-CI) and monoenergetic images at 55 keV (SF-MI). Objective and subjective image quality were compared among single-energy images (SEI), SF-CI and SF-MI. CNR and FOM were separately calculated for the liver (e.g. CNR liv ) and the portal vein (CNR pv ). Radiation dose was compared using size-specific dose estimate (SSDE). Results of the three groups were compared using non-parametric tests. Image noise of SF-CI was 18% lower compared to SEI and 48% lower compared to SF-MI (p < 0.001). Composed images yielded higher CNR liv over single-energy images (23.4 vs. 20.9; p < 0.001), whereas CNR pv was significantly lower (3.5 vs. 5.2; p < 0.001). Monoenergetic images overcame this inferiority in CNR pv and achieved similar results compared to single-energy images (5.1 vs. 5.2; p > 0.628). Subjective sharpness was equal between single-energy and monoenergetic images and diagnostic confidence was equal between single-energy and composed images. FOM liv was highest for SF-CI. FOM pv was equal for SEI and SF-MI (p = 0.78). SSDE was significant lower for SF-DECT compared to SECT (p < 0.022). The combined use of split-filter dual-energy CT images provides comparable objective and subjective image quality at lower radiation dose compared to single-energy CT with ATVS. • Split-filter dual-energy results in 18% lower noise compared to single-energy with ATVS. • Split-filter dual-energy results in 11% lower SSDE compared to single-energy with ATVS. • Spectral shaping of split-filter dual-energy leads to an increased dose-efficiency.

VX-222, a non-nucleoside NS5B polymerase inhibitor, in telaprevir-based regimens for genotype 1 hepatitis C virus infection.

PubMed

Di Bisceglie, Adrian M; Sulkowski, Mark; Gane, Ed; Jacobson, Ira M; Nelson, David; DeSouza, Cynthia; Alves, Katia; George, Shelley; Kieffer, Tara; Zhang, Eileen Z; Kauffman, Robert; Asmal, Mohammed; Koziel, Margaret J

2014-07-01

To investigate in this phase 2a study (ZENITH) the safety, tolerability, and antiviral activity of VX-222, a selective, non-nucleoside inhibitor of hepatitis C virus (HCV) NS5B polymerase, combined with various telaprevir-based regimens for treatment of genotype 1 HCV. In total, 152 treatment-naive patients received VX-222+telaprevir ('DUAL' regimen; n=47), with ribavirin ('TRIPLE' regimen; n=46), or with peginterferon+ribavirin ('QUAD' regimen; n=59) for 12 weeks. Patients with detectable HCV RNA at weeks 2 and/or 8 received peginterferon+ribavirin for 24 (DUAL and TRIPLE) or 12 (QUAD) additional weeks. VX-222 (100 or 400 mg twice daily) was well tolerated, with an increased rate of gastrointestinal adverse events observed with the higher dose. Across VX-222 400-mg twice-daily regimens, the QUAD was associated with the highest frequency of grade 3/4 adverse events. The DUAL was discontinued because of high viral breakthrough before week 12. Sustained virologic response (SVR) 24 weeks after end of treatment (SVR24), including patients treated with 12 or 24 additional weeks of peginterferon+ribavirin, was 67% for TRIPLE (VX-222 400 mg twice daily) and 79 and 90% for QUAD (VX-222 100 and 400 mg twice daily, respectively). These results provide valuable information regarding the safety, tolerability, and efficacy of telaprevir combined with a non-nucleoside polymerase inhibitor, as dual therapy or with ribavirin without or with peginterferon. Telaprevir and VX-222, alone or with ribavirin without or with peginterferon, were generally well tolerated, with improved tolerability without peginterferon. SVR24 rates achieved with TRIPLE and QUAD regimens containing telaprevir and VX-222 were comparable to those observed with telaprevir-based therapy.

A dual-route approach to orthographic processing.

PubMed

Grainger, Jonathan; Ziegler, Johannes C

2011-01-01

In the present theoretical note we examine how different learning constraints, thought to be involved in optimizing the mapping of print to meaning during reading acquisition, might shape the nature of the orthographic code involved in skilled reading. On the one hand, optimization is hypothesized to involve selecting combinations of letters that are the most informative with respect to word identity (diagnosticity constraint), and on the other hand to involve the detection of letter combinations that correspond to pre-existing sublexical phonological and morphological representations (chunking constraint). These two constraints give rise to two different kinds of prelexical orthographic code, a coarse-grained and a fine-grained code, associated with the two routes of a dual-route architecture. Processing along the coarse-grained route optimizes fast access to semantics by using minimal subsets of letters that maximize information with respect to word identity, while coding for approximate within-word letter position independently of letter contiguity. Processing along the fined-grained route, on the other hand, is sensitive to the precise ordering of letters, as well as to position with respect to word beginnings and endings. This enables the chunking of frequently co-occurring contiguous letter combinations that form relevant units for morpho-orthographic processing (prefixes and suffixes) and for the sublexical translation of print to sound (multi-letter graphemes).

A Dual-Route Approach to Orthographic Processing

PubMed Central

Grainger, Jonathan; Ziegler, Johannes C.

2011-01-01

In the present theoretical note we examine how different learning constraints, thought to be involved in optimizing the mapping of print to meaning during reading acquisition, might shape the nature of the orthographic code involved in skilled reading. On the one hand, optimization is hypothesized to involve selecting combinations of letters that are the most informative with respect to word identity (diagnosticity constraint), and on the other hand to involve the detection of letter combinations that correspond to pre-existing sublexical phonological and morphological representations (chunking constraint). These two constraints give rise to two different kinds of prelexical orthographic code, a coarse-grained and a fine-grained code, associated with the two routes of a dual-route architecture. Processing along the coarse-grained route optimizes fast access to semantics by using minimal subsets of letters that maximize information with respect to word identity, while coding for approximate within-word letter position independently of letter contiguity. Processing along the fined-grained route, on the other hand, is sensitive to the precise ordering of letters, as well as to position with respect to word beginnings and endings. This enables the chunking of frequently co-occurring contiguous letter combinations that form relevant units for morpho-orthographic processing (prefixes and suffixes) and for the sublexical translation of print to sound (multi-letter graphemes). PMID:21716577

The functional neuroanatomy of multitasking: combining dual tasking with a short term memory task.

PubMed

Deprez, Sabine; Vandenbulcke, Mathieu; Peeters, Ron; Emsell, Louise; Amant, Frederic; Sunaert, Stefan

2013-09-01

Insight into the neural architecture of multitasking is crucial when investigating the pathophysiology of multitasking deficits in clinical populations. Presently, little is known about how the brain combines dual-tasking with a concurrent short-term memory task, despite the relevance of this mental operation in daily life and the frequency of complaints related to this process, in disease. In this study we aimed to examine how the brain responds when a memory task is added to dual-tasking. Thirty-three right-handed healthy volunteers (20 females, mean age 39.9 ± 5.8) were examined with functional brain imaging (fMRI). The paradigm consisted of two cross-modal single tasks (a visual and auditory temporal same-different task with short delay), a dual-task combining both single tasks simultaneously and a multi-task condition, combining the dual-task with an additional short-term memory task (temporal same-different visual task with long delay). Dual-tasking compared to both individual visual and auditory single tasks activated a predominantly right-sided fronto-parietal network and the cerebellum. When adding the additional short-term memory task, a larger and more bilateral frontoparietal network was recruited. We found enhanced activity during multitasking in components of the network that were already involved in dual-tasking, suggesting increased working memory demands, as well as recruitment of multitask-specific components including areas that are likely to be involved in online holding of visual stimuli in short-term memory such as occipito-temporal cortex. These results confirm concurrent neural processing of a visual short-term memory task during dual-tasking and provide evidence for an effective fMRI multitasking paradigm. © 2013 Elsevier Ltd. All rights reserved.

The development of strategy use in elementary school children: working memory and individual differences.

PubMed

Imbo, Ineke; Vandierendonck, André

2007-04-01

The current study tested the development of working memory involvement in children's arithmetic strategy selection and strategy efficiency. To this end, an experiment in which the dual-task method and the choice/no-choice method were combined was administered to 10- to 12-year-olds. Working memory was needed in retrieval, transformation, and counting strategies, but the ratio between available working memory resources and arithmetic task demands changed across development. More frequent retrieval use, more efficient memory retrieval, and more efficient counting processes reduced the working memory requirements. Strategy efficiency and strategy selection were also modified by individual differences such as processing speed, arithmetic skill, gender, and math anxiety. Short-term memory capacity, in contrast, was not related to children's strategy selection or strategy efficiency.

Silica- and germania-based dual-ligand sol-gel organic-inorganic hybrid sorbents combining superhydrophobicity and π-π interaction. The role of inorganic substrate in sol-gel capillary microextraction.

PubMed

Seyyal, Emre; Malik, Abdul

2017-04-29

Principles of sol-gel chemistry were utilized to create silica- and germania-based dual-ligand surface-bonded sol-gel coatings providing enhanced performance in capillary microextraction (CME) through a combination of ligand superhydrophobicity and π-π interaction. These organic-inorganic hybrid coatings were prepared using sol-gel precursors with bonded perfluorododecyl (PF-C 12 ) and phenethyl (PhE) ligands. Here, the ability of the PF-C 12 ligand to provide enhanced hydrophobic interaction was advantageously combined with π-π interaction capability of the PhE moiety to attain the desired sorbent performance in CME. The effect of the inorganic sorbent component on microextraction performance of was explored by comparing microextraction characteristics of silica- and germania-based sol-gel sorbents. The germania-based dual-ligand sol-gel sorbent demonstrated superior CME performance compared to its silica-based counterpart. Thermogravimetric analysis (TGA) of the created silica- and germania-based dual-ligand sol-gel sorbents suggested higher carbon loading on the germania-based sorbent. This might be indicative of more effective condensation of the organic ligand-bearing sol-gel-active chemical species to the germania-based sol-gel network (than to its silica-based counterpart) evolving in the sol solution. The type and concentration of the organic ligands were varied in the sol-gel sorbents to fine-tune extraction selectivity toward different classes of analytes. Specific extraction (SE) values were used for an objective comparison of the prepared sol-gel CME sorbents. The sorbents with higher content of PF-C 12 showed remarkable affinity for aliphatic hydrocarbons. Compared to their single-ligand sol-gel counterparts, the dual-ligand sol-gel coatings demonstrated significantly superior CME performance in the extraction of alkylbenzenes, providing up to ∼65.0% higher SE values. The prepared sol-gel CME coatings provided low ng L -1 limit of detections (LOD) (4.2-26.3 ng L -1 ) for environmentally important analytes including polycyclic aromatic hydrocarbons, ketones and aliphatic hydrocarbons. In CME-GC experiments (n = 5), the capillary-to-capillary RSD value was ∼2.1%; such a low RSD value is indicative of excellent reproducibility of the sol-gel method used for the preparation of these CME coatings. The dual-ligand sol-gel coating provided stable performance in capillary microextraction of analytes from saline samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Novel Dual-Band Miniaturized Frequency Selective Surface based on Fractal Structures

NASA Astrophysics Data System (ADS)

Zhong, Tao; Zhang, Hou; Wu, Rui; Min, Xueliang

2017-01-01

A novel single-layer dual-band miniaturized frequency selective surface (FSS) based on fractal structures is proposed and analyzed in this paper. A prototype with enough dimensions is fabricated and measured in anechoic chamber, and the measured results provide good agreement with the simulated. The simulations and measurements indicate that the dual-band FSS with bandstop selectivity center at 3.95 GHz and 7.10 GHz, and the whole dimension of the proposed FSS cell is only 7×7 mm2, amount to 0.092λ0×0.092λ0, that λ0 is free space wavelength at first resonant frequency. In addition, the center frequencies have scarcely any changes for different polarizations and incidences. What's more, dual-band mechanism is analyzed clearly and it provides a new way to design novel miniaturized FSS structures.

Innovative spectrophotometric methods for simultaneous estimation of the novel two-drug combination: Sacubitril/Valsartan through two manipulation approaches and a comparative statistical study.

PubMed

Eissa, Maya S; Abou Al Alamein, Amal M

2018-03-15

Different innovative spectrophotometric methods were introduced for the first time for simultaneous quantification of sacubitril/valsartan in their binary mixture and in their combined dosage form without prior separation through two manipulation approaches. These approaches were developed and based either on two wavelength selection in zero-order absorption spectra namely; dual wavelength method (DWL) at 226nm and 275nm for valsartan, induced dual wavelength method (IDW) at 226nm and 254nm for sacubitril and advanced absorbance subtraction (AAS) based on their iso-absorptive point at 246nm (λ iso ) and 261nm (sacubitril shows equal absorbance values at the two selected wavelengths) or on ratio spectra using their normalized spectra namely; ratio difference spectrophotometric method (RD) at 225nm and 264nm for both of them in their ratio spectra, first derivative of ratio spectra (DR 1 ) at 232nm for valsartan and 239nm for sacubitril and mean centering of ratio spectra (MCR) at 260nm for both of them. Both sacubitril and valsartan showed linearity upon application of these methods in the range of 2.5-25.0μg/mL. The developed spectrophotmetric methods were successfully applied to the analysis of their combined tablet dosage form ENTRESTO™. The adopted spectrophotometric methods were also validated according to ICH guidelines. The results obtained from the proposed methods were statistically compared to a reported HPLC method using Student t-test, F-test and a comparative study was also developed with one-way ANOVA, showing no statistical difference in accordance to precision and accuracy. Copyright © 2017 Elsevier B.V. All rights reserved.

Investigations of morphological features of picosecond dual-wavelength laser ablation of stainless steel

NASA Astrophysics Data System (ADS)

Zhao, Wanqin; Wang, Wenjun; Mei, Xuesong; Jiang, Gedong; Liu, Bin

2014-06-01

Investigations on the morphological features of holes and grooves ablated on the surface of stainless steel using the picosecond dual-wavelength laser system with different powers combinations are presented based on the scarce researches on morphology of dual-wavelength laser ablation. The experimental results show the profiles of holes ablated by the visible beam appear V-shaped while those for the near-infrared have large openings and display U-shaped, which are independent of the ablation mechanism of ultrafast laser. For the dual-wavelength beam (a combination of visible beam and near-infrared), the holes resemble sunflower-like structures and have smoother ring patterns on the bottom. In general, the holes ablated by the dual-wavelength beam appear to have much flatter bottoms, linearly sloped side-walls and spinodal structures between the bottoms of the holes and the side-walls. Furthermore, through judiciously combining the powers of the dual-wavelength beam, high-quality grooves could be obtained with a flat worm-like structure at the bottom surface and less resolidified melt ejection edges. This study provides insight into optimizing ultrafast laser micromachining in order to obtain desired morphology.

Dual Therapy Treatment Strategies for the Management of Patients Infected with HIV: A Systematic Review of Current Evidence in ARV-Naive or ARV-Experienced, Virologically Suppressed Patients.

PubMed

Baril, Jean-Guy; Angel, Jonathan B; Gill, M John; Gathe, Joseph; Cahn, Pedro; van Wyk, Jean; Walmsley, Sharon

2016-01-01

We reviewed the current literature regarding antiretroviral (ARV)-sparing therapy strategies to determine whether these novel regimens can be considered appropriate alternatives to standard regimens for the initial treatment of ARV-naive patients or as switch therapy for those patients with virologically suppressed HIV infection. A search for studies related to HIV dual therapy published from January 2000 through April 2014 was performed using Biosis, Derwent Drug File, Embase, International Pharmaceutical Abstracts, Medline, Pascal, SciSearch, and TOXNET databases; seven major trial registries, and the abstracts of major conferences. Using predetermined criteria for inclusion, an expert review committee critically reviewed and qualitatively evaluated all identified trials for efficacy and safety results and potential limitations. Sixteen studies of dual therapy regimens were critiqued for the ARV-naive population. Studies of a protease inhibitor/ritonavir in combination with the integrase inhibitor raltegravir or the nucleoside reverse transcriptase inhibitor lamivudine provided the most definitive evidence supporting a role for dual therapy. In particular, lopinavir/ritonavir or darunavir/ritonavir combined with raltegravir and lopinavir/ritonavir combined with lamivudine demonstrated noninferiority to standard of care triple therapy after 48 weeks of treatment. Thirteen trials were critiqued in ARV-experienced, virologically suppressed patients. The virologic efficacy outcomes were mixed. Although overall data regarding toxicity are limited, when compared with standard triple therapy, certain dual therapy regimens may offer advantages in renal function, bone mineral density, and limb fat changes; however, some dual combinations may elevate lipid or bilirubin levels. The potential benefits of dual therapy regimens include reduced toxicity, improved tolerability and adherence, and reduced cost. Although the data reviewed here provide valuable insights into the effectiveness and tolerability of dual therapy regimens, it remains unclear whether these potential benefits can be maintained long-term. Appropriately powered studies with longer follow-up periods are needed to more definitively assess potential toxicity reduction advantages with dual therapy.

Dual Antiplatelet Therapy for 6 Months vs 12 Months After New-generation Drug-eluting Stent Implantation: Matched Analysis of ESTROFA-DAPT and ESTROFA-2.

PubMed

de la Torre Hernández, José M; Oteo Domínguez, Juan F; Hernández, Felipe; García Camarero, Tamara; Abdul-Jawad Altisent, Omar; Rivero Crespo, Fernando; Cascón, José D; Zavala, Germán; Gimeno, Federico; Arrebola Moreno, Antonio L; Andraka, Leire; Gómez Menchero, Antonio; Bosa, Francisco; Carrillo, Xavier; Sánchez Recalde, Ángel; Alfonso, Fernando; Pérez de Prado, Armando; López Palop, Ramón; Sanchis, Juan; Diarte de Miguel, José A; Jiménez Navarro, Manuel; Muñoz, Luz; Ramírez Moreno, Antonio; Tizón Marcos, Helena

2015-10-01

The recommendation for dual antiplatelet therapy following drug-eluting stent implantation ranges from 6 months to 12 months or beyond. Recent trials have suggested the safety of a 6-month dual antiplatelet therapy regimen, yet certain caveats to these studies limit the applicability of this shorter duration dual antiplatelet therapy strategy in real world settings. A registry was constructed with consecutive recruitment of patients undergoing new-generation drug-eluting stent implantation and prescribed 6 months of dual antiplatelet therapy. Propensity score matching was undertaken with a historical cohort of patients treated with second-generation drug-eluting stents who received 12 months of dual antiplatelet therapy from the ESTROFA-2 registry. The sample size was calculated using a noninferiority basis and the primary endpoint was the combination of cardiac death, myocardial infarction, revascularization, or major bleeding at 12 months. The analysis included 1286 patients in each group, with no significant differences in baseline characteristics. The primary endpoint occurred in 5.0% and 6.6% in the 6-month and 12-month groups, respectively (P = .001 for noninferiority). The incidence of definite or probable stent thrombosis was 0.5% and 0.7% in the 6-month and 12-month groups, respectively (P = .4). Major bleeding events were lower in the 6-month group than in the 12-month group (0.8% vs 1.4%; P = .2) CONCLUSIONS: In selected patients in this large multicenter study, the safety and efficacy of a 6-month dual antiplatelet therapy regimen after implantation of new-generation drug-eluting stents appeared to be noninferior to those of a 12-month dual antiplatelet therapy regimen. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Long-range transcriptional interference in E. coli used to construct a dual positive selection system for genetic switches

PubMed Central

Hoffmann, Stefan A.; Kruse, Sabrina M.; Arndt, Katja M.

2016-01-01

Abstract We have investigated transcriptional interference between convergent genes in E. coli and demonstrate substantial interference for inter-promoter distances of as far as 3 kb. Interference can be elicited by both strong σ70 dependent and T7 promoters. In the presented design, a strong promoter driving gene expression of a ‘forward’ gene interferes with the expression of a ‘reverse’ gene by a weak promoter. This arrangement allows inversely correlated gene expression without requiring further regulatory components. Thus, modulation of the activity of the strong promoter alters expression of both the forward and the reverse gene. We used this design to develop a dual selection system for conditional operator site binding, allowing positive selection both for binding and for non-binding to DNA. This study demonstrates the utility of this novel system using the Lac repressor as a model protein for conditional DNA binding, and spectinomycin and chloramphenicol resistance genes as positive selection markers in liquid culture. Randomized LacI libraries were created and subjected to subsequent dual selection, but mispairing IPTG and selection cues in respect to the wild-type LacI response, allowing the isolation of a LacI variant with a reversed IPTG response within three rounds of library generation and dual selection. PMID:26932362

Concurrent deployment of visual attention and response selection bottleneck in a dual-task: Electrophysiological and behavioural evidence.

PubMed

Reimer, Christina B; Strobach, Tilo; Schubert, Torsten

2017-12-01

Visual attention and response selection are limited in capacity. Here, we investigated whether visual attention requires the same bottleneck mechanism as response selection in a dual-task of the psychological refractory period (PRP) paradigm. The dual-task consisted of an auditory two-choice discrimination Task 1 and a conjunction search Task 2, which were presented at variable temporal intervals (stimulus onset asynchrony, SOA). In conjunction search, visual attention is required to select items and to bind their features resulting in a serial search process around the items in the search display (i.e., set size). We measured the reaction time of the visual search task (RT2) and the N2pc, an event-related potential (ERP), which reflects lateralized visual attention processes. If the response selection processes in Task 1 influence the visual attention processes in Task 2, N2pc latency and amplitude would be delayed and attenuated at short SOA compared to long SOA. The results, however, showed that latency and amplitude were independent of SOA, indicating that visual attention was concurrently deployed to response selection. Moreover, the RT2 analysis revealed an underadditive interaction of SOA and set size. We concluded that visual attention does not require the same bottleneck mechanism as response selection in dual-tasks.

SU-F-I-41: Calibration-Free Material Decomposition for Dual-Energy CT

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

Zhao, W; Xing, L; Zhang, Q

2016-06-15

Purpose: To eliminate tedious phantom calibration or manually region of interest (ROI) selection as required in dual-energy CT material decomposition, we establish a new projection-domain material decomposition framework with incorporation of energy spectrum. Methods: Similar to the case of dual-energy CT, the integral of the basis material image in our model is expressed as a linear combination of basis functions, which are the polynomials of high- and low-energy raw projection data. To yield the unknown coefficients of the linear combination, the proposed algorithm minimizes the quadratic error between the high- and low-energy raw projection data and the projection calculated usingmore » material images. We evaluate the algorithm with an iodine concentration numerical phantom at different dose and iodine concentration levels. The x-ray energy spectra of the high and low energy are estimated using an indirect transmission method. The derived monochromatic images are compared with the high- and low-energy CT images to demonstrate beam hardening artifacts reduction. Quantitative results were measured and compared to the true values. Results: The differences between the true density value used for simulation and that were obtained from the monochromatic images, are 1.8%, 1.3%, 2.3%, and 2.9% for the dose levels from standard dose to 1/8 dose, and are 0.4%, 0.7%, 1.5%, and 1.8% for the four iodine concentration levels from 6 mg/mL to 24 mg/mL. For all of the cases, beam hardening artifacts, especially streaks shown between dense inserts, are almost completely removed in the monochromatic images. Conclusion: The proposed algorithm provides an effective way to yield material images and artifacts-free monochromatic images at different dose levels without the need for phantom calibration or ROI selection. Furthermore, the approach also yields accurate results when the concentration of the iodine concentrate insert is very low, suggesting the algorithm is robust with respect to the low-contrast scenario.« less

Midazolam inhibits hippocampal long-term potentiation and learning through dual central and peripheral benzodiazepine receptor activation and neurosteroidogenesis.

PubMed

Tokuda, Kazuhiro; O'Dell, Kazuko A; Izumi, Yukitoshi; Zorumski, Charles F

2010-12-15

Benzodiazepines (BDZs) enhance GABA(A) receptor inhibition by direct actions on central BDZ receptors (CBRs). Although some BDZs also bind mitochondrial receptors [translocator protein (18 kDa) (TSPO)] and promote the synthesis of GABA-enhancing neurosteroids, the role of neurosteroids in the clinical effects of BDZs is unknown. In rat hippocampal slices, we compared midazolam, an anesthetic BDZ, with clonazepam, an anticonvulsant/anxiolytic BDZ that activates CBRs selectively. Midazolam, but not clonazepam, increased neurosteroid levels in CA1 pyramidal neurons without changing TSPO immunostaining. Midazolam, but not clonazepam, also augmented a form of spike inhibition after stimulation adjacent to the pyramidal cell layer and inhibited induction of long-term potentiation. These effects were prevented by finasteride, an inhibitor of neurosteroid synthesis, or 17PA [17-phenyl-(3α,5α)-androst-16-en-3-ol], a blocker of neurosteroid effects on GABA(A) receptors. Moreover, the synaptic effects were mimicked by a combination of clonazepam with FGIN (2-[2-(4-fluorophenyl)-1H-indol-3-yl]-N,N-dihexylacetamide), a selective TSPO agonist, or a combination of clonazepam with exogenous allopregnanolone. Consistent with these in vitro results, finasteride abolished the effects of midazolam on contextual fear learning when administrated 1 d before midazolam injection. Thus, dual activation of CBRs and TSPO appears to result in unique actions of clinically important BDZs. Furthermore, endogenous neurosteroids are shown to be important regulators of pyramidal neuron function and synaptic plasticity.

Midazolam inhibits hippocampal long-term potentiation and learning through dual central and peripheral benzodiazepine receptor activation and neurosteroidogenesis

PubMed Central

Tokuda, Kazuhiro; O’Dell, Kazuko A.; Izumi, Yukitoshi; Zorumski, Charles F.

2010-01-01

Benzodiazepines (BDZs) enhance γ-aminobutyric acid-A (GABAA) receptor inhibition by direct actions on central BDZ receptors (CBRs). Although some BDZs also bind mitochondrial receptors (translocator protein 18kDa, TSPO) and promote the synthesis of GABA-enhancing neurosteroids, the role of neurosteroids in the clinical effects of BDZs is unknown. In rat hippocampal slices, we compared midazolam, an anesthetic BDZ with clonazepam, an anticonvulsant/anxiolytic BDZ that activates CBRs selectively. Midazolam, but not clonazepam, increased neurosteroid levels in CA1 pyramidal neurons without changing TSPO immunostaining. Midazolam, but not clonazepam, also augmented a form of spike inhibition following stimulation adjacent to the pyramidal cell layer and inhibited induction of long-term potentiation. These effects were prevented by finasteride, an inhibitor of neurosteroid synthesis, or 17PA (17-phenyl-(3α, 5α)-androst-16-en-3-ol), a blocker of neurosteroid effects on GABAA receptors. Moreover, the synaptic effects were mimicked by a combination of clonazepam with FGIN, a selective TSPO agonist, or a combination of clonazepam with exogenous allopregnanolone. Consistent with these in vitro results, finasteride abolished the effects of midazolam on contextual fear learning when administrated one day prior to midazolam injection. Thus, dual activation of CBRs and TSPO appears to result in unique actions of clinically-important BDZs. Furthermore, endogenous neurosteroids are shown to be important regulators of pyramidal neuron function and synaptic plasticity. PMID:21159950

Chin plate with a detachable C-tube head serves for both osteotomy fixation and orthodontic anchorage.

PubMed

Seo, Kyung-Won; Nahm, Kyung-Yen; Kim, Seong-Hun; Chung, Kyu-Rhim; Nelson, Gerald

2013-07-01

This article reports the dual function of a double-Y miniplate with a detachable C-tube head (C-chin plate; Jin Biomed Co., Bucheon, Korea) used to fixate an anterior segmental osteotomy and provide skeletal anchorage during orthodontic tooth movement. Cases were selected for this study from patients who underwent anterior segmental osteotomy under local anesthesia. A detachable C-tube head portion was combined with a double-Y chin plate. The double-Y chin plates were fixated between the osteotomy segments and the mandibular base with screws in a conventional way. The C-tube head portion exited the tissue near the mucogingival junction. Biocreative Chin Plates were placed on the anterior segmental osteotomy sites. The device allowed 3 points of fixation: 1, minor postosteotomy vertical adjustment of the segment during healing; 2, minor shift of the midline during healing; and 3, to serve as temporary skeletal anchorage device during the post-anterior segmental osteotomy orthodontic treatment. When tooth movement goals are accomplished, the C-tube head of the chin plate can be easily detached from the fixation miniplate by twisting the head using a Weingart plier under local anesthesia. This dual-purpose device spares the patient from the need for 2 separate installations for stabilization of osteotomy segments. The dual-purpose double-Y miniplate combined with a C-tube head (Biocreative Chin Plate) provided versatile application of 3 points of post-osteotomy fixation and of temporary skeletal anchorage for orthodontic tooth movement.

Cotransduction with MGMT and Ubiquitous or Erythroid-Specific GFP Lentiviruses Allows Enrichment of Dual-Positive Hematopoietic Progenitor Cells In Vivo

PubMed Central

Roth, Justin C.; Ismail, Mourad; Reese, Jane S.; Lingas, Karen T.; Ferrari, Giuliana; Gerson, Stanton L.

2012-01-01

The P140K point mutant of MGMT allows robust hematopoietic stem cell (HSC) enrichment in vivo. Thus, dual-gene vectors that couple MGMT and therapeutic gene expression have allowed enrichment of gene-corrected HSCs in animal models. However, expression levels from dual-gene vectors are often reduced for one or both genes. Further, it may be desirable to express selection and therapeutic genes at distinct stages of cell differentiation. In this regard, we evaluated whether hematopoietic cells could be efficiently cotransduced using low MOIs of two separate single-gene lentiviruses, including MGMT for dual-positive cell enrichment. Cotransduction efficiencies were evaluated using a range of MGMT : GFP virus ratios, MOIs, and selection stringencies in vitro. Cotransduction was optimal when equal proportions of each virus were used, but low MGMT : GFP virus ratios resulted in the highest proportion of dual-positive cells after selection. This strategy was then evaluated in murine models for in vivo selection of HSCs cotransduced with a ubiquitous MGMT expression vector and an erythroid-specific GFP vector. Although the MGMT and GFP expression percentages were variable among engrafted recipients, drug selection enriched MGMT-positive leukocyte and GFP-positive erythroid cell populations. These data demonstrate cotransduction as a mean to rapidly enrich and evaluate therapeutic lentivectors in vivo. PMID:22888445

The Combine Project: An Experience in a Dual-Language Classroom = El proyecto de la cosechadora: una experiencia en una clase bilingue.

ERIC Educational Resources Information Center

Wilson, Rebecca

This article, also available in Spanish, describes what happened when a bilingual kindergarten class in West Liberty, Iowa, investigated a combine. The dual-language Kindergarten program supports content area instruction in both Spanish and English. The first part of the article tells the story of the Combine Project, this class's first project…

Underwater wireless optical MIMO system with spatial modulation and adaptive power allocation

NASA Astrophysics Data System (ADS)

Huang, Aiping; Tao, Linwei; Niu, Yilong

2018-04-01

In this paper, we investigate the performance of underwater wireless optical multiple-input multiple-output communication system combining spatial modulation (SM-UOMIMO) with flag dual amplitude pulse position modulation (FDAPPM). Channel impulse response for coastal and harbor ocean water links are obtained by Monte Carlo (MC) simulation. Moreover, we obtain the closed-form and upper bound average bit error rate (BER) expressions for receiver diversity including optical combining, equal gain combining and selected combining. And a novel adaptive power allocation algorithm (PAA) is proposed to minimize the average BER of SM-UOMIMO system. Our numeric results indicate an excellent match between the analytical results and numerical simulations, which confirms the accuracy of our derived expressions. Furthermore, the results show that adaptive PAA outperforms conventional fixed factor PAA and equal PAA obviously. Multiple-input single-output system with adaptive PAA obtains even better BER performance than MIMO one, at the same time reducing receiver complexity effectively.

Filtered cathodic arc deposition with ion-species-selective bias.

PubMed

Anders, André; Pasaja, Nitisak; Sansongsiri, Sakon

2007-06-01

A dual-cathode arc plasma source was combined with a computer-controlled bias amplifier to synchronize substrate bias with the pulsed production of plasma. In this way, bias can be applied in a material-selective way. The principle has been applied to the synthesis of metal-doped diamondlike carbon films, where the bias was applied and adjusted when the carbon plasma was condensing and the substrate was at ground when the metal was incorporated. In doing so, excessive sputtering by energetic metal ions can be avoided while the sp(3)sp(2) ratio can be adjusted. It is shown that the resistivity of the film can be tuned by this species-selective bias; Raman spectroscopy was used to confirm expected changes of the amorphous ta-C:Mo films. The species-selective bias principle could be extended to multiple material plasma sources and complex materials.

The Effects of Combining Videogame Dancing and Pelvic Floor Training to Improve Dual-Task Gait and Cognition in Women with Mixed-Urinary Incontinence.

PubMed

Fraser, Sarah A; Elliott, Valerie; de Bruin, Eling D; Bherer, Louis; Dumoulin, Chantal

2014-06-01

Many women over 65 years of age suffer from mixed urinary incontinence (MUI) and executive function (EF) deficits. Both incontinence and EF declines increase fall risk. The current study assessed EF and dual-task gait after a multicomponent intervention that combined pelvic floor muscle (PFM) training and videogame dancing (VGD). Baseline (Pre1), pretraining (Pre2), and post-training (Post) neuropsychological and dual-task gait assessments were completed by 23 women (mean age, 70.4 years) with MUI. During the dual-task, participants walked and performed an auditory n-back task. From Pre2 to Post, all women completed 12 weeks of combined PFM and VGD training. After training (Pre2 to Post), the number of errors in the Inhibition/Switch Stroop condition decreased significantly, the Trail Making Test difference score improved marginally, and the number of n-back errors during dual-task gait significantly decreased. A subgroup analysis based on continence improvements (pad test) revealed that only those subjects who improved in the pad test had significantly reduced numbers of n-back errors during dual-task gait. The results of this study suggest that a multicomponent intervention can improve EFs and the dual-task gait of older women with MUI. Future research is needed to determine if the training-induced improvements in these factors reduce fall risk.

Dual-task results and the lateralization of spatial orientation: artifact of test selection?

PubMed

Bowers, C A; Milham, L M; Price, C

1998-01-01

An investigation was conducted to identify the degree to which results regarding the lateralization of spatial orientation among men and women are artifacts of test selection. A dual-task design was used to study possible lateralization differences, providing baseline and dual-task measures of spatial-orientation performance, right- and left-hand tapping, and vocalization of "cat, dog, horse." The Guilford-Zimmerman Test (Guilford & Zimmerman, 1953), the Eliot-Price Test (Eliot & Price, 1976), and the Stumpf-Fay Cube Perspectives Test (Stumpf & Fay, 1983) were the three spatial-orientation tests used to investigate possible artifacts of test selection. Twenty-eight right-handed male and 39 right-handed female undergraduates completed random baseline and dual-task sessions. Analyses indicated no significant sex-related differences in spatial-orientation ability for all three tests. Furthermore, there was no evidence of differential lateralization of spatial orientation between the sexes.

Modified beacon probe assisted dual signal amplification for visual detection of microRNA.

PubMed

Sun, Xiuwei; Ying, Na; Ju, Chuanjing; Li, Zhongyi; Xu, Na; Qu, Guijuan; Liu, Wensen; Wan, Jiayu

2018-06-01

In a recent study, we reported a novel assay for the detection of microRNA-21 based on duplex-specific nuclease (DSN)-assisted isothermal cleavage and hybridization chain reaction (HCR) dual signal amplification. The Fam modified double-stranded DNA products were generated after the HCR, another biotin modified probe was digested by DSN and released from the magnetic beads after the addition of the target miRNA. The released sequence was then combined with HCR products to form a double-tagging dsDNA, which can be recognized by the lateral flow strips. In this study, we introduced a 2-OMethyl-RNA modified beacon probe (2-OMe-MB) to make some improvements based on the previous study. Firstly, the substitution of modified probe combined on magnetic beads avoids the fussy washing steps for the separation of un-reacted probes. Furthermore, the modification of 2-OMe on the stem of the probe avoided the unnecessary cleavage by DSN, which greatly reduce the background signal. Compared to the previous work, these improvements save us a lot of steps but possess the comparable sensitivity and selectivity. Copyright © 2018 Elsevier Inc. All rights reserved.

Dual targeting of MDM2 and BCL2 as a therapeutic strategy in neuroblastoma.

PubMed

Van Goethem, Alan; Yigit, Nurten; Moreno-Smith, Myrthala; Vasudevan, Sanjeev A; Barbieri, Eveline; Speleman, Frank; Shohet, Jason; Vandesompele, Jo; Van Maerken, Tom

2017-08-22

Wild-type p53 tumor suppressor activity in neuroblastoma tumors is hampered by increased MDM2 activity, making selective MDM2 antagonists an attractive therapeutic strategy for this childhood malignancy. Since monotherapy in cancer is generally not providing long-lasting clinical responses, we here aimed to identify small molecule drugs that synergize with idasanutlin (RG7388). To this purpose we evaluated 15 targeted drugs in combination with idasanutlin in three p53 wild type neuroblastoma cell lines and identified the BCL2 inhibitor venetoclax (ABT-199) as a promising interaction partner. The venetoclax/idasanutlin combination was consistently found to be highly synergistic in a diverse panel of neuroblastoma cell lines, including cells with high MCL1 expression levels. A more pronounced induction of apoptosis was found to underlie the synergistic interaction, as evidenced by caspase-3/7 and cleaved PARP measurements. Mice carrying orthotopic xenografts of neuroblastoma cells treated with both idasanutlin and venetoclax had drastically lower tumor weights than mice treated with either treatment alone. In conclusion, these data strongly support the further evaluation of dual BCL2/MDM2 targeting as a therapeutic strategy in neuroblastoma.

A multi writable thiophene-based selective and reversible chromogenic fluoride probe with dual -NH functionality.

PubMed

Vishwakarma, Siddharth; Kumar, Ajit; Pandey, Abha; Upadhyay, K K

2017-01-05

A chromogenic fluoride probe bearing bis imine groups having dual -NH functionality (BSB) has been designed, synthesised and structurally characterized by its single crystal X-ray diffraction studies. The BSB could visually and spectroscopically recognise F(-) with high selectivity over other anions by exhibiting intense chromogenic response (from colourless to red) for F(-) in acetonitrile solution. The UV-visible titration and (1)H NMR titration experiments indicated that the observed changes occur via a combined process including hydrogen bonding and deprotonation between the BSB and F(-). Moreover theoretical calculations at the Density Functional Theory (DFT) level shed further light upon probe design strategy and the nature of interactions between BSB and F(-). The limit of detection and binding constant of BSB towards F(-) were found to be 6.9×10(-7)M and 1.42±0.069×10(8)M(-2) respectively. Finally, by using F(-)and H(+) as chemical inputs and the absorbance as output, a INHIBIT logic gate was constructed, which exhibits "Multi-write" ability without obvious degradation in its optical output. Copyright © 2016 Elsevier B.V. All rights reserved.

A systematic review of interventions conducted in clinical or community settings to improve dual-task postural control in older adults

PubMed Central

Agmon, Maayan; Belza, Basia; Nguyen, Huong Q; Logsdon, Rebecca G; Kelly, Valerie E

2014-01-01

Background Injury due to falls is a major problem among older adults. Decrements in dual-task postural control performance (simultaneously performing two tasks, at least one of which requires postural control) have been associated with an increased risk of falling. Evidence-based interventions that can be used in clinical or community settings to improve dual-task postural control may help to reduce this risk. Purpose The aims of this systematic review are: 1) to identify clinical or community-based interventions that improved dual-task postural control among older adults; and 2) to identify the key elements of those interventions. Data sources Studies were obtained from a search conducted through October 2013 of the following electronic databases: PubMed, CINAHL, PsycINFO, and Web of Science. Study selection Randomized and nonrandomized controlled studies examining the effects of interventions aimed at improving dual-task postural control among community-dwelling older adults were selected. Data extraction All studies were evaluated based on methodological quality. Intervention characteristics including study purpose, study design, and sample size were identified, and effects of dual-task interventions on various postural control and cognitive outcomes were noted. Data synthesis Twenty-two studies fulfilled the selection criteria and were summarized in this review to identify characteristics of successful interventions. Limitations The ability to synthesize data was limited by the heterogeneity in participant characteristics, study designs, and outcome measures. Conclusion Dual-task postural control can be modified by specific training. There was little evidence that single-task training transferred to dual-task postural control performance. Further investigation of dual-task training using standardized outcome measurements is needed. PMID:24741296

Carbon Nanodots as Dual-Mode Nanosensors for Selective Detection of Hydrogen Peroxide

NASA Astrophysics Data System (ADS)

Shen, Cheng-Long; Su, Li-Xia; Zang, Jin-Hao; Li, Xin-Jian; Lou, Qing; Shan, Chong-Xin

2017-07-01

Hydrogen peroxide (H2O2) is an important product of oxidase-based enzymatic reactions, such as glucose/glucose oxidase (GOD) reaction. Therefore, the probing of generated H2O2 for achieving the detection of various carbohydrates and their oxidases is very significative. Herein, we report one kind of dual-emission carbon nanodots (CDs) that can serve as novel dual-mode nanosensors with both fluorometric and colorimetric output for the selective detection of H2O2. The dual-model nanosensors are established only by the undecorated dual-emission CDs, where significant fluorometric and colorimetric changes are observed with the addition of different concentrations of H2O2 in the CD solution, which benefit to the achievement of the naked-eye detection for H2O2. The mechanism of the nanosensors can be attributed to the fact that the external chemical stimuli like hydroxyl radicals from H2O2 bring about the change of surface properties and the aggregation of CDs, which dominate the emission and absorption of CDs. The constructed dual-mode nanosensors exhibit good biocompatibility and high selectivity toward H2O2 with a linear detection range spanning from 0.05 to 0.5 M and allow the detection of H2O2 as low as 14 mM.

Antithrombotic therapy in patients with non-valvular atrial fibrillation undergoing percutaneous coronary intervention: should we change our practice after the PIONEER AF-PCI and RE-DUAL PCI trials?

PubMed

Duerschmied, D; Brachmann, J; Darius, H; Frey, N; Katus, H A; Rottbauer, W; Schäfer, A; Thiele, H; Bode, C; Zeymer, Uwe

2018-04-20

The number of patients with atrial fibrillation undergoing percutaneous coronary intervention (PCI) is increasing. Since these patients have a CHA 2 DS 2 -VASc score of 1 or higher, they should be treated with oral anticoagulation to prevent stroke. However, combination therapy with oral anticoagulation for prevention of embolic stroke and dual platelet inhibition for prevention of coronary thrombosis significantly increases bleeding complications. The optimal combination, intensity and duration of antithrombotic combination therapy is still not known. In the rather small randomized WOEST trial, the combination of a vitamin K antagonist (VKA) and clopidogrel decreased bleeding compared to the conventional triple therapy with VKA, clopidogrel and aspirin. In the PIONEER AF-PCI trial, two rivaroxaban-based treatment regimens significantly reduced bleeding complications compared to conventional triple therapy without increasing embolic or ischemic complications following PCI. Dual therapy with rivaroxaban and clopidogrel appeared to provide an optimal risk-benefit ratio. In the RE-DUAL PCI trial, dual therapy with dabigatran also reduced bleeding complications compared to conventional triple therapy. With respect to the composite efficacy end point of thromboembolic events (myocardial infarction, stroke, or systemic embolism), death, or unplanned revascularization dabigatran-based dual therapy was non-inferior to VKA-based triple therapy. The upcoming trials AUGUSTUS with apixaban and ENTRUST-PCI with edoxaban will further examine the use of NOACs in this setting. While recent guidelines recommend NOAC-based dual therapy in only a subset of patients (those who are at increased risk of bleeding), the available data now suggest that this should be the preferred choice for the majority of patients. Adding aspirin to this primary choice for up to 4 weeks in patients at especially high ischemic risk would likely prevent atherothrombotic events, but this needs further investigation. Taken together, it is time to adjust our practice and move to dual therapy consisting of a NOAC plus clopidogrel in most patients.

Dual-Objective Item Selection Criteria in Cognitive Diagnostic Computerized Adaptive Testing

ERIC Educational Resources Information Center

Kang, Hyeon-Ah; Zhang, Susu; Chang, Hua-Hua

2017-01-01

The development of cognitive diagnostic-computerized adaptive testing (CD-CAT) has provided a new perspective for gaining information about examinees' mastery on a set of cognitive attributes. This study proposes a new item selection method within the framework of dual-objective CD-CAT that simultaneously addresses examinees' attribute mastery…

Inihibition of Glycolysis by Using a Micro/Nano-Lipid Bromopyruvic Chitosan Carrier as a Promising Tool to Improve Treatment of Hepatocellular Carcinoma

PubMed Central

Dini, Luciana; Citti, Cinzia; Cannazza, Giuseppe

2018-01-01

Glucose consumption in many types of cancer cells, in particular hepatocellular carcinoma (HCC), was followed completely by over-expression of type II hexokinase (HKII). This evidence has been used in modern pharmacotherapy to discover therapeutic target against glycolysis in cancer cells. Bromopyruvate (BrPA) exhibits antagonist property against HKII and can be used to inhibit glycolysis. However, the clinical application of BrPA is mostly combined with inhibition effect for healthy cells particularly erythrocytes. Our strategy is to encapsulate BrPA in a selected vehicle, without any leakage of BrPA out of vehicle in blood stream. This structure has been constructed from chitosan embedded into oleic acid layer and then coated by dual combination of folic acid (FA) and bovine serum albumin (BSA). With FA as specific ligand for cancer folate receptor and BSA that can be an easy binding for hepatocytes, they can raise the potential selection of carrier system. PMID:29320411

Dual trigger of final oocyte maturation with a combination of GnRH agonist and hCG versus a hCG alone trigger in GnRH antagonist cycle for in vitro fertilization: A Systematic Review and Meta-analysis.

PubMed

Ding, Nan; Liu, Xingchen; Jian, Qiliang; Liang, Zhongzhen; Wang, Fang

2017-11-01

Increasing evidence indicates that a dual trigger (a gonadotrophin-releasing hormone agonist [GnRH-a] with a human chorionic gonadotrophin [hCG] trigger) is the best choice for final oocyte maturation in the GnRH antagonist (GnRH-ant) cycle. However, this conclusion remains controversial. Therefore, we performed this meta-analysis to systematically evaluate the efficacy of a GnRH-a combined with a standard hCG trigger in comparison with hCG alone for final oocyte maturation in the GnRH-ant cycle for in vitro fertilization. Complete electronic databases, including PubMed, Embase, The Cochrane Library, and Web of Science, were searched for relevant randomized controlled trials (RCT). The search was not restricted by language or publication time. Two reviewers selected trials and assessed trial quality independently by using the Cochrane Handbook 5.1.0. Four eligible RCT studies involving 527 women were included. The results of this meta-analysis indicated that the dual trigger group had a significantly higher pregnancy rate (relative risk [RR], 1.55; 95% confidence interval [CI], 1.17-2.06) than the hCG-only trigger group. No significant differences were found in the number of oocytes retrieved (weighted mean difference [WMD], 0.47; 95% CI, -0.42 to 1.37), number of mature oocytes retrieved (WMD, 0.41; 95% CI, -0.48 to 1.30), number of fertilized oocytes (WMD, 0.47; 95% CI, -0.32 to 1.26), number of good-quality embryos (WMD, 0.17; 95% CI, -0.29 to 0.64), or implantation rate (RR, 1.17; 95% CI, 0.69-2.00) between the two groups. GnRH-a and hCG as dual trigger was equivalent to hCG in triggering oocyte maturation and may be beneficial in improving reproductive outcomes. Further intensive randomized-controlled studies should be conducted to investigate the efficacy of the dual trigger. Copyright © 2017 Elsevier B.V. All rights reserved.

Dual-Enrollment High-School Graduates' College-Enrollment Considerations

ERIC Educational Resources Information Center

Damrow, Roberta J.

2017-01-01

This quantitative study examined college enrollment considerations of dual-enrollment students enrolling at one Wisconsin credit-granting technical college. A combined college-choice theoretical framework guided this quantitative study that addressed two research questions: To what extent, if any, did the number of dual credits predict likelihood…

Needs and Challenges of Seniors with Combined Hearing and Vision Loss

ERIC Educational Resources Information Center

McDonnall, Michele C.; Crudden, Adele; LeJeune, B. J.; Steverson, Anne; O'Donnell, Nancy

2016-01-01

Introduction: The purpose of this study was to identify the needs and challenges of seniors with dual sensory loss (combined hearing and vision loss) and to determine priorities for training family members, community service providers, and professionals who work with them. Methods: Individuals (N = 131) with dual sensory loss between the ages of…

Effects of Practice on Task Architecture: Combined Evidence from Interference Experiments and Random-Walk Models of Decision Making

ERIC Educational Resources Information Center

Kamienkowski, Juan E.; Pashler, Harold; Dehaene, Stanislas; Sigman, Mariano

2011-01-01

Does extensive practice reduce or eliminate central interference in dual-task processing? We explored the reorganization of task architecture with practice by combining interference analysis (delays in dual-task experiment) and random-walk models of decision making (measuring the decision and non-decision contributions to RT). The main delay…

Selecting and Assessing the Family-Friendly Community: Adaptive Strategies of Middle-Class, Dual-Earner Couples

ERIC Educational Resources Information Center

Sweet, Stephen; Swisher, Raymond; Moen, Phyllis

2005-01-01

Using a life course perspective, this study analyzes the adaptive strategy of community selection utilized by middle-class dual-earner couples, as well as the perceived family friendliness of their communities. Although many common concerns exist (most paramount being safety, jobs, and housing quality), parents are more apt than nonparents to…

'Dual hit' metabolic modulator LDCA selectively kills cancer cells by efficient competitive inhibition of LDH-A.

PubMed

Ghosh, Monisankar; Saha, Suchandrima; Dutta, Samir Kumar

2016-02-07

Herein, we synthesize and elucidate the potential of a novel 'dual hit' molecule, LDCA, to constitutively block lactate dehydrogenase isoform-A (LDH-A) to selectively subvert apoptosis and rigorously attenuate breast tumor progression in a mouse model, comprehensively delineating the therapeutic prospectus of LDCA in the field of cancer metabolics.

Simultaneous dual-task performance reveals parallel response selection after practice

NASA Technical Reports Server (NTRS)

Hazeltine, Eliot; Teague, Donald; Ivry, Richard B.

2002-01-01

E. H. Schumacher, T. L. Seymour, J. M. Glass, D. E. Kieras, and D. E. Meyer (2001) reported that dual-task costs are minimal when participants are practiced and give the 2 tasks equal emphasis. The present research examined whether such findings are compatible with the operation of an efficient response selection bottleneck. Participants trained until they were able to perform both tasks simultaneously without interference. Novel stimulus pairs produced no reaction time costs, arguing against the development of compound stimulus-response associations (Experiment 1). Manipulating the relative onsets (Experiments 2 and 4) and durations (Experiments 3 and 4) of response selection processes did not lead to dual-task costs. The results indicate that the 2 tasks did not share a bottleneck after practice.

Dual genetic selection of synthetic riboswitches in Escherichia coli.

PubMed

Nomura, Yoko; Yokobayashi, Yohei

2014-01-01

This chapter describes a genetic selection strategy to engineer synthetic riboswitches that can chemically regulate gene expression in Escherichia coli. Riboswitch libraries are constructed by randomizing the nucleotides that potentially comprise an expression platform and fused to the hybrid selection/screening marker tetA-gfpuv. Iterative ON and OFF selections are performed under appropriate conditions that favor the survival or the growth of the cells harboring the desired riboswitches. After the selection, rapid screening of individual riboswitch clones is performed by measuring GFPuv fluorescence without subcloning. This optimized dual genetic selection strategy can be used to rapidly develop synthetic riboswitches without detailed computational design or structural knowledge.

Decreases in Cocaine Self-Administration with Dual Inhibition of the Dopamine Transporter and σ Receptors

PubMed Central

Hiranita, Takato; Soto, Paul L.; Kohut, Stephen J.; Kopajtic, Theresa; Cao, Jianjing; Newman, Amy H.; Tanda, Gianluigi

2011-01-01

Sigma receptor (σR) antagonists attenuate many behavioral effects of cocaine but typically not its reinforcing effects in self-administration procedures. However, the σR antagonist rimcazole and its N-propylphenyl analogs, [3-(cis-3,5-dimethyl-4-[3-phenylpropyl]-1-piperazinyl)-propyl]diphenylamine hydrochloride (SH 3-24) and 9-[3-(cis-3,5-dimethyl-4-[3-phenylpropyl]-1-piperazinyl)-propyl]carbazole hydrobromide (SH 3-28), dose-dependently decreased the maximal rates of cocaine self-administration without affecting comparable responding maintained by food reinforcement. In contrast, a variety of σR antagonists [N-phenethylpiperidine oxalate (AC927), N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine dihydrobromide (BD 1008), N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino) ethylamine dihydrobromide (BD 1047), N-[2-(3,4-dichlorophenyl) ethyl]-4-methylpiperazine dihydrochloride (BD 1063), and N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine monohydrochloride (NE-100)] had no effect on cocaine self-administration across the range of doses that decreased rates of food-maintained responding. Rimcazole analogs differed from selective σR antagonists in their dual affinities for σRs and the dopamine transporter (DAT) assessed with radioligand binding. Selective DAT inhibitors and σR antagonists were studied alone and in combination on cocaine self-administration to determine whether actions at both σRs and the DAT were sufficient to reproduce the effects of rimcazole analogs. Typical DAT inhibitors [2β-carbomethoxy-3β-(4-fluorophenyl)tropane (WIN 35,428), methylphenidate, and nomifensine] dose-dependently shifted the cocaine dose-effect curve leftward. Combinations of DAT inhibitor and σR antagonist doses that were behaviorally inactive alone decreased cocaine self-administration without effects on food-maintained responding. In addition, whereas the DAT inhibitors were self-administered at rates similar to those of cocaine, neither rimcazole analogs nor typical σR antagonists (NE-100 and AC927) maintained responding above control levels across a wide range of doses. These findings suggest that the unique effects of rimcazole analogs are due to dual actions at the DAT and σRs and that a combined target approach may have utility in development of medical treatments for cocaine abuse. PMID:21859929

Diversity Order Analysis of Dual-Hop Relaying with Partial Relay Selection

NASA Astrophysics Data System (ADS)

Bao, Vo Nguyen Quoc; Kong, Hyung Yun

In this paper, we study the performance of dual hop relaying in which the best relay selected by partial relay selection will help the source-destination link to overcome the channel impairment. Specifically, closed-form expressions for outage probability, symbol error probability and achievable diversity gain are derived using the statistical characteristic of the signal-to-noise ratio. Numerical investigation shows that the system achieves diversity of two regardless of relay number and also confirms the correctness of the analytical results. Furthermore, the performance loss due to partial relay selection is investigated.

Perceived Factors Influencing High School Student Participation in an Integrated Statewide Dual Credit Program: An Examination of Program Success and Student Higher Education Selection Decisions

ERIC Educational Resources Information Center

Touchstone, Allison J. L.

2010-01-01

Dual credit programs have become increasingly popular with 71% U.S. public high schools offering dual credit courses in 2002-2003. As this popularity has grown, so have concerns regarding academic rigor, course quality, parity with college courses, and effects on higher education. Determining actual dual credit course equivalent in higher…

Application of quality by design concept to develop a dual gradient elution stability-indicating method for cloxacillin forced degradation studies using combined mixture-process variable models.

PubMed

Zhang, Xia; Hu, Changqin

2017-09-08

Penicillins are typical of complex ionic samples which likely contain large number of degradation-related impurities (DRIs) with different polarities and charge properties. It is often a challenge to develop selective and robust high performance liquid chromatography (HPLC) methods for the efficient separation of all DRIs. In this study, an analytical quality by design (AQbD) approach was proposed for stability-indicating method development of cloxacillin. The structures, retention and UV characteristics rules of penicillins and their impurities were summarized and served as useful prior knowledge. Through quality risk assessment and screen design, 3 critical process parameters (CPPs) were defined, including 2 mixture variables (MVs) and 1 process variable (PV). A combined mixture-process variable (MPV) design was conducted to evaluate the 3 CPPs simultaneously and a response surface methodology (RSM) was used to achieve the optimal experiment parameters. A dual gradient elution was performed to change buffer pH, mobile-phase type and strength simultaneously. The design spaces (DSs) was evaluated using Monte Carlo simulation to give their possibility of meeting the specifications of CQAs. A Plackett-Burman design was performed to test the robustness around the working points and to decide the normal operating ranges (NORs). Finally, validation was performed following International Conference on Harmonisation (ICH) guidelines. To our knowledge, this is the first study of using MPV design and dual gradient elution to develop HPLC methods and improve separations for complex ionic samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Synthesis and biological evaluation of N-difluoromethyl-1,2-dihydropyrid-2-one acetic acid regioisomers: dual inhibitors of cyclooxygenases and 5-lipoxygenase.

PubMed

Yu, Gang; Praveen Rao, P N; Chowdhury, Morshed A; Abdellatif, Khaled R A; Dong, Ying; Das, Dipankar; Velázquez, Carlos A; Suresh, Mavanur R; Knaus, Edward E

2010-04-01

A new group of acetic acid (7a-c, R(1) = H), and propionic acid (7d-f, R(1) = Me), regioisomers wherein a N-difluoromethyl-1,2-dihydropyrid-2-one moiety is attached via its C-3, C-4, and C-5 position was synthesized. This group of compounds exhibited a more potent inhibition, and hence selectivity, for the cyclooxygenase-2 (COX-2) relative to the COX-1 isozyme. Attachment of the N-difluoromethyl-1,2-dihydropyrid-2-one ring system to an acetic acid, or propionic acid, moiety confers potent 5-LOX inhibitory activity, that is, absent in traditional arylacetic acid NSAIDs. 2-(1-Difluoromethyl-2-oxo-1,2-dihydropyridin-5-yl)acetic acid (7c) exhibited the best combination of dual COX-2 and 5-LOX inhibitory activities. Molecular modeling (docking) studies showed that the highly electronegative CHF(2) substituent present in 7c, that showed a modest selectivity for the COX-2 isozyme, is oriented within the secondary pocket (Val523) present in COX-2 similar to the sulfonamide (SO(2)NH(2)) COX-2 pharmacophore present in celecoxib, and that the N-difluoromethyl-1,2-dihydropyrid-2-one pharmacophore is oriented close to the region containing the LOX enzyme catalytic iron (His361, His366, and His545). Accordingly, the N-difluoromethyl-1,2-dihyrdopyrid-2-one moiety possesses properties suitable for the design of dual COX-2/5-LOX inhibitory drugs. 2010 Elsevier Ltd. All rights reserved.

Insight into structural requirements for selective and/or dual CXCR3 and CXCR4 allosteric modulators.

PubMed

Kolarič, Anja; Švajger, Urban; Tomašič, Tihomir; Brox, Regine; Frank, Theresa; Minovski, Nikola; Tschammer, Nuska; Anderluh, Marko

2018-05-11

Based on the previously published pyrazolopyridine-based hit compound for which negative allosteric modulation of both CXCR3 and CXCR4 receptors was disclosed, we designed, synthesized and biologically evaluated a set of novel, not only negative, but also positive allosteric modulators with preserved pyrazolopyridine core. Compound 9e is a dual negative modulator, inhibiting G protein activity of both receptors. For CXCR4 receptor para-substituted aromatic group of compounds distinguishes between negative and positive modulation. Para-methoxy substitution leads to functional antagonism, while para-chloro triggers agonism. Additionally, we discovered that chemotaxis is not completely correlated with G protein pathways. This is the first work in which we have on a series of compounds successfully demonstrated that it is possible to produce selective as well as dual-acting modulators of chemokine receptors, which is very promising for future research in the field of discovery of selective or dual modulators of chemokine receptors. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Poorer divided attention in children born very preterm can be explained by difficulty with each component task, not the executive requirement to dual-task.

PubMed

Delane, Louise; Campbell, Catherine; Bayliss, Donna M; Reid, Corinne; Stephens, Amelia; French, Noel; Anderson, Mike

2017-07-01

Children born very preterm (VP, ≤ 32 weeks) exhibit poor performance on tasks of executive functioning. However, it is largely unknown whether this reflects the cumulative impact of non-executive deficits or a separable impairment in executive-level abilities. A dual-task paradigm was used in the current study to differentiate the executive processes involved in performing two simple attention tasks simultaneously. The executive-level contribution to performance was indexed by the within-subject cost incurred to single-task performance under dual-task conditions, termed dual-task cost. The participants included 77 VP children (mean age: 7.17 years) and 74 peer controls (mean age: 7.16 years) who completed Sky Search (selective attention), Score (sustained attention) and Sky Search DT (divided attention) from the Test of Everyday Attention for Children. The divided-attention task requires the simultaneous performance of the selective- and sustained-attention tasks. The VP group exhibited poorer performance on the selective- and divided-attention tasks, and showed a strong trend toward poorer performance on the sustained-attention task. However, there were no significant group differences in dual-task cost. These results suggest a cumulative impact of vulnerable lower-level cognitive processes on dual-tasking or divided attention in VP children, and fail to support the hypothesis that VP children show a separable impairment in executive-level abilities.

Black start research of the wind and storage system based on the dual master-slave control

NASA Astrophysics Data System (ADS)

Leng, Xue; Shen, Li; Hu, Tian; Liu, Li

2018-02-01

Black start is the key to solving the problem of large-scale power failure, while the introduction of new renewable clean energy as a black start power supply was a new hotspot. Based on the dual master-slave control strategy, the wind and storage system was taken as the black start reliable power, energy storage and wind combined to ensure the stability of the micorgrid systems, to realize the black start. In order to obtain the capacity ratio of the storage in the small system based on the dual master-slave control strategy, and the black start constraint condition of the wind and storage combined system, obtain the key points of black start of wind storage combined system, but also provide reference and guidance for the subsequent large-scale wind and storage combined system in black start projects.

Use of CRISPR/Cas9-engineered INS-1 pancreatic β cells to define the pharmacology of dual GIPR/GLP-1R agonists.

PubMed

Naylor, Jacqueline; Suckow, Arthur T; Seth, Asha; Baker, David J; Sermadiras, Isabelle; Ravn, Peter; Howes, Rob; Li, Jianliang; Snaith, Mike R; Coghlan, Matthew P; Hornigold, David C

2016-09-15

Dual-agonist molecules combining glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) activity represent an exciting therapeutic strategy for diabetes treatment. Although challenging due to shared downstream signalling pathways, determining the relative activity of dual agonists at each receptor is essential when developing potential novel therapeutics. The challenge is exacerbated in physiologically relevant cell systems expressing both receptors. To this end, either GIP receptors (GIPR) or GLP-1 receptors (GLP-1R) were ablated via RNA-guided clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 endonucleases in the INS-1 pancreatic β-cell line. Multiple clonal cell lines harbouring gene disruptions for each receptor were isolated and assayed for receptor activity to identify functional knockouts (KOs). cAMP production in response to GIPR or GLP-1R activation was abolished and GIP- or GLP-1-induced potentiation of glucose-stimulated insulin secretion (GSIS) was attenuated in the cognate KO cell lines. The contributions of individual receptors derived from cAMP and GSIS assays were confirmed in vivo using GLP-1R KO mice in combination with a monoclonal antibody antagonist of GIPR. We have successfully applied CRISPR/Cas9-engineered cell lines to determining selectivity and relative potency contributions of dual-agonist molecules targeting receptors with overlapping native expression profiles and downstream signalling pathways. Specifically, we have characterised molecules as biased towards GIPR or GLP-1R, or with relatively balanced potency in a physiologically relevant β-cell system. This demonstrates the broad utility of CRISPR/Cas9 when applied to native expression systems for the development of drugs that target multiple receptors, particularly where the balance of receptor activity is critical. © 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

What Makes Dual-Career Marriages Tick?

ERIC Educational Resources Information Center

Gilbert, Lucia Albino

A dual-career family is a family in which both spouses are committed to occupational work and to a family life together and support each other's desires to combine roles that traditionally were viewed as incompatible. Male socialization in the areas of entitlement, dependency, and nurturance can cause problems for men in dual-career marriages. In…

Aptamer-conjugated nanoparticles for cancer cell detection.

PubMed

Medley, Colin D; Bamrungsap, Suwussa; Tan, Weihong; Smith, Joshua E

2011-02-01

Aptamer-conjugated nanoparticles (ACNPs) have been used for a variety of applications, particularly dual nanoparticles for magnetic extraction and fluorescent labeling. In this type of assay, silica-coated magnetic and fluorophore-doped silica nanoparticles are conjugated to highly selective aptamers to detect and extract targeted cells in a variety of matrixes. However, considerable improvements are required in order to increase the selectivity and sensitivity of this two-particle assay to be useful in a clinical setting. To accomplish this, several parameters were investigated, including nanoparticle size, conjugation chemistry, use of multiple aptamer sequences on the nanoparticles, and use of multiple nanoparticles with different aptamer sequences. After identifying the best-performing elements, the improvements made to this assay's conditional parameters were combined to illustrate the overall enhanced sensitivity and selectivity of the two-particle assay using an innovative multiple aptamer approach, signifying a critical feature in the advancement of this technique.

Selective interference with image retention and generation: evidence for the workspace model.

PubMed

van der Meulen, Marian; Logie, Robert H; Della Sala, Sergio

2009-08-01

We address three types of model of the relationship between working memory (WM) and long-term memory (LTM): (a) the gateway model, in which WM acts as a gateway between perceptual input and LTM; (b) the unitary model, in which WM is seen as the currently activated areas of LTM; and (c) the workspace model, in which perceptual input activates LTM, and WM acts as a separate workspace for processing and temporary retention of these activated traces. Predictions of these models were tested, focusing on visuospatial working memory and using dual-task methodology to combine two main tasks (visual short-term retention and image generation) with two interference tasks (irrelevant pictures and spatial tapping). The pictures selectively disrupted performance on the generation task, whereas the tapping selectively interfered with the retention task. Results are consistent with the predictions of the workspace model.

Highly efficient SO2 capture by dual functionalized ionic liquids through a combination of chemical and physical absorption.

PubMed

Cui, Guokai; Wang, Congmin; Zheng, Junjie; Guo, Yan; Luo, Xiaoyan; Li, Haoran

2012-03-07

Two kinds of dual functionalized ionic liquids with ether-functionalized cations and tetrazolate anions were designed, prepared, and used for SO(2) capture, which exhibit an extremely high SO(2) capacity and excellent reversibility through a combination of chemical and physical absorption. This journal is © The Royal Society of Chemistry 2012

Masking agent-free and channel-switch-mode simultaneous sensing of Fe(3+) and Hg(2+) using dual-excitation graphene quantum dots.

PubMed

Xu, Fengzhou; Shi, Hui; He, Xiaoxiao; Wang, Kemin; He, Dinggeng; Yan, Lv'an; Ye, Xiaosheng; Tang, Jinlu; Shangguan, Jingfang; Luo, Lan

2015-06-21

A novel channel-switch-mode strategy for simultaneous sensing of Fe(3+) and Hg(2+) is developed with dual-excitation single-emission graphene quantum dots (GQDs). By utilizing the dual-channel fluorescence response performance of GQDs, this strategy achieved a facile, low-cost, masking agent-free, quantitative and selective dual-ion assay even in mixed ion samples and practical water samples.

Combined MEK and PI3K inhibition in a mouse model of pancreatic cancer.

PubMed

Alagesan, Brinda; Contino, Gianmarco; Guimaraes, Alex R; Corcoran, Ryan B; Deshpande, Vikram; Wojtkiewicz, Gregory R; Hezel, Aram F; Wong, Kwok-Kin; Loda, Massimo; Weissleder, Ralph; Benes, Cyril H; Engelman, Jeffrey; Bardeesy, Nabeel

2015-01-15

Improved therapeutic approaches are needed for the treatment of pancreatic ductal adenocarcinoma (PDAC). As dual MEK and PI3K inhibition is presently being used in clinical trials for patients with PDAC, we sought to test the efficacy of combined targeting of these pathways in PDAC using both in vitro drug screens and genetically engineered mouse models (GEMM). We performed high-throughput screening of >500 human cancer cell lines (including 46 PDAC lines), for sensitivity to 50 clinically relevant compounds, including MEK and PI3K inhibitors. We tested the top hit in the screen, the MEK1/2 inhibitor, AZD6244, for efficacy alone or in combination with the PI3K inhibitors, BKM120 or GDC-0941, in a Kras(G12D)-driven GEMM that recapitulates the histopathogenesis of human PDAC. In vitro screens revealed that PDAC cell lines are relatively resistant to single-agent therapies. The response profile to the MEK1/2 inhibitor, AZD6244, was an outlier, showing the highest selective efficacy in PDAC. Although MEK inhibition alone was mainly cytostatic, apoptosis was induced when combined with PI3K inhibitors (BKM120 or GDC-0941). When tested in a PDAC GEMM and compared with the single agents or vehicle controls, the combination delayed tumor formation in the setting of prevention and extended survival when used to treat advanced tumors, although no durable responses were observed. Our studies point to important contributions of MEK and PI3K signaling to PDAC pathogenesis and suggest that dual targeting of these pathways may provide benefit in some patients with PDAC. Clin Cancer Res; 21(2); 396-404. ©2014 AACR. ©2014 American Association for Cancer Research.

Combined MEK and PI3K inhibition in a mouse model of pancreatic cancer

PubMed Central

Guimaraes, Alex R.; Corcoran, Ryan B.; Deshpande, Vikram; Wojtkiewicz, Gregory R.; Hezel, Aram F.; Wong, Kwok-Kin; Loda, Massimo; Weissleder, Ralph; Benes, Cyril H.; Engelman, Jeffrey; Bardeesy, Nabeel

2015-01-01

Purpose Improved therapeutic approaches are needed for the treatment of pancreatic ductal adenocarcinoma (PDAC). As dual MEK and PI3K inhibition is presently being employed in clinical trials for PDAC patients, we sought to test the efficacy of combined targeting of these pathways in PDAC using both in vitro drug screens and genetically engineered mouse models (GEMMs). Experimental Design We performed high-throughput screening of >500 human cancer cell lines (including 46 PDAC lines), for sensitivity to 50 clinically-relevant compounds, including MEK and PI3K inhibitors. We tested the top hit in the screen, the MEK1/2 inhibitor, AZD-6244, for efficacy alone or in combination with the PI3K inhibitors, BKM-120 or GDC-0941, in a KRASG12D-driven GEMM that recapitulates the histopathogenesis of human PDAC. Results In vitro screens revealed that PDAC cell lines are relatively resistant to single-agent therapies. The response profile to the MEK1/2 inhibitor, AZD-6244, was an outlier, showing the highest selective efficacy in PDAC. While MEK inhibition alone was mainly cytostatic, apoptosis was induced when combined with PI3K inhibitors (BKM-120 or GDC-0941). When tested in a PDAC GEMM and compared to the single agents or vehicle controls, the combination delayed tumor formation in the setting of prevention and extended survival when used to treat advanced tumors, although no durable responses were observed. Conclusions Our studies point to important contributions of MEK and PI3K signaling to PDAC pathogenesis and suggest that dual targeting of these pathways may provide benefit in some PDAC patients. PMID:25348516

Sensor feature fusion for detecting buried objects

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

Clark, G.A.; Sengupta, S.K.; Sherwood, R.J.

1993-04-01

Given multiple registered images of the earth`s surface from dual-band sensors, our system fuses information from the sensors to reduce the effects of clutter and improve the ability to detect buried or surface target sites. The sensor suite currently includes two sensors (5 micron and 10 micron wavelengths) and one ground penetrating radar (GPR) of the wide-band pulsed synthetic aperture type. We use a supervised teaming pattern recognition approach to detect metal and plastic land mines buried in soil. The overall process consists of four main parts: Preprocessing, feature extraction, feature selection, and classification. These parts are used in amore » two step process to classify a subimage. Thee first step, referred to as feature selection, determines the features of sub-images which result in the greatest separability among the classes. The second step, image labeling, uses the selected features and the decisions from a pattern classifier to label the regions in the image which are likely to correspond to buried mines. We extract features from the images, and use feature selection algorithms to select only the most important features according to their contribution to correct detections. This allows us to save computational complexity and determine which of the sensors add value to the detection system. The most important features from the various sensors are fused using supervised teaming pattern classifiers (including neural networks). We present results of experiments to detect buried land mines from real data, and evaluate the usefulness of fusing feature information from multiple sensor types, including dual-band infrared and ground penetrating radar. The novelty of the work lies mostly in the combination of the algorithms and their application to the very important and currently unsolved operational problem of detecting buried land mines from an airborne standoff platform.« less

Selection of drug-resistant HIV-1 during the early phase of viral decay is uncommon in treatment-naïve patients initiated on a three- or four-drug antiretroviral regimen including lamivudine.

PubMed

Bergroth, Tobias; Ekici, Halime; Gisslén, Magnus; Loes, Sabine Kinloch-de; Goh, Li-Ean; Freedman, Andrew; Lampe, Fiona; Johnson, Margaret A; Sönnerborg, Anders

2009-01-01

Therapy failure due to drug resistance development is a common phenomenon in HIV-infected patients. However, when the drug pressure leads to the earliest selection of drug-resistant HIV-1 populations is still unclear. In this study, the extent to which selection of the HIV-1 reverse transcriptase M184I/V mutations occur during the initial phase of viral decay in treatment-naïve HIV-1 infected patients receiving antiretroviral therapy (ART) was examined. Plasma virus from three cohorts of treatment-naïve patients initiating quadruple (n = 43), triple (n = 14) or dual (n = 15) lamivudine-containing ART were analyzed for M184I/V during the first 6 months of therapy using direct sequencing and a sensitive selective real-time PCR method. Among quadruple ART patients, who all were treated at primary HIV-1 infection, only one patient developed M184V after 6 weeks of therapy, having had wild-type virus at baseline. No mutations were found in chronically infected patients on triple ART. In patients on dual therapy, M184I/V mutants were found frequently. Selection of M184I/V mutants was found to be rare during the initial phase of viral decay after initiation of ART in adherent patients given a three or four-drug combination, in contrast to those receiving a less potent regimen. The results suggest that triple and quadruple lamivudine + PI or PI/r containing ART given to treatment-naïve adherent patients is potent enough to prevent development of resistance during the first months of therapy.

Discovery of a series of dihydroquinoxalin-2(1H)-ones as selective BET inhibitors from a dual PLK1-BRD4 inhibitor.

PubMed

Hu, Jianping; Wang, Yingqing; Li, Yanlian; Xu, Lin; Cao, Danyan; Song, ShanShan; Damaneh, Mohammadali Soleimani; Wang, Xin; Meng, Tao; Chen, Yue-Lei; Shen, Jingkang; Miao, Zehong; Xiong, Bing

2017-09-08

Recent years have seen much effort to discover new chemotypes of BRD4 inhibitors. Interestingly, some kinase inhibitors have been demonstrated to be potent bromodomain inhibitors, especially the PLK1 inhibitor BI-2536 and the JAK2 inhibitor TG101209, which can bind to BRD4 with IC 50 values of 0.025 μM and 0.13 μM, respectively. Although the concept of dual inhibition is intriguing, selective BRD4 inhibitors are preferred as they may diminish off-target effects and provide more flexibility in anticancer drug combination therapy. Inspired by BI-2536, we designed and prepared a series of dihydroquinoxalin-2(1H)-one derivatives as selective bromodomain inhibitors. We found compound 54 had slightly higher activity than (+)-JQ1 in the fluorescence anisotropy assay and potent antiproliferative cellular activity in the MM.1S cell line. We have successfully solved the cocrystal structure of 52 in complex with BRD4-BD1, providing a solid structural basis for the binding mode of compounds of this series. Compound 54 exhibited high selectivity over most non-BET subfamily members and did not show bioactivity towards the PLK1 kinase at 10 or 1 μM. From in vivo studies, compound 54 demonstrated a good PK profile, and the results from in vivo pharmacological studies clearly showed the efficacy of 54 in the mouse MM.1S xenograft model. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

In vivo real-time rectal wall dosimetry for prostate radiotherapy

PubMed Central

Hardcastle, Nicholas; Cutajar, Dean L.; Metcalfe, Peter E.; Lerch, Michael L. F.; Perevertaylo, Vladimir L.; Tomé, Wolfgang A.; Rosenfeld, Anatoly B.

2010-01-01

Rectal balloons are used in external beam prostate radiotherapy to provide reproducible anatomy and rectal dose reductions. This is an investigation into the combination of a MOSFET radiation detector with a rectal balloon for real time in vivo rectal wall dosimetry. The MOSFET used in the study is a radiation detector that provides a water equivalent depth of measurement of 70μm. Two MOSFETs were combined in a face-to-face orientation. The reproducibility, sensitivity and angular dependence were measured for the dual MOSFET in a 6MV photon beam. The dual MOSFET was combined with a rectal balloon and irradiated with hypothetical prostate treatments in a phantom. The anterior rectal wall dose was measured in real time and compared with the planning system calculated dose. The dual MOSFET showed angular dependence within ± 2.5% in the azimuth and +2.5%/-4% in the polar axes. When compared with an ion chamber measurement in a phantom, the dual MOSFET agreed within 2.5% for a range of radiation path lengths and incident angles. The dual MOSFET had reproducible sensitivity for fraction sizes of 2-10Gy. For the hypothetical prostate treatments the measured anterior rectal wall dose was 2.6% and 3.2% lower than the calculated dose for 3DCRT and IMRT plans. This was expected due to limitations of the dose calculation method used at the balloon cavity interface. A dual MOSFET combined with a commercial rectal balloon was shown to provide reproducible measurements of the anterior rectal wall dose in real time. The measured anterior rectal wall dose agreed with the expected dose from the treatment plan for 3DCRT and IMRT plans. The dual MOSFET could be read out in real time during the irradiation, providing capability for real time dose monitoring of the rectal wall dose during treatment. PMID:20571209

Fringe Formation in Dual-Hologram Interferometry

NASA Technical Reports Server (NTRS)

Burner, A. W.

1989-01-01

A first order geometrical optics treatment of holograms combined with the generation of interference fringes by two point sources is used to describe reference fringe formation in non-diffuse dual-hologram interferometry.

A combinatorial feature selection approach to describe the QSAR of dual site inhibitors of acetylcholinesterase.

PubMed

Asadabadi, Ebrahim Barzegari; Abdolmaleki, Parviz; Barkooie, Seyyed Mohsen Hosseini; Jahandideh, Samad; Rezaei, Mohammad Ali

2009-12-01

Regarding the great potential of dual binding site inhibitors of acetylcholinesterase as the future potent drugs of Alzheimer's disease, this study was devoted to extraction of the most effective structural features of these inhibitors from among a large number of quantitative descriptors. To do this, we adopted a unique approach in quantitative structure-activity relationships. An efficient feature selection method was emphasized in such an approach, using the confirmative results of different routine and novel feature selection methods. The proposed methods generated quite consistent results ensuring the effectiveness of the selected structural features.

Targeted Fluoro Positioning for the Discovery of a Potent and Highly Selective Matrix Metalloproteinase Inhibitor.

PubMed

Fischer, Thomas; Riedl, Rainer

2017-04-01

Invited for this month's cover picture is the group of Professor Rainer Riedl from the Institute of Chemistry and Biotechnology at the Zurich University of Applied Sciences (ZHAW), Switzerland. The cover picture depicts the structure-based design of a drug-like small molecule inhibitor of matrix metalloproteinase-13 (MMP-13) with a combined dual binding motif. The targeted introduction of a single fluoro atom was of vital importance for the optimization of the inhibitor. For more details, read the full text of the Communication at 10.1002/open.201600158.

IDSA update from the city of brotherly love.

PubMed

Ghandi, R

2000-01-01

Data from a major new trial called START II (Selection of Thymidine Analog Therapy), was presented at this year's Infectious Diseases Society of America (IDSA) conference. One trial compared d4T/ddI/IDV combination therapy with AZT/3TC/IDV in treatment-naive individuals. A second trial, CNA 3003, compared triple NRTI therapy with AZT/3TC/abacavir to dual therapy with AZT/3TC; patients who added abacavir to the treatment showed decreased viral loads. Additional clinical trials using 3TC are detailed. Drug resistance, investigational agents, HIV diagnostic testing, and opportunistic infections are also discussed.

The value and throughput of rest Thallium-201/stress Technetium -99m sestamibi dual-isotope myocardial SPECT.

PubMed

Okudan, Berna; Smitherman, Thomas C

2004-06-01

Myocardial perfusion scintigraphy is an established method in cardiology for the diagnosis and evaluation of coronary artery disease (CAD). Thallium-201 and Tc-99m sestamibi myocardial perfusion imaging has been widely accepted as non-invasive diagnostic procedure for detection of CAD, risk stratification and myocardial viability assessment. But, standard Tl-201 redistribution and same day or 2-day rest/stress Tc-99m sestamibi protocols are time-consuming. Hence, the dual isotope rest thallium-201/stress technetium-99m sestamibi gated single-photon emission tomography protocol has gained increasing popularity for these applications. Combining the use of thallium-201 with technetium-99m agents permits optimal image resolution and simultaneous assessment of viability. Dual-isotope imaging may be separate or simultaneous acquisition set-up. The more rapid completion of these studies is appreciated as an advantage by patients, technologists, interpreting and referring physicians, nurses and hospital management. Simultaneous imaging has the potential advantages of precise pixel registration and artifacts, if present, are identical in both thallium and sestamibi, and require only one set of imaging. Also, there are some disadvantages of spillover of activity from the Tc-99m to the Tl-201 window. Fortunately, despite this problem it can be overcome. Separate acquisition dual isotope also has some disadvantages. Difference in defect resolution in attenuation and scatter between T-201 and Tc-99m sestamibi potentially results in interpretation problems. But, studies about cost-effectiveness of dual isotope imaging showed that some selective elimination of the rest studies may decrease the cost of the nuclear procedures and should be considered in the current care health system.

Selection of Streptomyces against soil borne fungal pathogens by a standardized dual culture assay and evaluation of their effects on seed germination and plant growth.

PubMed

Kunova, Andrea; Bonaldi, Maria; Saracchi, Marco; Pizzatti, Cristina; Chen, Xiaoyulong; Cortesi, Paolo

2016-11-09

In the search for new natural resources for crop protection, streptomycetes are gaining interest in agriculture as plant growth promoting bacteria and/or biological control agents. Because of their peculiar life cycle, in which the production of secondary metabolites is synchronized with the development of aerial hyphae and sporulation, the commonly used methods to screen for bacterial antagonists need to be adapted. The dual culture assay was standardized in terms of inoculation timing of Streptomyces antagonist and pathogen, and growth rate of different fungal pathogens. In case of fast-growing fungi, inoculation of the antagonist 2 or 3 days prior to the pathogen resulted in significantly stronger inhibition of mycelium growth. One hundred and thirty Streptomyces strains were evaluated against six destructive soil borne pathogens. The activity of strains varied from broad-spectrum to highly specific inhibition of individual pathogens. All strains inhibited at least one tested pathogen. Three strains, which combined the largest broad-spectrum with the highest inhibition activity, were selected for further characterization with four vegetable species. All of them were able to colonize seed surface of all tested vegetable crops. They mostly improved radicle and hypocotyl growth in vitro, although no statistically significant enhancement of biomass weight was observed in vivo. Occasionally, transient negative effects on germination and plant growth were observed. The adapted dual culture assay allowed us to compare the inhibition of individual Streptomyces strains against six fungal soil borne pathogens. The best selected strains were able to colonize the four vegetable crops and have a potential to be developed into biocontrol products. Although they occasionally negatively influenced plant growth, these effects did not persist during the further development. Additional in vivo studies are needed to confirm their potential as biological control or plant growth promoting agents.

A Dual System Model of Preferences under Risk

ERIC Educational Resources Information Center

Mukherjee, Kanchan

2010-01-01

This article presents a dual system model (DSM) of decision making under risk and uncertainty according to which the value of a gamble is a combination of the values assigned to it independently by the affective and deliberative systems. On the basis of research on dual process theories and empirical research in Hsee and Rottenstreich (2004) and…

Integrating the behavioral and neural dynamics of response selection in a dual-task paradigm: a dynamic neural field model of Dux et al. (2009).

PubMed

Buss, Aaron T; Wifall, Tim; Hazeltine, Eliot; Spencer, John P

2014-02-01

People are typically slower when executing two tasks than when only performing a single task. These dual-task costs are initially robust but are reduced with practice. Dux et al. (2009) explored the neural basis of dual-task costs and learning using fMRI. Inferior frontal junction (IFJ) showed a larger hemodynamic response on dual-task trials compared with single-task trial early in learning. As dual-task costs were eliminated, dual-task hemodynamics in IFJ reduced to single-task levels. Dux and colleagues concluded that the reduction of dual-task costs is accomplished through increased efficiency of information processing in IFJ. We present a dynamic field theory of response selection that addresses two questions regarding these results. First, what mechanism leads to the reduction of dual-task costs and associated changes in hemodynamics? We show that a simple Hebbian learning mechanism is able to capture the quantitative details of learning at both the behavioral and neural levels. Second, is efficiency isolated to cognitive control areas such as IFJ, or is it also evident in sensory motor areas? To investigate this, we restrict Hebbian learning to different parts of the neural model. None of the restricted learning models showed the same reductions in dual-task costs as the unrestricted learning model, suggesting that efficiency is distributed across cognitive control and sensory motor processing systems.

A next-generation dual-recombinase system for time and host specific targeting of pancreatic cancer

PubMed Central

Schachtler, Christina; Zukowska, Magdalena; Eser, Stefan; Feyerabend, Thorsten B.; Paul, Mariel C.; Eser, Philipp; Klein, Sabine; Lowy, Andrew M.; Banerjee, Ruby; Yang, Fangtang; Lee, Chang-Lung; Moding, Everett J.; Kirsch, David G.; Scheideler, Angelika; Alessi, Dario R.; Varela, Ignacio; Bradley, Allan; Kind, Alexander; Schnieke, Angelika E.; Rodewald, Hans-Reimer; Rad, Roland; Schmid, Roland M.; Schneider, Günter; Saur, Dieter

2014-01-01

Genetically engineered mouse models (GEMMs) have dramatically improved our understanding of tumor evolution and therapeutic resistance. However, sequential genetic manipulation of gene expression and targeting of the host is almost impossible using conventional Cre-loxP–based models. We have developed an inducible dual-recombinase system by combining flippase-FRT (Flp-FRT) and Cre-loxP recombination technologies to improve GEMMs of pancreatic cancer. This enables investigation of multistep carcinogenesis, genetic manipulation of tumor subpopulations (such as cancer stem cells), selective targeting of the tumor microenvironment and genetic validation of therapeutic targets in autochthonous tumors on a genome-wide scale. As a proof of concept, we performed tumor cell–autonomous and nonautonomous targeting, recapitulated hallmarks of human multistep carcinogenesis, validated genetic therapy by 3-phosphoinositide-dependent protein kinase inactivation as well as cancer cell depletion and show that mast cells in the tumor microenvironment, which had been thought to be key oncogenic players, are dispensable for tumor formation. PMID:25326799

A next-generation dual-recombinase system for time- and host-specific targeting of pancreatic cancer.

PubMed

Schönhuber, Nina; Seidler, Barbara; Schuck, Kathleen; Veltkamp, Christian; Schachtler, Christina; Zukowska, Magdalena; Eser, Stefan; Feyerabend, Thorsten B; Paul, Mariel C; Eser, Philipp; Klein, Sabine; Lowy, Andrew M; Banerjee, Ruby; Yang, Fangtang; Lee, Chang-Lung; Moding, Everett J; Kirsch, David G; Scheideler, Angelika; Alessi, Dario R; Varela, Ignacio; Bradley, Allan; Kind, Alexander; Schnieke, Angelika E; Rodewald, Hans-Reimer; Rad, Roland; Schmid, Roland M; Schneider, Günter; Saur, Dieter

2014-11-01

Genetically engineered mouse models (GEMMs) have dramatically improved our understanding of tumor evolution and therapeutic resistance. However, sequential genetic manipulation of gene expression and targeting of the host is almost impossible using conventional Cre-loxP-based models. We have developed an inducible dual-recombinase system by combining flippase-FRT (Flp-FRT) and Cre-loxP recombination technologies to improve GEMMs of pancreatic cancer. This enables investigation of multistep carcinogenesis, genetic manipulation of tumor subpopulations (such as cancer stem cells), selective targeting of the tumor microenvironment and genetic validation of therapeutic targets in autochthonous tumors on a genome-wide scale. As a proof of concept, we performed tumor cell-autonomous and nonautonomous targeting, recapitulated hallmarks of human multistep carcinogenesis, validated genetic therapy by 3-phosphoinositide-dependent protein kinase inactivation as well as cancer cell depletion and show that mast cells in the tumor microenvironment, which had been thought to be key oncogenic players, are dispensable for tumor formation.

Dual-channel current valve in a three terminal zigzag graphene nanoribbon junction

NASA Astrophysics Data System (ADS)

Zhang, L.

2017-02-01

We theoretically propose a dual-channel current valve based on a three terminal zigzag graphene nanoribbon (ZGNR) junction driven by three asymmetric time-dependent pumping potentials. By means of the Keldysh Green’s function method, we show that two asymmetric charge currents can be pumped in the different left-right terminals of the device at a zero bias, which mainly stems from the single photon-assisted pumping approximation and the valley valve effect in a ZGNR p-n junction. The ON and OFF states of pumped charge currents are crucially dependent on the even-odd chain widths of the three electrodes, the pumping frequency, the lattice potential and the Fermi level. Two-tunneling spin valves are also considered to spatially separate and detect 100% polarized spin currents owing to the combined spin pump effect and the valley selective transport in a three terminal ZGNR ferromagnetic junction. Our investigations might be helpful to control the spatial and spin degrees of freedom of electrons in graphene pumping devices.

Evaluating the potential of a novel dual heat-pulse sensor to measure volumetric water use in grapevines under a range of flow conditions

USDA-ARS?s Scientific Manuscript database

The aim of this study was to validate dual sap flow sensors that combine two heat pulse techniques to measure volumetric water use over the full range of sap flows found in grapevines. The heat ratio method (HRM), which works well at measuring low and reverse flows, was combined with the compensati...

Fluorescence and Magnetic Resonance Dual-Modality Imaging-Guided Photothermal and Photodynamic Dual-Therapy with Magnetic Porphyrin-Metal Organic Framework Nanocomposites

NASA Astrophysics Data System (ADS)

Zhang, Hui; Li, Yu-Hao; Chen, Yang; Wang, Man-Man; Wang, Xue-Sheng; Yin, Xue-Bo

2017-03-01

Phototherapy shows some unique advantages in clinical application, such as remote controllability, improved selectivity, and low bio-toxicity, than chemotherapy. In order to improve the safety and therapeutic efficacy, imaging-guided therapy seems particularly important because it integrates visible information to speculate the distribution and metabolism of the probe. Here we prepare biocompatible core-shell nanocomposites for dual-modality imaging-guided photothermal and photodynamic dual-therapy by the in situ growth of porphyrin-metal organic framework (PMOF) on Fe3O4@C core. Fe3O4@C core was used as T2-weighted magnetic resonance (MR) imaging and photothermal therapy (PTT) agent. The optical properties of porphyrin were well remained in PMOF, and PMOF was therefore selected for photodynamic therapy (PDT) and fluorescence imaging. Fluorescence and MR dual-modality imaging-guided PTT and PDT dual-therapy was confirmed with tumour-bearing mice as model. The high tumour accumulation of Fe3O4@C@PMOF and controllable light excitation at the tumour site achieved efficient cancer therapy, but low toxicity was observed to the normal tissues. The results demonstrated that Fe3O4@C@PMOF was a promising dual-imaging guided PTT and PDT dual-therapy platform for tumour diagnosis and treatment with low cytotoxicity and negligible in vivo toxicity.

Dual salt precipitation for the recovery of a recombinant protein from Escherichia coli.

PubMed

Balasundaram, Bangaru; Sachdeva, Soam; Bracewell, Daniel G

2011-01-01

When considering worldwide demand for biopharmaceuticals, it becomes necessary to consider alternative process strategies to improve the economics of manufacturing such molecules. To address this issue, the current study investigates precipitation to selectively isolate the product or remove contaminants and thus assist the initial purification of a intracellular protein. The hypothesis tested was that the combination of two or more precipitating agents will alter the solubility profile of the product through synergistic or antagonistic effects. This principle was investigated through several combinations of ammonium sulfate and sodium citrate at different ratios. A synergistic effect mediated by a known electrostatic interaction of citrate ions with Fab' in addition to the typical salting-out effects was observed. On the basis of the results of the solubility studies, a two step primary recovery route was investigated. In the first step termed conditioning, post-homogenization and before clarification, addition of 0.8 M ammonium sulfate extracted 30% additional product. Clarification performance measured using a scale-down disc stack centrifugation mimic determined a four-fold reduction in centrifuge size requirements. Dual salt precipitation in the second step resulted in >98% recovery of Fab' while removing 36% of the contaminant proteins simultaneously. Copyright © 2011 American Institute of Chemical Engineers (AIChE).

Rethinking of the heuristic-analytic dual process theory: a comment on Wada and Nittono (2004) and the reasoning process in the Wason selection task.

PubMed

Cardaci, Maurizio; Misuraca, Raffaella

2005-08-01

This paper raises some methodological problems in the dual process explanation provided by Wada and Nittono for their 2004 results using the Wason selection task. We maintain that the Nittono rethinking approach is weak and that it should be refined to grasp better the evidence of analytic processes.

Discovery of peptide drug carrier candidates for targeted multi-drug delivery into prostate cancer cells.

PubMed

Bashari, O; Redko, B; Cohen, A; Luboshits, G; Gellerman, G; Firer, M A

2017-11-01

Metastatic castration-resistant prostate cancer (mCRPC) remains essentially incurable. Targeted Drug Delivery (TDD) systems may overcome the limitations of current mCRPC therapies. We describe the use of strict criteria to isolate novel prostate cancer cell targeting peptides that specifically deliver drugs into target cells. Phage from a libraries displaying 7mer peptides were exposed to PC-3 cells and only internalized phage were recovered. The ability of these phage to internalize into other prostate cancer cells (LNCaP, DU-145) was validated. The displayed peptides of selected phage clones were synthesized and their specificity for target cells was validated in vitro and in vivo. One peptide (P12) which specifically targeted PC-3 tumors in vivo was incorporated into mono-drug (Chlorambucil, Combretastatin or Camptothecin) and dual-drug (Chlorambucil/Combretastatin or Chlorambucil/Camptothecin) PDCs and the cytotoxic efficacy of these conjugates for target cells was tested. Conjugation of P12 into dual-drug PDCs allowed discovery of new drug combinations with synergistic effects. The use of strict selection criteria can lead to discovery of novel peptides for use as drug carriers for TDD. PDCs represent an effective alternative to current modes of free drug chemotherapy for prostate cancer. Copyright © 2017. Published by Elsevier B.V.

De novo design and synthesis of ultra-short peptidomimetic antibiotics having dual antimicrobial and anti-inflammatory activities.

PubMed

Murugan, Ravichandran N; Jacob, Binu; Ahn, Mija; Hwang, Eunha; Sohn, Hoik; Park, Hyo-Nam; Lee, Eunjung; Seo, Ji-Hyung; Cheong, Chaejoon; Nam, Ky-Youb; Hyun, Jae-Kyung; Jeong, Ki-Woong; Kim, Yangmee; Shin, Song Yub; Bang, Jeong Kyu

2013-01-01

Much attention has been focused on the design and synthesis of potent, cationic antimicrobial peptides (AMPs) that possess both antimicrobial and anti-inflammatory activities. However, their development into therapeutic agents has been limited mainly due to their large size (12 to 50 residues in length) and poor protease stability. In an attempt to overcome the issues described above, a set of ultra-short, His-derived antimicrobial peptides (HDAMPs) has been developed for the first time. Through systematic tuning of pendant hydrophobic alkyl tails at the N(π)- and N(τ)-positions on His, and the positive charge of Arg, much higher prokaryotic selectivity was achieved, compared to human AMP LL-37. Additionally, the most potent HDAMPs showed promising dual antimicrobial and anti-inflammatory activities, as well as anti-methicillin-resistant Staphylococcus aureus (MRSA) activity and proteolytic resistance. Our results from transmission electron microscopy, membrane depolarization, confocal laser-scanning microscopy, and calcein-dye leakage experiments propose that HDAMP-1 kills microbial cells via dissipation of the membrane potential by forming pore/ion channels on bacterial cell membranes. The combination of the ultra-short size, high-prokaryotic selectivity, potent anti-MRSA activity, anti-inflammatory activity, and proteolytic resistance of the designed HDAMP-1, -3, -5, and -6 makes these molecules promising candidates for future antimicrobial therapeutics.

Beamspace dual signal space projection (bDSSP): a method for selective detection of deep sources in MEG measurements.

PubMed

Sekihara, Kensuke; Adachi, Yoshiaki; Kubota, Hiroshi K; Cai, Chang; Nagarajan, Srikantan S

2018-06-01

Magnetoencephalography (MEG) has a well-recognized weakness at detecting deeper brain activities. This paper proposes a novel algorithm for selective detection of deep sources by suppressing interference signals from superficial sources in MEG measurements. The proposed algorithm combines the beamspace preprocessing method with the dual signal space projection (DSSP) interference suppression method. A prerequisite of the proposed algorithm is prior knowledge of the location of the deep sources. The proposed algorithm first derives the basis vectors that span a local region just covering the locations of the deep sources. It then estimates the time-domain signal subspace of the superficial sources by using the projector composed of these basis vectors. Signals from the deep sources are extracted by projecting the row space of the data matrix onto the direction orthogonal to the signal subspace of the superficial sources. Compared with the previously proposed beamspace signal space separation (SSS) method, the proposed algorithm is capable of suppressing much stronger interference from superficial sources. This capability is demonstrated in our computer simulation as well as experiments using phantom data. The proposed bDSSP algorithm can be a powerful tool in studies of physiological functions of midbrain and deep brain structures.

Beamspace dual signal space projection (bDSSP): a method for selective detection of deep sources in MEG measurements

NASA Astrophysics Data System (ADS)

Sekihara, Kensuke; Adachi, Yoshiaki; Kubota, Hiroshi K.; Cai, Chang; Nagarajan, Srikantan S.

2018-06-01

Objective. Magnetoencephalography (MEG) has a well-recognized weakness at detecting deeper brain activities. This paper proposes a novel algorithm for selective detection of deep sources by suppressing interference signals from superficial sources in MEG measurements. Approach. The proposed algorithm combines the beamspace preprocessing method with the dual signal space projection (DSSP) interference suppression method. A prerequisite of the proposed algorithm is prior knowledge of the location of the deep sources. The proposed algorithm first derives the basis vectors that span a local region just covering the locations of the deep sources. It then estimates the time-domain signal subspace of the superficial sources by using the projector composed of these basis vectors. Signals from the deep sources are extracted by projecting the row space of the data matrix onto the direction orthogonal to the signal subspace of the superficial sources. Main results. Compared with the previously proposed beamspace signal space separation (SSS) method, the proposed algorithm is capable of suppressing much stronger interference from superficial sources. This capability is demonstrated in our computer simulation as well as experiments using phantom data. Significance. The proposed bDSSP algorithm can be a powerful tool in studies of physiological functions of midbrain and deep brain structures.

Radiogenetic therapy: strategies to overcome tumor resistance.

PubMed

Marples, B; Greco, O; Joiner, M C; Scott, S D

2003-01-01

The aim of cancer gene therapy is to selectively kill malignant cells at the tumor site, by exploiting traits specific to cancer cells and/or solid tumors. Strategies that take advantage of biological features common to different tumor types are particularly promising, since they have wide clinical applicability. Much attention has focused on genetic methods that complement radiotherapy, the principal treatment modality, or that exploit hypoxia, the most ubiquitous characteristic of most solid cancers. The goal of this review is to highlight two promising gene therapy methods developed specifically to target the tumor volume that can be readily used in combination with radiotherapy. The first approach uses radiation-responsive gene promoters to control the selective expression of a suicide gene (e.g., herpes simplex virus thymidine kinase) to irradiated tissue only, leading to targeted cell killing in the presence of a prodrug (e.g., ganciclovir). The second method utilizes oxygen-dependent promoters to produce selective therapeutic gene expression and prodrug activation in hypoxic cells, which are refractive to conventional radiotherapy. Further refining of tumor targeting can be achieved by combining radiation and hypoxia responsive elements in chimeric promoters activated by either and dual stimuli. The in vitro and in vivo studies described in this review suggest that the combination of gene therapy and radiotherapy protocols has potential for use in cancer care, particularly in cases currently refractory to treatment as a result of inherent or hypoxia-mediated radioresistance.

Including the effect of motion artifacts in noise and performance analysis of dual-energy contrast-enhanced mammography

NASA Astrophysics Data System (ADS)

Allec, N.; Abbaszadeh, S.; Scott, C. C.; Lewin, J. M.; Karim, K. S.

2012-12-01

In contrast-enhanced mammography (CEM), the dual-energy dual-exposure technique, which can leverage existing conventional mammography infrastructure, relies on acquiring the low- and high-energy images using two separate exposures. The finite time between image acquisition leads to motion artifacts in the combined image. Motion artifacts can lead to greater anatomical noise in the combined image due to increased mismatch of the background tissue in the images to be combined, however the impact has not yet been quantified. In this study we investigate a method to include motion artifacts in the dual-energy noise and performance analysis. The motion artifacts are included via an extended cascaded systems model. To validate the model, noise power spectra of a previous dual-energy clinical study are compared to that of the model. The ideal observer detectability is used to quantify the effect of motion artifacts on tumor detectability. It was found that the detectability can be significantly degraded when motion is present (e.g., detectability of 2.5 mm radius tumor decreased by approximately a factor of 2 for translation motion on the order of 1000 μm). The method presented may be used for a more comprehensive theoretical noise and performance analysis and fairer theoretical performance comparison between dual-exposure techniques, where motion artifacts are present, and single-exposure techniques, where low- and high-energy images are acquired simultaneously and motion artifacts are absent.

Including the effect of motion artifacts in noise and performance analysis of dual-energy contrast-enhanced mammography.

PubMed

Allec, N; Abbaszadeh, S; Scott, C C; Lewin, J M; Karim, K S

2012-12-21

In contrast-enhanced mammography (CEM), the dual-energy dual-exposure technique, which can leverage existing conventional mammography infrastructure, relies on acquiring the low- and high-energy images using two separate exposures. The finite time between image acquisition leads to motion artifacts in the combined image. Motion artifacts can lead to greater anatomical noise in the combined image due to increased mismatch of the background tissue in the images to be combined, however the impact has not yet been quantified. In this study we investigate a method to include motion artifacts in the dual-energy noise and performance analysis. The motion artifacts are included via an extended cascaded systems model. To validate the model, noise power spectra of a previous dual-energy clinical study are compared to that of the model. The ideal observer detectability is used to quantify the effect of motion artifacts on tumor detectability. It was found that the detectability can be significantly degraded when motion is present (e.g., detectability of 2.5 mm radius tumor decreased by approximately a factor of 2 for translation motion on the order of 1000 μm). The method presented may be used for a more comprehensive theoretical noise and performance analysis and fairer theoretical performance comparison between dual-exposure techniques, where motion artifacts are present, and single-exposure techniques, where low- and high-energy images are acquired simultaneously and motion artifacts are absent.

Dual Activity of Hydroxypropyl-β-Cyclodextrin and Water-Soluble Carriers on the Solubility of Carvedilol.

PubMed

Zoghbi, Abdelmoumin; Geng, Tianjiao; Wang, Bo

2017-11-01

Carvedilol (CAR) is a non-selective α and β blocker categorized as class II drug with low water solubility. Several recent studies have investigated ways to overcome this problem. The aim of the present study was to combine two of these methods: the inclusion complex using hydroxypropyl-β-cyclodextrin (HPβCD) with solid dispersion using two carriers: Poloxamer 188 (PLX) and Polyvinylpyrrolidone K-30 (PVP) to enhance the solubility, bioavailability, and the stability of CAR. Kneading method was used to prepare CAR-HPβCD inclusion complex (KD). The action of different carriers separately and in combination on Carvedilol solubility was investigated in three series. CAR-carrier and KD-carrier solid dispersions were prepared by solvent evaporation method. In vitro dissolution test was conducted in three different media: double-distilled water (DDW), simulative gastric fluid (SGF), and PBS pH 6.8 (PBS). The interactions between CAR, HPβCD, and different carriers were explored by Fourier transform infrared spectroscopy (FTIR), powder X-ray diffractometry (XRD), and differential scanning colorimetry (DSC). The results showed higher solubility of CAR in KD-PVP solid dispersions up to 70, 25, and 22 fold compared to pure CAR in DDW, SGF, and PBS, respectively. DSC and XRD analyses indicated an improved degree of transformation of CAR in KD-PVP solid dispersion from crystalline to amorphous state. This study provides a new successful combination of two polymers with the dual action of HPβCD and PLX/PVP on water solubility and bioavailability of CAR.

Aspects of image recognition in Vivid Technologies' dual-energy x-ray system for explosives detection

NASA Astrophysics Data System (ADS)

Eilbert, Richard F.; Krug, Kristoph D.

1993-04-01

The Vivid Rapid Explosives Detection Systems is a true dual energy x-ray machine employing precision x-ray data acquisition in combination with unique algorithms and massive computation capability. Data from the system's 960 detectors is digitally stored and processed by powerful supermicro-computers organized as an expandable array of parallel processors. The algorithms operate on the dual energy attenuation image data to recognize and define objects in the milieu of the baggage contents. Each object is then systematically examined for a match to a specific effective atomic number, density, and mass threshold. Material properties are determined by comparing the relative attenuations of the 75 kVp and 150 kVp beams and electronically separating the object from its local background. Other heuristic algorithms search for specific configurations and provide additional information. The machine automatically detects explosive materials and identifies bomb components in luggage with high specificity and throughput, X-ray dose is comparable to that of current airport x-ray machines. The machine is also configured to find heroin, cocaine, and US currency by selecting appropriate settings on-site. Since January 1992, production units have been operationally deployed at U.S. and European airports for improved screening of checked baggage.

Combinatorial support vector machines approach for virtual screening of selective multi-target serotonin reuptake inhibitors from large compound libraries.

PubMed

Shi, Z; Ma, X H; Qin, C; Jia, J; Jiang, Y Y; Tan, C Y; Chen, Y Z

2012-02-01

Selective multi-target serotonin reuptake inhibitors enhance antidepressant efficacy. Their discovery can be facilitated by multiple methods, including in silico ones. In this study, we developed and tested an in silico method, combinatorial support vector machines (COMBI-SVMs), for virtual screening (VS) multi-target serotonin reuptake inhibitors of seven target pairs (serotonin transporter paired with noradrenaline transporter, H(3) receptor, 5-HT(1A) receptor, 5-HT(1B) receptor, 5-HT(2C) receptor, melanocortin 4 receptor and neurokinin 1 receptor respectively) from large compound libraries. COMBI-SVMs trained with 917-1951 individual target inhibitors correctly identified 22-83.3% (majority >31.1%) of the 6-216 dual inhibitors collected from literature as independent testing sets. COMBI-SVMs showed moderate to good target selectivity in misclassifying as dual inhibitors 2.2-29.8% (majority <15.4%) of the individual target inhibitors of the same target pair and 0.58-7.1% of the other 6 targets outside the target pair. COMBI-SVMs showed low dual inhibitor false hit rates (0.006-0.056%, 0.042-0.21%, 0.2-4%) in screening 17 million PubChem compounds, 168,000 MDDR compounds, and 7-8181 MDDR compounds similar to the dual inhibitors. Compared with similarity searching, k-NN and PNN methods, COMBI-SVM produced comparable dual inhibitor yields, similar target selectivity, and lower false hit rate in screening 168,000 MDDR compounds. The annotated classes of many COMBI-SVMs identified MDDR virtual hits correlate with the reported effects of their predicted targets. COMBI-SVM is potentially useful for searching selective multi-target agents without explicit knowledge of these agents. Copyright © 2011 Elsevier Inc. All rights reserved.

A comparison of novel, selective fatty acid amide hydrolase (FAAH), monoacyglycerol lipase (MAGL) or dual FAAH/MAGL inhibitors to suppress acute and anticipatory nausea in rat models.

PubMed

Parker, Linda A; Limebeer, Cheryl L; Rock, Erin M; Sticht, Martin A; Ward, Jordan; Turvey, Greig; Benchama, Othman; Rajarshi, Girija; Wood, JodiAnne T; Alapafuja, Shakiru O; Makriyannis, Alexandros

2016-06-01

Drugs that block fatty acid amide hydrolase (FAAH, which elevates anandamide [AEA]) and drugs which block monoacylglycerol (MAGL, which elevates 2-arachidonyl glycerol [2-AG]) have promise in treating both acute and anticipatory nausea in human patients. This study aims to evaluate the relative effectiveness of dual MAGL/FAAH inhibition with either alone to reduce acute and anticipatory nausea in rat models. AM4302, a new dual MAGL/FAAH inhibitor, was compared with a new selective MAGL inhibitor, AM4301, and new selective FAAH inhibitor, AM4303, for their potential to reduce acute nausea (gaping in taste reactivity) and anticipatory nausea (contextually elicited conditioned gaping) in two rat models. Our in vitro studies indicate that AM4302 blocks human and rat FAAH: IC50 60 and 31 nM, respectively, with comparable potencies against human MAGL (IC50 41 nM) and rat MAGL (IC50 200 nM). AM4301 selectively blocks human and rat MAGL (IC50 8.9 and 36 nM, respectively), while AM4303 selectively inhibits human and rat FAAH (IC50 2 and 1.9 nM), respectively. Our in vivo studies show that the MAGL inhibitor, AM4301, suppressed acute nausea in a CB1-mediated manner, when delivered systemically or into the interoceptive insular cortex. Although the dual FAAH/MAGL inhibitor, AM4302, was equally effective as the FAAH inhibitor or MAGL inhibitor in reducing acute nausea, it was more effective than both in suppressing anticipatory nausea. Dual FAAH and MAGL inhibition with AM4302 may be an especially effective treatment for the very difficult to treat symptom of anticipatory nausea.

A comparison of novel, selective fatty acid amide hydrolase (FAAH), monoacyglycerol lipase (MAGL) or dual FAAH/MAGL inhibitors to suppress acute and anticipatory nausea in rat models

PubMed Central

Limebeer, Cheryl L.; Rock, Erin M.; Sticht, Martin A.; Ward, Jordan; Turvey, Greig; Benchama, Othman; Rajarshi, Girija; Wood, JodiAnne T.; Alapafuja, Shakiru O.; Makriyannis, Alexandros

2017-01-01

Rationale Drugs that block fatty acid amide hydrolase (FAAH, which elevates anandamide [AEA]) and drugs which block monoacylglycerol (MAGL, which elevates 2-arachidonyl glycerol [2-AG]) have promise in treating both acute and anticipatory nausea in human patients. Objective This study aims to evaluate the relative effectiveness of dual MAGL/FAAH inhibition with either alone to reduce acute and anticipatory nausea in rat models. Materials and methods AM4302, a new dual MAGL/FAAH inhibitor, was compared with a new selective MAGL inhibitor, AM4301, and new selective FAAH inhibitor, AM4303, for their potential to reduce acute nausea (gaping in taste reactivity) and anticipatory nausea (contextually elicited conditioned gaping) in two rat models. Results Our in vitro studies indicate that AM4302 blocks human and rat FAAH: IC50 60 and 31 nM, respectively, with comparable potencies against human MAGL (IC50 41 nM) and rat MAGL (IC50 200 nM). AM4301 selectively blocks human and rat MAGL (IC50 8.9 and 36 nM, respectively), while AM4303 selectively inhibits human and rat FAAH (IC50 2 and 1.9 nM), respectively. Our in vivo studies show that the MAGL inhibitor, AM4301, suppressed acute nausea in a CB1-mediated manner, when delivered systemically or into the interoceptive insular cortex. Although the dual FAAH/MAGL inhibitor, AM4302, was equally effective as the FAAH inhibitor or MAGL inhibitor in reducing acute nausea, it was more effective than both in suppressing anticipatory nausea. Conclusions Dual FAAH and MAGL inhibition with AM4302 may be an especially effective treatment for the very difficult to treat symptom of anticipatory nausea. PMID:27048155

2GETHER - The Dual Protection Project: Design and rationale of a randomized controlled trial to increase dual protection strategy selection and adherence among African American adolescent females

PubMed Central

Ewing, Alexander C.; Kottke, Melissa J.; Kraft, Joan Marie; Sales, Jessica M.; Brown, Jennifer L.; Goedken, Peggy; Wiener, Jeffrey; Kourtis, Athena P.

2018-01-01

Background African American adolescent females are at elevated risk for unintended pregnancy and sexually transmitted infections (STIs). Dual protection (DP) is defined as concurrent prevention of pregnancy and STIs. This can be achieved by abstinence, consistent condom use, or the dual methods of condoms plus an effective non-barrier contraceptive. Previous clinic-based interventions showed short-term effects on increasing dual method use, but evidence of sustained effects on dual method use and decreased incident pregnancies and STIs are lacking. Methods/Design This manuscript describes the 2GETHER Project. 2GETHER is a randomized controlled trial of a multi-component intervention to increase dual protection use among sexually active African American females aged 14–19 years not desiring pregnancy at a Title X clinic in Atlanta, GA. The intervention is clinic-based and includes a culturally tailored interactive multimedia component and counseling sessions, both to assist in selection of a DP method and to reinforce use of the DP method. The participants are randomized to the study intervention or the standard of care, and followed for 12 months to evaluate how the intervention influences DP method selection and adherence, pregnancy and STI incidence, and participants’ DP knowledge, intentions, and self-efficacy. Discussion The 2GETHER Project is a novel trial to reduce unintended pregnancies and STIs among African American adolescents. The intervention is unique in the comprehensive and complementary nature of its components and its individual tailoring of provider-patient interaction. If the trial interventions are shown to be effective, then it will be reasonable to assess their scalability and applicability in other populations. PMID:28007634

2GETHER - The Dual Protection Project: Design and rationale of a randomized controlled trial to increase dual protection strategy selection and adherence among African American adolescent females.

PubMed

Ewing, Alexander C; Kottke, Melissa J; Kraft, Joan Marie; Sales, Jessica M; Brown, Jennifer L; Goedken, Peggy; Wiener, Jeffrey; Kourtis, Athena P

2017-03-01

African American adolescent females are at elevated risk for unintended pregnancy and sexually transmitted infections (STIs). Dual protection (DP) is defined as concurrent prevention of pregnancy and STIs. This can be achieved by abstinence, consistent condom use, or the dual methods of condoms plus an effective non-barrier contraceptive. Previous clinic-based interventions showed short-term effects on increasing dual method use, but evidence of sustained effects on dual method use and decreased incident pregnancies and STIs are lacking. This manuscript describes the 2GETHER Project. 2GETHER is a randomized controlled trial of a multi-component intervention to increase dual protection use among sexually active African American females aged 14-19years not desiring pregnancy at a Title X clinic in Atlanta, GA. The intervention is clinic-based and includes a culturally tailored interactive multimedia component and counseling sessions, both to assist in selection of a DP method and to reinforce use of the DP method. The participants are randomized to the study intervention or the standard of care, and followed for 12months to evaluate how the intervention influences DP method selection and adherence, pregnancy and STI incidence, and participants' DP knowledge, intentions, and self-efficacy. The 2GETHER Project is a novel trial to reduce unintended pregnancies and STIs among African American adolescents. The intervention is unique in the comprehensive and complementary nature of its components and its individual tailoring of provider-patient interaction. If the trial interventions are shown to be effective, then it will be reasonable to assess their scalability and applicability in other populations. Published by Elsevier Inc.

Potentiating action of 5-fluorouracil when used in combination with platinium compounds and cyclophosphamide in treatment of advanced L1210 leukemia.

PubMed

Gale, G R; Atkins, L M; Schwartz, P; Meischen, S J

1978-01-01

Nine new organoplatinum (Pt) compounds, cyclophosphamide (CY), and 5-fluorouracil (FU) were used singly and in combination in treatment of advanced L1210 leukemia in C57BL/6 X DBA/2 hybrid mice. In each experiment the Pt + CY dual combination was minimally supra-additive at the doses chosen. However, eight of the nine Pt + CY + FU combination regimens enhanced markedly the increased life span of treated mice as compared with the corresponding dual Pt + CY combination. Collectively, the cure rate (greater than 60-day survival) was less than 6% with the various Pt + CY combinations, and was increased to over 63% upon inclusion of FU in the regimens.

Dual-wavelength phase-shifting digital holography selectively extracting wavelength information from wavelength-multiplexed holograms.

PubMed

Tahara, Tatsuki; Mori, Ryota; Kikunaga, Shuhei; Arai, Yasuhiko; Takaki, Yasuhiro

2015-06-15

Dual-wavelength phase-shifting digital holography that selectively extracts wavelength information from five wavelength-multiplexed holograms is presented. Specific phase shifts for respective wavelengths are introduced to remove the crosstalk components and extract only the object wave at the desired wavelength from the holograms. Object waves in multiple wavelengths are selectively extracted by utilizing 2π ambiguity and the subtraction procedures based on phase-shifting interferometry. Numerical results show the validity of the proposed technique. The proposed technique is also experimentally demonstrated.

Protocol for a randomized comparison of integrated versus consecutive dual task practice in Parkinson’s disease: the DUALITY trial

PubMed Central

2014-01-01

Background Multiple tasking is an integral part of daily mobility. Patients with Parkinson’s disease have dual tasking difficulties due to their combined motor and cognitive deficits. Two contrasting physiotherapy interventions have been proposed to alleviate dual tasking difficulties: either to discourage simultaneous execution of dual tasks (consecutive training); or to practice their concurrent use (integrated training). It is currently unclear which of these training methods should be adopted to achieve safe and consolidated dual task performance in daily life. Therefore, the proposed randomized controlled trial will compare the effects of integrated versus consecutive training of dual tasking (tested by combining walking with cognitive exercises). Methods and design Hundred and twenty patients with Parkinson’s disease will be recruited to participate in this multi-centered, single blind, randomized controlled trial. Patients in Hoehn & Yahr stage II-III, with or without freezing of gait, and who report dual task difficulties will be included. All patients will undergo a six-week control period without intervention after which they will be randomized to integrated or consecutive task practice. Training will consist of standardized walking and cognitive exercises delivered at home four times a week during six weeks. Treatment is guided by a physiotherapist twice a week and consists of two sessions of self-practice using an MP3 player. Blinded testers will assess patients before and after the control period, after the intervention period and after a 12-week follow-up period. The primary outcome measure is dual task gait velocity, i.e. walking combined with a novel untrained cognitive task to evaluate the consolidation of learning. Secondary outcomes include several single and dual task gait and cognitive measures, functional outcomes and a quality of life scale. Falling will be recorded as a possible adverse event using a weekly phone call for the entire study period. Discussion This randomized study will evaluate the effectiveness and safety of integrated versus consecutive task training in patients with Parkinson’s disease. The study will also highlight whether dual task gait training leads to robust motor learning effects, and whether these can be retained and carried-over to untrained dual tasks and functional mobility. Trial registration Clinicaltrials.gov NCT01375413. PMID:24674594

Searching for Dual AGNs in Galaxy Mergers: Understanding Double-Peaked [O III] and Ultra Hard X-rays as Selection Method

NASA Astrophysics Data System (ADS)

McGurk, Rosalie C.; Max, Claire E.; Medling, Anne; Shields, Gregory A.

2015-01-01

When galaxies merge, gas accretes onto both central supermassive black holes. Thus, one expects to see close pairs of active galactic nuclei (AGNs), or dual AGNs, in a fraction of galaxy mergers. However, finding them remains a challenge. The presence of double-peaked [O III] or of ultra hard X-rays have been proposed as techniques to select dual AGNs efficiently. We studied a sample of double-peaked narrow [O III] emitting AGNs from SDSS DR7. By obtaining new and archival high spatial resolution images taken with the Keck 2 Laser Guide Star Adaptive Optics system and the near-infrared (IR) camera NIRC2, we showed that 30% of double-peaked [O III] emission line SDSS AGNs have two spatial components within a 3' radius. However, spatially resolved spectroscopy or X-ray observations are needed to confirm these galaxy pairs as systems containing two AGNs. We followed up these spatially-double candidate dual AGNs with integral field spectroscopy from Keck OSIRIS and Gemini GMOS and with long-slit spectroscopy from Keck NIRSPEC and Shane Kast Double Spectrograph. We find double-peaked emitters are caused sometimes by dual AGN and sometimes by outflows or narrow line kinematics. We also performed Chandra X-ray ACIS-S observations on 12 double-peaked candidate dual AGNs. Using our observations and 8 archival observations, we compare the distribution of X-ray photons to our spatially double near-IR images, measure X-ray luminosities and hardness ratios, and estimate column densities. By assessing what fraction of double-peaked emission line SDSS AGNs are true dual AGNs, we can better determine whether double-peaked [O III] is an efficient dual AGN indicator and constrain the statistics of dual AGNs. A second technique to find dual AGN is the detection of ultra hard X-rays by the Swift Burst Alert Telescope. We use CARMA observations to measure and map the CO(1-0) present in nearby ultra-hard X-ray Active Galactic Nuclei (AGNs) merging with either a quiescent companion galaxy or a companion galaxy hosting a second AGN, in order to understand the role molecular gas plays in feeding this unusual population of ultra-hard X-ray AGNs and to understand ultra-hard X-rays as a dual AGN selection method.

A dual-targeting PDGFRbeta/VEGF-A molecule assembled from stable antibody fragments demonstrates anti-angiogenic activity in vitro and in vivo.

PubMed

Mabry, Robert; Gilbertson, Debra G; Frank, Amanda; Vu, Tuyen; Ardourel, Dan; Ostrander, Craig; Stevens, Brenda; Julien, Susan; Franke, Secil; Meengs, Brent; Brody, Jennifer; Presnell, Scott; Hamacher, Nels B; Lantry, Megan; Wolf, Anitra; Bukowski, Tom; Rosler, Robert; Yen, Cindy; Anderson-Haley, Monica; Brasel, Kenneth; Pan, Qi; Franklin, Hank; Thompson, Penny; Dodds, Mike; Underwood, Sara; Peterson, Scott; Sivakumar, Pallavur V; Snavely, Mark

2010-01-01

Targeting angiogenesis is a promising approach to the treatment of solid tumors and age-related macular degeneration (AMD). Inhibition of vascularization has been validated by the successful marketing of monoclonal antibodies (mAbs) that target specific growth factors or their receptors, but there is considerable room for improvement in existing therapies. Combination of mAbs targeting both the VEGF and PDGF pathways has the potential to increase the efficacy of anti-angiogenic therapy without the accompanying toxicities of tyrosine kinase inhibitors and the inability to combine efficiently with traditional chemotherapeutics. However, development costs and regulatory issues have limited the use of combinatorial approaches for the generation of more efficacious treatments. The concept of mediating disease pathology by targeting two antigens with one therapeutic was proposed over two decades ago. While mAbs are particularly suitable candidates for a dual-targeting approach, engineering bispecificity into one molecule can be difficult due to issues with expression and stability, which play a significant role in manufacturability. Here, we address these issues upstream in the process of developing a bispecific antibody (bsAb). Single-chain antibody fragments (scFvs) targeting PDGFRbeta and VEGF-A were selected for superior stability. The scFvs were fused to both termini of human Fc to generate a bispecific, tetravalent molecule. The resulting molecule displays potent activity, binds both targets simultaneously, and is stable in serum. The assembly of a bsAb using stable monomeric units allowed development of an anti-PDGFRB/VEGF-A antibody capable of attenuating angiogenesis through two distinct pathways and represents an efficient method for rapid engineering of dual-targeting molecules.

Dual activation of Toll-like receptors 7 and 9 impairs the efficacy of antitumor vaccines in murine models of metastatic breast cancer.

PubMed

Moreno Ayala, Mariela A; Gottardo, María Florencia; Gori, María Soledad; Nicola Candia, Alejandro Javier; Caruso, Carla; De Laurentiis, Andrea; Imsen, Mercedes; Klein, Slobodanka; Bal de Kier Joffé, Elisa; Salamone, Gabriela; Castro, Maria G; Seilicovich, Adriana; Candolfi, Marianela

2017-09-01

Since combination of Toll-like receptor (TLR) ligands could boost antitumor immunity, we evaluated the efficacy of dendritic cell (DC) vaccines upon dual activation of TLR9 and TLR7 in breast cancer models. DCs were generated from mouse bone marrow or peripheral blood from healthy human donors and stimulated with CpG1826 (mouse TLR9 agonist), CpG2006 or IMT504 (human TLR9 agonists) and R848 (TLR7 agonist). Efficacy of antitumor vaccines was evaluated in BALB/c mice bearing metastatic mammary adenocarcinomas. CpG-DCs improved the survival of tumor-bearing mice, reduced the development of lung metastases and generated immunological memory. However, dual activation of TLRs impaired the efficacy of DC vaccines. In vitro, we found that R848 inhibited CpG-mediated maturation of murine DCs. A positive feedback loop in TLR9 mRNA expression was observed upon CpG stimulation that was inhibited in the presence of R848. Impaired activation of NF-κB was detected when TLR9 and TLR7 were simultaneously activated. Blockade of nitric oxide synthase (NOS) and indoleamine-pyrrole-2,3-dioxygenase (IDO) improved the activation of CpG-DCs. When we evaluated the effect of combined activation of TLR9 and TLR7 in human DCs, we found that R848 induced robust DC activation that was inhibited by TLR9 agonists. These observations provide insight in the biology of TLR9 and TLR7 crosstalk and suggest caution in the selection of agonists for multiple TLR stimulation. Blockade of NOS and IDO could improve the maturation of antitumor DC vaccines. R848 could prove a useful adjuvant for DC vaccines in human patients.

Simultaneous targeting of prostate stem cell antigen and prostate-specific membrane antigen improves the killing of prostate cancer cells using a novel modular T cell-retargeting system.

PubMed

Arndt, Claudia; Feldmann, Anja; Koristka, Stefanie; Cartellieri, Marc; Dimmel, Maria; Ehninger, Armin; Ehninger, Gerhard; Bachmann, Michael

2014-09-01

Recently, we described a novel modular platform technology in which T cell-recruitment and tumor-targeting domains of conventional bispecific antibodies are split to independent components, a universal effector module (EM) and replaceable monospecific/monovalent target modules (TMs) that form highly efficient T cell-retargeting complexes. Theoretically, our unique strategy should allow us to simultaneously retarget T cells to different tumor antigens by combining the EM with two or more different monovalent/monospecific TMs or even with bivalent/bispecific TMs, thereby overcoming limitations of a monospecific treatment such as the selection of target-negative tumor escape variants. In order to advance our recently introduced prostate stem cell antigen (PSCA)-specific modular system for a dual-targeting of prostate cancer cells, two additional TMs were constructed: a monovalent/monospecific TM directed against the prostate-specific membrane antigen (PSMA) and a bivalent/bispecific TM (bsTM) with specificity for PSMA and PSCA. The functionality of the novel dual-targeting strategies was analyzed by performing T cell activation and chromium release assays. Similar to the PSCA-specific modular system, the novel PSMA-specific modular system mediates an efficient target-dependent and -specific tumor cell lysis at low E:T ratios and picomolar Ab concentrations. Moreover, by combination of the EM with either the bispecific TM directed to PSMA and PSCA or both monospecifc TMs directed to either PSCA or PSMA, dual-specific targeting complexes were formed which allowed us to kill potential escape variants expressing only one or the other target antigen. Overall, the novel modular system represents a promising tool for multiple tumor targeting. © 2014 Wiley Periodicals, Inc.

[Changes of serum TOS and TAS levels and their association with apolipoprotein(a) in patients with polycystic ovary syndrome and infertility].

PubMed

Tu, An-Su; Zhong, Ying; Mao, Xi-Guang

2016-03-01

To investigate changes of serum total oxidation status (TOS) and total antioxidant status (TAS) and their association with apolipoprotein (a) [Apo(a)] in patients with polycystic ovary syndrome (PCOS) combined with infertility. Ninety patients with PCOS and infertility were selected as the study group, including 45 patients treated with antioxidants combined with Diane-35(group A) and 45 with Diane-35 therapy only (group B), with 45 healthy volunteers with normal menstruation and normal dual phase basic body temperatures as the control group. Serum TOS of the participants was determined by dual xylenol orange method, and serum TAS was determined with ABTS method; plasma Apo(a) level was determined by dual wavelength immune transmission turbidity method. Before treatment, serum TOS, OSI, and Apo(a) levels were significantly higher and TAS level was significantly lower in the study group than in the control group (P<0.05). Serum TOS, OSI, and Apo (a) were significantly lowered and TAS was significantly increased in group A after the therapy as compared with the levels before therapy and the levels in group B. The rate of natural recovery of menstruation was significantly higher and the incidence of cardiovascular disease was significantly lower in group A than in group B (P<0.05). Pearson correlation analysis showed that serum TOS and OSI were positively correlated with plasma Apo(a) (r=0.524 and 0.531, P<0.05), and serum TAS was negatively correlated with plasma Apo(a) (r=-0.519, P<0.05). Antioxidant therapy can lower TOS, OSI and Apo(a) levels and increase TAS level to lessen oxidative stress, improve the prognosis, and reduce the risks of cardiovascular disease in patients with PCOS and infertility.

Technical note: optimization for improved tube-loading efficiency in the dual-energy computed tomography coupled with balanced filter method.

PubMed

Saito, Masatoshi

2010-08-01

This article describes the spectral optimization of dual-energy computed tomography using balanced filters (bf-DECT) to reduce the tube loadings and dose by dedicating to the acquisition of electron density information, which is essential for treatment planning in radiotherapy. For the spectral optimization of bf-DECT, the author calculated the beam-hardening error and air kerma required to achieve a desired noise level in an electron density image of a 50-cm-diameter cylindrical water phantom. The calculation enables the selection of beam parameters such as tube voltage, balanced filter material, and its thickness. The optimal combination of tube voltages was 80 kV/140 kV in conjunction with Tb/Hf and Bi/Mo filter pairs; this combination agrees with that obtained in a previous study [M. Saito, "Spectral optimization for measuring electron density by the dual-energy computed tomography coupled with balanced filter method," Med. Phys. 36, 3631-3642 (2009)], although the thicknesses of the filters that yielded a minimum tube output were slightly different from those obtained in the previous study. The resultant tube loading of a low-energy scan of the present bf-DECT significantly decreased from 57.5 to 4.5 times that of a high-energy scan for conventional DECT. Furthermore, the air kerma of bf-DECT could be reduced to less than that of conventional DECT, while obtaining the same figure of merit for the measurement of electron density and effective atomic number. The tube-loading and dose efficiencies of bf-DECT were considerably improved by sacrificing the quality of the noise level in the images of effective atomic number.

Selective oxidation of dual phase steel after annealing at different dew points

NASA Astrophysics Data System (ADS)

Lins, Vanessa de Freitas Cunha; Madeira, Laureanny; Vilela, Jose Mario Carneiro; Andrade, Margareth Spangler; Buono, Vicente Tadeu Lopes; Guimarães, Juliana Porto; Alvarenga, Evandro de Azevedo

2011-04-01

Hot galvanized steels have been extensively used in the automotive industry. Selective oxidation on the steel surface affects the wettability of zinc on steel and the grain orientation of inhibition layer (Fe-Al-Zn alloy) and reduces the iron diffusion to the zinc layer. The aim of this work is to identify and quantify selective oxidation on the surface of a dual phase steel, and an experimental steel with a lower content of manganese, annealed at different dew points. The techniques employed were atomic force microscopy, X-ray photoelectron spectroscopy, and glow discharge optical emission spectroscopy. External selective oxidation was observed for phosphorus on steel surface annealed at 0 °C dp, and for manganese, silicon, and aluminum at a lower dew point. The concentration of manganese was higher on the dual phase steel surface than on the surface of the experimental steel. The concentration of molybdenum on the surface of both steels increased as the depth increased.

Single cell dual adherent-suspension co-culture micro-environment for studying tumor-stromal interactions with functionally selected cancer stem-like cells.

PubMed

Chen, Yu-Chih; Zhang, Zhixiong; Fouladdel, Shamileh; Deol, Yadwinder; Ingram, Patrick N; McDermott, Sean P; Azizi, Ebrahim; Wicha, Max S; Yoon, Euisik

2016-08-07

Considerable evidence suggests that cancer stem-like cells (CSCs) are critical in tumor pathogenesis, but their rarity and transience has led to much controversy about their exact nature. Although CSCs can be functionally identified using dish-based tumorsphere assays, it is difficult to handle and monitor single cells in dish-based approaches; single cell-based microfluidic approaches offer better control and reliable single cell derived sphere formation. However, like normal stem cells, CSCs are heavily regulated by their microenvironment, requiring tumor-stromal interactions for tumorigenic and proliferative behaviors. To enable single cell derived tumorsphere formation within a stromal microenvironment, we present a dual adherent/suspension co-culture device, which combines a suspension environment for single-cell tumorsphere assays and an adherent environment for co-culturing stromal cells in close proximity by selectively patterning polyHEMA in indented microwells. By minimizing dead volume and improving cell capture efficiency, the presented platform allows for the use of small numbers of cells (<100 cells). As a proof of concept, we co-cultured single T47D (breast cancer) cells and primary cancer associated fibroblasts (CAF) on-chip for 14 days to monitor sphere formation and growth. Compared to mono-culture, co-cultured T47D have higher tumorigenic potential (sphere formation rate) and proliferation rates (larger sphere size). Furthermore, 96-multiplexed single-cell transcriptome analyses were performed to compare the gene expression of co-cultured and mono-cultured T47D cells. Phenotypic changes observed in co-culture correlated with expression changes in genes associated with proliferation, apoptotic suppression, tumorigenicity and even epithelial-to-mesechymal transition. Combining the presented platform with single cell transcriptome analysis, we successfully identified functional CSCs and investigated the phenotypic and transcriptome effects induced by tumor-stromal interactions.

Non-invasive methods for the determination of body and carcass composition in livestock: dual-energy X-ray absorptiometry, computed tomography, magnetic resonance imaging and ultrasound: invited review.

PubMed

Scholz, A M; Bünger, L; Kongsro, J; Baulain, U; Mitchell, A D

2015-07-01

The ability to accurately measure body or carcass composition is important for performance testing, grading and finally selection or payment of meat-producing animals. Advances especially in non-invasive techniques are mainly based on the development of electronic and computer-driven methods in order to provide objective phenotypic data. The preference for a specific technique depends on the target animal species or carcass, combined with technical and practical aspects such as accuracy, reliability, cost, portability, speed, ease of use, safety and for in vivo measurements the need for fixation or sedation. The techniques rely on specific device-driven signals, which interact with tissues in the body or carcass at the atomic or molecular level, resulting in secondary or attenuated signals detected by the instruments and analyzed quantitatively. The electromagnetic signal produced by the instrument may originate from mechanical energy such as sound waves (ultrasound - US), 'photon' radiation (X-ray-computed tomography - CT, dual-energy X-ray absorptiometry - DXA) or radio frequency waves (magnetic resonance imaging - MRI). The signals detected by the corresponding instruments are processed to measure, for example, tissue depths, areas, volumes or distributions of fat, muscle (water, protein) and partly bone or bone mineral. Among the above techniques, CT is the most accurate one followed by MRI and DXA, whereas US can be used for all sizes of farm animal species even under field conditions. CT, MRI and US can provide volume data, whereas only DXA delivers immediate whole-body composition results without (2D) image manipulation. A combination of simple US and more expensive CT, MRI or DXA might be applied for farm animal selection programs in a stepwise approach.

A systematic review of interventions conducted in clinical or community settings to improve dual-task postural control in older adults.

PubMed

Agmon, Maayan; Belza, Basia; Nguyen, Huong Q; Logsdon, Rebecca G; Kelly, Valerie E

2014-01-01

Injury due to falls is a major problem among older adults. Decrements in dual-task postural control performance (simultaneously performing two tasks, at least one of which requires postural control) have been associated with an increased risk of falling. Evidence-based interventions that can be used in clinical or community settings to improve dual-task postural control may help to reduce this risk. THE AIMS OF THIS SYSTEMATIC REVIEW ARE: 1) to identify clinical or community-based interventions that improved dual-task postural control among older adults; and 2) to identify the key elements of those interventions. Studies were obtained from a search conducted through October 2013 of the following electronic databases: PubMed, CINAHL, PsycINFO, and Web of Science. Randomized and nonrandomized controlled studies examining the effects of interventions aimed at improving dual-task postural control among community-dwelling older adults were selected. All studies were evaluated based on methodological quality. Intervention characteristics including study purpose, study design, and sample size were identified, and effects of dual-task interventions on various postural control and cognitive outcomes were noted. Twenty-two studies fulfilled the selection criteria and were summarized in this review to identify characteristics of successful interventions. The ability to synthesize data was limited by the heterogeneity in participant characteristics, study designs, and outcome measures. Dual-task postural control can be modified by specific training. There was little evidence that single-task training transferred to dual-task postural control performance. Further investigation of dual-task training using standardized outcome measurements is needed.

Cascaded systems analysis of noise and detectability in dual-energy cone-beam CT

PubMed Central

Gang, Grace J.; Zbijewski, Wojciech; Webster Stayman, J.; Siewerdsen, Jeffrey H.

2012-01-01

Purpose: Dual-energy computed tomography and dual-energy cone-beam computed tomography (DE-CBCT) are promising modalities for applications ranging from vascular to breast, renal, hepatic, and musculoskeletal imaging. Accordingly, the optimization of imaging techniques for such applications would benefit significantly from a general theoretical description of image quality that properly incorporates factors of acquisition, reconstruction, and tissue decomposition in DE tomography. This work reports a cascaded systems analysis model that includes the Poisson statistics of x rays (quantum noise), detector model (flat-panel detectors), anatomical background, image reconstruction (filtered backprojection), DE decomposition (weighted subtraction), and simple observer models to yield a task-based framework for DE technique optimization. Methods: The theoretical framework extends previous modeling of DE projection radiography and CBCT. Signal and noise transfer characteristics are propagated through physical and mathematical stages of image formation and reconstruction. Dual-energy decomposition was modeled according to weighted subtraction of low- and high-energy images to yield the 3D DE noise-power spectrum (NPS) and noise-equivalent quanta (NEQ), which, in combination with observer models and the imaging task, yields the dual-energy detectability index (d′). Model calculations were validated with NPS and NEQ measurements from an experimental imaging bench simulating the geometry of a dedicated musculoskeletal extremities scanner. Imaging techniques, including kVp pair and dose allocation, were optimized using d′ as an objective function for three example imaging tasks: (1) kidney stone discrimination; (2) iodine vs bone in a uniform, soft-tissue background; and (3) soft tissue tumor detection on power-law anatomical background. Results: Theoretical calculations of DE NPS and NEQ demonstrated good agreement with experimental measurements over a broad range of imaging conditions. Optimization results suggest a lower fraction of total dose imparted by the low-energy acquisition, a finding consistent with previous literature. The selection of optimal kVp pair reveals the combined effect of both quantum noise and contrast in the kidney stone discrimination and soft-tissue tumor detection tasks, whereas the K-edge effect of iodine was the dominant factor in determining kVp pairs in the iodine vs bone task. The soft-tissue tumor task illustrated the benefit of dual-energy imaging in eliminating anatomical background noise and improving detectability beyond that achievable by single-energy scans. Conclusions: This work established a task-based theoretical framework that is predictive of DE image quality. The model can be utilized in optimizing a broad range of parameters in image acquisition, reconstruction, and decomposition, providing a useful tool for maximizing DE-CBCT image quality and reducing dose. PMID:22894440

[Treatment program for dual-diagnosis substance abusers].

PubMed

Kandel, Isack

2007-01-01

Dual-diagnosis mentally ill patients, i.e. those characterized with substance abuse problems combined with mental health problems, are a challenge both for systems treating substance abusers and for mental health services. These patients are not easily integrated in either of these healthcare systems and/or are treated only for one aspect of their problem by each of these systems. For such patients it is necessary to create a separate treatment model, combining care of the problem of substance abuse and attention to the patient's mental pathology, according to his individual personality traits. For purposes of this programme a treatment setting operating on the model of a therapeutic community is proposed. This setting will open an affiliated treatment programme for dual-diagnosed patients in a separate treatment programme that is not part of the therapeutic community but will be affiliated with it and will accept dual-diagnosis patients.

Optimum allocation for a dual-frame telephone survey.

PubMed

Wolter, Kirk M; Tao, Xian; Montgomery, Robert; Smith, Philip J

2015-12-01

Careful design of a dual-frame random digit dial (RDD) telephone survey requires selecting from among many options that have varying impacts on cost, precision, and coverage in order to obtain the best possible implementation of the study goals. One such consideration is whether to screen cell-phone households in order to interview cell-phone only (CPO) households and exclude dual-user household, or to take all interviews obtained via the cell-phone sample. We present a framework in which to consider the tradeoffs between these two options and a method to select the optimal design. We derive and discuss the optimum allocation of sample size between the two sampling frames and explore the choice of optimum p , the mixing parameter for the dual-user domain. We illustrate our methods using the National Immunization Survey , sponsored by the Centers for Disease Control and Prevention.

Controlling the dual mechanisms of oxide interface doping

NASA Astrophysics Data System (ADS)

Dai, Weitao; Cen, Cheng

The formation of two dimensional electron gas (2DEG) at LaAlO3/SrTiO3 interfaces involves multiple electronic and structural causes. The interplay between them makes the investigation of individual mechanism very challenging. Here we demonstrate the nanoscale selective control of two interface doping pathways: charge transfers from surface adsorbed protons and oxygen vacancies created in LaAlO3 layers. The selective control is achieved by combining intensive electric field generated by conducting AFM probe which controls both the creation/migration of oxygen vacancies and the surface proton density, with plasma assisted surface hydroxylation and solvent based proton solvation that act mainly on surface adsorbates. Robust nanoscale reversible metal-insulator transition was achieved at the interfaces with the LaAlO3 layer thicker than the critic thickness. Different combinations of the experimental methods and doping mechanisms enable highly flexible tuning of the 2DEG's carrier density, mobility and sensitivity to ambient environments. The reversible and independent controls of surface states and vacancies add to the fundamental material research capabilities and can benefit future exploration of designed 2DEG nanoelectronics.

Bias Selectable Dual Band AlGaN Ultra-violet Detectors

NASA Technical Reports Server (NTRS)

Yan, Feng; Miko, Laddawan; Franz, David; Guan, Bing; Stahle, Carl M.

2007-01-01

Bias selectable dual band AlGaN ultra-violet (UV) detectors, which can separate UV-A and UV-B using one detector in the same pixel by bias switching, have been designed, fabricated and characterized. A two-terminal n-p-n photo-transistor-like structure was used. When a forward bias is applied between the top electrode and the bottom electrode, the detectors can successfully detect W-A and reject UV-B. Under reverse bias, they can detect UV-B and reject UV-A. The proof of concept design shows that it is feasible to fabricate high performance dual-band UV detectors based on the current AlGaN material growth and fabrication technologies.

Combined use of nonsteroidal anti-inflammatory drugs with diuretics and/or renin-angiotensin system inhibitors in the community increases the risk of acute kidney injury.

PubMed

Dreischulte, Tobias; Morales, Daniel R; Bell, Samira; Guthrie, Bruce

2015-08-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of acute kidney injury (AKI) when used in triple combination with renin-angiotensin system inhibitors and diuretics, but previous research reported that NSAIDs in dual combinations with either renin-angiotensin system inhibitors or diuretics alone were not. However, earlier studies relied on hospital coding to define AKI, which may underestimate true risk. This nested case-control study characterized the risk of community-acquired AKI associated with NSAID use among 78,379 users of renin-angiotensin system inhibitors and/or diuretics, where AKI was defined as a 50% or greater increase in creatinine from baseline. The AKI incidence was 68/10,000 person-years. The relative increase in AKI risk was similar for NSAID use in both triple (adjusted rate ratio 1.64 (95% CI 1.25-2.14)) and dual combinations with either renin-angiotensin system inhibitors (1.60 (1.18-2.17)) or diuretics (1.64 (1.17-2.29)). However, the absolute increase in AKI risk was higher for NSAIDs used in triple versus dual combinations with renin-angiotensin system inhibitors or diuretics alone (numbers needed to harm for 1 year treatment with NSAID of 158 vs. over 300). AKI risk was highest among users of loop diuretic/aldosterone antagonist combinations, in those over 75 years of age, and in those with renal impairment. Thus, the nephrotoxic potential of both dual and triple combinations of NSAIDs with renin-angiotensin system inhibitors and/or diuretics yields a higher incidence of AKI than previously thought.

Dapagliflozin and saxagliptin tablets for adults with type 2 diabetes.

PubMed

Scheen, André J

2017-12-01

Saxagliptin (a dipeptidyl peptidase-4 inhibitor, DPP-4i) and dapagliflozin (a sodium-glucose cotransporter type 2 inhibitor, SGLT2i) improve glucose control in type 2 diabetes (T2D) through different potentially complementary mechanisms, thus offering the opportunity for a combined therapy. Area covered: The characteristics of the saxagliptin/dapagliflozin combination are analysed, focusing on: 1) pharmacokinetic and pharmacodynamic properties; 2) efficacy and safety in phase III trials with concurrent and sequential add-on therapy; and 3) potential use in clinical practice, including in special populations (cardiovascular disease, heart failure, chronic kidney disease, elderly). Expert commentary: Conclusions drawn from clinical trials investigating combination with the separate drugs are considered to apply to the fixed-dose combination (FDC) that demonstrates bioequivalence. Dual saxagliptin/dapagliflozin therapy is more potent than either monotherapy and can be used as an initial combination or a stepwise sequential approach. Dual therapy is generally well tolerated and may be used in special populations, with some limitations because of the presence of dapagliflozin. However, the latter may offer some advantages because of multiple effects attributed to SGLT2i. The best place of this dual combination for the management of T2D and the profile of patients who will make the most of this combined therapy remains to be defined.

The source of dual-task limitations: Serial or parallel processing of multiple response selections?

PubMed Central

Marois, René

2014-01-01

Although it is generally recognized that the concurrent performance of two tasks incurs costs, the sources of these dual-task costs remain controversial. The serial bottleneck model suggests that serial postponement of task performance in dual-task conditions results from a central stage of response selection that can only process one task at a time. Cognitive-control models, by contrast, propose that multiple response selections can proceed in parallel, but that serial processing of task performance is predominantly adopted because its processing efficiency is higher than that of parallel processing. In the present study, we empirically tested this proposition by examining whether parallel processing would occur when it was more efficient and financially rewarded. The results indicated that even when parallel processing was more efficient and was incentivized by financial reward, participants still failed to process tasks in parallel. We conclude that central information processing is limited by a serial bottleneck. PMID:23864266

Optical design of f-theta lens for dual wavelength selective laser melting

NASA Astrophysics Data System (ADS)

Feng, Lianhua; Cao, Hongzhong; Zhang, Ning; Xu, Xiping; Duan, Xuanming

2016-10-01

F-theta lens is an important unit for selective laser melting (SLM) manufacture. The dual wavelength f-theta lens has not been used in SLM manufacture. Here, we present the design of the f-theta lens which satisfies SLM manufacture with coaxial 532 nm and 1030 nm 1080 nm laser beams. It is composed of three pieces of spherical lenses. The focal spots for 532 nm laser and 1030 nm 1080 nm laser are smaller than 35 μm and 70 μm, respectively. The results meet the demands of high precision SLM. The chromatic aberration could cause separation between two laser focal spots in the scanning plane, so chromatic aberration correction is very important to our design. The lateral color of the designed f-theta lens is less than 11 μm within the scan area of 150 mm x 150 mm, which meet the application requirements of dual wavelength selective laser melting.

Design of a dual-band radiation system for a complex magnetically insulated line oscillator

NASA Astrophysics Data System (ADS)

Yu, Yuanqiang; Wang, Xiaoyu; Fan, Yuwei; Li, Ankun; Li, Sirui

2018-05-01

In this paper, a dual-band radiation system for a complex magnetically insulated line oscillator (MILO) is designed and investigated numerically. The radiation system comprises a coaxial plate-inserted mode converter, a power combiner and a conical horn antenna. The mode converter converts the coaxial TEM mode microwaves (1.775 GHz and 3.175 GHz) which are generated by the complex MILO into the coaxial TE11 mode microwaves, and then the coaxial TE11 mode microwaves are combined by the power combiner in a circular waveguide. Lastly, the microwaves are radiated by a conical horn antenna into the air. The gains of the dual-band radiation system are calculated to be 17.8 dB at 1.775 GHz and 18.9 dB at 3.175 GHz. The 3 dB beam widths are 20.5° in E-plane, 26.4° in H-plane at 1.775 GHz and 20.8° in E-plane, 15.1° in H-plane at 3.175 GHz. The power transmission efficiencies of the dual-band radiation system are 98.5% at 1.775 GHz and 95.7% at 3.175 GHz respectively. The power handling capacities of the dual-band radiation system are 4.2 GW at 1.775 GHz and 4.7 GW at 3.175 GHz, respectively.

Sustained Release d-Amphetamine Reduces Cocaine but not ‘Speedball'-Seeking in Buprenorphine-Maintained Volunteers: A Test of Dual-Agonist Pharmacotherapy for Cocaine/Heroin Polydrug Abusers

PubMed Central

Greenwald, Mark K; Lundahl, Leslie H; Steinmiller, Caren L

2010-01-01

The aim of this study was to determine whether oral sustained release d-amphetamine (SR-AMP) reduces cocaine and opioid/cocaine combination (‘speedball'-like) seeking in volunteers with current opioid dependence and cocaine dependence. Following outpatient buprenorphine (BUP) 8 mg/day stabilization without SR-AMP, eight participants completed a 3-week in-patient study with continued BUP 8 mg/day maintenance and double-blind ascending SR-AMP weekly doses of 0, 30, and 60 mg/day, respectively. After 3 days (Saturday–Monday) stabilization at each SR-AMP weekly dose (0, 15, or 30 mg administered at 0700 and 1225 each day), on Tuesday–Friday mornings (0900–1200 hours), participants sampled four drug combinations in randomized, counterbalanced order under double-blind, double-dummy (intranasal cocaine and intramuscular hydromorphone) conditions: cocaine (COC 100 mg+saline); hydromorphone (COC 4 mg+HYD 24 mg); ‘speedball' (COC 100 mg+HYD 24 mg); and placebo (COC 4 mg+saline). Subjective and physiological effects of these drug combinations were measured. From 1230 to 1530 hours, participants could respond on a choice, 12-trial progressive ratio schedule to earn drug units (1/12th of total morning dose) or money units (US$2). SR-AMP significantly reduced COC, but not HYD or speedball, choices and breakpoints. SR-AMP also significantly reduced COC subjective (eg, abuse-related) effects and did not potentiate COC-induced cardiovascular responses. This study shows the ability of SR-AMP to attenuate COC self-administration, as well as its selectivity, in cocaine/heroin polydrug abusers. Further research is warranted to ascertain whether SR-AMP combined with BUP could be a useful dual-agonist pharmacotherapy. PMID:20881947

Design of pH-sensitive methotrexate prodrug-targeted curcumin nanoparticles for efficient dual-drug delivery and combination cancer therapy.

PubMed

Xie, Jiajiang; Fan, Zhongxiong; Li, Yang; Zhang, Yinying; Yu, Fei; Su, Guanghao; Xie, Liya; Hou, Zhenqing

2018-01-01

We designed acid-labile methotrexate (MTX) targeting prodrug self-assembling nanoparticles loaded with curcumin (CUR) drug for simultaneous delivery of multi-chemotherapeutic drugs and combination cancer therapy. A dual-acting MTX, acting as both an anticancer drug and as a tumor-targeting ligand, was coupled to 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[aldehyde(polyethylene glycol)-2000] via Schiff's base reaction. The synthesized prodrug conjugate (DSPE-PEG-Imine-MTX) could be self-assembled into micellar nanoparticles (MTX-Imine-M) in aqueous solution, which encapsulated CUR into their core by hydrophobic interactions (MTX-Imine-M-CUR). The prepared MTX-Imine-M-CUR nanoparticles were composed of an inner hydrophobic DSPE/CUR core and an outside hydrophilic bishydroxyl poly (ethyleneglycol) (PEG) shell with a self-targeting MTX prodrug corona. The imine linker between 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[aldehyde(polyethyleneglycol)-2000] and MTX, as a dynamic covalent bond, was strong enough to remain intact in physiological pH, even though it is rapidly cleaved in acidic pH. The MTX-Imine-M-CUR could codeliver MTX and CUR selectively and efficiently into the cancer cells via folate receptor-mediated endocytosis followed by the rapid intracellular release of CUR and the active form of MTX via the acidity of endosomes/lysosomes. Moreover, the MTX-Imine-M-CUR resulted in significantly higher in vitro and in vivo anticancer activity than pH-insensitive DSPE-PEGAmide-MTX assembling nanoparticles loaded with CUR (MTX-Amide-M-CUR), MTX unconjugated DSPE-PEG assembling micellar nanoparticles loaded with CUR (M-CUR), combination of both free drugs, and individual free drugs. The smart system provided a simple, yet feasible, drug delivery strategy for targeted combination chemotherapy.

Evaluation of dual-loop data accuracy using video ground truth data

DOT National Transportation Integrated Search

2002-01-01

Washington State Department of Transportation (WSDOT) initiated a : research project entitled Monitoring Freight on Puget Sound Freeways in September : 1999. Dual-loop data from the Seattle area freeway system were selected as the main data : s...

Multiwavelength Studies of Dual AGN in the Swift/BAT Sample

NASA Astrophysics Data System (ADS)

Treister, Ezequiel; Privon, George; Sartori, Lia; Nagar, Neil; Bauer, Franz Erik; Schawinski, Kevin; Ricci, Claudio; U, Vivian; Comerford, Julie; Muller-Sanchez, Francisco; Evans, Aaron; Koss, Michael; Sanders, David B.; Urry, Meg; MODA Collaboration

2018-01-01

For the last 30 years there has been growing evidence for a strong connection between major galaxy mergers and simultaneous episodes ofstrong star formation and signicant central supermassive black hole (SMBH) growth. A natural consequence of this scenario is that dual Active Galactic Nuclei (AGN), i.e., systems in which the two nuclear SMBHs are growing simultaneously at separations <10 kpc should be relatively common. This particular stage in a major galaxy merger, albeit short at ~hundreds Myears, is very relevant for galaxy evolution.Here we present the first results from an ongoing survey aimed to study the multiwavelength properties of the dual AGN in the neary universe, z<0.1 selected from mostly-unbiased observations at hard X-rays, E>10 keV, obtained from the Swift-BAT extragalactic survey and complemented by NuSTAR observations. Our work focuses on the study of the physical properties of the ionized, atomic and molecular gas and the dust in confirmed dual AGN by combining observations with ALMA, VLT/MUSE and SINFONI and Keck/OSIRIS among others. In addition to providing general properties of this poulation, we will further focus on two remarkable systems, NGC6240 and Mrk 463. Both systems show evidence of large kpc-scale tidal features, complex gas dynamics and kinematical evidence for both inflows and outflows.These results clearly show the importance of performing high resolution multi wavelength studies covering kpc scales in order to understandthe complex connection between black hole growth and galaxy evolution in this critical phase.Support from this work has been provided by CONICYT FONDECYT 1160999 and PFB-06/2007.

Integrated signal probe based aptasensor for dual-analyte detection.

PubMed

Xiang, Juan; Pi, Xiaomei; Chen, Xiaoqing; Xiang, Lei; Yang, Minghui; Ren, Hao; Shen, Xiaojuan; Qi, Ning; Deng, Chunyan

2017-10-15

For the multi-analyte detection, although the sensitivity has commonly met the practical requirements, the reliability, reproducibility and stability need to be further improved. In this work, two different aptamer probes labeled with redox tags were used as signal probe1 (sP1) and signal probe2 (sP2), which were integrated into one unity DNA architecture to develop the integrated signal probe (ISP). Comparing with the conventional independent signal probes for the simultaneous multi-analyte detection, the proposed ISP was more reproducible and accurate. This can be due to that ISP in one DNA structure can ensure the completely same modification condition and an equal stoichiometric ratio between sP1 and sP2, and furthermore the cross interference between sP1 and sP2 can be successfully prevented by regulating the complementary position of sP1 and sP2. The ISP-based assay system would be a great progress for the dual-analyte detection. Combining with gold nanoparticles (AuNPs) signal amplification, the ISP/AuNPs-based aptasensor for the sensitive dual-analyte detection was explored. Based on DNA structural switching induced by targets binding to aptamer, the simultaneous dual-analyte detection was simply achieved by monitoring the electrochemical responses of methylene blue (MB) and ferrocene (Fc) This proposed detection system possesses such advantages as simplicity in design, easy operation, good reproducibility and accuracy, high sensitivity and selectivity, which indicates the excellent application of this aptasensor in the field of clinical diagnosis or other molecular sensors. Copyright © 2017 Elsevier B.V. All rights reserved.

Dual throat engine design for a SSTO launch vehicle

NASA Technical Reports Server (NTRS)

Obrien, C. J.; Salmon, J. W.

1980-01-01

A propulsion system analysis of a dual fuel, dual throat engine for launch vehicle application was conducted. Basic dual throat engine characterization data are presented to allow vehicle optimization studies to be conducted. A preliminary baseline engine system was defined. Dual throat engine performance, envelope, and weight parametric data were generated over the parametric range of thrust from 890 to 8896 KN (200K to 2M lb-force), chamber pressure from 6.89 million to 34.5 million N/sq m (1000 to 5000 psia) thrust ratio from 1.2 to 5, and a range of mixture ratios for the two tripropellant combinations: LO2/RP-1 + LH2 and LO2/LCH4 + LH2. The results of the study indicate that the dual fuel dual throat engine is a viable single stage to orbit candidate.

Endothelin ETA Receptor Blockade, by Activating ETB Receptors, Increases Vascular Permeability and Induces Exaggerated Fluid Retention.

PubMed

Vercauteren, Magali; Trensz, Frederic; Pasquali, Anne; Cattaneo, Christophe; Strasser, Daniel S; Hess, Patrick; Iglarz, Marc; Clozel, Martine

2017-05-01

Endothelin (ET) receptor antagonists have been associated with fluid retention. It has been suggested that, of the two endothelin receptor subtypes, ET B receptors should not be blocked, because of their involvement in natriuresis and diuresis. Surprisingly, clinical data suggest that ET A -selective antagonists pose a greater risk of fluid overload than dual antagonists. The purpose of this study was to evaluate the contribution of each endothelin receptor to fluid retention and vascular permeability in rats. Sitaxentan and ambrisentan as ET A -selective antagonists and bosentan and macitentan as dual antagonists were used as representatives of each class, respectively. ET A -selective antagonism caused a dose-dependent hematocrit/hemoglobin decrease that was prevented by ET B -selective receptor antagonism. ET A -selective antagonism led to a significant blood pressure reduction, plasma volume expansion, and a greater increase in vascular permeability than dual antagonism. Isolated vessel experiments showed that ET A -selective antagonism increased vascular permeability via ET B receptor overstimulation. Acutely, ET A -selective but not dual antagonism activated sympathetic activity and increased plasma arginine vasopressin and aldosterone concentrations. The hematocrit/hemoglobin decrease induced by ET A -selective antagonism was reduced in Brattleboro rats and in Wistar rats treated with an arginine vasopressin receptor antagonist. Finally, the decrease in hematocrit/hemoglobin was larger in the venous than in the arterial side, suggesting fluid redistribution. In conclusion, by activating ET B receptors, endothelin receptor antagonists (particularly ET A -selective antagonists) favor edema formation by causing: 1) fluid retention resulting from arginine vasopressin and aldosterone activation secondary to vasodilation, and 2) increased vascular permeability. Plasma volume redistribution may explain the clinical observation of a hematocrit/hemoglobin decrease even in the absence of signs of fluid retention. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Trazodone Addition to Paroxetine and Mirtazapine in a Patient with Treatment-Resistant Depression: The Pros and Cons of Combining Three Antidepressants

PubMed Central

Alves, José Carlos; Rego, Raquel Garcia

2016-01-01

Dual antidepressant combination for treatment-resistant depression is a strategy well supported by literature and accepted in clinical practice. Rather, the usefulness of the combination of more than two antidepressants is controversial. This may be related to the possibility of higher side-effect burden and to doubts about its pharmacological effectiveness and therapeutic advantage compared to other standard treatment options. We report a relapse of moderate-to-severe depressive symptoms with insomnia that successfully remitted after the addition of trazodone to a dual combination of paroxetine and mirtazapine (in standard effective doses) in a patient with treatment-resistant depression. We also review the literature and discuss the utility of triple antidepressant combination in treatment-resistant depression. This clinical case highlights the utility of combining trazodone as a third antidepressant for the relapse of depressive symptoms after the failure of a dual antidepressant combination. Trazodone may be advantageous in patients presenting recurrence of moderate-to-severe depressive symptoms that include sleep problems and/or insomnia and may be particularly useful when benzodiazepines are not recommended. Although its use may be controversial and associated with higher risk of side-effects, more investigation is needed to determine the efficacy and safety for triple antidepressant combinations as reliable strategies for treatment-resistant depression in clinical practice. PMID:27807450

Arrhythmia discrimination by physician and defibrillator: importance of atrial channel.

PubMed

Diemberger, Igor; Martignani, Cristian; Biffi, Mauro; Frabetti, Lorenzo; Valzania, Cinzia; Cooke, Robin M T; Rapezzi, Claudio; Branzi, Angelo; Boriani, Giuseppe

2012-01-26

Many ICD carriers experience inappropriate shocks, but the relative merits of dual- /single-chamber devices for arrhythmia discrimination still remain unclear. We explored possible advantages of the atrial data provided by dual-chamber implantable defibrillators (ICD) for discrimination of real-life supraventricular/ventricular tachyarrhythmias (SVT/VT). 100 dual-chamber traces from 24 ICD were blindly reviewed in dual-chamber and simulated single-chamber (with/without discriminator data) reading modes by five electrophysiologists who determined chamber of origin and provided Likert-scale "confidence" ratings. We assessed 1) intra/interobserver concordance; 2) diagnostic accuracy, using expert diagnoses as a reference standard; 3) ROC curves of sensitivity/specificity of "likelihood perception" scores, generated by combining chamber-of-origin diagnostic judgments with Likert-scale "confidence" ratings. We also assessed diagnostic accuracy of automated discrimination by all possible dual-/single-chamber algorithm configurations. Interobserver concordance was "substantial" (modified Cohen kappa-test values for dual-/single-chamber, 0.79/0.68); intraobserver concordance "almost complete" (kappa ≥ 0.89). Dual-chamber mode provided best diagnostic sensitivity/specificity (99%/92%) and highest reader confidence (p<0.001). Area under ROC curves of sensitivity/specificity values for the "likelihood perception" score (representing electrophysiologists' perceptions of the likelihood that an episode was of ventricular origin) was highest in dual-chamber mode (0.98 vs. 0.93 for both single-chamber modes; p<0.001). Regarding automated discrimination, all four dual-chamber configurations conferred 100% sensitivity (specificity values ranged 39%-88%), whereas single-chamber configurations appeared inferior (best sensitivity/specificity combination, 89%/64%). Availability of the atrial channel helps in reducing inappropriate ICD therapies by providing relevant advantages in terms of both appropriate cardiologist's post-hoc discrimination of SVT/VT (improving program tailoring) and automated arrhythmia discrimination. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Mechanisms of Practice-Related Reductions of Dual-Task Interference with Simple Tasks: Data and Theory

PubMed Central

Strobach, Tilo; Torsten, Schubert

2017-01-01

In dual-task situations, interference between two simultaneous tasks impairs performance. With practice, however, this impairment can be reduced. To identify mechanisms leading to a practice-related improvement in sensorimotor dual tasks, the present review applied the following general hypothesis: Sources that impair dual-task performance at the beginning of practice are associated with mechanisms for the reduction of dual-task impairment at the end of practice. The following types of processes provide sources for the occurrence of this impairment: (a) capacity-limited processes within the component tasks, such as response-selection or motor response stages, and (b) cognitive control processes independent of these tasks and thus operating outside of component-task performance. Dual-task practice studies show that, under very specific conditions, capacity-limited processes within the component tasks are automatized with practice, reducing the interference between two simultaneous tasks. Further, there is evidence that response-selection stages are shortened with practice. Thus, capacity limitations at these stages are sources for dual-task costs at the beginning of practice and are overcome with practice. However, there is no evidence demonstrating the existence of practice-related mechanisms associated with capacity-limited motor-response stages. Further, during practice, there is an acquisition of executive control skills for an improved allocation of limited attention resources to two tasks as well as some evidence supporting the assumption of improved task coordination. These latter mechanisms are associated with sources of dual-task interference operating outside of component task performance at the beginning of practice and also contribute to the reduction of dual-task interference at its end. PMID:28439319

Dual targeting of gene delivery by genetic modification of adenovirus serotype 5 fibers and cell-selective transcriptional control.

PubMed

Work, L M; Ritchie, N; Nicklin, S A; Reynolds, P N; Baker, A H

2004-08-01

Adenovirus (Ad)-mediated gene delivery is a promising approach for genetic manipulation of the vasculature and is being used in both preclinical models and clinical trials. However, safety concerns relating to infection of nontarget tissue and the poor infectivity of vascular cells compared to other cell types necessitates Ad vector refinement. Here, we combine a transductional targeting approach to improve vascular cell infectivity through RGD peptide insertion into adenovirus fibers, combined with transcriptional targeting to endothelial cells using a approximately 1 kb fragment of the fms-like tyrosine kinase receptor-1 (FLT-1) promoter. Single- and double-modified vectors were characterized in human cell lines that either support or have silenced FLT-1 expression. In rat hepatocytes and endothelial cells, the double modification substantially shifted transduction profiles toward vascular endothelial cells. Furthermore, in intact aortae derived from spontaneously hypertensive rats that display enhanced alphav integrin expression on dysfunctional endothelium, enhanced levels of transduction were observed using the double-modified vector but not in aortae derived from normotensive control rats. Our data indicate that Ad-mediated transduction can be beneficially modified in vitro and in vivo by combining fiber modification and a cell-selective promoter within a single-component vector system.

Assimilation efficiency for sediment-sorbed benzo(a)pyrene by Diporeia spp.

USGS Publications Warehouse

Lydy, M.J.; Landrum, P.F.

1993-01-01

Two methods are currently available for determining contaminant assimilation efficiencies (AE) from ingested material in benthic invertebrates. These methods were compared using the Great Lakes amphipod Diporeia spp. and [14C]benzo(a)pyrene (BaP) sorbed to Florissant sediment (< 63 µm). The first approach, the direct measurement method, uses total organic carbon as a tracer and yielded AE values ranging from 45.9~50.4%. The second approach, the dual-labeled method, uses 51Cr as a non-assimilated tracer and did not yield AE values for our data. The inability of the dual-labeled approach to estimate AEs was due, in part, to the selective feeding by Diporeia resulting in a failure of the non-assimilated tracer (51Cr) to track with the assimilated tracer ([14C]BaP). The failure of the dual-labeled approach was not a result of an uneven distribution of the labels among particle size classes, but more likely resulted from differential sorption of the two isotopically labeled materials to particles of differing composition. The [14C]BaP apparently sorbs to organic particles that are selectively ingested, while the 51Cr apparently sorbs to particles which are selectively excluded by Diporeia. The dual-labeled approach would be a viable and easier experimental approach for determining AE values if the characteristics that govern selective feeding can be determined.

Single dose sublingual testosterone and oral sildenafil vs. a dual route/dual release fixed dose combination tablet: a pharmacokinetic comparison

PubMed Central

van Rooij, Kim; de Leede, Leo; Frijlink, Henderik W.; Koppeschaar, Hans P. F.; Olivier, Berend; Tuiten, Adriaan

2016-01-01

Aim The aim was to compare the pharmacokinetic profiles of two formulations of a combination drug product containing 0.5 mg testosterone and 50 mg sildenafil for female sexual interest/arousal disorder. The prototype (formulation 1) consists of a testosterone solution for sublingual administration and a sildenafil tablet that is administered 2.5 h later. The dual route/dual release fixed dose combination tablet (formulation 2) employs a sublingual and an oral route for systemic uptake. This tablet has an inner core of sildenafil with a polymeric time delay coating and an outer polymeric coating containing testosterone. It was designed to increase dosing practicality and decrease potential temporal non‐adherence through circumventing the relatively complex temporal dosing scheme. Methods Twelve healthy premenopausal subjects received both formulations randomly on separate days. Blood was sampled frequently to determine the pharmacokinetics of free testosterone, total testosterone, dihydrotestosterone, sildenafil and N‐desmethyl‐sildenafil. Results Formulation 2 had a higher maximum concentration (C max) for testosterone, 8.06 ng ml–1 (95% confidence interval [CI] 6.84, 9.28) and higher area under the plasma concentration–time curve (AUC), 7.69 ng ml–1 h (95% CI 6.22, 9.16) than formulation 1, 5.66 ng ml–1 (95% CI 4.63, 6.69) and 5.12 ng ml–1 h (95% CI 4.51, 5.73), respectively. Formulation 2 had a lower C max for sildenafil, 173 ng ml–1 (95% CI 126, 220) and a lower AUC, 476 ng ml–1 h (95% CI 401, 551) than formulation 1, 268 ng ml–1 (95% CI 188, 348) and 577 ng ml–1 h (95% CI 462, 692), respectively. Formulation 2 released sildenafil after 2.75 h (95% CI 2.40, 3.10). Conclusions The dual route/dual release fixed dose combination tablet fulfilled its design criteria and is considered suitable for further clinical testing. What is Already Known about this Subject Female sexual interest/arousal disorder (FSIAD) is a significant problem impacting psychological well‐being, but the pharmacotherapeutic options for this problem are lacking.The combined, on‐demand, sublingual administration of low dose sublingual testosterone and oral administration of sildenafil is a novel pharmacotherapeutic option under development for FSIAD.In proof‐of‐concept trials, these compounds were successfully administered via different dosage forms (sublingual and oral) at different time points (separated by 2.5 h) because of their markedly different pharmacokinetic–pharmacodynamic profiles. For future larger scale studies and the clinical practice, this raises obvious adherence issues. What this Study Adds A newly developed dual route/dual release fixed dose combination tablet containing testosterone and sildenafil mimics the pharmacokinetic profile of these components when they are administered as different dosage forms, 2.5 h apart.This combination tablet is a suitable final pharmaceutical drug product that will be used in future studies. PMID:26804967

Dual Vector Spaces and Physical Singularities

NASA Astrophysics Data System (ADS)

Rowlands, Peter

Though we often refer to 3-D vector space as constructed from points, there is no mechanism from within its definition for doing this. In particular, space, on its own, cannot accommodate the singularities that we call fundamental particles. This requires a commutative combination of space as we know it with another 3-D vector space, which is dual to the first (in a physical sense). The combination of the two spaces generates a nilpotent quantum mechanics/quantum field theory, which incorporates exact supersymmetry and ultimately removes the anomalies due to self-interaction. Among the many natural consequences of the dual space formalism are half-integral spin for fermions, zitterbewegung, Berry phase and a zero norm Berwald-Moor metric for fermionic states.

Absolute distance measurement by dual-comb interferometry with multi-channel digital lock-in phase detection

NASA Astrophysics Data System (ADS)

Yang, Ruitao; Pollinger, Florian; Meiners-Hagen, Karl; Krystek, Michael; Tan, Jiubin; Bosse, Harald

2015-08-01

We present a dual-comb-based heterodyne multi-wavelength absolute interferometer capable of long distance measurements. The phase information of the various comb modes is extracted in parallel by a multi-channel digital lock-in phase detection scheme. Several synthetic wavelengths of the same order are constructed and the corresponding phases are averaged to deduce the absolute lengths with significantly reduced uncertainty. Comparison experiments with an incremental HeNe reference interferometer show a combined relative measurement uncertainty of 5.3 × 10-7 at a measurement distance of 20 m. Combining the advantage of synthetic wavelength interferometry and dual-comb interferometry, our compact and simple approach provides sufficient precision for many industrial applications.

A novel "signal-on/off" sensing platform for selective detection of thrombin based on target-induced ratiometric electrochemical biosensing and bio-bar-coded nanoprobe amplification strategy.

PubMed

Wang, Lanlan; Ma, Rongna; Jiang, Liushan; Jia, Liping; Jia, Wenli; Wang, Huaisheng

2017-06-15

A novel dual-signal ratiometric electrochemical aptasensor for highly sensitive and selective detection of thrombin has been designed on the basis of signal-on and signal-off strategy. Ferrocene labeled hairpin probe (Fc-HP), thrombin aptamer and methyl blue labeled bio-bar-coded AuNPs (MB-P3-AuNPs) were rationally introduced for the construction of the assay platform, which combined the advantages of the recognition of aptamer, the amplification of bio-bar-coded nanoprobe, and the ratiometric signaling readout. In the presence of thrombin, the interaction between thrombin and the aptamer leads to the departure of MB-P3-AuNPs from the sensing interface, and the conformation of the single stranded Fc-HP to a hairpin structure to take the Fc confined near the electrode surface. Such conformational changes resulted in the oxidation current of Fc increased and that of MB decreased. Therefore, the recognition event of the target can be dual-signal ratiometric electrochemical readout in both the "signal-off" of MB and the "signal-on" of Fc. The proposed strategy showed a wide linear detection range from 0.003 to 30nM with a detection limit of 1.1 pM. Moreover, it exhibits good performance of excellent selectivity, good stability, and acceptable fabrication reproducibility. By changing the recognition probe, this protocol could be easily expanded into the detection of other targets, showing promising potential applications in disease diagnostics and bioanalysis. Copyright © 2016. Published by Elsevier B.V.

Dual methods and approximation concepts in structural synthesis

NASA Technical Reports Server (NTRS)

Fleury, C.; Schmit, L. A., Jr.

1980-01-01

Approximation concepts and dual method algorithms are combined to create a method for minimum weight design of structural systems. Approximation concepts convert the basic mathematical programming statement of the structural synthesis problem into a sequence of explicit primal problems of separable form. These problems are solved by constructing explicit dual functions, which are maximized subject to nonnegativity constraints on the dual variables. It is shown that the joining together of approximation concepts and dual methods can be viewed as a generalized optimality criteria approach. The dual method is successfully extended to deal with pure discrete and mixed continuous-discrete design variable problems. The power of the method presented is illustrated with numerical results for example problems, including a metallic swept wing and a thin delta wing with fiber composite skins.

Potassium-Based Dual Ion Battery with Dual-Graphite Electrode.

PubMed

Fan, Ling; Liu, Qian; Chen, Suhua; Lin, Kairui; Xu, Zhi; Lu, Bingan

2017-08-01

A potassium ion battery has potential applications for large scale electric energy storage systems due to the abundance and low cost of potassium resources. Dual graphite batteries, with graphite as both anode and cathode, eliminate the use of transition metal compounds and greatly lower the overall cost. Herein, combining the merits of the potassium ion battery and dual graphite battery, a potassium-based dual ion battery with dual-graphite electrode is developed. It delivers a reversible capacity of 62 mA h g -1 and medium discharge voltage of ≈3.96 V. The intercalation/deintercalation mechanism of K + and PF 6 - into/from graphite is proposed and discussed in detail, with various characterizations to support. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nonequilibrium atmospheric pressure plasma jet using a combination of 50 kHz/2 MHz dual-frequency power sources

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

Zhou, Yong-Jie; Yuan, Qiang-Hua; Li, Fei

2013-11-15

An atmospheric pressure plasma jet is generated by dual sinusoidal wave (50 kHz and 2 MHz). The dual-frequency plasma jet exhibits the advantages of both low frequency and radio frequency plasmas, namely, the long plasma plume and the high electron density. The radio frequency ignition voltage can be reduced significantly by using dual-frequency excitation compared to the conventional radio frequency without the aid of the low frequency excitation source. A larger operating range of α mode discharge can be obtained using dual-frequency excitation which is important to obtain homogeneous and low-temperature plasma. A larger controllable range of the gas temperaturemore » of atmospheric pressure plasma could also be obtained using dual-frequency excitation.« less

ACCESS 3. Approximation concepts code for efficient structural synthesis: User's guide

NASA Technical Reports Server (NTRS)

Fleury, C.; Schmit, L. A., Jr.

1980-01-01

A user's guide is presented for ACCESS-3, a research oriented program which combines dual methods and a collection of approximation concepts to achieve excellent efficiency in structural synthesis. The finite element method is used for structural analysis and dual algorithms of mathematical programming are applied in the design optimization procedure. This program retains all of the ACCESS-2 capabilities and the data preparation formats are fully compatible. Four distinct optimizer options were added: interior point penalty function method (NEWSUMT); second order primal projection method (PRIMAL2); second order Newton-type dual method (DUAL2); and first order gradient projection-type dual method (DUAL1). A pure discrete and mixed continuous-discrete design variable capability, and zero order approximation of the stress constraints are also included.

New knowledge-based genetic algorithm for excavator boom structural optimization

NASA Astrophysics Data System (ADS)

Hua, Haiyan; Lin, Shuwen

2014-03-01

Due to the insufficiency of utilizing knowledge to guide the complex optimal searching, existing genetic algorithms fail to effectively solve excavator boom structural optimization problem. To improve the optimization efficiency and quality, a new knowledge-based real-coded genetic algorithm is proposed. A dual evolution mechanism combining knowledge evolution with genetic algorithm is established to extract, handle and utilize the shallow and deep implicit constraint knowledge to guide the optimal searching of genetic algorithm circularly. Based on this dual evolution mechanism, knowledge evolution and population evolution can be connected by knowledge influence operators to improve the configurability of knowledge and genetic operators. Then, the new knowledge-based selection operator, crossover operator and mutation operator are proposed to integrate the optimal process knowledge and domain culture to guide the excavator boom structural optimization. Eight kinds of testing algorithms, which include different genetic operators, are taken as examples to solve the structural optimization of a medium-sized excavator boom. By comparing the results of optimization, it is shown that the algorithm including all the new knowledge-based genetic operators can more remarkably improve the evolutionary rate and searching ability than other testing algorithms, which demonstrates the effectiveness of knowledge for guiding optimal searching. The proposed knowledge-based genetic algorithm by combining multi-level knowledge evolution with numerical optimization provides a new effective method for solving the complex engineering optimization problem.

Synthesis, biological evaluation, and computational studies of Tri- and tetracyclic nitrogen-bridgehead compounds as potent dual-acting AChE inhibitors and hH3 receptor antagonists.

PubMed

Darras, Fouad H; Pockes, Steffen; Huang, Guozheng; Wehle, Sarah; Strasser, Andrea; Wittmann, Hans-Joachim; Nimczick, Martin; Sotriffer, Christoph A; Decker, Michael

2014-03-19

Combination of AChE inhibiting and histamine H3 receptor antagonizing properties in a single molecule might show synergistic effects to improve cognitive deficits in Alzheimer's disease, since both pharmacological actions are able to enhance cholinergic neurotransmission in the cortex. However, whereas AChE inhibitors prevent hydrolysis of acetylcholine also peripherally, histamine H3 antagonists will raise acetylcholine levels mostly in the brain due to predominant occurrence of the receptor in the central nervous system. In this work, we designed and synthesized two novel classes of tri- and tetracyclic nitrogen-bridgehead compounds acting as dual AChE inhibitors and histamine H3 antagonists by combining the nitrogen-bridgehead moiety of novel AChE inhibitors with a second N-basic fragment based on the piperidinylpropoxy pharmacophore with different spacer lengths. Intensive structure-activity relationships (SARs) with regard to both biological targets led to compound 41 which showed balanced affinities as hAChE inhibitor with IC50 = 33.9 nM, and hH3R antagonism with Ki = 76.2 nM with greater than 200-fold selectivity over the other histamine receptor subtypes. Molecular docking studies were performed to explain the potent AChE inhibition of the target compounds and molecular dynamics studies to explain high affinity at the hH3R.

Orthogonal Injection Ion Funnel Interface Providing Enhanced Performance for Selected Reaction Monitoring-Triple Quadrupole Mass Spectrometry

DOE PAGES

Chen, Tsung-Chi; Fillmore, Thomas L.; Prost, Spencer A.; ...

2015-06-24

The electrodynamic ion funnel facilitates efficient focusing and transfer of charged particles in the higher pressure regions (e.g. ion source interfaces) of mass spectrometers, and thus providing increased sensitivity. An “off-axis” ion funnel design has been developed to reduce the source contamination and interferences from, e.g. ESI droplet residue and other poorly focused neutral or charged particles with very high mass-to charge ratios. In this study a dual ion funnel interface consisting of an orthogonal higher pressure electrodynamic ion funnel (HPIF) and an ion funnel trap combined with a triple quadruple mass spectrometer was developed and characterized. An orthogonal ionmore » injection inlet and a repeller plate electrode was used to direct ions to an ion funnel HPIF at 9-10 Torr pressure. Several critical factors for the HPIF were characterized, including the effects of RF amplitude, DC gradient and operating pressure. Compared to the triple quadrupole standard interface more than 4-fold improvement in the limit of detection for the direct quantitative MS analysis of low abundance peptides was observed. Lastly, the sensitivity enhancement in liquid chromatography selected reaction monitoring (SRM) analyses of low abundance peptides spiked into a highly complex mixture was also compared with that obtained using a both commercial s-lens interface and a in-line dual ion funnel interface.« less

Orthogonal Injection Ion Funnel Interface Providing Enhanced Performance for Selected Reaction Monitoring-Triple Quadrupole Mass Spectrometry

PubMed Central

Chen, Tsung-Chi; Fillmore, Thomas L.; Prost, Spencer A.; Moore, Ronald J.; Ibrahim, Yehia M.; Smith, Richard D.

2016-01-01

The electrodynamic ion funnel facilitates efficient focusing and transfer of charged particles in the higher-pressure regions (e.g., ion source interfaces) of mass spectrometers, thus providing increased sensitivity. An “off-axis” ion funnel design has been developed to reduce the source contamination and interferences from, e.g. ESI droplet residue and other poorly focused neutral or charged particles with very high mass-to-charge ratios. In this study, a dual ion funnel interface consisting of an orthogonal higher pressure electrodynamic ion funnel (HPIF) and an ion funnel trap combined with a triple quadrupole mass spectrometer was developed and characterized. An orthogonal ion injection inlet and a repeller plate electrode was used to direct ions to an ion funnel HPIF at a pressure of 9–10 Torr. Key factors for the HPIF performance characterized included the effects of RF amplitude, the DC gradient, and operating pressure. Compared to the triple quadrupole standard interface more than 4-fold improvement in the limit of detection for the direct quantitative MS analysis of low abundance peptides was observed. The sensitivity enhancement in liquid chromatography selected reaction monitoring (LC-SRM) analyses of low-abundance peptides spiked into a highly complex mixture was also compared with that obtained using both a commercial S-lens interface and an in-line dual-ion funnel interface. PMID:26107611

De Novo Design and Synthesis of Ultra-Short Peptidomimetic Antibiotics Having Dual Antimicrobial and Anti-Inflammatory Activities

PubMed Central

Ahn, Mija; Hwang, Eunha; Sohn, Hoik; Park, Hyo-Nam; Lee, Eunjung; Seo, Ji-Hyung; Cheong, Chaejoon; Nam, Ky-Youb; Hyun, Jae-Kyung; Jeong, Ki-Woong; Kim, Yangmee; Shin, Song Yub; Bang, Jeong Kyu

2013-01-01

Background Much attention has been focused on the design and synthesis of potent, cationic antimicrobial peptides (AMPs) that possess both antimicrobial and anti-inflammatory activities. However, their development into therapeutic agents has been limited mainly due to their large size (12 to 50 residues in length) and poor protease stability. Methodology/Principal Findings In an attempt to overcome the issues described above, a set of ultra-short, His-derived antimicrobial peptides (HDAMPs) has been developed for the first time. Through systematic tuning of pendant hydrophobic alkyl tails at the N(π)- and N(τ)-positions on His, and the positive charge of Arg, much higher prokaryotic selectivity was achieved, compared to human AMP LL-37. Additionally, the most potent HDAMPs showed promising dual antimicrobial and anti-inflammatory activities, as well as anti–methicillin-resistant Staphylococcus aureus (MRSA) activity and proteolytic resistance. Our results from transmission electron microscopy, membrane depolarization, confocal laser-scanning microscopy, and calcein-dye leakage experiments propose that HDAMP-1 kills microbial cells via dissipation of the membrane potential by forming pore/ion channels on bacterial cell membranes. Conclusion/Significance The combination of the ultra-short size, high-prokaryotic selectivity, potent anti-MRSA activity, anti-inflammatory activity, and proteolytic resistance of the designed HDAMP-1, -3, -5, and -6 makes these molecules promising candidates for future antimicrobial therapeutics. PMID:24302996

Fluorescent carbon dot-gated multifunctional mesoporous silica nanocarriers for redox/enzyme dual-responsive targeted and controlled drug delivery and real-time bioimaging.

PubMed

Wang, Ying; Cui, Yu; Zhao, Yating; He, Bing; Shi, Xiaoli; Di, Donghua; Zhang, Qiang; Wang, Siling

2017-08-01

A distinctive and personalized nanocarrier is described here for controlled and targeted antitumor drug delivery and real-time bioimaging by combining a redox/enzyme dual-responsive disulfide-conjugated carbon dot with mesoporous silica nanoparticles (MSN-SS-CD HA ). The carbon dot with controlling and targeting abilities was prepared through a polymerizing reaction by applying citric acid and HA as starting materials (named CD HA ). The as-prepared MSN-SS-CD HA exhibited not only superior photostability and excellent biocompatibility, but also the ability to target A549 cells with overexpression of CD44 receptors. Upon loading the antitumor drug, doxorubicin (DOX), into the mesoporous channels of MSN nanoparticles, CD HA with a diameter size of 3nm completely blocked the pore entrance of DOX-encapsulated MSN nanoparticles with a pore size of about 3nm, thus preventing the premature leakage of DOX and increasing the antitumor activity until being triggered by specific stimuli in the tumor environment. The results of the cell imaging and cytotoxicity studies demonstrated that the redox/enzyme dual-responsive DOX-encapsulated MSN-SS-CD HA nanoparticles can selectively deliver and control the release of DOX into tumor cells. Ex vivo fluorescence images showed a much stronger fluorescence of MSN-SS-CD HA -DOX in the tumor site than in normal tissues, greatly facilitating the accumulation of DOX in the target tissue. However, its counterpart, MSN-SH-DOX exhibited no or much lower tumor cytotoxicity and drug accumulation in tumor tissue. In addition, MSN-SS-CD was also used as a control to investigate the ability of MSN-SS-CD HA to target A549 cells. The results obtained indicated that MSN-SS-CD HA possessed a higher cellular uptake through the CD44 receptor-mediated endocytosis compared with MSN-SS-CD in the A549 cells. Such specific redox/enzyme dual-responsive targeted nanocarriers are a useful strategy achieving selective controlled and targeted delivery of therapeutic reagents with real-time bioimaging, and may also facilitate the development of drug delivery systems for a number of clinical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Fabrication of scalable tissue engineering scaffolds with dual-pore microarchitecture by combining 3D printing and particle leaching.

PubMed

Mohanty, Soumyaranjan; Sanger, Kuldeep; Heiskanen, Arto; Trifol, Jon; Szabo, Peter; Dufva, Marin; Emnéus, Jenny; Wolff, Anders

2016-04-01

Limitations in controlling scaffold architecture using traditional fabrication techniques are a problem when constructing engineered tissues/organs. Recently, integration of two pore architectures to generate dual-pore scaffolds with tailored physical properties has attracted wide attention in tissue engineering community. Such scaffolds features primary structured pores which can efficiently enhance nutrient/oxygen supply to the surrounding, in combination with secondary random pores, which give high surface area for cell adhesion and proliferation. Here, we present a new technique to fabricate dual-pore scaffolds for various tissue engineering applications where 3D printing of poly(vinyl alcohol) (PVA) mould is combined with salt leaching process. In this technique the sacrificial PVA mould, determining the structured pore architecture, was filled with salt crystals to define the random pore regions of the scaffold. After crosslinking the casted polymer the combined PVA-salt mould was dissolved in water. The technique has advantages over previously reported ones, such as automated assembly of the sacrificial mould, and precise control over pore architecture/dimensions by 3D printing parameters. In this study, polydimethylsiloxane and biodegradable poly(ϵ-caprolactone) were used for fabrication. However, we show that this technique is also suitable for other biocompatible/biodegradable polymers. Various physical and mechanical properties of the dual-pore scaffolds were compared with control scaffolds with either only structured or only random pores, fabricated using previously reported methods. The fabricated dual-pore scaffolds supported high cell density, due to the random pores, in combination with uniform cell distribution throughout the scaffold, and higher cell proliferation and viability due to efficient nutrient/oxygen transport through the structured pores. In conclusion, the described fabrication technique is rapid, inexpensive, scalable, and compatible with different polymers, making it suitable for engineering various large scale organs/tissues. Copyright © 2015. Published by Elsevier B.V.

The action of chemical and mechanical stresses on single and dual species biofilm removal of drinking water bacteria.

PubMed

Gomes, I B; Lemos, M; Mathieu, L; Simões, M; Simões, L C

2018-08-01

The presence of biofilms in drinking water distribution systems (DWDS) is a global public health concern as they can harbor pathogenic microorganisms. Sodium hypochlorite (NaOCl) is the most commonly used disinfectant for microbial growth control in DWDS. However, its effect on biofilm removal is still unclear. This work aims to evaluate the effects of the combination of chemical (NaOCl) and mechanical stresses on the removal of single and dual species biofilms of two bacteria isolated from DWDS and considered opportunistic, Acinectobacter calcoaceticus and Stenotrophomonas maltophilia. A rotating cylinder reactor was successfully used for the first time in drinking water biofilm studies with polyvinyl chloride as substratum. The single and dual species biofilms presented different characteristics in terms of metabolic activity, mass, density, thickness and content of proteins and polysaccharides. Their complete removal was not achieved even when a high NaOCl concentrations and an increasing series of shear stresses (from 2 to 23Pa) were applied. In general, NaOCl pre-treatment did not improve the impact of mechanical stress on biofilm removal. Dual species biofilms were colonized mostly by S. maltophilia and were more susceptible to chemical and mechanical stresses than these single species. The most efficient treatment (93% biofilm removal) was the combination of NaOCl at 175mg·l -1 with mechanical stress against dual species biofilms. Of concern was the high tolerance of S. maltophilia to chemical and mechanical stresses in both single and dual species biofilms. The overall results demonstrate the inefficacy of NaOCl on biofilm removal even when combined with high shear stresses. Copyright © 2018 Elsevier B.V. All rights reserved.

Cancel and rethink in the Wason selection task: further evidence for the heuristic-analytic dual process theory.

PubMed

Wada, Kazushige; Nittono, Hiroshi

2004-06-01

The reasoning process in the Wason selection task was examined by measuring card inspection times in the letter-number and drinking-age problems. 24 students were asked to solve the problems presented on a computer screen. Only the card touched with a mouse pointer was visible, and the total exposure time of each card was measured. Participants were allowed to cancel their previous selections at any time. Although rethinking was encouraged, the cards once selected were rarely cancelled (10% of the total selections). Moreover, most of the cancelled cards were reselected (89% of the total cancellations). Consistent with previous findings, inspection times were longer for selected cards than for nonselected cards. These results suggest that card selections are determined largely by initial heuristic processes and rarely reversed by subsequent analytic processes. The present study gives further support for the heuristic-analytic dual process theory.

Nonmathematical models for evolution of altruism, and for group selection (peck order-territoriality-ant colony-dual-determinant model-tri-determinant model).

PubMed

Darlington, P J

1972-02-01

Mathematical biologists have failed to produce a satisfactory general model for evolution of altruism, i.e., of behaviors by which "altruists" benefit other individuals but not themselves; kin selection does not seem to be a sufficient explanation of nonreciprocal altruism. Nonmathematical (but mathematically acceptable) models are now proposed for evolution of negative altruism in dual-determinant and of positive altruism in tri-determinant systems. Peck orders, territorial systems, and an ant society are analyzed as examples. In all models, evolution is primarily by individual selection, probably supplemented by group selection. Group selection is differential extinction of populations. It can act only on populations preformed by selection at the individual level, but can either cancel individual selective trends (effecting evolutionary homeostasis) or supplement them; its supplementary effect is probably increasingly important in the evolution of increasingly organized populations.

Rational adaptation under task and processing constraints: implications for testing theories of cognition and action.

PubMed

Howes, Andrew; Lewis, Richard L; Vera, Alonso

2009-10-01

The authors assume that individuals adapt rationally to a utility function given constraints imposed by their cognitive architecture and the local task environment. This assumption underlies a new approach to modeling and understanding cognition-cognitively bounded rational analysis-that sharpens the predictive acuity of general, integrated theories of cognition and action. Such theories provide the necessary computational means to explain the flexible nature of human behavior but in doing so introduce extreme degrees of freedom in accounting for data. The new approach narrows the space of predicted behaviors through analysis of the payoff achieved by alternative strategies, rather than through fitting strategies and theoretical parameters to data. It extends and complements established approaches, including computational cognitive architectures, rational analysis, optimal motor control, bounded rationality, and signal detection theory. The authors illustrate the approach with a reanalysis of an existing account of psychological refractory period (PRP) dual-task performance and the development and analysis of a new theory of ordered dual-task responses. These analyses yield several novel results, including a new understanding of the role of strategic variation in existing accounts of PRP and the first predictive, quantitative account showing how the details of ordered dual-task phenomena emerge from the rational control of a cognitive system subject to the combined constraints of internal variance, motor interference, and a response selection bottleneck.

Microstrip Yagi Antenna with Dual Aperture-Coupled Feed

NASA Technical Reports Server (NTRS)

Pogorzelski, Ronald; Venkatesan, Jaikrishna

2008-01-01

A proposed microstrip Yagi antenna would operate at a frequency of 8.4 GHz (which is in the X band) and would feature a mechanically simpler, more elegant design, relative to a prior L-band microstrip Yagi antenna. In general, the purpose of designing a microstrip Yagi antenna is to combine features of a Yagi antenna with those of a microstrip patch to obtain an antenna that can be manufactured at low cost, has a low profile, and radiates a directive beam that, as plotted on an elevation plane perpendicular to the antenna plane, appears tilted away from the broadside. Such antennas are suitable for flush mounting on surfaces of diverse objects, including spacecraft, aircraft, land vehicles, and computers. Stated somewhat more precisely, what has been proposed is a microstrip antenna comprising an array of three Yagi elements. Each element would include four microstrip-patch Yagi subelements: one reflector patch, one driven patch, and two director patches. To obtain circular polarization, each driven patch would be fed by use of a dual offset aperture-coupled feed featuring bow-tie-shaped apertures. The selection of the dual offset bow-tie aperture geometry is supported by results found in published literature that show that this geometry would enable matching of the impedances of the driven patches to the 50-Omega impedance of the microstrip feedline while maintaining a desirably large front-to-back lobe ratio.

Fringe formation in dual-hologram interferometry

NASA Technical Reports Server (NTRS)

Burner, A. W.

1990-01-01

Reference-fringe formation in nondiffuse dual-hologram interferometry is described by combining a first-order geometrical hologram treatment with interference fringes generated by two point sources. The first-order imaging relationships can be used to describe reference-fringe patterns for the geometry of the dual-hologram interferometry. The process can be completed without adjusting the two holograms when the reconstructing wavelength is less than the exposing wavelength, and the process is found to facilitate basic intereferometer adjustments.

The Incidence of Buried Dual AGN in Advanced Mergers: New results from Chandra

NASA Astrophysics Data System (ADS)

Pfeifle, Ryan William; Satyapal, Shobita; Secrest, Nathan; Gliozzi, Mario; Ricci, Claudio; Ellison, Sara L.; Blecha, Laura; Rothberg, Barry; Constantin, Anca

2018-01-01

Since the vast majority of galaxies contain supermassive black holes (SMBHs) and galaxy interactions trigger nuclear gas accretion, a direct consequence of the hierarchical model of galaxy formation would be the existence of dual active galactic nuclei (AGN). The existence, frequency, and characteristics of such dual AGN have important astrophysical implications on the SMBH mass function, the interplay between SMBHs and the host galaxy, and the M-sigma relation. Despite decades of searching, and strong theoretical reasons for their existence, observationally confirmed cases of dual AGN are extremely rare, and most have been discovered serendipitously. Using the all-sky WISE survey, we identified a population of over one hundred strongly interacting galaxies that display extreme red mid-infrared colors thus far exclusively associated with extragalactic sources possessing powerful AGN. In a recent Chandra, XMM-Newton, and NuSTAR investigation of advanced mergers selected by WISE, we find dual AGN candidates in 8 out of 15 mergers, all of which show no evidence for AGN based on optical spectroscopy. Our results demonstrate that 1) optical studies miss a significant fraction of single and dual AGN in advanced mergers, and 2) mid-infrared pre-selection is extremely effective in identifying dual AGN candidates in late-stage mergers. Our multi-wavelength observations suggest that the buried AGN in these mergers are highly absorbed, with intrinsic column densities in excess of NH > 1024 cm-2, consistent with hydrodynamic simulations.

Assessment of Risk Reduction for Lymphedema Following Sentinel Lymph Noded Guided Surgery for Primary Breast Cancer

DTIC Science & Technology

2006-10-01

patients with breast cancer underwent scanning with a hybrid camera which combined a dual-head SPECT camera and a low-dose, single slice CT scanner , (GE...investigated a novel approach which combines the output of a dual-head SPECT camera and a low-dose, single slice CT scanner , (GE Hawkeye®). This... scanner , (Hawkeye®, GE Medical system) is attempted in this study. This device is widely available in cardiology community and has the potential to

Dual-color three-dimensional STED microscopy with a single high-repetition-rate laser

PubMed Central

Han, Kyu Young; Ha, Taekjip

2016-01-01

We describe a dual-color three-dimensional stimulated emission depletion (3D-STED) microscopy employing a single laser source with a repetition rate of 80 MHz. Multiple excitation pulses synchronized with a STED pulse were generated by a photonic crystal fiber and the desired wavelengths were selected by an acousto-optic tunable filter with high spectral purity. Selective excitation at different wavelengths permits simultaneous imaging of two fluorescent markers at a nanoscale resolution in three dimensions. PMID:26030581

Enhancement of the static extinction ratio by using a dual-section distributed feedback laser integrated with an electro-absorption modulator

NASA Astrophysics Data System (ADS)

Cho, Chun-Hyung; Kim, Jongseong; Sung, Hyuk-Kee

2016-09-01

We report on the enhancement of the static extinction ratio by using a dual-section distributed feedback laser diode integrated with an electro-absorption modulator. A directly- modulated dual-section laser can provide improved modulation performance under a low bias level ( i.e., below the threshold level) compared with a standard directly-modulated laser. By combining the extinction ratio from a dual-section laser with that from an electro-absorption modulator section, a total extinction ratio of 49.6. dB are successfully achieved.

Proteasome inhibition by new dual warhead containing peptido vinyl sulfonyl fluorides.

PubMed

Brouwer, Arwin J; Herrero Álvarez, Natalia; Ciaffoni, Adriano; van de Langemheen, Helmus; Liskamp, Rob M J

2016-08-15

The success of inhibition of the proteasome by formation of covalent bonds is a major victory over the long held-view that this would lead to binding the wrong targets and undoubtedly lead to toxicity. Great challenges are now found in uncovering ensembles of new moieties capable of forming long lasting ties. We have introduced peptido sulfonyl fluorides for this purpose. Tuning the reactivity of this electrophilic trap may be crucial for modulating the biological action. Here we describe incorporation of a vinyl moiety into a peptido sulfonyl fluoride backbone, which should lead to a combined attack of the proteasome active site threonine on the double bond and the sulfonyl fluoride. Although this led to strong proteasome inhibitors, in vitro studies did not unambiguously demonstrate the formation of the proposed seven-membered ring structure. Possibly, formation of a seven-membered covalent adduct with the proteosomal active site threonine can only be achieved within the context of the enzyme. Nevertheless, this dual warhead concept may provide exclusive possibilities for duration and selectivity of proteasome inhibition. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dual-Pitch Processing Mechanisms in Primate Auditory Cortex

PubMed Central

Bendor, Daniel; Osmanski, Michael S.

2012-01-01

Pitch, our perception of how high or low a sound is on a musical scale, is a fundamental perceptual attribute of sounds and is important for both music and speech. After more than a century of research, the exact mechanisms used by the auditory system to extract pitch are still being debated. Theoretically, pitch can be computed using either spectral or temporal acoustic features of a sound. We have investigated how cues derived from the temporal envelope and spectrum of an acoustic signal are used for pitch extraction in the common marmoset (Callithrix jacchus), a vocal primate species, by measuring pitch discrimination behaviorally and examining pitch-selective neuronal responses in auditory cortex. We find that pitch is extracted by marmosets using temporal envelope cues for lower pitch sounds composed of higher-order harmonics, whereas spectral cues are used for higher pitch sounds with lower-order harmonics. Our data support dual-pitch processing mechanisms, originally proposed by psychophysicists based on human studies, whereby pitch is extracted using a combination of temporal envelope and spectral cues. PMID:23152599

Gastrointestinal Hemorrhage Related to Fluoxetine in a Patient With Stroke.

PubMed

Wee, Tze Chao

2017-11-01

We report on a patient who developed massive gastrointestinal hemorrhage related to the use of fluoxetine in combination with aspirin and clopidogrel. A 58-year-old man was admitted with a posterior circulation infarct with significant weakness in all four limbs and dysarthria. Aspirin and clopidogrel were started. Fluoxetine was started for pharmacological neurostimulation to promote motor recovery and for low mood. He developed gastrointestinal hemorrhage a week after fluoxetine was started. Fluoxetine was suspended and investigations failed to reveal the source of the bleeding. He was then restarted on fluoxetine along with dual antiplatelets, and gastrointestinal hemorrhage recurred after 1 week. He was extensively investigated for a source of gastrointestinal hemorrhage, and again no source could be identified. Eventually, fluoxetine was switched to mirtazapine with no further gastrointestinal hemorrhage. He remained on dual antiplatelets. A number of case-control and cohort studies had identified the association of gastrointestinal hemorrhage with the use of selective serotonin reuptake inhibitor (SSRI). We hope to raise awareness of this association in physical medicine and rehabilitation physicians as the use of SSRI is expected to rise.

Inhibition of the renin-angiotensin-aldosterone system: is there room for dual blockade in the cardiorenal continuum?

PubMed

Volpe, Massimo; Danser, A H Jan; Menard, Joël; Waeber, Bernard; Mueller, Dominik N; Maggioni, Aldo P; Ruilope, Luis M

2012-04-01

Antagonism of renin-angiotensin-aldosterone system is exerted through angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists, renin inhibitors and mineralocorticoid receptor antagonists. These drugs have been successfully tested in numerous trials and in different clinical settings. The original indications of renin-angiotensin-aldosterone system blockers have progressively expanded from the advanced stages to the earlier stages of cardiorenal continuum. To optimize the degree of blockade of renin-angiotensin-aldosterone system, dose uptitrations of angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists or the use of a dual blockade, initially identified with the combination of angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists, have been proposed. The data from the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) study do not support this specific dual blockade approach. However, the dual blockade of angiotensin-converting enzyme inhibitors/angiotensin receptor antagonists with direct renin inhibitors is currently under investigation while that based on an aldosterone blocker with any of the previous three drugs requires more evidence beyond heart failure. In this review, we revisited potential advantages of dual blockade of renin-angiotensin-aldosterone system in arterial hypertension and diabetes.

A Combined Cognitive Stimulation and Physical Exercise Programme (MINDVital) in Early Dementia: Differential Effects on Single- and Dual-Task Gait Performance.

PubMed

Tay, Laura; Lim, Wee Shiong; Chan, Mark; Ali, Noorhazlina; Chong, Mei Sian

2016-01-01

Gait disorders are common in early dementia, with particularly pronounced dual-task deficits, contributing to the increased fall risk and mobility decline associated with cognitive impairment. This study examines the effects of a combined cognitive stimulation and physical exercise programme (MINDVital) on gait performance under single- and dual-task conditions in older adults with mild dementia. Thirty-nine patients with early dementia participated in a multi-disciplinary rehabilitation programme comprising both physical exercise and cognitive stimulation. The programme was conducted in 8-week cycles with participants attending once weekly, and all participants completed 2 successive cycles. Cognitive, functional performance and behavioural symptoms were assessed at baseline and at the end of each 8-week cycle. Gait speed was examined under both single- (Timed Up and Go and 6-metre walk tests) and dual-task (animal category and serial counting) conditions. A random effects model was performed for the independent effect of MINDVital on the primary outcome variable of gait speed under dual-task conditions. The mean age of patients enroled in the rehabilitation programme was 79 ± 6.2 years; 25 (64.1%) had a diagnosis of Alzheimer's dementia, and 26 (66.7%) were receiving a cognitive enhancer therapy. There was a significant improvement in cognitive performance [random effects coefficient (standard error) = 0.90 (0.31), p = 0.003] and gait speed under both dual-task situations [animal category: random effects coefficient = 0.04 (0.02), p = 0.039; serial counting: random effects coefficient = 0.05 (0.02), p = 0.013], with reduced dual-task cost for gait speed [serial counting: random effects coefficient = -4.05 (2.35), p = 0.086] following successive MINDVital cycles. No significant improvement in single-task gait speed was observed. Improved cognitive performance over time was a significant determinant of changes in dual-task gait speed [random effects coefficients = 0.01 (0.005), p = 0.048, and 0.02 (0.005), p = 0.003 for category fluency and counting backwards, respectively]. A combined physical and cognitive rehabilitation programme leads to significant improvements in dual-task walking in early dementia, which may be contributed by improvement in cognitive performance, as single-task gait performance remained stable. © 2016 S. Karger AG, Basel.

Direct synthesis of ethanol from dimethyl ether and syngas over combined H-Mordenite and Cu/ZnO catalysts.

PubMed

Li, Xingang; San, Xiaoguang; Zhang, Yi; Ichii, Takashi; Meng, Ming; Tan, Yisheng; Tsubaki, Noritatsu

2010-10-25

Ethanol was directly synthesized from dimethyl ether (DME) and syngas with the combined H-Mordenite and Cu/ZnO catalysts that were separately loaded in a dual-catalyst bed reactor. Methyl acetate (MA) was formed by DME carbonylation over the H-Mordenite catalyst. Thereafter, ethanol and methanol were produced by MA hydrogenation over the Cu/ZnO catalyst. With the reactant gas containing 1.0% DME, the optimized temperature for the reaction was at 493 K to reach 100% conversion. In the products, the yield of methanol and ethanol could reach 46.3% and 42.2%, respectively, with a small amount of MA, ethyl acetate, and CO(2). This process is environmentally friendly as the main byproduct methanol can be recycled to DME by a dehydration reaction. In contrast, for the physically mixed catalysts, the low conversion of DME and high selectivity of methanol were observed.

Near-field spectroscopic investigation of dual-band heavy fermion metamaterials.

PubMed

Gilbert Corder, Stephanie N; Chen, Xinzhong; Zhang, Shaoqing; Hu, Fengrui; Zhang, Jiawei; Luan, Yilong; Logan, Jack A; Ciavatti, Thomas; Bechtel, Hans A; Martin, Michael C; Aronson, Meigan; Suzuki, Hiroyuki S; Kimura, Shin-Ichi; Iizuka, Takuya; Fei, Zhe; Imura, Keiichiro; Sato, Noriaki K; Tao, Tiger H; Liu, Mengkun

2017-12-22

Broadband tunability is a central theme in contemporary nanophotonics and metamaterials research. Combining metamaterials with phase change media offers a promising approach to achieve such tunability, which requires a comprehensive investigation of the electromagnetic responses of novel materials at subwavelength scales. In this work, we demonstrate an innovative way to tailor band-selective electromagnetic responses at the surface of a heavy fermion compound, samarium sulfide (SmS). By utilizing the intrinsic, pressure sensitive, and multi-band electron responses of SmS, we create a proof-of-principle heavy fermion metamaterial, which is fabricated and characterized using scanning near-field microscopes with <50 nm spatial resolution. The optical responses at the infrared and visible frequency ranges can be selectively and separately tuned via modifying the occupation of the 4f and 5d band electrons. The unique pressure, doping, and temperature tunability demonstrated represents a paradigm shift for nanoscale metamaterial and metasurface design.

Comparison of element-specific capillary chromotography detectors for the identification of heteroatomic species in coal liquids

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

Mitchell, S.C.; Bartle, K.D.; Holden, K.M.L.

1994-12-31

A series of heteroatom-rich coal and coal-derived liquids have been analysed using gas chromatography (GC) in combination with three different element-selective detectors. Selected chromatograms, including a supercritical extract (Mequinenza lignite) and aromatic fractions isolated from coal tar pitch samples are presented. In each case a series of sulphur- and/or nitrogen-containing compounds have been identified using either flame photometric detection (GC/FID/FPD) or nitrogen-phosphorous detection (GC/FID/NPD) and the information compared with that obtained from a GC coupled to an atomic emission detector (GC-AED). Preliminary results have demonstrated the relative response characteristics of each detector and their respective ability to acquire qualitative andmore » quantitative information in interfering background matrices. Further, due to the unique capabilities of GC-AED, a number of dual heteroatomic (sulphur-oxygen and nitrogen-oxygen) compounds have been identified.« less

Near-field spectroscopic investigation of dual-band heavy fermion metamaterials

DOE PAGES

Gilbert Corder, Stephanie N.; Chen, Xinzhong; Zhang, Shaoqing; ...

2017-12-22

Broadband tunability is a central theme in contemporary nanophotonics and metamaterials research. Combining metamaterials with phase change media offers a promising approach to achieve such tunability, which requires a comprehensive investigation of the electromagnetic responses of novel materials at subwavelength scales. In this work, we demonstrate an innovative way to tailor band-selective electromagnetic responses at the surface of a heavy fermion compound, samarium sulfide (SmS). By utilizing the intrinsic, pressure sensitive, and multi-band electron responses of SmS, we create a proof-of-principle heavy fermion metamaterial, which is fabricated and characterized using scanning near-field microscopes with < 50 nm spatial resolution. Themore » optical responses at the infrared and visible frequency ranges can be selectively and separately tuned via modifying the occupation of the 4f and 5d band electrons. The unique pressure, doping, and temperature tunability demonstrated represents a paradigm shift for nanoscale metamaterial and metasurface design.« less

Automatic-heuristic and executive-analytic processing during reasoning: Chronometric and dual-task considerations.

PubMed

De Neys, Wim

2006-06-01

Human reasoning has been shown to overly rely on intuitive, heuristic processing instead of a more demanding analytic inference process. Four experiments tested the central claim of current dual-process theories that analytic operations involve time-consuming executive processing whereas the heuristic system would operate automatically. Participants solved conjunction fallacy problems and indicative and deontic selection tasks. Experiment 1 established that making correct analytic inferences demanded more processing time than did making heuristic inferences. Experiment 2 showed that burdening the executive resources with an attention-demanding secondary task decreased correct, analytic responding and boosted the rate of conjunction fallacies and indicative matching card selections. Results were replicated in Experiments 3 and 4 with a different secondary-task procedure. Involvement of executive resources for the deontic selection task was less clear. Findings validate basic processing assumptions of the dual-process framework and complete the correlational research programme of K. E. Stanovich and R. F. West (2000).

Discovery of OSI-906: a selective and orally efficacious dual inhibitor of the IGF-1 receptor and insulin receptor.

PubMed

Mulvihill, Mark J; Cooke, Andrew; Rosenfeld-Franklin, Maryland; Buck, Elizabeth; Foreman, Ken; Landfair, Darla; O'Connor, Matthew; Pirritt, Caroline; Sun, Yingchaun; Yao, Yan; Arnold, Lee D; Gibson, Neil W; Ji, Qun-Sheng

2009-09-01

The IGF-1 receptor (IGF-1R) has been implicated in the promotion of tumorigenesis, metastasis and resistance to cancer therapies. Therefore, this receptor has become a major focus for the development of anticancer agents. Our lead optimization efforts that blended structure-based design and empirical medicinal chemistry led to the discovery of OSI-906, a novel small-molecule dual IGF-1R/insulin receptor (IR) kinase inhibitor. OSI-906 potently and selectively inhibits autophosphorylation of both human IGF-1R and IR, displays in vitro antiproliferative effects in a variety of tumor cell lines and shows robust in vivo anti-tumor efficacy in an IGF-1R-driven xenograft model when administered orally once daily. OSI-906 is a novel, potent, selective and orally bioavailable dual IGF-1R/IR kinase inhibitor with favorable preclinical drug-like properties, which has demonstrated in vivo efficacy in tumor models and is currently in clinical testing.

Dual-comb spectroscopy of water vapor with a free-running semiconductor disk laser.

PubMed

Link, S M; Maas, D J H C; Waldburger, D; Keller, U

2017-06-16

Dual-comb spectroscopy offers the potential for high accuracy combined with fast data acquisition. Applications are often limited, however, by the complexity of optical comb systems. Here we present dual-comb spectroscopy of water vapor using a substantially simplified single-laser system. Very good spectroscopy measurements with fast sampling rates are achieved with a free-running dual-comb mode-locked semiconductor disk laser. The absolute stability of the optical comb modes is characterized both for free-running operation and with simple microwave stabilization. This approach drastically reduces the complexity for dual-comb spectroscopy. Band-gap engineering to tune the center wavelength from the ultraviolet to the mid-infrared could optimize frequency combs for specific gas targets, further enabling dual-comb spectroscopy for a wider range of industrial applications. Copyright © 2017, American Association for the Advancement of Science.

A Small Business Management Entrepreneurship Curriculum: A Dual Progression Experience.

ERIC Educational Resources Information Center

Kuratko, Donald; LaFollette, William R.

1986-01-01

Describes Ball State University's "dual progression" curriculum for the small business management program. The program seeks to combine the best elements of entrepreneurial theory with the difficult facets of practical experience. The five major component courses (small business ventures, entrepreneurship, management information systems,…

Passive dual spin misalignment compensators. [gyrostabilized device

NASA Technical Reports Server (NTRS)

Donohue, J. H.; Zimmerman, B. G. (Inventor)

1974-01-01

A combination dual-spin gyroscopically stabilized device is described having a spinning rotor and a non-spinning platform. Two substantially lossless mechanical resonators, resonant at the spin frequency, are orthogonally positioned on the platform for compensation for the disturbing torque acting on the platform due to rotor misalignment.

Decision Making in Concurrent Multitasking: Do People Adapt to Task Interference?

PubMed Central

Nijboer, Menno; Taatgen, Niels A.; Brands, Annelies; Borst, Jelmer P.; van Rijn, Hedderik

2013-01-01

While multitasking has received a great deal of attention from researchers, we still know little about how well people adapt their behavior to multitasking demands. In three experiments, participants were presented with a multicolumn subtraction task, which required working memory in half of the trials. This primary task had to be combined with a secondary task requiring either working memory or visual attention, resulting in different types of interference. Before each trial, participants were asked to choose which secondary task they wanted to perform concurrently with the primary task. We predicted that if people seek to maximize performance or minimize effort required to perform the dual task, they choose task combinations that minimize interference. While performance data showed that the predicted optimal task combinations indeed resulted in minimal interference between tasks, the preferential choice data showed that a third of participants did not show any adaptation, and for the remainder it took a considerable number of trials before the optimal task combinations were chosen consistently. On the basis of these results we argue that, while in principle people are able to adapt their behavior according to multitasking demands, selection of the most efficient combination of strategies is not an automatic process. PMID:24244527

The pyrrolo-1,5-benzoxazepine, PBOX-15, enhances TRAIL-induced apoptosis by upregulation of DR5 and downregulation of core cell survival proteins in acute lymphoblastic leukaemia cells

PubMed Central

NATHWANI, SEEMA-MARIA; GREENE, LISA M.; BUTINI, STEFANIA; CAMPIANI, GIUSEPPE; WILLIAMS, D. CLIVE; SAMALI, AFSHIN; SZEGEZDI, EVA; ZISTERER, DANIELA M.

2016-01-01

Apoptotic defects are frequently associated with poor outcome in pediatric acute lymphoblastic leukaemia (ALL) hence there is an ongoing demand for novel strategies that counteract apoptotic resistance. The death ligand TRAIL (tumour necrosis factor-related apoptosis-inducing ligand) and its selective tumour receptor system has attracted exceptional clinical interest. However, many malignancies including ALL are resistant to TRAIL monotherapy. Tumour resistance can be overcome by drug combination therapy. TRAIL and its agonist antibodies are currently undergoing phase II clinical trials with established chemotherapeutics. Herein, we present promising therapeutic benefits in combining TRAIL with the selective anti-leukaemic agents, the pyrrolo-1,5-benzoxazepines (PBOXs) for the treatment of ALL. PBOX-15 synergistically enhanced apoptosis induced by TRAIL and a DR5-selective TRAIL variant in ALL-derived cells. PBOX-15 enhanced TRAIL-induced apoptosis by dual activation of extrinsic and intrinsic apoptotic pathways. The specific caspase-8 inhibitor, Z-IETD-FMK, identified the extrinsic pathway as the principal mode of apoptosis. We demonstrate that PBOX-15 can enhance TRAIL-induced apoptosis by upregulation of DR5, reduction of cellular mitochondrial potential, activation of the caspase cascade and downregulation of PI3K/Akt, c-FLIP, Mcl-1 and IAP survival pathways. Of note, the PI3K pathway inhibitor LY-294002 significantly enhanced the apoptotic potential of TRAIL and PBOX-15 validating the importance of Akt downregulation in the TRAIL/PBOX-15 synergistic combination. Considering the lack of cytotoxicity to normal cells and ability to downregulate several survival pathways, PBOX-15 may represent an effective agent for use in combination with TRAIL for the treatment of ALL. PMID:27176505

Method for making field-structured memory materials

DOEpatents

Martin, James E.; Anderson, Robert A.; Tigges, Chris P.

2002-01-01

A method of forming a dual-level memory material using field structured materials. The field structured materials are formed from a dispersion of ferromagnetic particles in a polymerizable liquid medium, such as a urethane acrylate-based photopolymer, which are applied as a film to a support and then exposed in selected portions of the film to an applied magnetic or electric field. The field can be applied either uniaxially or biaxially at field strengths up to 150 G or higher to form the field structured materials. After polymerizing the field-structure materials, a magnetic field can be applied to selected portions of the polymerized field-structured material to yield a dual-level memory material on the support, wherein the dual-level memory material supports read-and-write binary data memory and write once, read many memory.

Using dual-domain advective-transport simulation to reconcile multiple-tracer ages and estimate dual-porosity transport parameters

NASA Astrophysics Data System (ADS)

Sanford, Ward E.; Niel Plummer, L.; Casile, Gerolamo; Busenberg, Ed; Nelms, David L.; Schlosser, Peter

2017-06-01

Dual-domain transport is an alternative conceptual and mathematical paradigm to advection-dispersion for describing the movement of dissolved constituents in groundwater. Here we test the use of a dual-domain algorithm combined with advective pathline tracking to help reconcile environmental tracer concentrations measured in springs within the Shenandoah Valley, USA. The approach also allows for the estimation of the three dual-domain parameters: mobile porosity, immobile porosity, and a domain exchange rate constant. Concentrations of CFC-113, SF6, 3H, and 3He were measured at 28 springs emanating from carbonate rocks. The different tracers give three different mean composite piston-flow ages for all the springs that vary from 5 to 18 years. Here we compare four algorithms that interpret the tracer concentrations in terms of groundwater age: piston flow, old-fraction mixing, advective-flow path modeling, and dual-domain modeling. Whereas the second two algorithms made slight improvements over piston flow at reconciling the disparate piston-flow age estimates, the dual-domain algorithm gave a very marked improvement. Optimal values for the three transport parameters were also obtained, although the immobile porosity value was not well constrained. Parameter correlation and sensitivities were calculated to help quantify the uncertainty. Although some correlation exists between the three parameters being estimated, a watershed simulation of a pollutant breakthrough to a local stream illustrates that the estimated transport parameters can still substantially help to constrain and predict the nature and timing of solute transport. The combined use of multiple environmental tracers with this dual-domain approach could be applicable in a wide variety of fractured-rock settings.

Interobserver reproducibility and accuracy of p16/Ki-67 dual-stain cytology in cervical cancer screening.

PubMed

Wentzensen, Nicolas; Fetterman, Barbara; Tokugawa, Diane; Schiffman, Mark; Castle, Philip E; Wood, Shannon N; Stiemerling, Eric; Poitras, Nancy; Lorey, Thomas; Kinney, Walter

2014-12-01

Dual-stain cytology for p16 and Ki-67 has been proposed as a biomarker in cervical cancer screening. The authors evaluated the reproducibility and accuracy of dual-stain cytology among 10 newly trained evaluators. In total, 480 p16/Ki-67-stained slides from human papillomavirus-positive women were evaluated in masked fashion by 10 evaluators. None of the evaluators had previous experience with p16 or p16/Ki-67 cytology. All participants underwent p16/Ki-67 training and subsequent proficiency testing. Reproducibility of dual-stain cytology was measured using the percentage agreement, individual and aggregate κ values, as well as McNemar statistics. Clinical performance for the detection of cervical intraepithelial neoplasia grade 2 or greater (CIN2+) was evaluated for each individual evaluator and for all evaluators combined compared with the reference evaluation by a cytotechnologist who had extensive experience with dual-stain cytology. The percentage agreement of individual evaluators with the reference evaluation ranged from 83% to 91%, and the κ values ranged from 0.65 to 0.81. The combined κ value was 0.71 for all evaluators and 0.73 for cytotechnologists. The average sensitivity and specificity for the detection of CIN2+ among novice evaluators was 82% and 64%, respectively; whereas the reference evaluation had 84% sensitivity and 63% specificity, respectively. Agreement on dual-stain positivity increased with greater numbers of p16/Ki-67-positive cells on the slides. Good to excellent reproducibility of p16/Ki-67 dual-stain cytology was observed with almost identical clinical performance of novice evaluators compared with reference evaluations. The current findings suggest that p16/Ki-67 dual-stain evaluation can be implemented in routine cytology practice with limited training. © 2014 American Cancer Society.

Capillary electrophoresis separation of peptide diastereomers that contain methionine sulfoxide by dual cyclodextrin-crown ether systems.

PubMed

Zhu, Qingfu; Heinemann, Stefan H; Schönherr, Roland; Scriba, Gerhard K E

2014-12-01

A dual-selector system employing achiral crown ethers in combination with cyclodextrins has been developed for the separation of peptide diastereomers that contain methionine sulfoxide. The combinations of the crown ethers 15-crown-5, 18-crown-6, Kryptofix® 21 and Kryptofix® 22 and β-cyclodextrin, carboxymethyl-β-cyclodextrin, and sulfated β-cyclodextrin were screened at pH 2.5 and pH 8.0 using a 40/50.2 cm, 50 μm id fused-silica capillary and a separation voltage of 25 kV. No diastereomer separation was observed in the sole presence of crown ethers, while only sulfated β-cyclodextrin was able to resolve some peptide diastereomers at pH 8.0. Depending on the amino acid sequence of the peptide and the applied cyclodextrin, the addition of crown ethers, especially the Krpytofix® diaza-crown ethers, resulted in significantly enhanced chiral recognition. Keeping one selector of the dual system constant, increasing concentrations of the second selector resulted in increased peak resolution and analyte migration time for peptide-crown ether-cyclodextrin combinations. The simultaneous diastereomer separation of three structurally related peptides was achieved using the dual selector system. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Development of materials and process technology for dual alloy disks

NASA Technical Reports Server (NTRS)

Marder, J. M.; Kortovich, C. S.

1981-01-01

Techniques for the preparation of dual alloy disks were developed and evaluated. Four material combinations were evaluated in the form of HIP consolidated and heat treated cylindrical and plate shapes in terms of elevated temperature tensile, stress rupture and low cycle fatigue properties. The process evaluation indicated that the pe-HIP AF-115 rim/loose powder Rene 95 hub combination offered the best overall range of mechanical properties for dual disk applications. The feasibility of this dual alloy concept for the production of more complex components was demonstrated by the scale up fabrication of a prototype CFM-56 disk made from this AF-115/Rene 95 combination. The hub alloy ultimate tensile strength was approximately 92 percent of the program goal of 1520 MPa (220 ksi) at 480 C (900 F) and the rim alloy stress rupture goal of 300 hours at 675 C (1250 F)/925 MPa (134 ksi) was exceeded by 200 hours. The low cycle fatigue properties were equivalent to those exhibited by HIP and heat treated alloys. There was an absence of rupture notch sensitivity in both alloys. The joint tensile properties were approximately 85 percent of the weaker of the two materials (Rene 95) and the stress rupture properties were equivalent to those of the weaker of the two materials (Rene 95).

Dual-threshold segmentation using Arimoto entropy based on chaotic bee colony optimization

NASA Astrophysics Data System (ADS)

Li, Li

2018-03-01

In order to extract target from complex background more quickly and accurately, and to further improve the detection effect of defects, a method of dual-threshold segmentation using Arimoto entropy based on chaotic bee colony optimization was proposed. Firstly, the method of single-threshold selection based on Arimoto entropy was extended to dual-threshold selection in order to separate the target from the background more accurately. Then intermediate variables in formulae of Arimoto entropy dual-threshold selection was calculated by recursion to eliminate redundant computation effectively and to reduce the amount of calculation. Finally, the local search phase of artificial bee colony algorithm was improved by chaotic sequence based on tent mapping. The fast search for two optimal thresholds was achieved using the improved bee colony optimization algorithm, thus the search could be accelerated obviously. A large number of experimental results show that, compared with the existing segmentation methods such as multi-threshold segmentation method using maximum Shannon entropy, two-dimensional Shannon entropy segmentation method, two-dimensional Tsallis gray entropy segmentation method and multi-threshold segmentation method using reciprocal gray entropy, the proposed method can segment target more quickly and accurately with superior segmentation effect. It proves to be an instant and effective method for image segmentation.

The influence of training on the attentional blink and psychological refractory period.

PubMed

Garner, K G; Tombu, M N; Dux, P E

2014-05-01

A growing body of research suggests that dual-task interference in sensory consolidation (e.g., the attentional blink, AB) and response selection (e.g., the psychological refractory period, PRP) stems from a common central bottleneck of information processing. With regard to response selection, it is well known that training reduces dual-task interference. We tested whether training that is known to be effective for response selection can also reduce dual-task interference in sensory consolidation. Over two experiments, performance on a PRP paradigm (Exp. 1) and on AB paradigms (differing in their stimuli and task demands, Exps. 1 and 2) was examined after participants had completed a relevant training regimen (T1 practice for both paradigms), an irrelevant training regimen (comparable sensorimotor training, not related to T1 for both tasks), a visual-search training regimen (Exp. 2 only), or after participants had been allocated to a no-training control group. Training that had shown to be effective for reducing dual-task interference in response selection was also found to be effective for reducing interference in sensory consolidation. In addition, we found some evidence that training benefits transferred to the sensory consolidation of untrained stimuli. Collectively, these findings show that training benefits can transfer across cognitive operations that draw on the central bottleneck in information processing. These findings have implications for theories of the AB and for the design of cognitive-training regimens that aim to produce transferable training benefits.

Age-related decrements in dual-task performance: Comparison of different mobility and cognitive tasks. A cross sectional study.

PubMed

Brustio, Paolo Riccardo; Magistro, Daniele; Zecca, Massimiliano; Rabaglietti, Emanuela; Liubicich, Monica Emma

2017-01-01

This cross-sectional study investigated the age-related differences in dual-task performance both in mobility and cognitive tasks and the additive dual-task costs in a sample of older, middle-aged and young adults. 74 older adults (M = 72.63±5.57 years), 58 middle-aged adults (M = 46.69±4.68 years) and 63 young adults (M = 25.34±3.00 years) participated in the study. Participants performed different mobility and subtraction tasks under both single- and dual-task conditions. Linear regressions, repeated-measures and one-way analyses of covariance were used, The results showed: significant effects of the age on the dual and mobility tasks (p<0.05) and differences among the age-groups in the combined dual-task costs (p<0.05); significant decreases in mobility performance under dual-task conditions in all groups (p<0.05) and a decrease in cognitive performance in the older group (p<0.05). Dual-task activity affected mobility and cognitive performance, especially in older adults who showed a higher dual-task cost, suggesting that dual-tasks activities are affected by the age and consequently also mobility and cognitive tasks are negatively influenced.

Machine learning-based dual-energy CT parametric mapping

NASA Astrophysics Data System (ADS)

Su, Kuan-Hao; Kuo, Jung-Wen; Jordan, David W.; Van Hedent, Steven; Klahr, Paul; Wei, Zhouping; Helo, Rose Al; Liang, Fan; Qian, Pengjiang; Pereira, Gisele C.; Rassouli, Negin; Gilkeson, Robert C.; Traughber, Bryan J.; Cheng, Chee-Wai; Muzic, Raymond F., Jr.

2018-06-01

The aim is to develop and evaluate machine learning methods for generating quantitative parametric maps of effective atomic number (Zeff), relative electron density (ρ e), mean excitation energy (I x ), and relative stopping power (RSP) from clinical dual-energy CT data. The maps could be used for material identification and radiation dose calculation. Machine learning methods of historical centroid (HC), random forest (RF), and artificial neural networks (ANN) were used to learn the relationship between dual-energy CT input data and ideal output parametric maps calculated for phantoms from the known compositions of 13 tissue substitutes. After training and model selection steps, the machine learning predictors were used to generate parametric maps from independent phantom and patient input data. Precision and accuracy were evaluated using the ideal maps. This process was repeated for a range of exposure doses, and performance was compared to that of the clinically-used dual-energy, physics-based method which served as the reference. The machine learning methods generated more accurate and precise parametric maps than those obtained using the reference method. Their performance advantage was particularly evident when using data from the lowest exposure, one-fifth of a typical clinical abdomen CT acquisition. The RF method achieved the greatest accuracy. In comparison, the ANN method was only 1% less accurate but had much better computational efficiency than RF, being able to produce parametric maps in 15 s. Machine learning methods outperformed the reference method in terms of accuracy and noise tolerance when generating parametric maps, encouraging further exploration of the techniques. Among the methods we evaluated, ANN is the most suitable for clinical use due to its combination of accuracy, excellent low-noise performance, and computational efficiency.

Machine learning-based dual-energy CT parametric mapping.

PubMed

Su, Kuan-Hao; Kuo, Jung-Wen; Jordan, David W; Van Hedent, Steven; Klahr, Paul; Wei, Zhouping; Al Helo, Rose; Liang, Fan; Qian, Pengjiang; Pereira, Gisele C; Rassouli, Negin; Gilkeson, Robert C; Traughber, Bryan J; Cheng, Chee-Wai; Muzic, Raymond F

2018-06-08

The aim is to develop and evaluate machine learning methods for generating quantitative parametric maps of effective atomic number (Z eff ), relative electron density (ρ e ), mean excitation energy (I x ), and relative stopping power (RSP) from clinical dual-energy CT data. The maps could be used for material identification and radiation dose calculation. Machine learning methods of historical centroid (HC), random forest (RF), and artificial neural networks (ANN) were used to learn the relationship between dual-energy CT input data and ideal output parametric maps calculated for phantoms from the known compositions of 13 tissue substitutes. After training and model selection steps, the machine learning predictors were used to generate parametric maps from independent phantom and patient input data. Precision and accuracy were evaluated using the ideal maps. This process was repeated for a range of exposure doses, and performance was compared to that of the clinically-used dual-energy, physics-based method which served as the reference. The machine learning methods generated more accurate and precise parametric maps than those obtained using the reference method. Their performance advantage was particularly evident when using data from the lowest exposure, one-fifth of a typical clinical abdomen CT acquisition. The RF method achieved the greatest accuracy. In comparison, the ANN method was only 1% less accurate but had much better computational efficiency than RF, being able to produce parametric maps in 15 s. Machine learning methods outperformed the reference method in terms of accuracy and noise tolerance when generating parametric maps, encouraging further exploration of the techniques. Among the methods we evaluated, ANN is the most suitable for clinical use due to its combination of accuracy, excellent low-noise performance, and computational efficiency.

Improved Persistent Scatterer analysis using Amplitude Dispersion Index optimization of dual polarimetry data

NASA Astrophysics Data System (ADS)

Esmaeili, Mostafa; Motagh, Mahdi

2016-07-01

Time-series analysis of Synthetic Aperture Radar (SAR) data using the two techniques of Small BAseline Subset (SBAS) and Persistent Scatterer Interferometric SAR (PSInSAR) extends the capability of conventional interferometry technique for deformation monitoring and mitigating many of its limitations. Using dual/quad polarized data provides us with an additional source of information to improve further the capability of InSAR time-series analysis. In this paper we use dual-polarized data and combine the Amplitude Dispersion Index (ADI) optimization of pixels with phase stability criterion for PSInSAR analysis. ADI optimization is performed by using Simulated Annealing algorithm to increase the number of Persistent Scatterer Candidate (PSC). The phase stability of PSCs is then measured using their temporal coherence to select the final sets of pixels for deformation analysis. We evaluate the method for a dataset comprising of 17 dual polarization SAR data (HH/VV) acquired by TerraSAR-X data from July 2013 to January 2014 over a subsidence area in Iran and compare the effectiveness of the method for both agricultural and urban regions. The results reveal that using optimum scattering mechanism decreases the ADI values in urban and non-urban regions. As compared to single-pol data the use of optimized polarization increases initially the number of PSCs by about three times and improves the final PS density by about 50%, in particular in regions with high rate of deformation which suffer from losing phase stability over the time. The classification of PS pixels based on their optimum scattering mechanism revealed that the dominant scattering mechanism of the PS pixels in the urban area is double-bounce while for the non-urban regions (ground surfaces and farmlands) it is mostly single-bounce mechanism.

Design of dual band FSS by using quadruple L-slot technique

NASA Astrophysics Data System (ADS)

Fauzi, Noor Azamiah Md; Aziz, Mohamad Zoinol Abidin Abd.; Said, Maizatul Alice Meor; Othman, Mohd Azlishah; Ahmad, Badrul Hisham; Malek, Mohd Fareq Abd

2015-05-01

This paper presents a new design of dual band frequency selective surface (FSS) for band pass microwave transmission application. FSS can be used on energy saving glass to improve the transmission of wireless communication signals through the glass. The microwave signal will be attenuate when propagate throughout the different structure such as building. Therefore, some of the wireless communication system cannot be used in the optimum performance. The aim of this paper is designed, simulated and analyzed the new dual band FSS structure for microwave transmission. This design is based on a quadruple L slot combined with cross slot to produce pass band at 900 MHz and 2.4 GHz. The vertical of pair inverse L slot is used as the band pass for the frequency of 2.4GHz. While, the horizontal of pair inverse L slot is used as the band pass at frequency 900MHz. This design is simulated and analyzed by using Computer Simulation Technology (CST) Microwave Studio (MWS) software. The characteristics of the transmission (S21) and reflection (S11) of the dual band FSS were simulater and analyzed. The bandwidth of the first band is 118.91MHz which covered the frequency range from 833.4MHz until 952.31MHz. Meanwhile, the bandwidth for the second band is 358.84MHz which covered the frequency range from 2.1475GHz until 2.5063GHz. The resonance/center frequency of this design is obtained at 900MHz with a 26.902dB return loss and 2.37GHz with 28.506dB a return loss. This FSS is suitable as microwave filter for GSM900 and WLAN 2.4GHz application.

The impact of manual threshold selection in medical additive manufacturing.

PubMed

van Eijnatten, Maureen; Koivisto, Juha; Karhu, Kalle; Forouzanfar, Tymour; Wolff, Jan

2017-04-01

Medical additive manufacturing requires standard tessellation language (STL) models. Such models are commonly derived from computed tomography (CT) images using thresholding. Threshold selection can be performed manually or automatically. The aim of this study was to assess the impact of manual and default threshold selection on the reliability and accuracy of skull STL models using different CT technologies. One female and one male human cadaver head were imaged using multi-detector row CT, dual-energy CT, and two cone-beam CT scanners. Four medical engineers manually thresholded the bony structures on all CT images. The lowest and highest selected mean threshold values and the default threshold value were used to generate skull STL models. Geometric variations between all manually thresholded STL models were calculated. Furthermore, in order to calculate the accuracy of the manually and default thresholded STL models, all STL models were superimposed on an optical scan of the dry female and male skulls ("gold standard"). The intra- and inter-observer variability of the manual threshold selection was good (intra-class correlation coefficients >0.9). All engineers selected grey values closer to soft tissue to compensate for bone voids. Geometric variations between the manually thresholded STL models were 0.13 mm (multi-detector row CT), 0.59 mm (dual-energy CT), and 0.55 mm (cone-beam CT). All STL models demonstrated inaccuracies ranging from -0.8 to +1.1 mm (multi-detector row CT), -0.7 to +2.0 mm (dual-energy CT), and -2.3 to +4.8 mm (cone-beam CT). This study demonstrates that manual threshold selection results in better STL models than default thresholding. The use of dual-energy CT and cone-beam CT technology in its present form does not deliver reliable or accurate STL models for medical additive manufacturing. New approaches are required that are based on pattern recognition and machine learning algorithms.

Differentially pumped dual linear quadrupole ion trap mass spectrometer

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

Owen, Benjamin C.; Kenttamaa, Hilkka I.

The present disclosure provides a new tandem mass spectrometer and methods of using the same for analyzing charged particles. The differentially pumped dual linear quadrupole ion trap mass spectrometer of the present disclose includes a combination of two linear quadrupole (LQIT) mass spectrometers with differentially pumped vacuum chambers.

Academic Couples, Parenthood and Women's Research Careers

ERIC Educational Resources Information Center

Vohlídalová, Marta

2017-01-01

The paper focuses on dual-career academic couples, how they combine careers and parenthood and how their strategies translate into employment pathways of researchers, and especially women researchers. Based on sixteen in-depth interviews with dual-career academic couples, the analysis identified two types of partnerships which differed in terms of…

Dual Meaning Vocabulary (DMV) Words in Learning Chemistry

ERIC Educational Resources Information Center

Song, Youngjin; Carheden, Shannon

2014-01-01

Learning chemistry vocabulary that has both scientific and everyday meanings, which we call dual meaning vocabulary (DMV), can be challenging for many students. This qualitative study investigated how college students understand 11 selected DMV words before and after traditional chemistry instruction and to what extent they retain the scientific…

Dual fluidized bed design for the fast pyrolysis of biomass

USDA-ARS?s Scientific Manuscript database

A mechanism for the transport of solids between fluidised beds in dual fluidised bed systems for the fast pyrolysis of biomass process was selected. This mechanism makes use of an overflow standpipe to transport solids from the fluidised bed used for the combustion reactions to a second fluidised be...

Boric-Acid-Functional Lanthanide Metal-Organic Frameworks for Selective Ratiometric Fluorescence Detection of Fluoride Ions.

PubMed

Yang, Zhong-Rui; Wang, Man-Man; Wang, Xue-Sheng; Yin, Xue-Bo

2017-02-07

Here, we report that boric acid is used to tune the optical properties of lanthanide metal-organic frameworks (LMOFs) for dual-fluorescence emission and improves the selectivity of LMOFs for the determination of F - ions. The LMOFs are prepared with 5-boronoisophthalic acid (5-bop) and Eu 3+ ions as the precursors. Emission mechanism study indicates that 5-bop is excited with UV photons to produce its triplet state, which then excites Eu 3+ ions for their red emission. This is the general story of the antenna effect, but electron-deficient boric acid decreases the energy transfer efficiency from the triplet state of 5-bop to Eu 3+ ions, so dual emission from both 5-bop and Eu 3+ ions is efficiently excited at the single excitation of 275 nm. Moreover, boric acid is used to identify fluoride specifically as a free accessible site. The ratiometric fluorescent detection of F - ions is validated with the dual emission at single excitation. The LMOFs are very monodisperse, so the determination of aqueous F - ions is easily achieved with high selectivity and a low detection limit (2 μM). For the first time, we reveal that rational selection of functional ligands can improve the sensing efficiency of LMOFs through tuning their optical property and enhancing the selectivity toward targets.

Brain activity during divided and selective attention to auditory and visual sentence comprehension tasks

PubMed Central

Moisala, Mona; Salmela, Viljami; Salo, Emma; Carlson, Synnöve; Vuontela, Virve; Salonen, Oili; Alho, Kimmo

2015-01-01

Using functional magnetic resonance imaging (fMRI), we measured brain activity of human participants while they performed a sentence congruence judgment task in either the visual or auditory modality separately, or in both modalities simultaneously. Significant performance decrements were observed when attention was divided between the two modalities compared with when one modality was selectively attended. Compared with selective attention (i.e., single tasking), divided attention (i.e., dual-tasking) did not recruit additional cortical regions, but resulted in increased activity in medial and lateral frontal regions which were also activated by the component tasks when performed separately. Areas involved in semantic language processing were revealed predominantly in the left lateral prefrontal cortex by contrasting incongruent with congruent sentences. These areas also showed significant activity increases during divided attention in relation to selective attention. In the sensory cortices, no crossmodal inhibition was observed during divided attention when compared with selective attention to one modality. Our results suggest that the observed performance decrements during dual-tasking are due to interference of the two tasks because they utilize the same part of the cortex. Moreover, semantic dual-tasking did not appear to recruit additional brain areas in comparison with single tasking, and no crossmodal inhibition was observed during intermodal divided attention. PMID:25745395

Brain activity during divided and selective attention to auditory and visual sentence comprehension tasks.

PubMed

Moisala, Mona; Salmela, Viljami; Salo, Emma; Carlson, Synnöve; Vuontela, Virve; Salonen, Oili; Alho, Kimmo

2015-01-01

Using functional magnetic resonance imaging (fMRI), we measured brain activity of human participants while they performed a sentence congruence judgment task in either the visual or auditory modality separately, or in both modalities simultaneously. Significant performance decrements were observed when attention was divided between the two modalities compared with when one modality was selectively attended. Compared with selective attention (i.e., single tasking), divided attention (i.e., dual-tasking) did not recruit additional cortical regions, but resulted in increased activity in medial and lateral frontal regions which were also activated by the component tasks when performed separately. Areas involved in semantic language processing were revealed predominantly in the left lateral prefrontal cortex by contrasting incongruent with congruent sentences. These areas also showed significant activity increases during divided attention in relation to selective attention. In the sensory cortices, no crossmodal inhibition was observed during divided attention when compared with selective attention to one modality. Our results suggest that the observed performance decrements during dual-tasking are due to interference of the two tasks because they utilize the same part of the cortex. Moreover, semantic dual-tasking did not appear to recruit additional brain areas in comparison with single tasking, and no crossmodal inhibition was observed during intermodal divided attention.

Screening and selection of artificial riboswitches.

PubMed

Harbaugh, Svetlana V; Martin, Jennifer; Weinstein, Jenna; Ingram, Grant; Kelley-Loughnane, Nancy

2018-05-17

Synthetic riboswitches are engineered to regulate gene expression in response to a variety of non-endogenous small molecules, and a challenge to select this engineered response requires robust screening tools. A new synthetic riboswitch can be created by linking an in vitro-selected aptamer library with a randomized expression platform followed by in vivo selection and screening. In order to determine response to analyte, we developed a dual-color reporter comprising elements of the E. coli fimbriae phase variation system: recombinase FimE controlled by a synthetic riboswitch and an invertible DNA segment (fimS) containing a constitutively active promoter placed between two fluorescent protein genes. Without an analyte, the fluorescent reporter constitutively expressed green fluorescent protein (GFPa1). Addition of the analyte initiated translation of fimE causing unidirectional inversion of the fimS segment and constitutive expression of red fluorescent protein (mKate2). The dual color reporter system can be used to select and to optimize artificial riboswitches in E. coli cells. In this work, the enriched library of aptamers incorporated into the riboswitch architecture reduces the sequence search space by offering a higher percentage of potential ligand binders. The study was designed to produce structure switching aptamers, a necessary feature for riboswitch function and efficiently quantify this function using the dual color reporter system. Copyright © 2018. Published by Elsevier Inc.

Dental Cements for Luting and Bonding Restorations: Self-Adhesive Resin Cements.

PubMed

Manso, Adriana P; Carvalho, Ricardo M

2017-10-01

Self-adhesive resin cements combine easy application of conventional luting materials with improved mechanical properties and bonding capability of resin cements. The presence of functional acidic monomers, dual cure setting mechanism, and fillers capable of neutralizing the initial low pH of the cement are essential elements of the material and should be understood when selecting the ideal luting material for each clinical situation. This article addresses the most relevant aspects of self-adhesive resin cements and their potential impact on clinical performance. Although few clinical studies are available to establish solid clinical evidence, the information presented provides clinical guidance in the dynamic environment of material development. Copyright © 2017 Elsevier Inc. All rights reserved.

Investigation of some selected strategies for multi-GNSS instantaneous RTK positioning

NASA Astrophysics Data System (ADS)

Paziewski, Jacek; Wielgosz, Pawel

2017-01-01

It is clear that we can benefit from multi-constellation GNSS in precise relative positioning. On the other hand, it is still an open problem how to combine multi-GNSS signals in a single functional model. This study presents methodology and quality assessment of selected methods allowing for multi-GNSS observations combining in relative kinematic positioning using baselines up to tens of kilometers. In specific, this paper characterizes loose and tight integration strategies applied to the ionosphere and troposphere weighted model. Performance assessment of the established strategies was based on the analyses of the integer ambiguity resolution and rover coordinates' repeatability obtained in the medium range instantaneous RTK positioning with the use of full constellation dual frequency GPS and Galileo signals. Since full constellation of Galileo satellites is not yet available, the observational data were obtained from a hardware GNSS signal simulator using regular geodetic GNSS receivers. The results indicate on similar and high performance of the loose, and tight integration with calibrated receiver ISBs strategies. These approaches have undeniable advantage over single system positioning in terms of reliability of the integer ambiguity resolution as well as rover coordinate repeatability.

Investigating the Evolution of Progressive Die Wear on Uncoated Dp1180 Steel in Production Environment

NASA Astrophysics Data System (ADS)

Wu, W.; Zhou, D. J.; Adamski, D. J.; Young, D.; Wang, Y. W.

2017-09-01

A study of die wear was performed using an uncoated dual phase, 1,180 MPa ultimate tensile strength steel (DP1180) in a progressive die. The objectives of the current study are to evaluate the die durability of various tooling materials and coatings for forming operations on uncoated DP1180 steel and update OEM’s die standards based on the experimental results in the real production environment. In total, 100,800 hits were performed in manufacturing production conditions, where 33 die inserts with the combination of 10 die materials and 9 coatings were investigated. The die inserts were evaluated for surface wear using scanning electron microscopy and characterized in terms of die material and/or coating defects, failure mode, failure initiation and propagation. Surface roughness of the formed parts was characterized using a WYKO NT110 machine. The analytical analysis of the die inserts and formed parts, combined with the failure mode and service life, provide a basis for die material and coating selection for forming AHSS components. The conclusions of this study will guide the selection of die material and coatings for high-volume production of AHSS components.

Pump-Induced, Dual-Frequency Switching in a Short-Cavity, Ytterbium-Doped Fiber Laser

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

Guan, W.; Marciante, J.R.

2008-07-23

Using a short linear cavity composed of a section of highly ytterbium-doped fiber surrounded by two fiber Bragg gratings, dual frequency switching is achieved by tuning the pump power of the laser. The dual-frequency switching is generated by the thermal effects of the absorbed pump in the ytterbium-doped fiber. At each frequency, the laser shows single-longitudinal-mode behavior. In each single-mode regime, the optical signal-to-noise ratio of the laser is greater than 50 dB. The dual-frequency, switchable, fiber laser can be designed for various applications by the careful selection of the two gratings.

An Investigation of Single- and Dual-Rotation Propellers at Positive and Negative Thrust, and in Combination with an NACA 1-series D-Type Cowling at Mach Numbers up to 0.84

NASA Technical Reports Server (NTRS)

Reynolds, Robert M; Samonds, Robert I; Walker, John H

1957-01-01

An investigation has been made to determine the aerodynamic characteristics of the NACA 4-(5)(05)-041 four-blade, single-relation propeller and the NACA 4-(5)(05)-037 six- and eight-blade, dual-rotation propellers in combination with various spinners and NACA d-type spinner-cowling combinations at Mach numbers up to 0.84. Propeller force characteristics, local velocity distributions in the propeller planes, inlet pressure recoveries, and static-pressure distributions on the cowling surfaces were measured for a wide range of blade angles, advance ratios, and inlet-velocity ratios. Included are data showing: (a) the effect of extended cylindrical spinners on the characteristics of the single-rotation propeller, (b) the effect of variation of the difference in blade angle setting between the front and rear components of the dual-rotation propellers, (c) the negative- and static-thrust characteristics of the propellers with 1 series spinners, and (d) the effects of ideal- and platform-type propeller-spinner junctures on the pressure-recovery characteristics of the single-rotation propeller-spinner-cowling combination.

Improving the hydrocarbon production via co-pyrolysis of bagasse with bio-plastic and dual-catalysts layout.

PubMed

Zhang, Huiyan; Likun, Peter Keliona Wani; Xiao, Rui

2018-03-15

Catalytic fast pyrolysis (CFP) of bagasse and bio-plastic (chicken feather keratin) and their mixtures were conducted to produce aromatic hydrocarbons over a HZSM-5, USY, and dual-catalysts layout. The effects of temperature, co-feeding ratios, feed-to-catalyst ratios and dual catalysts on hydrocarbon yields and selectivities were investigated. The results show a general improvement in the aromatic hydrocarbons yields in all cases compared to non-catalytic and pure biomass pyrolysis. The aromatic hydrocarbons increased by 10 fold with the increase of temperature from 400°C to 700°C. The aromatic yields increased 1.5 times at co-feeding, 2.0 greater at feed/HZSM-5 ratio of 1:6, 1.2 times at feed/USY ratio of 1:16, and 2.66 times at USY/HZSM-5 scenario. The selectivities towards benzene increased, at higher co-feeding ratios, while that of toluene shows an opposite trend. Xylenes selectivities were less sensitive to the changes of co-feeding ratios. In contrast, the USY catalyst only produced little amount of toluene and xylenes. The dual catalyst design (USY/HZSM-5) resulted in the highest aromatic yields, than other catalyst design scenarios. The pyrolysis temperature is a significant parameter for hydrocarbon production. Co-feeding bagasse and bio-plastic enhanced biomass conversion to aromatic compounds. For any type of zeolite catalyst, there was an optimum feed-to-catalyst ratio that generated maximum hydrocarbons. Dual catalyst layout shows a new opportunity for efficient conversion of biomass materials into hydrocarbons. Copyright © 2017 Elsevier B.V. All rights reserved.

Application of dual-fuel propulsion to a single stage AMLS vehicle

NASA Technical Reports Server (NTRS)

Lepsch, Roger A., Jr.; Stanley, Douglas O.; Unal, Resit

1993-01-01

As part of NASA's Advanced Manned Launch System (AMLS) study to determine a follow-on, or complement, to the Space Shuttle, a reusable single-stage-to-orbit concept utilizing dual-fuel rocket propulsion has been examined. Several dual-fuel propulsion concepts were investigated. These include: a separate engine concept combining Russian RD-170 kerosene-fueled engines with SSME-derivative engines; the kerosene and hydrogen-fueled Russian RD-701 engine concept; and a dual-fuel, dual-expander engine concept. Analysis to determine vehicle weight and size characteristics was performed using conceptual level design techniques. A response surface methodology for multidisciplinary design was utilized to optimize the dual-fuel vehicle concepts with respect to several important propulsion system and vehicle design parameters in order to achieve minimum empty weight. Comparisons were then made with a hydrogen-fueled reference, single-stage vehicle. The tools and methods employed in the analysis process are also summarized.

MD/MBA Students: An Analysis of Medical Student Career Choice.

PubMed

Sherrill, Windsor Westbrook

2004-12-01

An increasing number of medical schools are offering dual degree MD/MBA programs. Career choices and factors influencing students to enter these programs provide an indicator of the roles in which dual degree students will serve in health care as well as the future of dual degree programs. Using career choice theory as a conceptual framework, career goals and factors influencing decisions to enter dual degree programs were assessed among dual degree medical students. Students enrolled at dual degree programs at six medical schools were surveyed and interviewed. A control group of traditional medical students was also surveyed. Factors influencing students to seek both medical and business training are varied but are often related to a desire for leadership opportunities, concerns about change in medicine and job security and personal career goals. Most students expect to combine clinical and administrative roles. Students entering these programs do so for a variety of reasons and plan diverse careers. These findings can provide guidance for program development and recruitment for dual degree medical education programs.

Effects of three silane primers and five adhesive agents on the bond strength of composite material for a computer-aided design and manufacturing system.

PubMed

Shinohara, Ayano; Taira, Yohsuke; Sakihara, Michino; Sawase, Takashi

2018-01-01

Objective The objective of this study was to evaluate the effects of combinations of silane primers and adhesive agents on the bond strength of a composite block for a computer-aided design and manufacturing system. Material and Methods Three silane primers [Clearfil Ceramic Primer (CP), Super-Bond PZ Primer (PZ), and GC Ceramic Primer II (GP)] were used in conjunction with five adhesive agents [G-Premio Bond (P-Bond), Repair Adhe Adhesive (R-Adhesive), Super-Bond D-Liner Dual (SB-Dual), Super-Bond C&B (SB-Self), and SB-Dual without tributylborane derivative (SB-Light)]. The surface of a composite block (Gradia Block) was ground with silicon carbide paper. After treatment with a silane primer, a adhesive agent was applied to each testing specimen. The specimens were then bonded with a light-curing resin composite. After 24 h, the shear bond strength values were determined and compared using a post hoc test (α=0.05, n=8/group). We also prepared control specimens without primer (No primer) and/or without adhesive agent (No adhesive). Results PZ/SB-Dual and GP/SB-Dual presented the highest bond strength, followed by GP/P-Bond, CP/SB-Dual, CP/R-Adhesive, No primer/SB-Dual, GP/R-Adhesive, CP/P-Bond, No primer/R-Adhesive, PZ/R-Adhesive, CP/SB-Self, PZ/P-Bond, PZ/SB-Self, and GP/SB-Self in descending order of bond strength. No primer/P-Bond, No primer/SB-Self, and all specimens in the SB-Light and No adhesive groups presented the lowest bond strengths. Conclusion A dual-curing adhesive agent (SB-Dual) containing a tributylborane derivative in combination with a silane primer (GP or PZ) presents a greater bond strength between the composite block and the repairing resin composite than the comparators used in the study.

Effects of three silane primers and five adhesive agents on the bond strength of composite material for a computer-aided design and manufacturing system

PubMed Central

2018-01-01

Abstract Objective The objective of this study was to evaluate the effects of combinations of silane primers and adhesive agents on the bond strength of a composite block for a computer-aided design and manufacturing system. Material and Methods Three silane primers [Clearfil Ceramic Primer (CP), Super-Bond PZ Primer (PZ), and GC Ceramic Primer II (GP)] were used in conjunction with five adhesive agents [G-Premio Bond (P-Bond), Repair Adhe Adhesive (R-Adhesive), Super-Bond D-Liner Dual (SB-Dual), Super-Bond C&B (SB-Self), and SB-Dual without tributylborane derivative (SB-Light)]. The surface of a composite block (Gradia Block) was ground with silicon carbide paper. After treatment with a silane primer, a adhesive agent was applied to each testing specimen. The specimens were then bonded with a light-curing resin composite. After 24 h, the shear bond strength values were determined and compared using a post hoc test (α=0.05, n=8/group). We also prepared control specimens without primer (No primer) and/or without adhesive agent (No adhesive). Results PZ/SB-Dual and GP/SB-Dual presented the highest bond strength, followed by GP/P-Bond, CP/SB-Dual, CP/R-Adhesive, No primer/SB-Dual, GP/R-Adhesive, CP/P-Bond, No primer/R-Adhesive, PZ/R-Adhesive, CP/SB-Self, PZ/P-Bond, PZ/SB-Self, and GP/SB-Self in descending order of bond strength. No primer/P-Bond, No primer/SB-Self, and all specimens in the SB-Light and No adhesive groups presented the lowest bond strengths. Conclusion A dual-curing adhesive agent (SB-Dual) containing a tributylborane derivative in combination with a silane primer (GP or PZ) presents a greater bond strength between the composite block and the repairing resin composite than the comparators used in the study. PMID:29742254

Dual delivery of biological therapeutics for multimodal and synergistic cancer therapies.

PubMed

Jang, Bora; Kwon, Hyokyoung; Katila, Pramila; Lee, Seung Jin; Lee, Hyukjin

2016-03-01

Cancer causes >8.2 million deaths annually worldwide; thus, various cancer treatments have been investigated over the past decades. Among them, combination drug therapy has become extremely popular, and treatment with more than one drug is often necessary to achieve appropriate anticancer efficacy. With the development of nanoformulations and nanoparticulate-based drug delivery, researchers have explored the feasibility of dual delivery of biological therapeutics to overcome the current drawbacks of cancer therapy. Compared with the conventional single drug therapy, dual delivery of therapeutics has provided various synergistic effects in addition to offering multimodality to cancer treatment. In this review, we highlight and summarize three aspects of dual-delivery systems for cancer therapy. These include (1) overcoming drug resistance by the dual delivery of chemical drugs with biological therapeutics for synergistic therapy, (2) targeted and controlled drug release by the dual delivery of drugs with stimuli-responsive nanomaterials, and (3) multimodal theranostics by the dual delivery of drugs and molecular imaging probes. Furthermore, recent developments, perspectives, and new challenges regarding dual-delivery systems for cancer therapy are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

Dual-Fuel Propulsion in Single-Stage Advanced Manned Launch System Vehicle

NASA Technical Reports Server (NTRS)

Lepsch, Roger A., Jr.; Stanley, Douglas O.; Unal, Resit

1995-01-01

As part of the United States Advanced Manned Launch System study to determine a follow-on, or complement, to the Space Shuttle, a reusable single-stage-to-orbit concept utilizing dual-fuel rocket propulsion has been examined. Several dual-fuel propulsion concepts were investigated. These include: a separate-engine concept combining Russian RD-170 kerosene-fueled engines with space shuttle main engine-derivative engines: the kerosene- and hydrogen-fueled Russian RD-701 engine; and a dual-fuel, dual-expander engine. Analysis to determine vehicle weight and size characteristics was performed using conceptual-level design techniques. A response-surface methodology for multidisciplinary design was utilized to optimize the dual-fuel vehicles with respect to several important propulsion-system and vehicle design parameters, in order to achieve minimum empty weight. The tools and methods employed in the analysis process are also summarized. In comparison with a reference hydrogen- fueled single-stage vehicle, results showed that the dual-fuel vehicles were from 10 to 30% lower in empty weight for the same payload capability, with the dual-expander engine types showing the greatest potential.

Exercise and BMI z-score in Overweight and Obese Children and Adolescents: A Systematic Review and Network Meta-Analysis of Randomized Trials.

PubMed

Kelley, George A; Kelley, Kristi S; Pate, Russell R

2017-05-01

Examine the effects of selected types of exercise (aerobic, strength training, both) on BMI z-score in overweight and obese children and adolescents. Randomized exercise intervention trials ≥ 4 weeks were included. Studies were retrieved by searching six electronic databases, cross-referencing and expert review. Dual selection and abstraction occurred. Risk of bias and confidence in cumulative evidence were assessed. Network meta-analysis was performed using multivariate random-effects meta-regression models while surface under the cumulative ranking curves were used to calculate a hierarchy of exercise treatments. The number needed to treat (NNT) and percentile improvement (U 3 ) were also calculated. Thirty-four studies representing 2,239 participants were included. Median exercise occurred 3 times per week, 50 minutes per session over a 12-week period. Statistically significant reductions in BMI z-score were found for aerobic exercise and combined aerobic and strength exercise, but not strength training alone (M±SD, 95% CI: aerobic, -0.10, -0.15 to -0.05; aerobic and strength, -0.11, -0.19 to -0.03; strength, 0.04, -0.07 to 0.15). Combined aerobic and strength training was ranked best, followed by aerobic exercise and strength training. The NNT was 2 for both aerobic exercise and combined aerobic exercise and strength training. Percentile improvements were 28.8% for aerobic exercise and 31.5% for combined aerobic exercise and strength training. Confidence in effect estimates was ranked as low for aerobic exercise and very low for combined aerobic and strength training as well as strength training. Aerobic exercise and combined aerobic exercise and strength training are associated with reductions in BMI z-score. © 2016 Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.

Exercise and BMI z-score in Overweight and Obese Children and Adolescents: A Systematic Review and Network Meta-Analysis of Randomized Trials

PubMed Central

George, Kelley; Kristi, Kelley; Russell, Pate

2017-01-01

Aim Examine the effects of selected types of exercise (aerobic, strength training, both) on BMI z-score in overweight and obese children and adolescents. Methods Randomized exercise intervention trials ≥ 4 weeks were included. Studies were retrieved by searching six electronic databases, cross-referencing and expert review. Dual selection and abstraction occurred. Risk of bias and confidence in cumulative evidence were assessed. Network meta-analysis was performed using multivariate random-effects meta-regression models while surface under the cumulative ranking curves were used to calculate a hierarchy of exercise treatments. The number needed to treat (NNT) and percentile improvement (U3) were also calculated. Results Thirty-four studies representing 2,239 participants were included. Median exercise occurred 3 times per week, 50 minutes per session over a 12-week period. Statistically significant reductions in BMI z-score were found for aerobic exercise and combined aerobic and strength exercise, but not strength training alone (M±SD, 95% CI: aerobic, -0.10, -0.15 to -0.05; aerobic and strength, -0.11, -0.19, -0.03; strength, 0.04, -0.07 to 0.15). Combined aerobic and strength training was ranked best, followed by aerobic exercise and strength training. The NNT was 2 for both aerobic exercise and combined aerobic exercise and strength training. Percentile improvements were 28.8% for aerobic exercise and 31.5% for combined aerobic exercise and strength training. Confidence in effect estimates was ranked as low for aerobic exercise and very low for combined aerobic and strength training as well as strength training. Conclusions Aerobic exercise and combined aerobic exercise and strength training are associated with reductions in BMI z-score. PMID:27792271

Recent Advances in Cancer Therapy Based on Dual Mode Gold Nanoparticles

PubMed Central

Spyratou, Ellas; Makropoulou, Mersini; Sihver, Lembit

2017-01-01

Many tumor-targeted strategies have been used worldwide to limit the side effects and improve the effectiveness of therapies, such as chemotherapy, radiotherapy (RT), etc. Biophotonic therapy modalities comprise very promising alternative techniques for cancer treatment with minimal invasiveness and side-effects. These modalities use light e.g., laser irradiation in an extracorporeal or intravenous mode to activate photosensitizer agents with selectivity in the target tissue. Photothermal therapy (PTT) is a minimally invasive technique for cancer treatment which uses laser-activated photoabsorbers to convert photon energy into heat sufficient to induce cells destruction via apoptosis, necroptosis and/or necrosis. During the last decade, PTT has attracted an increased interest since the therapy can be combined with customized functionalized nanoparticles (NPs). Recent advances in nanotechnology have given rise to generation of various types of NPs, like gold NPs (AuNPs), designed to act both as radiosensitizers and photothermal sensitizing agents due to their unique optical and electrical properties i.e., functioning in dual mode. Functionalized AuNPS can be employed in combination with non-ionizing and ionizing radiation to significantly improve the efficacy of cancer treatment while at the same time sparing normal tissues. Here, we first provide an overview of the use of NPs for cancer therapy. Then we review many recent advances on the use of gold NPs in PTT, RT and PTT/RT based on different types of AuNPs, irradiation conditions and protocols. We refer to the interaction mechanisms of AuNPs with cancer cells via the effects of non-ionizing and ionizing radiations and we provide recent existing experimental data as a baseline for the design of optimized protocols in PTT, RT and PTT/RT combined treatment. PMID:29257070

Feasibility of dual-low scheme combined with iterative reconstruction technique in acute cerebral infarction volume CT whole brain perfusion imaging.

PubMed

Wang, Tao; Gong, Yi; Shi, Yibing; Hua, Rong; Zhang, Qingshan

2017-07-01

The feasibility of application of low-concentration contrast agent and low tube voltage combined with iterative reconstruction in whole brain computed tomography perfusion (CTP) imaging of patients with acute cerebral infarction was investigated. Fifty-nine patients who underwent whole brain CTP examination and diagnosed with acute cerebral infarction from September 2014 to March 2016 were selected. Patients were randomly divided into groups A and B. There were 28 cases in group A [tube voltage, 100 kV; contrast agent, iohexol (350 mg I/ml), reconstructed by filtered back projection] and 31 cases in group B [tube voltage, 80 kV; contrast agent, iodixanol (270 mg I/ml), reconstructed by algebraic reconstruction technique]. The artery CT value, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), dose length product, effective dose (ED) of radiation and brain iodine intake of both groups were measured and statistically analyzed. Two physicians carried out kappa (κ) analysis on the consistency of image quality evaluation. The difference in subjective image quality evaluation between the groups was tested by χ 2 . The differences in CT value, SNR, CNR, CTP and CT angiography subjective image quality evaluation between both groups were not statistically significant (P>0.05); the diagnosis rate of the acute infarcts between the two groups was not significantly different; while the ED and iodine intake in group B (dual low-dose group) were lower than group A. In conclusion, combination of low tube voltage and iterative reconstruction technique, and application of low-concentration contrast agent (270 mg I/ml) in whole brain CTP examination reduced ED and iodine intake without compromising image quality, thereby reducing the risk of contrast-induced nephropathy.

The synergistic interaction of MEK and PI3K inhibitors is modulated by mTOR inhibition.

PubMed

Haagensen, E J; Kyle, S; Beale, G S; Maxwell, R J; Newell, D R

2012-04-10

Combined targeting of MAPK and PI3K signalling pathways may be necessary for optimal therapeutic activity in cancer. This study evaluated the MEK inhibitors AZD6244 and PD0325901, alone and in combination with the dual mTOR/PI3K inhibitor NVP-BEZ235 or the PI3K inhibitor GDC-0941, in three colorectal cancer cell lines. Growth inhibition, survival and signal transduction were measured using the Sulforhodamine B assay, clonogenicity and western blotting, respectively, in HCT116, HT29 and DLD1 cell lines. All MEK/PI3K inhibitor combinations exhibited marked synergistic growth inhibition; however, GDC-0941 displayed greater synergy in combination with either MEK inhibitor. NVP-BEZ235 exhibited stronger inhibition of 4EBP1 phosphorylation, and similar inhibition of S6 and AKT phosphorylation, compared with GDC-0941. Both PD0325901 and AZD6244 inhibited ERK phosphorylation, and with MEK/PI3K inhibitor combinations inhibition of S6 phosphorylation was increased. The reduced synergy exhibited by NVP-BEZ235 in combination with MEK inhibitors, compared with GDC-0941, may be due to inhibition of mTOR, and the addition of the mTORC1/2 inhibitor KU0063794 compromised the synergy of GDC-0941:PD0325901 combinations. These studies confirm that dual targeting of PI3K and MEK can induce synergistic growth inhibition; however, the combination of specific PI3K inhibitors, rather than dual mTOR/PI3K inhibitors, with MEK inhibitors results in greater synergy.

The synergistic interaction of MEK and PI3K inhibitors is modulated by mTOR inhibition

PubMed Central

Haagensen, E J; Kyle, S; Beale, G S; Maxwell, R J; Newell, D R

2012-01-01

Background: Combined targeting of MAPK and PI3K signalling pathways may be necessary for optimal therapeutic activity in cancer. This study evaluated the MEK inhibitors AZD6244 and PD0325901, alone and in combination with the dual mTOR/PI3K inhibitor NVP-BEZ235 or the PI3K inhibitor GDC-0941, in three colorectal cancer cell lines. Methods: Growth inhibition, survival and signal transduction were measured using the Sulforhodamine B assay, clonogenicity and western blotting, respectively, in HCT116, HT29 and DLD1 cell lines. Results: All MEK/PI3K inhibitor combinations exhibited marked synergistic growth inhibition; however, GDC-0941 displayed greater synergy in combination with either MEK inhibitor. NVP-BEZ235 exhibited stronger inhibition of 4EBP1 phosphorylation, and similar inhibition of S6 and AKT phosphorylation, compared with GDC-0941. Both PD0325901 and AZD6244 inhibited ERK phosphorylation, and with MEK/PI3K inhibitor combinations inhibition of S6 phosphorylation was increased. The reduced synergy exhibited by NVP-BEZ235 in combination with MEK inhibitors, compared with GDC-0941, may be due to inhibition of mTOR, and the addition of the mTORC1/2 inhibitor KU0063794 compromised the synergy of GDC-0941:PD0325901 combinations. Conclusion: These studies confirm that dual targeting of PI3K and MEK can induce synergistic growth inhibition; however, the combination of specific PI3K inhibitors, rather than dual mTOR/PI3K inhibitors, with MEK inhibitors results in greater synergy. PMID:22415236

A Simplified Micromechanical Modeling Approach to Predict the Tensile Flow Curve Behavior of Dual-Phase Steels

NASA Astrophysics Data System (ADS)

Nanda, Tarun; Kumar, B. Ravi; Singh, Vishal

2017-11-01

Micromechanical modeling is used to predict material's tensile flow curve behavior based on microstructural characteristics. This research develops a simplified micromechanical modeling approach for predicting flow curve behavior of dual-phase steels. The existing literature reports on two broad approaches for determining tensile flow curve of these steels. The modeling approach developed in this work attempts to overcome specific limitations of the existing two approaches. This approach combines dislocation-based strain-hardening method with rule of mixtures. In the first step of modeling, `dislocation-based strain-hardening method' was employed to predict tensile behavior of individual phases of ferrite and martensite. In the second step, the individual flow curves were combined using `rule of mixtures,' to obtain the composite dual-phase flow behavior. To check accuracy of proposed model, four distinct dual-phase microstructures comprising of different ferrite grain size, martensite fraction, and carbon content in martensite were processed by annealing experiments. The true stress-strain curves for various microstructures were predicted with the newly developed micromechanical model. The results of micromechanical model matched closely with those of actual tensile tests. Thus, this micromechanical modeling approach can be used to predict and optimize the tensile flow behavior of dual-phase steels.

Analysis of preservatives with different polarities in beverage samples by dual-phase dual stir bar sorptive extraction combined with high-performance liquid chromatography.

PubMed

Xu, Jin; Chen, Beibei; He, Man; Hu, Bin

2013-02-22

A new concept of "dual-phase dual stir bar sorptive extraction (SBSE)" was proposed to simultaneously extract six preservatives with different polarities (logKo/w values of 1.27-3.41), namely, benzoic acid (BA), sorbic acid (SA), methyl p-hydroxybenzoate (MP), ethyl p-hydroxybenzoate (EP), propyl p-hydroxybenzoate (PP), and butyl p-hydroxybenzoate (BP). The dual-phase dual SBSE apparatus was consisted of two differently coated stir bars, a 3-aminopropyltriethoxysilane (APTES)-hydroxy-terminated silicone oil (OH-TSO)-coated stir bar that was prepared by sol-gel technique and a C(18) silica (C(18))-polydimethylsiloxane (PDMS)-coated stir bar that was prepared by adhesion. In dual-phase dual SBSE, the two stir bars with different coatings were placed in the same sample solution for the simultaneous extraction of the target analytes with different polarities, and then the bars were desorbed in the same desorption solvent. The extraction performance of the dual-phase dual SBSE for the six preservatives was evaluated by comparing with the conventional SBSE (individual stir bar) with different coatings, including commercial PDMS, homemade PDMS, C(18)-APTES-OH-TSO, APTES-OH-TSO, and C(18)-PDMS. The experimental results showed that the dual-phase dual SBSE had the highest extraction efficiency for the six target preservatives. Based on this fact, a novel method by combining the dual-phase dual SBSE which was consisted of the APTES-OH-TSO-coated and C(18)-PDMS-coated stir bars with high-performance liquid chromatography-ultraviolet detection (HPLC-UV) was developed for the simultaneous analysis of six target beverage preservatives in beverages. Under optimal conditions, the limits of detection (LODs) for six target preservatives ranged from 0.6 to 2.7 μgL(-1) with the relative standard deviations (RSDs) of 4.6-9.2% (C(BA,SA)=5 μgL(-1),C(MP)=20 μgL(-1),C(EP,PP,BP)=10 μgL(-1), n=7). The enrichment factors (EFs) were approximately 16-42-fold (theoretical EF was 50-fold). The proposed method was validated by the analysis of six target preservatives in three kinds of beverage samples, and the recoveries for the spiked samples were in the range of 76.6-118.6% for cola, 74.6-17.5% for orange juice, and 83.0-119.1% for herbal tea, respectively. Copyright © 2013 Elsevier B.V. All rights reserved.

Comparison study of noise reduction algorithms in dual energy chest digital tomosynthesis

NASA Astrophysics Data System (ADS)

Lee, D.; Kim, Y.-S.; Choi, S.; Lee, H.; Choi, S.; Kim, H.-J.

2018-04-01

Dual energy chest digital tomosynthesis (CDT) is a recently developed medical technique that takes advantage of both tomosynthesis and dual energy X-ray images. However, quantum noise, which occurs in dual energy X-ray images, strongly interferes with diagnosis in various clinical situations. Therefore, noise reduction is necessary in dual energy CDT. In this study, noise-compensating algorithms, including a simple smoothing of high-energy images (SSH) and anti-correlated noise reduction (ACNR), were evaluated in a CDT system. We used a newly developed prototype CDT system and anthropomorphic chest phantom for experimental studies. The resulting images demonstrated that dual energy CDT can selectively image anatomical structures, such as bone and soft tissue. Among the resulting images, those acquired with ACNR showed the best image quality. Both coefficient of variation and contrast to noise ratio (CNR) were the highest in ACNR among the three different dual energy techniques, and the CNR of bone was significantly improved compared to the reconstructed images acquired at a single energy. This study demonstrated the clinical value of dual energy CDT and quantitatively showed that ACNR is the most suitable among the three developed dual energy techniques, including standard log subtraction, SSH, and ACNR.

Dual-Extrusion 3D Printing of Anatomical Models for Education

ERIC Educational Resources Information Center

Smith, Michelle L.; Jones, James F. X.

2018-01-01

Two material 3D printing is becoming increasingly popular, inexpensive and accessible. In this paper, freely available printable files and dual extrusion fused deposition modelling were combined to create a number of functional anatomical models. To represent muscle and bone FilaFlex[superscript 3D] flexible filament and polylactic acid (PLA)…

Two Universities, Two Degrees: A Dual Degree Program for Pharmacists.

ERIC Educational Resources Information Center

Milio, Frank

2001-01-01

Describes a dual degree program between Towson University and the University of Maryland School of Pharmacy, which allows a student to receive both a B.S. degree in Medicinal Chemistry and a Doctor of Pharmacy degree in a combined 7-year program. It also allows flexibility in pursuing alternate career goals. (EV)

The influence of interpreters' professional background and experience on the interpretation of multimodality imaging of pulmonary lesions using 18F-3'-deoxy-fluorothymidine and 18F-fluorodeoxyglucose PET/CT.

PubMed

Xu, Bai-xuan; Liu, Chang-bin; Wang, Rui-min; Shao, Ming-zhe; Fu, Li-ping; Li, Yun-gang; Tian, Jia-he

2013-01-01

Based on the results of a recently accomplished multicenter clinical trial for the incremental value of a dual-tracer (18F-FDG and 18F-FLT), dual-modality (PET and CT) imaging in the differential diagnosis of pulmonary lesions, we investigate some issues that might affect the image interpretation and result reporting. The images were read in two separate sessions. Firstly the images were read and reported by physician(s) of the imaging center on completion of each PET/CT scanning. By the end of MCCT, all images collected during the trial were re-read by a collective of readers in an isolated, blinded, and independent way. One hundred sixty two patients successfully passed the data verification and entered into the final analysis. The primary reporting result showed adding 18F-FDG image information did not change the clinical performance much in sensitivity, specifity and accuracy, but the ratio between SUVFLT and SUVFDG did help the differentiation efficacy among the three subgroups of patients. The collective reviewing result showed the diagnostic achievement varied with reading strategies. ANOVA indicated significant differences among (18)F-FDG, (18)F-FLT in SUV (F = 14.239, p = 0.004). CT had almost the same diagnostic performance as 18F-FLT. When the 18F-FDG, 18F-FLT and CT images read in pair, both diagnostic sensitivity and specificity improved. The best diagnostic figures were obtained in full-modality strategy, when dual-tracer PET worked in combination with CT. With certain experience and training both radiologists and nuclear physicians are qualified to read and to achieve the similar diagnostic accuracy in PET/CT study. Making full use of modality combination and selecting right criteria seems more practical than professional back ground and personal experience in the new hybrid imaging technology, at least when novel tracer or application is concerned.

Photoacoustic/ultrasound dual-modality contrast agent and its application to thermotherapy.

PubMed

Wang, Yu-Hsin; Liao, Ai-Ho; Chen, Jui-Hao; Wang, Churng-Ren Chris; Li, Pai-Chi

2012-04-01

This study investigates a photoacoustic/ultrasound dual-modality contrast agent, including extending its applications from image-contrast enhancement to combined diagnosis and therapy with site-specific targeting. The contrast agent comprises albumin-shelled microbubbles with encapsulated gold nanorods (AuMBs). The gas-filled microbubbles, whose diameters range from submicrometer to several micrometers, are not only echogenic but also can serve as drug-delivery vehicles. The gold nanorods are used to enhance the generation of both photoacoustic and photothermal signals. The optical absorption peak of the gold nanorods is tuned to 760 nm and is invariant after microbubble encapsulation. Dual-modality contrast enhancement is first described here, and the applications to cellular targeting and laser-induced thermotherapy in a phantom are demonstrated. Photoacoustic imaging can be used to monitor temperature increases during the treatment. The targeting capability of AuMBs was verified, and the temperature increased by 26°C for a laser power of 980 mW, demonstrating the potential of combined diagnosis and therapy with the dual-modality agent. Targeted photo- or acoustic-mediated delivery is also possible.

Automatic discrimination between safe and unsafe swallowing using a reputation-based classifier

PubMed Central

2011-01-01

Background Swallowing accelerometry has been suggested as a potential non-invasive tool for bedside dysphagia screening. Various vibratory signal features and complementary measurement modalities have been put forth in the literature for the potential discrimination between safe and unsafe swallowing. To date, automatic classification of swallowing accelerometry has exclusively involved a single-axis of vibration although a second axis is known to contain additional information about the nature of the swallow. Furthermore, the only published attempt at automatic classification in adult patients has been based on a small sample of swallowing vibrations. Methods In this paper, a large corpus of dual-axis accelerometric signals were collected from 30 older adults (aged 65.47 ± 13.4 years, 15 male) referred to videofluoroscopic examination on the suspicion of dysphagia. We invoked a reputation-based classifier combination to automatically categorize the dual-axis accelerometric signals into safe and unsafe swallows, as labeled via videofluoroscopic review. From these participants, a total of 224 swallowing samples were obtained, 164 of which were labeled as unsafe swallows (swallows where the bolus entered the airway) and 60 as safe swallows. Three separate support vector machine (SVM) classifiers and eight different features were selected for classification. Results With selected time, frequency and information theoretic features, the reputation-based algorithm distinguished between safe and unsafe swallowing with promising accuracy (80.48 ± 5.0%), high sensitivity (97.1 ± 2%) and modest specificity (64 ± 8.8%). Interpretation of the most discriminatory features revealed that in general, unsafe swallows had lower mean vibration amplitude and faster autocorrelation decay, suggestive of decreased hyoid excursion and compromised coordination, respectively. Further, owing to its performance-based weighting of component classifiers, the static reputation-based algorithm outperformed the democratic majority voting algorithm on this clinical data set. Conclusion Given its computational efficiency and high sensitivity, reputation-based classification of dual-axis accelerometry ought to be considered in future developments of a point-of-care swallow assessment where clinical informatics are desired. PMID:22085802

A Dual-Loop Opto-Electronic Oscillator

NASA Astrophysics Data System (ADS)

Yao, X. S.; Maleki, L.; Ji, Y.; Lutes, G.; Tu, M.

1998-07-01

We describe and demonstrate a multiloop technique for single-mode selection in an opto-electronic oscillator (OEO). We present experimental results of a dual-loop OEO free running at 10 GHz that has the lowest phase noise (-140 dBc/Hz at 10 kHz from the carrier) of all free-running room-temperature oscillators to date.

Locus of Semantic Interference in Picture Naming: Evidence from Dual-Task Performance

ERIC Educational Resources Information Center

Piai, Vitória; Roelofs, Ardi; Schriefers, Herbert

2014-01-01

Disagreement exists regarding the functional locus of semantic interference of distractor words in picture naming. This effect is a cornerstone of modern psycholinguistic models of word production, which assume that it arises in lexical response-selection. However, recent evidence from studies of dual-task performance suggests a locus in…

Dual Use of Cigarettes and Smokeless Tobacco among South African Adolescents

ERIC Educational Resources Information Center

Rantao, Masego; Ayo-Yusuf, Olalekan A.

2012-01-01

Objectives: To determine factors associated with dual use of tobacco products in a population of black South African adolescents. Methods: Data were obtained from a self-administered questionnaire completed by a representative sample of grade 8 students from 21 randomly selected secondary state schools in the Limpopo Province, South Africa (n =…

Preschool Teachers' Language and Literacy Practices with Dual Language Learners

ERIC Educational Resources Information Center

Sawyer, Brook E.; Hammer, Carol Scheffner; Cycyk, Lauren M.; Lopez, Lisa; Blair, Clancy; Sandilos, Lia; Komaroff, Eugene

2016-01-01

The purposes of this study were to (a) examine the degree to which teachers used linguistically responsive practices to support the language and literacy development of Spanish-speaking Dual Language Learners (DLL) and (b) to investigate the associations between these practices and select teacher-level factors. The sample consisted of 72 preschool…

Preschool Teachers' Language and Literacy Practices with Dual Language Learners

ERIC Educational Resources Information Center

Sawyer, Brook E.; Hammer, Carol Scheffner; Cycyk, Lauren M.; López, Lisa; Blair, Clancy; Sandilos, Lia; Komaroff, Eugene

2016-01-01

The purposes of this study were to (a) examine the degree to which teachers used linguistically responsive practices to support the language and literacy development of Spanish-speaking Dual Language Learners (DLL) and (b) to investigate the associations between these practices and select teacher-level factors. The sample consisted of 72 preschool…

Polarization and angle insensitive dual-band bandpass frequency selective surface using all-dielectric metamaterials

NASA Astrophysics Data System (ADS)

Yu, Fei; Wang, Jun; Wang, Jiafu; Ma, Hua; Du, Hongliang; Xu, Zhuo; Qu, Shaobo

2016-04-01

In this paper, we demonstrate a dual-band bandpass all-dielectric frequency selective surface (FSS), the building elements of which are high-permittivity ceramic particles rather than metallic patterns. With proper structural design and parameter adjustment, the resonant frequency can be tuned at will. Dual-band bandpass response can be realized due to the coupling between electric and magnetic resonances. As an example, a dual-band bandpass FSS is designed in Ku band, which is composed of two-dimensional periodic arrays of complementary quatrefoil structures (CQS) cut from dielectric plates. Moreover, cylindrical dielectric resonators are introduced and placed in the center of each CQS to broaden the bandwidth and to sharpen the cut-off frequency. Theoretical analysis shows that the bandpass response arises from impedance matching caused by electric and magnetic resonances. In addition, effective electromagnetic parameters and dynamic field distributions are presented to explain the mechanism of impedance matching. The proposed FSS has the merits of polarization independence, stable transmission, and sharp roll-off frequency. The method can also be used to design all-dielectric FSSs with continuum structures at other frequencies.

Evaluation of polymerization shrinkage of resin cements through in vitro and in situ experiments

NASA Astrophysics Data System (ADS)

Franco, A. P. G. O.; Karam, L. Z.; Pulido, C. A.; Gomes, O. M. M.; Kalinowski, H. J.

2014-08-01

The aim of this study was to evaluate the behavior of two types of resin cements , conventional dual and dual self adhesive, through in vitro and in situ experiments. For the in vitro assay were selected two resin cements that were handled and dispensed over a mylar strip supported by a glass plate. The Bragg grating sensors were positioned and another portion of cement. was placed, covered by another mylar strip. For the in situ experiment 16 single-rooted teeth were selected who were divided into 2 groups: group 1 - conventional dual resin cement Relyx ARC and group 2 - dual self adhesive resin cement Relyx U200 ( 3M/ESPE ). The teeth were treated and prepared to receive the intracanal posts. Two Bragg grating sensors were recorded and introduced into the root canal at different apical and coronal positions. The results showed that the in vitro experiment presented similar values of polymerization shrinkage that the in situ experiment made in cervical position; whereas Relyx ARC resulted lower values compared to Relyx U200; and cervical position showed higher shrinkage than the apical.

Efficacy and safety of different doses of tirofiban combined with ticagrelor on diabetic patients with AMI receiving in emergency percutaneous coronary intervention (PCI)

PubMed Central

Liu, Yang; Liu, Hengliang; Hao, Zhenxuan; Geng, Guoying; Chen, Qi; Han, Wenjie; Jia, Kailong; Zhou, Yuxin

2015-01-01

Objective: The aim of this study was to investigate the efficacy and safety of dual antiplatelet drugs combined with different doses of tirofiban on diabetic patients with acute myocardial infarction (AMI) receiving emergency percutaneous coronary intervention (PCI). Methods: 158 diabetic patients with AMI undergone emergency PCI were randomly divided into three groups: Group A (53 cases) as the control group-dual anti-platelet agents (aspirin + ticagrelor); Group B (52 cases)-dual anti-platelet agents + conventional dose of tirofiban [10 μg/kg by PCI and 0.15 μg/(kg·min) by continue venous pump for 24 h]; Group C (53 cases)-dual antiplatelet agents + half-dose tirofiban [10 μg/kg by PCI and 0.075 μg/(kg·min) by continue venous pump for 24 h]. Results: Compared with group A, thrombolysis in myocardial infarction 3 (TIMI3) blood flow and TIMI myocardial perfusion grade 3 (TMPG3) myocardial perfusion of patients in group B and group C after PCI was significantly higher (P < 0.05), the average day of hospitalization was significantly shorter (P < 0.05), reinfarction during hospitalization, post-infarction angina, severe arrhythmia, the incidence of cardiac function above KillipIII level was significantly lower (P < 0.05). And the differences between group B and C was not statistically significant (P > 0.05). Severe bleeding and moderate incidence of bleeding in group B was significantly higher than that in group A and group C (P < 0.05). Conclusions: Based on combination of dual the anti-platelet agents and ticagrelor for diabetic patients with AMI receiving PCI, the combination of half-dose tirofiban can effectively improve TIMI flow and TMPG myocardial tissue perfusion, and reduce the incidence of major adverse cardiac events (MACE) and severe bleeding. PMID:26379951

Determination of ureter stent appearance on dual-energy computed tomography scan.

PubMed

Jepperson, Maria A; Thiel, David D; Cernigliaro, Joesph G; Broderick, Gregory A; Parker, Alexander S; Haley, William E

2012-11-01

To examine the dual-energy computed tomography (DECT) properties of 7 commonly used ureteral stents to optimize stent selection for calculi monitored using DECT. The use of DECT to evaluate renal and ureteral calculi has recently increased. Seven stents were individually placed in a fish bowl phantom and imaged using a Siemens Somatom Definition Flash CT scanner. DECT peak tube potentials of 80 and 140 kVp and 100 and 140 kVp were used, reflecting our current dual-energy protocols. These were compared to 31 in vivo stents of known composition. The data were reconstructed on a multimodality WorkPlace (Siemens) using CT syngo Post-Processing Suite software. The average patient age was 64 years (range 27-90). The average body mass index was 31.9 kg/m(2) (range 24-51.6). Of the 27 patients, 4 had uric acid stones and 22 had calcium-based stones; 1 patient had undergone renal transplantation. No difference was seen in the dual-energy characterization of stents from the same manufacturer. All imaged Cook and Bard stents had a dual-energy characterization that approached that of calcium stones (blue). All Boston Scientific and Gyrus ACMI stents had a dual-energy characterization resembling that of uric acid stones (red). The present study evaluated the stent appearance on DECT for various stent manufacturers. This information will aid in the optimal stent selection for patients undergoing treatment of renal calculi and followed up with DECT. Copyright © 2012 Elsevier Inc. All rights reserved.

Age-related decrements in dual-task performance: Comparison of different mobility and cognitive tasks. A cross sectional study

PubMed Central

Brustio, Paolo Riccardo; Zecca, Massimiliano; Rabaglietti, Emanuela; Liubicich, Monica Emma

2017-01-01

This cross-sectional study investigated the age-related differences in dual-task performance both in mobility and cognitive tasks and the additive dual-task costs in a sample of older, middle-aged and young adults. 74 older adults (M = 72.63±5.57 years), 58 middle-aged adults (M = 46.69±4.68 years) and 63 young adults (M = 25.34±3.00 years) participated in the study. Participants performed different mobility and subtraction tasks under both single- and dual-task conditions. Linear regressions, repeated-measures and one-way analyses of covariance were used, The results showed: significant effects of the age on the dual and mobility tasks (p<0.05) and differences among the age-groups in the combined dual-task costs (p<0.05); significant decreases in mobility performance under dual-task conditions in all groups (p<0.05) and a decrease in cognitive performance in the older group (p<0.05). Dual-task activity affected mobility and cognitive performance, especially in older adults who showed a higher dual-task cost, suggesting that dual-tasks activities are affected by the age and consequently also mobility and cognitive tasks are negatively influenced. PMID:28732080

Age-Related Interference between the Selection of Input-Output Modality Mappings and Postural Control—a Pilot Study

PubMed Central

Stelzel, Christine; Schauenburg, Gesche; Rapp, Michael A.; Heinzel, Stephan; Granacher, Urs

2017-01-01

Age-related decline in executive functions and postural control due to degenerative processes in the central nervous system have been related to increased fall-risk in old age. Many studies have shown cognitive-postural dual-task interference in old adults, but research on the role of specific executive functions in this context has just begun. In this study, we addressed the question whether postural control is impaired depending on the coordination of concurrent response-selection processes related to the compatibility of input and output modality mappings as compared to impairments related to working-memory load in the comparison of cognitive dual and single tasks. Specifically, we measured total center of pressure (CoP) displacements in healthy female participants aged 19–30 and 66–84 years while they performed different versions of a spatial one-back working memory task during semi-tandem stance on an unstable surface (i.e., balance pad) while standing on a force plate. The specific working-memory tasks comprised: (i) modality compatible single tasks (i.e., visual-manual or auditory-vocal tasks), (ii) modality compatible dual tasks (i.e., visual-manual and auditory-vocal tasks), (iii) modality incompatible single tasks (i.e., visual-vocal or auditory-manual tasks), and (iv) modality incompatible dual tasks (i.e., visual-vocal and auditory-manual tasks). In addition, participants performed the same tasks while sitting. As expected from previous research, old adults showed generally impaired performance under high working-memory load (i.e., dual vs. single one-back task). In addition, modality compatibility affected one-back performance in dual-task but not in single-task conditions with strikingly pronounced impairments in old adults. Notably, the modality incompatible dual task also resulted in a selective increase in total CoP displacements compared to the modality compatible dual task in the old but not in the young participants. These results suggest that in addition to effects of working-memory load, processes related to simultaneously overcoming special linkages between input- and output modalities interfere with postural control in old but not in young female adults. Our preliminary data provide further evidence for the involvement of cognitive control processes in postural tasks. PMID:28484411

Dual Drug Targeting of Mutant Bcr-Abl Induces Inactive Conformation: New Strategy for the Treatment of Chronic Myeloid Leukemia and Overcoming Monotherapy Resistance.

PubMed

El Rashedy, Ahmed A; Olotu, Fisayo A; Soliman, Mahmoud E S

2018-03-01

Bcr-Abl is an oncogenic fusion protein which expression enhances tumorigenesis, and has been highly associated with chronic myeloid leukemia (CML). Acquired drug resistance in mutant Bcr-Abl has enhanced pathogenesis with the use of single therapy agents such as nilotinib. Moreover, allosteric targeting has been identified to consequentially inhibit Bcr-Abl activity, which led to the recent development of ABL-001 (asciminib) that selectively binds the myristoyl pocket. Experimental studies have revealed that the combination of nilotinib and ABL-001 induced a 'bent' conformation in the C-terminal helix of Bcr-Abl; a benchmark of inhibition, thereby exhibiting a greater potency in the treatment of CML, surmounting the setbacks of drug resistance, disease regression and relapse. Therefore, we report the first account of the dynamics and conformational analysis of oncogenic T334I Bcr-Abl by dual targeting. Our findings revealed that unlike in the Bcr-Abl-Nilotinib complex, dual targeting by both inhibitors induced the bent conformation in the C-terminal helix that varied with time. This was coupled with significant alteration in Bcr-Abl stability, flexibility, and compactness and an overall structural re-orientation inwards towards the hydrophobic core, which reduced the solvent-exposed residues indicative of protein folding. This study will facilitate allosteric targeting and the design of more potent allosteric inhibitors for resistive target proteins in cancer. © 2018 Wiley-VHCA AG, Zurich, Switzerland.

Triple antithrombotic therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention: a viewpoint.

PubMed

Gwyn, Jennifer C V; Thomas, Mark R; Kirchhof, Paulus

2017-07-01

Patients undergoing percutaneous coronary intervention (PCI) are treated with dual antiplatelet therapy to reduce the risk of subsequent myocardial infarction (MI) and stent thrombosis. Approximately 5-10% of patients undergoing PCI also have atrial fibrillation (AF). Patients with AF have an additional requirement for anticoagulation, as dual antiplatelet therapy alone is insufficient to adequately reduce the risk of stroke in patients with AF. However, it is now well established that combining anticoagulants with dual antiplatelet therapy also causes a significant increase in the risk of bleeding. Hence, there is great interest in discovering the optimal blend of antiplatelet therapy and oral anticoagulation in this situation, aiming to reduce the risk of stent thrombosis, recurrent MI, and stroke, while also minimizing the risk of bleeding. Recent studies have experimented with combining oral anticoagulation with a single antiplatelet agent, rather than combining oral anticoagulation with dual antiplatelet therapy. These studies show that this reduces the risk of bleeding but are underpowered to determine whether this still provides as much cardiovascular benefit. This review summarizes the currently available evidence on this topic and highlights the key questions that remain to be answered including ongoing clinical trials in the field. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Comparative study between recent methods manipulating ratio spectra and classical methods based on two-wavelength selection for the determination of binary mixture of antazoline hydrochloride and tetryzoline hydrochloride

NASA Astrophysics Data System (ADS)

Abdel-Halim, Lamia M.; Abd-El Rahman, Mohamed K.; Ramadan, Nesrin K.; EL Sanabary, Hoda F. A.; Salem, Maissa Y.

2016-04-01

A comparative study was developed between two classical spectrophotometric methods (dual wavelength method and Vierordt's method) and two recent methods manipulating ratio spectra (ratio difference method and first derivative of ratio spectra method) for simultaneous determination of Antazoline hydrochloride (AN) and Tetryzoline hydrochloride (TZ) in their combined pharmaceutical formulation and in the presence of benzalkonium chloride as a preservative without preliminary separation. The dual wavelength method depends on choosing two wavelengths for each drug in a way so that the difference in absorbance at those two wavelengths is zero for the other drug. While Vierordt's method, is based upon measuring the absorbance and the absorptivity values of the two drugs at their λmax (248.0 and 219.0 nm for AN and TZ, respectively), followed by substitution in the corresponding Vierordt's equation. Recent methods manipulating ratio spectra depend on either measuring the difference in amplitudes of ratio spectra between 255.5 and 269.5 nm for AN and 220.0 and 273.0 nm for TZ in case of ratio difference method or computing first derivative of the ratio spectra for each drug then measuring the peak amplitude at 250.0 nm for AN and at 224.0 nm for TZ in case of first derivative of ratio spectrophotometry. The specificity of the developed methods was investigated by analyzing different laboratory prepared mixtures of the two drugs. All methods were applied successfully for the determination of the selected drugs in their combined dosage form proving that the classical spectrophotometric methods can still be used successfully in analysis of binary mixture using minimal data manipulation rather than recent methods which require relatively more steps. Furthermore, validation of the proposed methods was performed according to ICH guidelines; accuracy, precision and repeatability are found to be within the acceptable limits. Statistical studies showed that the methods can be competitively applied in quality control laboratories.

Dual beta-lactam therapy for serious Gram-negative infections: is it time to revisit?

PubMed

Rahme, Christine; Butterfield, Jill M; Nicasio, Anthony M; Lodise, Thomas P

2014-12-01

We are rapidly approaching a crisis in antibiotic resistance, particularly among Gram-negative pathogens. This, coupled with the slow development of novel antimicrobial agents, underscores the exigency of redeploying existing antimicrobial agents in innovative ways. One therapeutic approach that was heavily studied in the 1980s but abandoned over time is dual beta-lactam therapy. This article reviews the evidence for combination beta-lactam therapy. Overall, in vitro, animal and clinical data are positive and suggest that beta-lactam combinations produce a synergistic effect against Gram-negative pathogens that rivals that of beta-lactam-aminoglycoside or beta-lactam-fluoroquinolone combination therapy. Although the precise mechanism of improved activity is not completely understood, it is likely attributable to an enhanced affinity to the diverse penicillin-binding proteins found among Gram negatives. The collective data indicate that dual beta-lactam therapy should be revisited for serious Gram-negative infections, especially in light of the near availability of potent beta-lactamase inhibitors, which neutralize the effect of problematic beta-lactamases. Copyright © 2014 Elsevier Inc. All rights reserved.

Elementary Education Program for Engineering by Dual System of Workshop and Teaching Program with Practical Subject

NASA Astrophysics Data System (ADS)

Hara, Toshitsugu

Elementary education program for engineering by the dual system combined with workshop program and teaching program with practical subject was discussed. The dual system which consists of several workshop programs and fundamental subjects (such as mathematics, English and physics) with practical material has been performed for the freshmen. The elementary workshop program (primary course) has four workshops and the related lectures. Fundamental subjects are taught with the practical or engineering texts. English subjects are taught by specified teachers who have ever worked in engineering field with English. The dual system was supported by such systems as the center for success initiative and the English education center.

Design, synthesis, and evaluation of a novel series of alpha-substituted phenylpropanoic acid derivatives as human peroxisome proliferator-activated receptor (PPAR) alpha/delta dual agonists for the treatment of metabolic syndrome.

PubMed

Kasuga, Jun-ichi; Yamasaki, Daisuke; Araya, Yoko; Nakagawa, Aya; Makishima, Makoto; Doi, Takefumi; Hashimoto, Yuichi; Miyachi, Hiroyuki

2006-12-15

A series of alpha-alkyl-substituted phenylpropanoic acids was prepared as dual agonists of peroxisome proliferator-activated receptors alpha and delta (PPARalpha/delta). Structure-activity relationship studies indicated that the shape of the linking group and the shape of the substituent at the distal benzene ring play key roles in determining the potency and the selectivity of PPAR subtype transactivation. Structure-activity relationships among the amide series (10) and the reversed amide series (13) are similar, but not identical, especially in the case of the compounds bearing a bulky hydrophobic substituent at the distal benzene ring, indicating that the hydrophobic tail part of the molecules in these two series binds at somewhat different positions in the large binding pocket of PPAR. alpha-Alkyl-substituted phenylpropanoic acids of (S)-configuration were identified as potent human PPARalpha/delta dual agonists. Representative compounds exhibited marked nuclear receptor selectivity for PPARalpha and PPARdelta. Subtype-selective PPAR activation was also examined by analysis of the mRNA expression of PPAR-regulated genes.

Performance of P16/Ki67 dual staining in triaging hr-HPV-positive population during cervical Cancer screening in the younger women.

PubMed

Qian, Qiu-Ping; Zhang, Xiaoan; Ding, Bo; Jiang, Shi-Wen; Li, Ze-Min; Ren, Mu-Lan; Shen, Yang

2018-08-01

Cervical cancer is the most common malignancy from the female reproductive tract, and usually develops from low-grade or high-grade squamous intraepithelial lesions (LSIL or HSIL). Detecting the precancerous lesion during the LSIL-HSIL-invasive cancer sequelae can effectively interrupt the oncogenesis and decrease the incidence of invasive carcinoma. The aim of this study is to evaluate the performance of P16/Ki67 dual staining in triaging hr-HPV-positive population. Conventional gynecological examination, cervical cytology and hr-HPV testing were given to all patients. Specimens were collected for cytology examination and HPV genotyping. According to cytology results, patients were divided into cervical cancer group, HSIL group, LSIL group and benign lesion group. Sensitivity and specificity of the dual staining method in each histopathologic group was obtained and compared. Among the108 patients participated in the study, 65 were diagnosed as normal, 15 as LSIL, 20 as HSIL and 8 as CC, by histopathologic examination. Dual staining of p16/Ki67 on cytology specimen provided a positive predictive value of 86% and the negative predictive value of 96%. The sensitivity approached 96.43% when combining ThinPrep cytological test (TCT) with the dual staining, with a specificity of 60% in detecting HSIL. Joint detection of TCT and p16/Ki67 dual staining displayed the highest specificity among all the attempted combinations of detection methods. This study demonstrated that p16/Ki-67 dual staining represents an effective method for cervical cancer screening. Application of this method could lead to a reduction of unnecessary colposcopy referrals and misdiagnosis. Copyright © 2018 Elsevier B.V. All rights reserved.

Spotlight on elotuzumab in the treatment of multiple myeloma: the evidence to date

PubMed Central

Weisel, Katja

2016-01-01

Despite advances in the treatment of multiple myeloma, it remains an incurable disease, with relapses and resistances frequently observed. Recently, immunotherapies, in particular, monoclonal antibodies, have become important treatment options in anticancer therapies. Elotuzumab is a humanized monoclonal antibody to signaling lymphocytic activation molecule F7, which is highly expressed on myeloma cells and, to a lower extent, on selected leukocyte subsets such as natural killer cells. By directly activating natural killer cells and by antibody-dependent cell-mediated cytotoxicity, elotuzumab exhibits a dual mechanism of action leading to myeloma cell death with minimal effects on normal tissue. In several nonclinical models of multiple myeloma, elotuzumab was effective as a single agent and in combination with standard myeloma treatments, supporting the use of elotuzumab in patients. In combination with lenalidomide and dexamethasone, elotuzumab showed a significant increase in tumor response rates and progression-free survival in patients with relapsed and/or refractory multiple myeloma. This review summarizes the nonclinical and clinical development of elotuzumab as a single agent and in combination with established therapies for the treatment of multiple myeloma. PMID:27785050

Combined Inhibition of mTORC1 and mTORC2 Signaling Pathways Is a Promising Therapeutic Option in Inhibiting Pheochromocytoma Tumor Growth: In Vitro and In Vivo Studies in Female Athymic Nude Mice

PubMed Central

Bullova, Petra; Nölting, Svenja; Turkova, Hana; Powers, James F.; Liu, Qingsong; Guichard, Sylvie; Tischler, Arthur S.; Grossman, Ashley B.

2013-01-01

Several lines of evidence, including the recent discovery of novel susceptibility genes, point out an important role for the mammalian target of rapamycin (mTOR) signaling pathway in the development of pheochromocytoma. Analyzing a set of pheochromocytomas from patients with different genetic backgrounds, we observed and confirmed a significant overexpression of key mTOR complex (mTORC) signaling mediators. Using selective ATP-competitive inhibitors targeting both mTORC1 and mTORC2, we significantly arrested the in vitro cell proliferation and blocked migration of pheochromocytoma cells as a result of the pharmacological suppression of the Akt/mTOR signaling pathway. Moreover, AZD8055, a selective ATP-competitive dual mTORC1/2 small molecular inhibitor, significantly reduced the tumor burden in a model of metastatic pheochromocytoma using female athymic nude mice. This study suggests that targeting both mTORC1 and mTORC2 is a potentially rewarding strategy and supports the application of selective inhibitors in combinatorial drug regimens for metastatic pheochromocytoma. PMID:23307788

Mechanics of dual-mode dilative failure in subaqueous sediment deposits

NASA Astrophysics Data System (ADS)

You, Yao; Flemings, Peter; Mohrig, David

2014-07-01

We introduce dual-mode dilative failure with flume experiments. Dual-mode dilative failure combines slow and steady release of sediments by breaching with periodic sliding, which rapidly releases an internally coherent wedge of sediments. It occurs in dilative sandy deposits. This periodic slope failure results from cyclic evolution of the excess pore pressure in the deposit. Sliding generates large, transient, negative excess pore pressure that strengthens the deposit and allows breaching to occur. During breaching, negative excess pore pressure dissipates, the deposit weakens, and ultimately sliding occurs once again. We show that the sliding frequency is proportional to the coefficient of consolidation. We find that thicker deposits are more susceptible to dual-mode dilative failure. Discovery of dual-mode dilative failure provides a new mechanism to consider when interpreting the sedimentary deposits linked to submarine slope failures.

Analysis of calibration materials to improve dual-energy CT scanning for petrophysical applications

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

Ayyalasomavaiula, K.; McIntyre, D.; Jain, J.

2011-01-01

Dual energy CT-scanning is a rapidly emerging imaging technique employed in non-destructive evaluation of various materials. Although CT (Computerized Tomography) has been used for characterizing rocks and visualizing and quantifying multiphase flow through rocks for over 25 years, most of the scanning is done at a voltage setting above 100 kV for taking advantage of the Compton scattering (CS) effect, which responds to density changes. Below 100 kV the photoelectric effect (PE) is dominant which responds to the effective atomic numbers (Zeff), which is directly related to the photo electric factor. Using the combination of the two effects helps inmore » better characterization of reservoir rocks. The most common technique for dual energy CT-scanning relies on homogeneous calibration standards to produce the most accurate decoupled data. However, the use of calibration standards with impurities increases the probability of error in the reconstructed data and results in poor rock characterization. This work combines ICP-OES (inductively coupled plasma optical emission spectroscopy) and LIBS (laser induced breakdown spectroscopy) analytical techniques to quantify the type and level of impurities in a set of commercially purchased calibration standards used in dual-energy scanning. The Zeff data on the calibration standards with and without impurity data were calculated using the weighted linear combination of the various elements present and used in calculating Zeff using the dual energy technique. Results show 2 to 5% difference in predicted Zeff values which may affect the corresponding log calibrations. The effect that these techniques have on improving material identification data is discussed and analyzed. The workflow developed in this paper will translate to a more accurate material identification estimates for unknown samples and improve calibration of well logging tools.« less

High accuracy fuel flowmeter

NASA Technical Reports Server (NTRS)

1986-01-01

All three flowmeter concepts (vortex, dual turbine, and angular momentum) were subjected to experimental and analytical investigation to determine the potential portotype performance. The three concepts were subjected to a comprehensive rating. Eight parameters of performance were evaluated on a zero-to-ten scale, weighted, and summed. The relative ratings of the vortex, dual turbine, and angular momentum flowmeters are 0.71, 1.00, and 0.95, respectively. The dual turbine flowmeter concept was selected as the primary candidate and the angular momentum flowmeter as the secondary candidate for prototype development and evaluation.

Initial Experience of the Application of Automated Tube Potential Selection Technique in High-pitch Dual-source CT Angiography of Whole Aorta Using Third-generation Dual-source CT Scanner.

PubMed

Kong, Lingyan; Liang, Jixiang; Xue, Huadan; Wang, Yining; Wang, Yun; Jin, Zhengyu; Zhang, Daming; Chen, Jin

2017-02-20

Objective To evaluate the application of automated tube potential selection technique in high-pitch dual-source CT aortic angiography on a third-generation dual-source CT scanner. Methods Whole aorta angiography were indiated in 59 patients,who were divided into 2 groups using a simple random method:in group 1 there were 31 patients who underwent the examination with automated tube potential selection using a vascular setting with a preferred image quality of 288 mA/100 kV;in group 2 there were 28 patients who underwent the examination with a tube voltage of 100 kV and automated tube current modulation using a reference tube current of 288 mA. Both groups were scanned on a third generation dual-source CT device operated in dual-source high-pitch ECG-gating mode with a pitch of 3.0,collimation of 2×192×0.6 mm,and a rotation time of 0.25 s. Iterative reconstruction algorithm was used. For group 1,the volume and flow of contrast medium and chasing saline were adapted to the tube voltage. For group 2,a contrast material bolus of 45 ml with a flow of 4.5 ml/s followed by a 50 ml saline chaser at 5 ml/s was used. CTA scan was automatically started using a bolus tracking technique at the level of the original part of aorta after a trigger threshold of 100 HU was reached. The start delay was set to 6 s in both groups. Effective dose (ED),signal to noise ratio (SNR),contrast to noise ratio (CNR),and subjective diagnostic quality of both groups were evaluated. Results The mean ED were 21.3% lower (t=-3.099,P=0.000) in group 1 [(2.48±0.80) mSv] than in group 2 [(3.15±0.86) mSv]. Two groups showed no significant difference in attenuation,SD,SNR,or CNR at all evaluational parts of aorta (ascending aorta,aortic arch,diaphragmatic aorta,or iliac bifurcation)(all P>0.05). There was no significant difference in subjective diagnostic quality values of two groups [(1.41±0.50) scores vs. (1.39±0.50) scores;W=828.5,P=0.837]. Conclusion Compared with automated tube current modulation,the automated tube potential selection technique in aorta CT angiography on a third-generation dual-source CT can dramatically reduce radiation dose without affecting image quality.

Brain activations during bimodal dual tasks depend on the nature and combination of component tasks

PubMed Central

Salo, Emma; Rinne, Teemu; Salonen, Oili; Alho, Kimmo

2015-01-01

We used functional magnetic resonance imaging to investigate brain activations during nine different dual tasks in which the participants were required to simultaneously attend to concurrent streams of spoken syllables and written letters. They performed a phonological, spatial or “simple” (speaker-gender or font-shade) discrimination task within each modality. We expected to find activations associated specifically with dual tasking especially in the frontal and parietal cortices. However, no brain areas showed systematic dual task enhancements common for all dual tasks. Further analysis revealed that dual tasks including component tasks that were according to Baddeley's model “modality atypical,” that is, the auditory spatial task or the visual phonological task, were not associated with enhanced frontal activity. In contrast, for other dual tasks, activity specifically associated with dual tasking was found in the left or bilateral frontal cortices. Enhanced activation in parietal areas, however, appeared not to be specifically associated with dual tasking per se, but rather with intermodal attention switching. We also expected effects of dual tasking in left frontal supramodal phonological processing areas when both component tasks required phonological processing and in right parietal supramodal spatial processing areas when both tasks required spatial processing. However, no such effects were found during these dual tasks compared with their component tasks performed separately. Taken together, the current results indicate that activations during dual tasks depend in a complex manner on specific demands of component tasks. PMID:25767443

Diapycnal Transport and Pattern Formation in Double-Diffusive Convection

DTIC Science & Technology

2015-12-01

of knowledge. The effects of turbulent-dominated and purely double-diffusive regimes are compared to dual turbulent/double-diffusive systems and...is presented to remedy this dearth of knowledge. The effects of turbulent-dominated and purely double-diffusive regimes are compared to dual...8 2. Double-Diffusion: The Constant Flux Ratio Model ..........................9 3. The Combined Effects of

Trichotomous Processes in Early Memory Development, Aging, and Neurocognitive Impairment: A Unified Theory

ERIC Educational Resources Information Center

Brainerd, C. J.; Reyna, V. F.; Howe, M. L.

2009-01-01

One of the most extensively investigated topics in the adult memory literature, dual memory processes, has had virtually no impact on the study of early memory development. The authors remove the key obstacles to such research by formulating a trichotomous theory of recall that combines the traditional dual processes of recollection and…

Language Use in a Spanish-English Dual Immersion Classroom: A Sociolinguistic Perspective.

ERIC Educational Resources Information Center

Potowski, Kimberly

Dual immersion classrooms combine students who speak a non-English language (in this case Spanish) with English speaking students learning the native language of the nonnative English speaking students. This case study recorded the output of Spanish first language (L1) and second language (L2) fifth graders over 5 months of Spanish language…

A Critical Look at Dual Language Immersion in the New Latin@ Diaspora

ERIC Educational Resources Information Center

Cervantes-Soon, Claudia G.

2014-01-01

Two-way immersion (TWI), an approach that combines language-minority students and native English speakers in dual-language classrooms, is growing in popularity in schools of newly Latinized regions of the U.S. Using North Carolina as an example, this critical review of the literature posits that as neoliberal trends increasingly shape the…

Dual kinase-bromodomain inhibitors for rationally designed polypharmacology

PubMed Central

Ciceri, Pietro; Müller, Susanne; O’Mahony, Alison; Fedorov, Oleg; Filippakopoulos, Panagis; Hunt, Jeremy P.; Lasater, Elisabeth A.; Pallares, Gabriel; Picaud, Sarah; Wells, Christopher; Martin, Sarah; Wodicka, Lisa M.; Shah, Neil P.; Treiber, Daniel K.; Knapp, Stefan

2014-01-01

Concomitant inhibition of multiple cancer-driving kinases is an established strategy to improve the durability of clinical responses to targeted therapies. The difficulty of discovering kinase inhibitors with an appropriate multi-target profile has, however, necessitated the application of combination therapies, which can pose significant clinical development challenges. Epigenetic reader domains of the bromodomain family have recently emerged as novel targets for cancer therapy. Here we report that several clinical kinase inhibitors also inhibit bromodomains with therapeutically relevant potencies and are best classified as dual kinase/bromodomain inhibitors. Nanomolar activity on BRD4 by BI-2536 and TG-101348, clinical PLK1 and JAK2/FLT3 kinase inhibitors, respectively, is particularly noteworthy as these combinations of activities on independent oncogenic pathways exemplify a novel strategy for rational single agent polypharmacological targeting. Furthermore, structure-activity relationships and co-crystal structures identify design features that enable a general platform for the rational design of dual kinase/bromodomain inhibitors. PMID:24584101

Surface topography acquisition method for double-sided near-right-angle structured surfaces based on dual-probe wavelength scanning interferometry.

PubMed

Zhang, Tao; Gao, Feng; Jiang, Xiangqian

2017-10-02

This paper proposes an approach to measure double-sided near-right-angle structured surfaces based on dual-probe wavelength scanning interferometry (DPWSI). The principle and mathematical model is discussed and the measurement system is calibrated with a combination of standard step-height samples for both probes vertical calibrations and a specially designed calibration artefact for building up the space coordinate relationship of the dual-probe measurement system. The topography of the specially designed artefact is acquired by combining the measurement results with white light scanning interferometer (WLSI) and scanning electron microscope (SEM) for reference. The relative location of the two probes is then determined with 3D registration algorithm. Experimental validation of the approach is provided and the results show that the method is able to measure double-sided near-right-angle structured surfaces with nanometer vertical resolution and micrometer lateral resolution.

Dual-mode endomicroscopy for detection of epithelial dysplasia in the mouth: a descriptive pilot study

NASA Astrophysics Data System (ADS)

Bodenschatz, Nico; Poh, Catherine F.; Lam, Sylvia; Lane, Pierre; Guillaud, Martial; MacAulay, Calum E.

2017-08-01

Dual-mode endomicroscopy is a diagnostic tool for early cancer detection. It combines the high-resolution nuclear tissue contrast of fluorescence endomicroscopy with quantified depth-dependent epithelial backscattering as obtained by diffuse optical microscopy. In an in vivo pilot imaging study of 27 oral lesions from 21 patients, we demonstrate the complementary diagnostic value of both modalities and show correlations between grade of epithelial dysplasia and relative depth-dependent shifts in light backscattering. When combined, the two modalities provide diagnostic sensitivity to both moderate and severe epithelial dysplasia in vivo.

Highly sensitive "signal-on" electrochemiluminescent biosensor for the detection of DNA based on dual quenching and strand displacement reaction.

PubMed

Lou, Jing; Wang, Zhaoyin; Wang, Xiao; Bao, Jianchun; Tu, Wenwen; Dai, Zhihui

2015-10-07

A "signal-on" electrochemiluminescent DNA biosensing platform was proposed based on the dual quenching and strand displacement reaction. This novel "signal-on" detection strategy revealed its sensitivity in achieving a detection limit of 2.4 aM and its selectivity in distinguishing single nucleotide polymorphism of target DNA.

Dual Language Development and Disorders: A Handbook on Bilingualism and Second Language Learning

ERIC Educational Resources Information Center

Genesee, Fred; Paradis, Johanne; Crago, Martha B.

2004-01-01

This book dispels many myths about dual language development and answers key questions that might arise as you work with children and their parents. Student profiles, definitions of key terms, and "clinical implications" sections for selected chapters make this a valuable reference for in-practice SLPs and educators, an accessible resource for…

Advanced Placement versus Dual Enrollment: Making the Best Choice for College Selection, Persistence, Early Success, and Time to Completion

ERIC Educational Resources Information Center

Gruman, Daniel H.

2013-01-01

A substantial amount of research examines the benefits of high school college-credit attainment programs against non-participation. The growth in popularity of these programs, particularly Advanced Placement (AP) and dual enrollment (DE), has them competing against one another for student attention. However, students, schools, and policymakers do…

Reliability and Validity of Dual-Task Mobility Assessments in People with Chronic Stroke

PubMed Central

Yang, Lei; He, Chengqi; Pang, Marco Yiu Chung

2016-01-01

Background The ability to perform a cognitive task while walking simultaneously (dual-tasking) is important in real life. However, the psychometric properties of dual-task walking tests have not been well established in stroke. Objective To assess the test-retest reliability, concurrent and known-groups validity of various dual-task walking tests in people with chronic stroke. Design Observational measurement study with a test-retest design. Methods Eighty-eight individuals with chronic stroke participated. The testing protocol involved four walking tasks (walking forward at self-selected and maximal speed, walking backward at self-selected speed, and crossing over obstacles) performed simultaneously with each of the three attention-demanding tasks (verbal fluency, serial 3 subtractions or carrying a cup of water). For each dual-task condition, the time taken to complete the walking task, the correct response rate (CRR) of the cognitive task, and the dual-task effect (DTE) for the walking time and CRR were calculated. Forty-six of the participants were tested twice within 3–4 days to establish test-retest reliability. Results The walking time in various dual-task assessments demonstrated good to excellent reliability [Intraclass correlation coefficient (ICC2,1) = 0.70–0.93; relative minimal detectable change at 95% confidence level (MDC95%) = 29%-45%]. The reliability of the CRR (ICC2,1 = 0.58–0.81) and the DTE in walking time (ICC2,1 = 0.11–0.80) was more varied. The reliability of the DTE in CRR (ICC2,1 = -0.31–0.40) was poor to fair. The walking time and CRR obtained in various dual-task walking tests were moderately to strongly correlated with those of the dual-task Timed-up-and-Go test, thus demonstrating good concurrent validity. None of the tests could discriminate fallers (those who had sustained at least one fall in the past year) from non-fallers. Limitation The results are generalizable to community-dwelling individuals with chronic stroke only. Conclusions The walking time derived from the various dual-task assessments generally demonstrated good to excellent reliability, making them potentially useful in clinical practice and future research endeavors. However, the usefulness of these measurements in predicting falls needs to be further explored. Relatively low reliability was shown in the cognitive outcomes and DTE, which may not be preferred measurements for assessing dual-task performance. PMID:26808662

Accuracy of iodine quantification using dual energy CT in latest generation dual source and dual layer CT.

PubMed

Pelgrim, Gert Jan; van Hamersvelt, Robbert W; Willemink, Martin J; Schmidt, Bernhard T; Flohr, Thomas; Schilham, Arnold; Milles, Julien; Oudkerk, Matthijs; Leiner, Tim; Vliegenthart, Rozemarijn

2017-09-01

To determine the accuracy of iodine quantification with dual energy computed tomography (DECT) in two high-end CT systems with different spectral imaging techniques. Five tubes with different iodine concentrations (0, 5, 10, 15, 20 mg/ml) were analysed in an anthropomorphic thoracic phantom. Adding two phantom rings simulated increased patient size. For third-generation dual source CT (DSCT), tube voltage combinations of 150Sn and 70, 80, 90, 100 kVp were analysed. For dual layer CT (DLCT), 120 and 140 kVp were used. Scans were repeated three times. Median normalized values and interquartile ranges (IQRs) were calculated for all kVp settings and phantom sizes. Correlation between measured and known iodine concentrations was excellent for both systems (R = 0.999-1.000, p < 0.0001). For DSCT, median measurement errors ranged from -0.5% (IQR -2.0, 2.0%) at 150Sn/70 kVp and -2.3% (IQR -4.0, -0.1%) at 150Sn/80 kVp to -4.0% (IQR -6.0, -2.8%) at 150Sn/90 kVp. For DLCT, median measurement errors ranged from -3.3% (IQR -4.9, -1.5%) at 140 kVp to -4.6% (IQR -6.0, -3.6%) at 120 kVp. Larger phantom sizes increased variability of iodine measurements (p < 0.05). Iodine concentration can be accurately quantified with state-of-the-art DECT systems from two vendors. The lowest absolute errors were found for DSCT using the 150Sn/70 kVp or 150Sn/80 kVp combinations, which was slightly more accurate than 140 kVp in DLCT. • High-end CT scanners allow accurate iodine quantification using different DECT techniques. • Lowest measurement error was found in scans with largest photon energy separation. • Dual-source CT quantified iodine slightly more accurately than dual layer CT.

Dual energy CT: How well can pseudo-monochromatic imaging reduce metal artifacts?

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

Kuchenbecker, Stefan, E-mail: stefan.kuchenbecker@dkfz.de; Faby, Sebastian; Sawall, Stefan

2015-02-15

Purpose: Dual Energy CT (DECT) provides so-called monoenergetic images based on a linear combination of the original polychromatic images. At certain patient-specific energy levels, corresponding to certain patient- and slice-dependent linear combination weights, e.g., E = 160 keV corresponds to α = 1.57, a significant reduction of metal artifacts may be observed. The authors aimed at analyzing the method for its artifact reduction capabilities to identify its limitations. The results are compared with raw data-based processing. Methods: Clinical DECT uses a simplified version of monochromatic imaging by linearly combining the low and the high kV images and by assigning an energymore » to that linear combination. Those pseudo-monochromatic images can be used by radiologists to obtain images with reduced metal artifacts. The authors analyzed the underlying physics and carried out a series expansion of the polychromatic attenuation equations. The resulting nonlinear terms are responsible for the artifacts, but they are not linearly related between the low and the high kV scan: A linear combination of both images cannot eliminate the nonlinearities, it can only reduce their impact. Scattered radiation yields additional noncanceling nonlinearities. This method is compared to raw data-based artifact correction methods. To quantify the artifact reduction potential of pseudo-monochromatic images, they simulated the FORBILD abdomen phantom with metal implants, and they assessed patient data sets of a clinical dual source CT system (100, 140 kV Sn) containing artifacts induced by a highly concentrated contrast agent bolus and by metal. In each case, they manually selected an optimal α and compared it to a raw data-based material decomposition in case of simulation, to raw data-based material decomposition of inconsistent rays in case of the patient data set containing contrast agent, and to the frequency split normalized metal artifact reduction in case of the metal implant. For each case, the contrast-to-noise ratio (CNR) was assessed. Results: In the simulation, the pseudo-monochromatic images yielded acceptable artifact reduction results. However, the CNR in the artifact-reduced images was more than 60% lower than in the original polychromatic images. In contrast, the raw data-based material decomposition did not significantly reduce the CNR in the virtual monochromatic images. Regarding the patient data with beam hardening artifacts and with metal artifacts from small implants the pseudo-monochromatic method was able to reduce the artifacts, again with the downside of a significant CNR reduction. More intense metal artifacts, e.g., as those caused by an artificial hip joint, could not be suppressed. Conclusions: Pseudo-monochromatic imaging is able to reduce beam hardening, scatter, and metal artifacts in some cases but it cannot remove them. In all cases, the CNR is significantly reduced, thereby rendering the method questionable, unless special post processing algorithms are implemented to restore the high CNR from the original images (e.g., by using a frequency split technique). Raw data-based dual energy decomposition methods should be preferred, in particular, because the CNR penalty is almost negligible.« less

The Cytoplasmic Prolyl-tRNA Synthetase of the Malaria Parasite is a Dual-Stage Target for Drug Development

PubMed Central

Herman, Jonathan D.; Pepper, Lauren R.; Cortese, Joseph F.; Estiu, Guillermina; Galinsky, Kevin; Zuzarte-Luis, Vanessa; Derbyshire, Emily R.; Ribacke, Ulf; Lukens, Amanda K.; Santos, Sofia A.; Patel, Vishal; Clish, Clary B.; Sullivan, William J.; Zhou, Huihao; Bopp, Selina E.; Schimmel, Paul; Lindquist, Susan; Clardy, Jon; Mota, Maria M.; Keller, Tracy L.; Whitman, Malcolm; Wiest, Olaf; Wirth, Dyann F.; Mazitschek, Ralph

2015-01-01

The emergence of drug resistance is a major limitation of current antimalarials. The discovery of new druggable targets and pathways including those that are critical for multiple life cycle stages of the malaria parasite is a major goal for the development of the next-generation of antimalarial drugs. Using an integrated chemogenomics approach that combined drug-resistance selection, whole genome sequencing and an orthogonal yeast model, we demonstrate that the cytoplasmic prolyl-tRNA synthetase (PfcPRS) of the malaria parasite Plasmodium falciparum is a biochemical and functional target of febrifugine and its synthetic derivatives such as halofuginone. Febrifugine is the active principle of a traditional Chinese herbal remedy for malaria. We show that treatment with febrifugine derivatives activated the amino acid starvation response in both P. falciparum and a transgenic yeast strain expressing PfcPRS. We further demonstrate in the P. berghei mouse model of malaria that halofuginol, a new halofuginone analog that we developed, is highly active against both liver and asexual blood stages of the malaria parasite. Halofuginol, unlike halofuginone and febrifugine, is well tolerated at efficacious doses, and represents a promising lead for the development of dual-stage next generation antimalarials. PMID:25995223

"Clickable", trifunctional magnetite nanoparticles and their chemoselective biofunctionalization.

PubMed

Das, Manasmita; Bandyopadhyay, Debarati; Mishra, Debasish; Datir, Satyajit; Dhak, Prasanta; Jain, Sanyog; Maiti, Tapas Kumar; Basak, Amit; Pramanik, Panchanan

2011-06-15

A multifunctional iron oxide based nanoformulation for combined cancer-targeted therapy and multimodal imaging has been meticulously designed and synthesized using a chemoselective ligation approach. Novel superparamagnetic magnetite nanoparticles simultaneously functionalized with amine, carboxyl, and azide groups were fabricated through a sequence of stoichiometrically controllable partial succinylation and Cu (II) catalyzed diazo transfer on the reactive amine termini of 2-aminoethylphosphonate grafted magnetite nanoparticles (MNPs). Functional moieties associated with MNP surface were chemoselectively conjugated with rhodamine B isothiocyanate (RITC), propargyl folate (FA), and paclitaxel (PTX) via tandem nucleophic addition of amine to isothithiocyanates, Cu (I) catalyzed azide--alkyne click chemistry and carbodiimide-promoted esterification. An extensive in vitro study established that the bioactives chemoselectively appended to the magnetite core bequeathed multifunctionality to the nanoparticles without any loss of activity of the functional molecules. Multifunctional nanoparticles, developed in the course of the study, could selectively target and induce apoptosis to folate-receptor (FR) overexpressing cancer cells with enhanced efficacy as compared to the free drug. In addition, the dual optical and magnetic properties of the synthesized nanoparticles aided in the real-time tracking of their intracellular pathways also as apoptotic events through dual fluorescence and MR-based imaging.

Efficient combination of a 3D Quasi-Newton inversion algorithm and a vector dual-primal finite element tearing and interconnecting method

NASA Astrophysics Data System (ADS)

Voznyuk, I.; Litman, A.; Tortel, H.

2015-08-01

A Quasi-Newton method for reconstructing the constitutive parameters of three-dimensional (3D) penetrable scatterers from scattered field measurements is presented. This method is adapted for handling large-scale electromagnetic problems while keeping the memory requirement and the time flexibility as low as possible. The forward scattering problem is solved by applying the finite-element tearing and interconnecting full-dual-primal (FETI-FDP2) method which shares the same spirit as the domain decomposition methods for finite element methods. The idea is to split the computational domain into smaller non-overlapping sub-domains in order to simultaneously solve local sub-problems. Various strategies are proposed in order to efficiently couple the inversion algorithm with the FETI-FDP2 method: a separation into permanent and non-permanent subdomains is performed, iterative solvers are favorized for resolving the interface problem and a marching-on-in-anything initial guess selection further accelerates the process. The computational burden is also reduced by applying the adjoint state vector methodology. Finally, the inversion algorithm is confronted to measurements extracted from the 3D Fresnel database.

Dual HER2 blockade in the neoadjuvant and adjuvant treatment of HER2-positive breast cancer

PubMed Central

Advani, Pooja; Cornell, Lauren; Chumsri, Saranya; Moreno-Aspitia, Alvaro

2015-01-01

Human epidermal growth factor receptor 2 (HER2) is a tyrosine kinase transmembrane receptor that is overexpressed on the surface of 15%–20% of breast tumors and has been associated with poor prognosis. Consistently improved pathologic response and survival rates have been demonstrated with use of trastuzumab in combination with standard chemotherapy in both early and advanced breast cancer. However, resistance to trastuzumab may pose a major problem in the effective treatment of HER2-positive breast cancer. Dual HER2 blockade, using agents that work in a complimentary fashion to trastuzumab, has more recently been explored to evade resistance in both the preoperative (neoadjuvant) and adjuvant settings. Increased effectiveness of dual anti-HER2 agents over single blockade has been recently reported in clinical studies. Pertuzumab in combination with trastuzumab and taxane is currently approved in the metastatic and neoadjuvant treatment of HER2-positive breast cancer. Various biomarkers have also been investigated to identify subsets of patients with HER2-positive tumors who would likely respond best to these targeted therapy combinations. In this article, available trial data regarding efficacy and toxicity of treatment with combination HER2 agents in the neoadjuvant and adjuvant setting have been reviewed, and relevant correlative biomarker data from these trials have been discussed. PMID:26451122

Enhanced therapeutic efficacy of budesonide in experimental colitis with enzyme/pH dual-sensitive polymeric nanoparticles.

PubMed

Naeem, Muhammad; Cao, Jiafu; Choi, Moonjeong; Kim, Woo Seong; Moon, Hyung Ryong; Lee, Bok Luel; Kim, Min-Soo; Jung, Yunjin; Yoo, Jin-Wook

2015-01-01

Current colon-targeted drug-delivery approaches for colitis therapy often utilize single pH-triggered systems, which are less reliable due to the variation of gut pH in individuals and in disease conditions. Herein, we prepared budesonide-loaded dual-sensitive nanoparticles using enzyme-sensitive azo-polyurethane and pH-sensitive methacrylate copolymer for the treatment of colitis. The therapeutic potential of the enzyme/pH dual-sensitive nanoparticles was evaluated using a rat colitis model and compared to single pH-triggered nanoparticles. Clinical activity scores, colon/body weight ratios, myeloperoxidase activity, and proinflammatory cytokine levels were markedly decreased by dual-sensitive nanoparticles compared to single pH-triggered nanoparticles and budesonide solution. Moreover, dual-sensitive nanoparticles accumulated selectively in inflamed segments of the colon. In addition, dual-sensitive nanoparticle plasma concentrations were lower than single pH-triggered nanoparticles, and no noticeable in vitro or in vivo toxicity was observed. Our results demonstrate that enzyme/pH dual-sensitive nanoparticles are an effective and safe colon-targeted delivery system for colitis therapy.

Enhanced therapeutic efficacy of budesonide in experimental colitis with enzyme/pH dual-sensitive polymeric nanoparticles

PubMed Central

Naeem, Muhammad; Cao, Jiafu; Choi, Moonjeong; Kim, Woo Seong; Moon, Hyung Ryong; Lee, Bok Luel; Kim, Min-Soo; Jung, Yunjin; Yoo, Jin-Wook

2015-01-01

Current colon-targeted drug-delivery approaches for colitis therapy often utilize single pH-triggered systems, which are less reliable due to the variation of gut pH in individuals and in disease conditions. Herein, we prepared budesonide-loaded dual-sensitive nanoparticles using enzyme-sensitive azo-polyurethane and pH-sensitive methacrylate copolymer for the treatment of colitis. The therapeutic potential of the enzyme/pH dual-sensitive nanoparticles was evaluated using a rat colitis model and compared to single pH-triggered nanoparticles. Clinical activity scores, colon/body weight ratios, myeloperoxidase activity, and proinflammatory cytokine levels were markedly decreased by dual-sensitive nanoparticles compared to single pH-triggered nanoparticles and budesonide solution. Moreover, dual-sensitive nanoparticles accumulated selectively in inflamed segments of the colon. In addition, dual-sensitive nanoparticle plasma concentrations were lower than single pH-triggered nanoparticles, and no noticeable in vitro or in vivo toxicity was observed. Our results demonstrate that enzyme/pH dual-sensitive nanoparticles are an effective and safe colon-targeted delivery system for colitis therapy. PMID:26213469

Vascular Effects of Endothelin Receptor Antagonists Depends on Their Selectivity for ETA Versus ETB Receptors and on the Functionality of Endothelial ETB Receptors.

PubMed

Iglarz, Marc; Steiner, Pauline; Wanner, Daniel; Rey, Markus; Hess, Patrick; Clozel, Martine

2015-10-01

The goal of this study was to characterize the role of Endothelin (ET) type B receptors (ETB) on vascular function in healthy and diseased conditions and demonstrate how it affects the pharmacological activity of ET receptor antagonists (ERAs). The contribution of the ETB receptor to vascular relaxation or constriction was characterized in isolated arteries from healthy and diseased rats with systemic (Dahl-S) or pulmonary hypertension (monocrotaline). Because the role of ETB receptors is different in pathological vis-à-vis normal conditions, we compared the efficacy of ETA-selective and dual ETA/ETB ERAs on blood pressure in hypertensive rats equipped with telemetry. In healthy vessels, ETB receptors stimulation with sarafotoxin S6c induced vasorelaxation and no vasoconstriction. In contrast, in arteries of rats with systemic or pulmonary hypertension, endothelial ETB-mediated relaxation was lost while vasoconstriction on stimulation by sarafotoxin S6c was observed. In hypertensive rats, administration of the dual ETA/ETB ERA macitentan on top of a maximal effective dose of the ETA-selective ERA ambrisentan further reduced blood pressure, indicating that ETB receptors blockade provides additional benefit. Taken together, these data suggest that in pathology, dual ETA/ETB receptor antagonism can provide superior vascular effects compared with ETA-selective receptor blockade.

Dual phase high-temperature membranes for CO2 separation - performance assessment in post- and pre-combustion processes.

PubMed

Anantharaman, Rahul; Peters, Thijs; Xing, Wen; Fontaine, Marie-Laure; Bredesen, Rune

2016-10-20

Dual phase membranes are highly CO 2 -selective membranes with an operating temperature above 400 °C. The focus of this work is to quantify the potential of dual phase membranes in pre- and post-combustion CO 2 capture processes. The process evaluations show that the dual phase membranes integrated with an NGCC power plant for CO 2 capture are not competitive with the MEA process for post-combustion capture. However, dual phase membrane concepts outperform the reference Selexol technology for pre-combustion CO 2 capture in an IGCC process. The two processes evaluated in this work, post-combustion NGCC and pre-combustion IGCC, represent extremes in CO 2 partial pressure fed to the separation unit. Based on the evaluations it is expected that dual phase membranes could be competitive for post-combustion capture from a pulverized coal fired power plant (PCC) and pre-combustion capture from an Integrated Reforming Cycle (IRCC).

Tumor resistance to vascular disrupting agents: mechanisms, imaging, and solutions

PubMed Central

Liang, Wenjie; Ni, Yicheng; Chen, Feng

2016-01-01

The emergence of vascular disrupting agents (VDAs) is a significant advance in the treatment of solid tumors. VDAs induce rapid and selective shutdown of tumor blood flow resulting in massive necrosis. However, a viable marginal tumor rim always remains after VDA treatment and is a major cause of recurrence. In this review, we discuss the mechanisms involved in the resistance of solid tumors to VDAs. Hypoxia, tumor-associated macrophages, and bone marrow-derived circulating endothelial progenitor cells all may contribute to resistance. Resistance can be monitored using magnetic resonance imaging markers. The various solutions proposed to manage tumor resistance to VDAs emphasize combining these agents with other approaches including antiangiogenic agents, chemotherapy, radiotherapy, radioimmunotherapy, and sequential dual-targeting internal radiotherapy. PMID:26812886

Dual-view inverted selective plane illumination microscopy (diSPIM) with improved background rejection for accurate 3D digital pathology

NASA Astrophysics Data System (ADS)

Hu, Bihe; Bolus, Daniel; Brown, J. Quincy

2018-02-01

Current gold-standard histopathology for cancerous biopsies is destructive, time consuming, and limited to 2D slices, which do not faithfully represent true 3D tumor micro-morphology. Light sheet microscopy has emerged as a powerful tool for 3D imaging of cancer biospecimens. Here, we utilize the versatile dual-view inverted selective plane illumination microscopy (diSPIM) to render digital histological images of cancer biopsies. Dual-view architecture enabled more isotropic resolution in X, Y, and Z; and different imaging modes, such as adding electronic confocal slit detection (eCSD) or structured illumination (SI), can be used to improve degraded image quality caused by background signal of large, scattering samples. To obtain traditional H&E-like images, we used DRAQ5 and eosin (D&E) staining, with 488nm and 647nm laser illumination, and multi-band filter sets. Here, phantom beads and a D&E stained buccal cell sample have been used to verify our dual-view method. We also show that via dual view imaging and deconvolution, more isotropic resolution has been achieved for optical cleared human prostate sample, providing more accurate quantitation of 3D tumor architecture than was possible with single-view SPIM methods. We demonstrate that the optimized diSPIM delivers more precise analysis of 3D cancer microarchitecture in human prostate biopsy than simpler light sheet microscopy arrangements.

Balancing the Demands of Two Tasks: An Investigation of Cognitive-Motor Dual-Tasking in Relapsing Remitting Multiple Sclerosis.

PubMed

Butchard-MacDonald, Emma; Paul, Lorna; Evans, Jonathan J

2018-03-01

People with relapsing remitting multiple sclerosis (PwRRMS) suffer disproportionate decrements in gait under dual-task conditions, when walking and a cognitive task are combined. There has been much less investigation of the impact of cognitive demands on balance. This study investigated whether: (1) PwRRMS show disproportionate decrements in postural stability under dual-task conditions compared to healthy controls, and (2) dual-task decrements are associated with everyday dual-tasking difficulties. The impact of mood, fatigue, and disease severity on dual-tasking was also examined. A total of 34 PwRRMS and 34 matched controls completed cognitive (digit span) and balance (movement of center of pressure on Biosway on stable and unstable surfaces) tasks under single- and dual-task conditions. Everyday dual-tasking was measured using the Dual-Tasking Questionnaire. Mood was measured by the Hospital Anxiety & Depression Scale. Fatigue was measured via the Modified Fatigue Index Scale. No differences in age, gender, years of education, estimated pre-morbid IQ, or baseline digit span between groups. Compared with controls, PwRRMS showed significantly greater decrement in postural stability under dual-task conditions on an unstable surface (p=.007), but not a stable surface (p=.679). Balance decrement scores were not correlated with everyday dual-tasking difficulties or fatigue. Stable surface balance decrement scores were significantly associated with levels of anxiety (rho=0.527; p=.001) and depression (rho=0.451; p=.007). RRMS causes dual-tasking difficulties, impacting balance under challenging conditions, which may contribute to increased risk of gait difficulties and falls. The relationship between anxiety/depression and dual-task decrement suggests that emotional factors may be contributing to dual-task difficulties. (JINS, 2018, 24, 247-258).

Tolerance development in Listeria monocytogenes-Escherichia coli dual-species biofilms after sublethal exposures to pronase-benzalkonium chloride combined treatments.

PubMed

Rodríguez-López, Pedro; Cabo, Marta López

2017-10-01

This study was designed to assess the effects that sublethal exposures to pronase (PRN) and benzalkonium chloride (BAC) combined treatments have on Listeria monocytogenes-Escherichia coli dual-species biofilms grown on stainless steel in terms of tolerance development (TD) to these compounds. Additionally, fluorescence microscopy was used to observe the changes of the biofilm structure. PRN-BAC exposure was carried out using three different approaches and TD was evaluated treating biofilms with a final 100 μg/ml PRN followed by 50 μg/ml BAC combined treatment. Results showed that exposure to PRN-BAC significantly decreased the number of adhered L. monocytogenes (P < 0.05), while E. coli counts remained generally unaltered. It was also demonstrated that the incorporation of recovery periods during sublethal exposures increased the tolerance of both species of the mixed biofilm to the final PRN-BAC treatment. Moreover, control biofilms became more resistant to PRN-BAC if longer incubation periods were used. Regardless of the treatment used, log reduction values were generally lower in L. monocytogenes compared to E. coli. Additionally, microscopy images showed an altered morphology produced by sublethal PRN-BAC in exposed L. monocytogenes-E. coli dual-species biofilms compared to control samples. Results also demonstrated that L. monocytogenes-E. coli dual-species biofilms are able to develop tolerance to PRN-BAC combined treatments depending on way they have been previously exposed. Moreover, they suggest that the generation of bacterial tolerance should be included as a parameter for sanitation procedures design. Copyright © 2017 Elsevier Ltd. All rights reserved.

Interactions between pacing and arrhythmia detection algorithms in the dual chamber implantable cardioverter defibrillator.

PubMed

Dijkman, B; Wellens, H J

2001-09-01

Dual chamber implantable cardioverter defibrillator (ICD) combines the possibility to detect and treat ventricular and atrial arrhythmias with the possibility of modern heart stimulation techniques. Advanced pacing algorithms together with extended arrhythmia detection capabilities can give rise to new types of device-device interactions. Some of the possible interactions are illustrated by four cases documented in four models of dual chamber ICDs. Functioning of new features in dual chamber devices is influenced by the fact that the pacemaker is not a separate device but a part of the ICD system and that both are being used in a patient with arrhythmia. Programming measures are suggested to optimize use of new pacing algorithms while maintaining correct arrhythmia detection.

Media Combinations and Learning Styles: A Dual Coding Approach.

ERIC Educational Resources Information Center

Beacham, N. A.; Elliott, A. C.; Alty, J. L.; Al-Sharrah, A.

This paper reports initial results from a study which investigated whether different media combinations could be shown to improve students' understanding of computer-based learning materials and to determine whether student learning style affected student understanding for different media combinations. Three groups of participants were given a…

Cellular Telephone Dialing Influences Kinematic and Spatiotemporal Gait Parameters in Healthy Adults.

PubMed

Seymour, Kelly M; Higginson, Christopher I; DeGoede, Kurt M; Bifano, Morgan K; Orr, Rachel; Higginson, Jill S

2016-01-01

Gait speed is typically reduced when individuals simultaneously perform other tasks. However, the impact of dual tasking on kinetic and kinematic gait parameters is unclear because these vary with gait speed. The objective of this study was to identify whether dual tasking impacts gait in healthy adults when speed is constant. Twenty-two healthy adults dialed a cell phone during treadmill walking at a self-selected speed while kinetic, kinematic, and spatial parameters were recorded. Results indicated that dual tasking did not impact phone dialing speed, but increased stride width, peak knee flexion during stance, and peak plantarflexion, and decreased knee and ankle range of motion. Dual tasking appears to influence kinematic gait variables in a manner consistent with promotion of stability.

Can machine learning complement traditional medical device surveillance? A case study of dual-chamber implantable cardioverter-defibrillators.

PubMed

Ross, Joseph S; Bates, Jonathan; Parzynski, Craig S; Akar, Joseph G; Curtis, Jeptha P; Desai, Nihar R; Freeman, James V; Gamble, Ginger M; Kuntz, Richard; Li, Shu-Xia; Marinac-Dabic, Danica; Masoudi, Frederick A; Normand, Sharon-Lise T; Ranasinghe, Isuru; Shaw, Richard E; Krumholz, Harlan M

2017-01-01

Machine learning methods may complement traditional analytic methods for medical device surveillance. Using data from the National Cardiovascular Data Registry for implantable cardioverter-defibrillators (ICDs) linked to Medicare administrative claims for longitudinal follow-up, we applied three statistical approaches to safety-signal detection for commonly used dual-chamber ICDs that used two propensity score (PS) models: one specified by subject-matter experts (PS-SME), and the other one by machine learning-based selection (PS-ML). The first approach used PS-SME and cumulative incidence (time-to-event), the second approach used PS-SME and cumulative risk (Data Extraction and Longitudinal Trend Analysis [DELTA]), and the third approach used PS-ML and cumulative risk (embedded feature selection). Safety-signal surveillance was conducted for eleven dual-chamber ICD models implanted at least 2,000 times over 3 years. Between 2006 and 2010, there were 71,948 Medicare fee-for-service beneficiaries who received dual-chamber ICDs. Cumulative device-specific unadjusted 3-year event rates varied for three surveyed safety signals: death from any cause, 12.8%-20.9%; nonfatal ICD-related adverse events, 19.3%-26.3%; and death from any cause or nonfatal ICD-related adverse event, 27.1%-37.6%. Agreement among safety signals detected/not detected between the time-to-event and DELTA approaches was 90.9% (360 of 396, k =0.068), between the time-to-event and embedded feature-selection approaches was 91.7% (363 of 396, k =-0.028), and between the DELTA and embedded feature selection approaches was 88.1% (349 of 396, k =-0.042). Three statistical approaches, including one machine learning method, identified important safety signals, but without exact agreement. Ensemble methods may be needed to detect all safety signals for further evaluation during medical device surveillance.

Sequence Learning and Selection Difficulty

ERIC Educational Resources Information Center

Rowland, Lee A.; Shanks, David R.

2006-01-01

The authors studied the role of attention as a selection mechanism in implicit learning by examining the effect on primary sequence learning of performing a demanding target-selection task. Participants were trained on probabilistic sequences in a novel version of the serial reaction time (SRT) task, with dual- and triple-stimulus participants…

Self-Calibrating Respiratory-Flowmeter Combination

NASA Technical Reports Server (NTRS)

Westenskow, Dwayne R.; Orr, Joseph A.

1990-01-01

Dual flowmeters ensure accuracy over full range of human respiratory flow rates. System for measurement of respiratory flow employs two flowmeters; one compensates for deficiencies of other. Combination yields easily calibrated system accurate over wide range of gas flow.

Effect of divided attention on gait in subjects with and without cognitive impairment.

PubMed

Pettersson, Anna F; Olsson, Elisabeth; Wahlund, Lars-Olof

2007-03-01

The aim of this study was to investigate the influence of cognition on motor function using 2 simple everyday tasks, talking and walking, in younger subjects with Alzheimer's disease and mild cognitive impairment. A second aim was to evaluate reliability for the dual-task test Talking While Walking. Walking speed during single and dual task and time change between single and dual task were compared between groups. The test procedure was repeated after 1 week. Subjects with AD had lower walking speed and greater time change between single and dual task compared with healthy controls. Reliability for Talking While Walking was very good. The results show that motor function in combination with a cognitive task, as well as motor function alone, influences subjects with Alzheimer's disease in a negative way and that decreased walking speed during single- and dual-task performance may be an early symptom in Alzheimer's disease.

Supertaskers: Profiles in extraordinary multitasking ability.

PubMed

Watson, Jason M; Strayer, David L

2010-08-01

Theory suggests that driving should be impaired for any motorist who is concurrently talking on a cell phone. But is everybody impaired by this dual-task combination? We tested 200 participants in a high-fidelity driving simulator in both single- and dual-task conditions. The dual task involved driving while performing a demanding auditory version of the operation span (OSPAN) task. Whereas the vast majority of participants showed significant performance decrements in dual-task conditions (compared with single-task conditions for either driving or OSPAN tasks), 2.5% of the sample showed absolutely no performance decrements with respect to performing single and dual tasks. In single-task conditions, these "supertaskers" scored in the top quartile on all dependent measures associated with driving and OSPAN tasks, and Monte Carlo simulations indicated that the frequency of supertaskers was significantly greater than chance. These individual differences help to sharpen our theoretical understanding of attention and cognitive control in naturalistic settings.

Study of removal of ammonia from urine vapor by dual catalyst

NASA Technical Reports Server (NTRS)

Budininkas, P.

1976-01-01

The feasibility of ammonia removal from urine vapor by a low temperature dual-catalyst system was investigated. The process is based on the initial catalytic oxidation of ammonia present in urine vapor to nitrogen and nitrous oxide, followed by a catalytic decomposition of the nitrous oxide formed into its elements. The most active catalysts for the oxidation of ammonia and for the decomposition of N2O, identified in screening tests, were then combined into dual catalyst systems and tested to establish their overall efficiencies for the removal of ammonia from artificial gas mixtures. Dual catalyst systems capable of ammonia removal from the artificial gas mixtures were then tested with the actual urine vapor produced by boiling untreated urine. A suitable dual catalyst bed arrangement was found that achieved the removal of ammonia and organic carbon, and recovered water of good quality from urine vapor.

Dual Coding Theory and Computer Education: Some Media Experiments To Examine the Effects of Different Media on Learning.

ERIC Educational Resources Information Center

Alty, James L.

Dual Coding Theory has quite specific predictions about how information in different media is stored, manipulated and recalled. Different combinations of media are expected to have significant effects upon the recall and retention of information. This obviously may have important consequences in the design of computer-based programs. The paper…

Age-Related Changes in Brain Activation Underlying Single- and Dual-Task Performance: Visuomanual Drawing and Mental Arithmetic

ERIC Educational Resources Information Center

Van Impe, A.; Coxon, J. P.; Goble, D. J.; Wenderoth, N.; Swinnen, S. P.

2011-01-01

Depending on task combination, dual-tasking can either be performed successfully or can lead to performance decrements in one or both tasks. Interference is believed to be caused by limitations in central processing, i.e. structural interference between the neural activation patterns associated with each task. In the present study, single- and…

Attentional load and attentional boost: a review of data and theory.

PubMed

Swallow, Khena M; Jiang, Yuhong V

2013-01-01

Both perceptual and cognitive processes are limited in capacity. As a result, attention is selective, prioritizing items and tasks that are important for adaptive behavior. However, a number of recent behavioral and neuroimaging studies suggest that, at least under some circumstances, increasing attention to one task can enhance performance in a second task (e.g., the attentional boost effect). Here we review these findings and suggest a new theoretical framework, the dual-task interaction model, that integrates these findings with current views of attentional selection. To reconcile the attentional boost effect with the effects of attentional load, we suggest that temporal selection results in a temporally specific enhancement across modalities, tasks, and spatial locations. Moreover, the effects of temporal selection may be best observed when the attentional system is optimally tuned to the temporal dynamics of incoming stimuli. Several avenues of research motivated by the dual-task interaction model are then discussed.

Selective excitation of LP01 and LP02 in dual-concentric cores fiber using an adiabatically tapered microstructured mode converter

NASA Astrophysics Data System (ADS)

Sammouda, Marwa; Taher, Aymen Belhadj; Bahloul, Faouzi; Bin, Philippe Di

2016-09-01

We propose to connect a single-mode fiber (SMF) to a dual-concentric cores fiber (DCCF) using an adiabatically tapered microstructured mode converter, and to evaluate the SMF LP01 mode and the DCCF LP01 and LP02 modes selective excitations performances. We theoretically and numerically study this selective excitation method by calculating the effective indices of the propagated modes, the adiabaticity criteria, the coupling loss, and the modes amplitudes along the tapered structure. This study shows that this method is able to achieve excellent selective excitations of the first two linearly polarized modes (LP01 and LP02) among the five guided modes in the DCCF with a negligible loss. The part of the LP01 and LP02 modes from the total power are 99% and 84% corresponding to 0.1 and 0.8 dB losses, respectively.

Attentional Load and Attentional Boost: A Review of Data and Theory

PubMed Central

Swallow, Khena M.; Jiang, Yuhong V.

2013-01-01

Both perceptual and cognitive processes are limited in capacity. As a result, attention is selective, prioritizing items and tasks that are important for adaptive behavior. However, a number of recent behavioral and neuroimaging studies suggest that, at least under some circumstances, increasing attention to one task can enhance performance in a second task (e.g., the attentional boost effect). Here we review these findings and suggest a new theoretical framework, the dual-task interaction model, that integrates these findings with current views of attentional selection. To reconcile the attentional boost effect with the effects of attentional load, we suggest that temporal selection results in a temporally specific enhancement across modalities, tasks, and spatial locations. Moreover, the effects of temporal selection may be best observed when the attentional system is optimally tuned to the temporal dynamics of incoming stimuli. Several avenues of research motivated by the dual-task interaction model are then discussed. PMID:23730294

Emerging trends in vibration control of wind turbines: a focus on a dual control strategy.

PubMed

Staino, Andrea; Basu, Biswajit

2015-02-28

The paper discusses some of the recent developments in vibration control strategies for wind turbines, and in this context proposes a new dual control strategy based on the combination and modification of two recently proposed control schemes. Emerging trends in the vibration control of both onshore and offshore wind turbines are presented. Passive, active and semi-active structural vibration control algorithms have been reviewed. Of the existing controllers, two control schemes, active pitch control and active tendon control, have been discussed in detail. The proposed new control scheme is a merger of active tendon control with passive pitch control, and is designed using a Pareto-optimal problem formulation. This combination of controllers is the cornerstone of a dual strategy with the feature of decoupling vibration control from optimal power control as one of its main advantages, in addition to reducing the burden on the pitch demand. This dual control strategy will bring in major benefits to the design of modern wind turbines and is expected to play a significant role in the advancement of offshore wind turbine technologies. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Dual Electrophoresis Detection System for Rapid and Sensitive Immunoassays with Nanoparticle Signal Amplification

NASA Astrophysics Data System (ADS)

Zhang, Fangfang; Ma, Junjie; Watanabe, Junji; Tang, Jinlong; Liu, Huiyu; Shen, Heyun

2017-02-01

An electrophoretic technique was combined with an enzyme-linked immunosorbent assay (ELISA) system to achieve a rapid and sensitive immunoassay. A cellulose acetate filter modified with polyelectrolyte multilayer (PEM) was used as a solid substrate for three-dimensional antigen-antibody reactions. A dual electrophoresis process was used to induce directional migration and local condensation of antigens and antibodies at the solid substrate, avoiding the long diffusion times associated with antigen-antibody reactions in conventional ELISAs. The electrophoretic forces drove two steps in the ELISA process, namely the adsorption of antigen, and secondary antibody-labelled polystyrene nanoparticles (NP-Ab). The total time needed for dual electrophoresis-driven detection was just 4 min, nearly 2 h faster than a conventional ELISA system. Moreover, the rapid NP-Ab electrophoresis system simultaneously achieved amplification of the specific signal and a reduction in noise, leading to a more sensitive NP-Ab immunoassay with a limit of detection (LOD) of 130 fM, and wide range of detectable concentrations from 0.13 to 130 pM. These results suggest that the combination of dual electrophoresis detection and NP-Ab signal amplification has great potential for future immunoassay systems.

New approach of delivering cytotoxic drugs towards CAIX expressing cells: A concept of dual-target drugs.

PubMed

van Kuijk, Simon J A; Parvathaneni, Nanda Kumar; Niemans, Raymon; van Gisbergen, Marike W; Carta, Fabrizio; Vullo, Daniela; Pastorekova, Silvia; Yaromina, Ala; Supuran, Claudiu T; Dubois, Ludwig J; Winum, Jean-Yves; Lambin, Philippe

2017-02-15

Carbonic anhydrase IX (CAIX) is a hypoxia-regulated and tumor-specific protein that maintains the pH balance of cells. Targeting CAIX might be a valuable approach for specific delivery of cytotoxic drugs, thereby reducing normal tissue side-effects. A series of dual-target compounds were designed and synthesized incorporating a sulfonamide, sulfamide, or sulfamate moiety combined with several different anti-cancer drugs, including the chemotherapeutic agents chlorambucil, tirapazamine, and temozolomide, two Ataxia Telangiectasia and Rad3-related protein inhibitors (ATRi), and the anti-diabetic biguanide agent phenformin. An ATRi derivative (12) was the only compound to show a preferred efficacy in CAIX overexpressing cells versus cells without CAIX expression when combined with radiation. Its efficacy might however not solely depend on binding to CAIX, since all described compounds generally display low activity as carbonic anhydrase inhibitors. The hypothesis that dual-target compounds specifically target CAIX expressing tumor cells was therefore not confirmed. Even though dual-target compounds remain an interesting approach, alternative options should also be investigated as novel treatment strategies. Copyright © 2016 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Qualifications with a Dual Orientation towards Employment and Higher Education. A Collaborative Investigation of Selected Issues in Seven European Countries. INTEQUAL Report II.

ERIC Educational Resources Information Center

Manning, Sabine, Ed.

This document is the second report on results achieved in the project, "The Acquisition of Integrated Qualifications for Professional Work and Study--An Assessment of Innovative Approaches in Seven European Countries (INTEQUAL)," which was undertaken to identify innovative approaches to granting dual qualifications that can ultimately…

Social Work and Public Health: Comparing Graduates from a Dual-Degree Program

ERIC Educational Resources Information Center

Ruth, Betty J.; Wyatt, Jamie; Chiasson, Emily; Geron, Scott Miyake; Bachman, Sally

2006-01-01

This study compared dual-degree master of social work/master of public health (MSW/MPH) and MSW-only graduates with 3 or more years of postgraduate experience. Thirty graduates from an MSW/MPH program were matched with 30 MSW-only graduates. All subjects were randomly selected from the alumni directory and interviewed via telephone. Results showed…

Health care utilization among Medicare-Medicaid dual eligibles: a count data analysis.

PubMed

Moon, Sangho; Shin, Jaeun

2006-04-05

Medicare-Medicaid dual eligibles are the beneficiaries of both Medicare and Medicaid. Dual eligibles satisfy the eligibility conditions for Medicare benefit. Dual eligibles also qualify for Medicaid because they are aged, blind, or disabled and meet the income and asset requirements for receiving Supplement Security Income (SSI) assistance. The objective of this study is to explore the relationship between dual eligibility and health care utilization among Medicare beneficiaries. The household component of the nationally representative Medical Expenditure Panel Survey (MEPS) 1996-2000 is used for the analysis. Total 8,262 Medicare beneficiaries are selected from the MEPS data. The Medicare beneficiary sample includes individuals who are covered by Medicare and do not have private health insurance during a given year. Zero-inflated negative binomial (ZINB) regression model is used to analyse the count data regarding health care utilization: office-based physician visits, hospital inpatient nights, agency-sponsored home health provider days, and total dental visits. Dual eligibility is positively correlated with the likelihood of using hospital inpatient care and agency-sponsored home health services and the frequency of agency-sponsored home health days. Frequency of dental visits is inversely associated with dual eligibility. With respect to racial differences, dually eligible Afro-Americans use more office-based physician and dental services than white duals. Asian duals use more home health services than white duals at the 5% statistical significance level. The dual eligibility programs seem particularly beneficial to Afro-American duals. Dual eligibility has varied impact on health care utilization across service types. More utilization of home healthcare among dual eligibles appears to be the result of delayed realization of their unmet healthcare needs under the traditional Medicare-only program rather than the result of overutilization in response to the expanded benefits of the dual eligibility program. The dual eligibility program is particularly beneficial to Asian and Afro-American duals in association with the provision of home healthcare and dental benefits.

Mental rotation impairs attention shifting and short-term memory encoding: neurophysiological evidence against the response-selection bottleneck model of dual-task performance.

PubMed

Pannebakker, Merel M; Jolicœur, Pierre; van Dam, Wessel O; Band, Guido P H; Ridderinkhof, K Richard; Hommel, Bernhard

2011-09-01

Dual tasks and their associated delays have often been used to examine the boundaries of processing in the brain. We used the dual-task procedure and recorded event-related potentials (ERPs) to investigate how mental rotation of a first stimulus (S1) influences the shifting of visual-spatial attention to a second stimulus (S2). Visual-spatial attention was monitored by using the N2pc component of the ERP. In addition, we examined the sustained posterior contralateral negativity (SPCN) believed to index the retention of information in visual short-term memory. We found modulations of both the N2pc and the SPCN, suggesting that engaging mechanisms of mental rotation impairs the deployment of visual-spatial attention and delays the passage of a representation of S2 into visual short-term memory. Both results suggest interactions between mental rotation and visual-spatial attention in capacity-limited processing mechanisms indicating that response selection is not pivotal in dual-task delays and all three processes are likely to share a common resource like executive control. Copyright © 2011 Elsevier Ltd. All rights reserved.

Virtual Screening for the Development of Dual-Inhibitors Targeting Topoisomerase IB and Tyrosyl-DNA Phosphodiesterase 1.

PubMed

Cardamone, Francesca; Pizzi, Simone; Iacovelli, Federico; Falconi, Mattia; Desideri, Alessandro

2017-01-01

Human topoisomerase IB is an important target in cancer therapy and drugs selectively stabilizing the topoisomerase IB-DNA covalent complex are in clinical use for several cancer types. Tyrosyl- DNA phosphodiesterase 1 is involved in the DNA repair resolving the topoisomerase IB-DNA covalent complex that is extremely dangerous for the survival of the cells since it produces an irreversible DNA damage. Given the close biological relationship between these two enzymes, the development of synergistic inhibitors, called dual-inhibitors, is an important challenge in cancer therapy and computer-aided drug design may help in the identification of the best compounds. In this review, an overview of the compounds inhibiting one of the two enzymes or acting as dual inhibitors is provided. Moreover, the general procedures of the virtual screening approach, providing a description of two widely used opensource programs, namely AutoDock4 and AutoDock Vina, are described. Finally, an application of the two programs on a selected number of dual inhibitors for tyrosyl-DNA phosphodiesterase 1 and topoisomerase IB and their performance is briefly discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Dual-energy CT for detection of contrast enhancement or leakage within high-density haematomas in patients with intracranial haemorrhage.

PubMed

Watanabe, Yoshiyuki; Tsukabe, Akio; Kunitomi, Yuki; Nishizawa, Mitsuo; Arisawa, Atsuko; Tanaka, Hisashi; Yoshiya, Kazuhisa; Shimazu, Takeshi; Tomiyama, Noriyuki

2014-04-01

Our study aimed to elucidate the diagnostic performance of dual-energy CT (DECT) in the detection of contrast enhancement in intracranial haematomas (ICrH) with early phase dual-energy computed tomography angiography (CTA) and compare the results with those obtained by delayed CT enhancement. Thirty-six patients with ICrH were retrospectively included in this study. All patients had undergone single-energy non-contrast CT and contrast-enhanced dual-source DECT. DECT images were post-processed with commercial software, followed by obtaining iodine images and virtual non-contrast images and generating combined images that created the impression of 120-kVp images. Two neuroradiologists, blinded to the patients' data, reviewed two reading sessions: session A (non-contrast CT and combined CT) and session B (non-contrast CT, combined CT, and iodine images) for detection of contrast enhancement in the haematomas. Contrast leakage or enhancement was detected in 23 (57.5 %) out of 40 haemorrhagic lesions in 36 patients on delayed CT. Three enhanced lesions were depicted only in the DECT iodine images. The sensitivity, specificity, positive predictive value, and negative predictive value of session A were 82.6, 94.1, 95.0, and 80.0 %, respectively, and those of session B were 95.7, 94.1, 95.7, and 94.1 %, respectively. DECT emphasised the iodine enhancement and facilitated the detection of contrast enhancement or leakage.

Improving Ambiguity Resolution for Medium Baselines Using Combined GPS and BDS Dual/Triple-Frequency Observations.

PubMed

Gao, Wang; Gao, Chengfa; Pan, Shuguo; Wang, Denghui; Deng, Jiadong

2015-10-30

The regional constellation of the BeiDou navigation satellite system (BDS) has been providing continuous positioning, navigation and timing services since 27 December 2012, covering China and the surrounding area. Real-time kinematic (RTK) positioning with combined BDS and GPS observations is feasible. Besides, all satellites of BDS can transmit triple-frequency signals. Using the advantages of multi-pseudorange and carrier observations from multi-systems and multi-frequencies is expected to be of much benefit for ambiguity resolution (AR). We propose an integrated AR strategy for medium baselines by using the combined GPS and BDS dual/triple-frequency observations. In the method, firstly the extra-wide-lane (EWL) ambiguities of triple-frequency system, i.e., BDS, are determined first. Then the dual-frequency WL ambiguities of BDS and GPS were resolved with the geometry-based model by using the BDS ambiguity-fixed EWL observations. After that, basic (i.e., L1/L2 or B1/B2) ambiguities of BDS and GPS are estimated together with the so-called ionosphere-constrained model, where the ambiguity-fixed WL observations are added to enhance the model strength. During both of the WL and basic AR, a partial ambiguity fixing (PAF) strategy is adopted to weaken the negative influence of new-rising or low-elevation satellites. Experiments were conducted and presented, in which the GPS/BDS dual/triple-frequency data were collected in Nanjing and Zhengzhou of China, with the baseline distance varying from about 28.6 to 51.9 km. The results indicate that, compared to the single triple-frequency BDS system, the combined system can significantly enhance the AR model strength, and thus improve AR performance for medium baselines with a 75.7% reduction of initialization time on average. Besides, more accurate and stable positioning results can also be derived by using the combined GPS/BDS system.

Improving Ambiguity Resolution for Medium Baselines Using Combined GPS and BDS Dual/Triple-Frequency Observations

PubMed Central

Gao, Wang; Gao, Chengfa; Pan, Shuguo; Wang, Denghui; Deng, Jiadong

2015-01-01

The regional constellation of the BeiDou navigation satellite system (BDS) has been providing continuous positioning, navigation and timing services since 27 December 2012, covering China and the surrounding area. Real-time kinematic (RTK) positioning with combined BDS and GPS observations is feasible. Besides, all satellites of BDS can transmit triple-frequency signals. Using the advantages of multi-pseudorange and carrier observations from multi-systems and multi-frequencies is expected to be of much benefit for ambiguity resolution (AR). We propose an integrated AR strategy for medium baselines by using the combined GPS and BDS dual/triple-frequency observations. In the method, firstly the extra-wide-lane (EWL) ambiguities of triple-frequency system, i.e., BDS, are determined first. Then the dual-frequency WL ambiguities of BDS and GPS were resolved with the geometry-based model by using the BDS ambiguity-fixed EWL observations. After that, basic (i.e., L1/L2 or B1/B2) ambiguities of BDS and GPS are estimated together with the so-called ionosphere-constrained model, where the ambiguity-fixed WL observations are added to enhance the model strength. During both of the WL and basic AR, a partial ambiguity fixing (PAF) strategy is adopted to weaken the negative influence of new-rising or low-elevation satellites. Experiments were conducted and presented, in which the GPS/BDS dual/triple-frequency data were collected in Nanjing and Zhengzhou of China, with the baseline distance varying from about 28.6 to 51.9 km. The results indicate that, compared to the single triple-frequency BDS system, the combined system can significantly enhance the AR model strength, and thus improve AR performance for medium baselines with a 75.7% reduction of initialization time on average. Besides, more accurate and stable positioning results can also be derived by using the combined GPS/BDS system. PMID:26528977

Imaging of gene expression in live pancreatic islet cell lines using dual-isotope SPECT.

PubMed

Tai, Joo Ho; Nguyen, Binh; Wells, R Glenn; Kovacs, Michael S; McGirr, Rebecca; Prato, Frank S; Morgan, Timothy G; Dhanvantari, Savita

2008-01-01

We are combining nuclear medicine with molecular biology to establish a sensitive, quantitative, and tomographic method with which to detect gene expression in pancreatic islet cells in vivo. Dual-isotope SPECT can be used to image multiple molecular events simultaneously, and coregistration of SPECT and CT images enables visualization of reporter gene expression in the correct anatomic context. We have engineered pancreatic islet cell lines for imaging with SPECT/CT after transplantation under the kidney capsule. INS-1 832/13 and alphaTC1-6 cells were stably transfected with a herpes simplex virus type 1-thymidine kinase-green fluorescent protein (HSV1-thymidine kinase-GFP) fusion construct (tkgfp). After clonal selection, radiolabel uptake was determined by incubation with 5-(131)I-iodo-1-(2-deoxy-2-fluoro-beta-d-arabinofuranosyl)uracil ((131)I-FIAU) (alphaTC1-6 cells) or (123)I-FIAU (INS-1 832/13 cells). For the first set of in vivo experiments, SPECT was conducted after alphaTC1-6/tkgfp cells had been labeled with either (131)I-FIAU or (111)In-tropolone and transplanted under the left kidney capsule of CD1 mice. Reconstructed SPECT images were coregistered to CT. In a second study using simultaneous acquisition dual-isotope SPECT, INS-1 832/13 clone 9 cells were labeled with (111)In-tropolone before transplantation. Mice were then systemically administered (123)I-FIAU and data for both (131)I and (111)In were acquired simultaneously. alphaTC1-6/tkgfp cells showed a 15-fold greater uptake of (131)I-FIAU, and INS-1/tkgfp cells showed a 12-fold greater uptake of (123)I-FIAU, compared with that of wild-type cells. After transplantation under the kidney capsule, both reporter gene expression and location of cells could be visualized in vivo with dual-isotope SPECT. Immunohistochemistry confirmed the presence of glucagon- and insulin-positive cells at the site of transplantation. Dual-isotope SPECT is a promising method to detect gene expression in and location of transplanted pancreatic cells in vivo.

Traits, properties, and performance: how woody plants combine hydraulic and mechanical functions in a cell, tissue, or whole plant.

PubMed

Lachenbruch, Barbara; McCulloh, Katherine A

2014-12-01

This review presents a framework for evaluating how cells, tissues, organs, and whole plants perform both hydraulic and mechanical functions. The morphological alterations that affect dual functionality are varied: individual cells can have altered morphology; tissues can have altered partitioning to functions or altered cell alignment; and organs and whole plants can differ in their allocation to different tissues, or in the geometric distribution of the tissues they have. A hierarchical model emphasizes that morphological traits influence the hydraulic or mechanical properties; the properties, combined with the plant unit's environment, then influence the performance of that plant unit. As a special case, we discuss the mechanisms by which the proxy property wood density has strong correlations to performance but without direct causality. Traits and properties influence multiple aspects of performance, and there can be mutual compensations such that similar performance occurs. This compensation emphasizes that natural selection acts on, and a plant's viability is determined by, its performance, rather than its contributing traits and properties. Continued research on the relationships among traits, and on their effects on multiple aspects of performance, will help us better predict, manage, and select plant material for success under multiple stresses in the future. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

Hexahydroquinolines are Antimalarial Candidates with Potent Blood Stage and Transmission-Blocking Activity

PubMed Central

Vanaerschot, Manu; Lucantoni, Leonardo; Li, Tao; Combrinck, Jill M.; Ruecker, Andrea; Kumar, T.R. Santha; Rubiano, Kelly; Ferreira, Pedro E.; Siciliano, Giulia; Gulati, Sonia; Henrich, Philipp P.; Ng, Caroline L.; Murithi, James M.; Corey, Victoria C.; Duffy, Sandra; Lieberman, Ori J.; Veiga, M. Isabel; Sinden, Robert E.; Alano, Pietro; Delves, Michael J.; Sim, Kim Lee; Winzeler, Elizabeth A.; Egan, Timothy J.; Hoffman, Stephen L.; Avery, Vicky M.; Fidock, David A.

2017-01-01

Antimalarial compounds with dual therapeutic and transmission-blocking activity are desired as high-value partners for combination therapies. Here, we report the identification and characterization of hexahydroquinolines (HHQs) that show low nanomolar potency against both pathogenic and transmissible intra-erythrocytic forms of the malaria parasite Plasmodium falciparum. This activity translates into potent transmission-blocking potential, as shown by in vitro male gamete formation assays and reduced oocyst infection and prevalence in Anopheles mosquitoes. In vivo studies illustrated the ability of lead HHQs to suppress P. berghei blood-stage parasite proliferation. Resistance selection studies, confirmed by CRISPR/Cas9-based gene editing, identified the digestive vacuole membrane-spanning transporter PfMDR1 as a determinant of parasite resistance to HHQs. Hemoglobin and heme fractionation assays suggest a mode of action that results in reduced hemozoin levels and might involve inhibition of host hemoglobin uptake into intra-erythrocytic parasites. Furthermore, parasites resistant to HHQs displayed increased susceptibility to several first-line antimalarial drugs including lumefantrine, confirming that HHQs have a different mode of action than other antimalarials drugs for which PfMDR1 is known to confer resistance. This work evokes therapeutic strategies that combine opposing selective pressures on this parasite transporter as an approach to countering the emergence and transmission of multidrug-resistant P. falciparum malaria. PMID:28808258

Combined inoculation of Pseudomonas fluorescens and Trichoderma harzianum for enhancing plant growth of vanilla (Vanilla planifolia).

PubMed

Sandheep, A R; Asok, A K; Jisha, M S

2013-06-15

This study was conducted to evaluate the plant growth promoting efficiency of combined inoculation of rhizobacteria on Vanilla plants. Based on the in vitro performance of indigenous Trichoderma spp. and Pseudomonas spp., four effective antagonists were selected and screened under greenhouse experiment for their growth enhancement potential. The maximum percentage of growth enhancement were observed in the combination of Trichoderma harzianum with Pseudomonas fluorescens treatment followed by Pseudomonas fluorescens, Trichoderma harzianum, Pseudomonas putida and Trichoderma virens, respectively in decreasing order. Combined inoculation of Trichoderma harzianum and Pseudomonas fluorescens registered the maximum length of vine (82.88 cm), highest number of leaves (26.67/plant), recorded the highest fresh weight of shoots (61.54 g plant(-1)), fresh weight of roots (4.46 g plant(-1)) and dry weight of shoot (4.56 g plant(-1)) where as the highest dry weight of roots (2.0806 g plant(-1)) were achieved with treatments of Pseudomonas fluorescens. Among the inoculated strains, combined inoculation of Trichoderma harzianum and Pseudomonas fluorescens recorded the maximum nitrogen uptake (61.28 mg plant(-1)) followed by the combined inoculation of Trichoderma harzianum (std) and Pseudomonas fluorescens (std) (55.03 mg plant(-1)) and the highest phosphorus uptake (38.80 mg plant(-1)) was recorded in dual inoculation of Trichoderma harzianum and Pseudomonas fluorescens.

The power of infrared AGN selection in mergers: a theoretical study

NASA Astrophysics Data System (ADS)

Blecha, Laura; Snyder, Gregory F.; Satyapal, Shobita; Ellison, Sara L.

2018-05-01

The role of galaxy mergers in fueling active galactic nuclei (AGN) is still debated, owing partly to selection effects inherent to studies of the merger/AGN connection. In particular, luminous AGN are often obscured in late-stage mergers. Mid-infrared (IR) color selection of dust-enshrouded AGN with, e.g., the Wide-field Infrared Survey Explorer (WISE) has uncovered large new populations of obscured AGN. However, this method is sensitive mainly to AGN that dominate emission from the host. To understand how selection biases affect mid-IR studies of the merger/AGN connection, we simulate the evolution of AGN throughout galaxy mergers. Although mid-IR colors closely trace luminous, obscured AGN, we show that nearly half of merger-triggered AGN are missed with common mid-IR selection criteria, even in late-stage, gas-rich major mergers. At z ⪉ 0.5, where merger signatures and dual nuclei can most easily be detected, we find that a more lenient W1 - W2 >0.5 cut greatly improves completeness without significantly decreasing reliability. Extreme nuclear starbursts are briefly able to mimic this AGN signature, but this is largely irrelevant in mergers, where such starbursts are accompanied by AGN. We propose a two-color cut that yields high completeness and reliability even in starbursting systems. Further, we show that mid-IR color selection very effectively identifies dual AGN hosts, with the highest fraction at the smallest separations (<3 kpc). Thus, many merger hosts of mid-IR AGN should contain unresolved dual AGN; these are ideal targets for high-resolution follow-up, particularly with the James Webb Space Telescope.

CuI/Pd0 cooperative dual catalysis: tunable stereoselective construction of tetra-substituted alkenes.

PubMed

Vercruysse, Sébastien; Cornelissen, Loïc; Nahra, Fady; Collard, Laurent; Riant, Olivier

2014-02-10

This paper describes a tunable and stereoselective dual catalytic system that uses copper and palladium reagents. This cooperative silylcupration and palladium-catalyzed allylation readily affords trisubstituted alkenylsilanes. Fine-tuning the reaction conditions allows selective access to one stereoisomer over the other. This new methodology tolerates different substituents on both coupling partners with high levels of stereoselectivity. The one-pot reaction involving a Cu(I)/Pd(0) cooperative dual catalyst directly addresses the need to develop more time-efficient and less-wasteful synthetic pathways. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Tunable dual-wavelength fiber laser based on an MMI filter in a cascaded Sagnac loop interferometer

NASA Astrophysics Data System (ADS)

Ma, Lin; Kang, Zexin; Qi, Yanhui; Jian, Shuisheng

2014-04-01

A widely tunable dual-wavelength erbium-doped fiber laser based on a cascaded Sagnac loop interferometer incorporating a multimode interference filter is proposed and experimentally demonstrated in this paper. The mode selection is implemented by using the cascaded Sagnac loop interferometer with two segments of polarization maintaining fibers, and the wavelength tuning was achieved by using the refractive index characteristic of multimode interference effects. The tunable dual-wavelength fiber laser has a wavelength tuning of about 40 nm with a signal-to-noise ratio of more than 50 dB.

Dual-stage trapped-flux magnet cryostat for measurements at high magnetic fields

DOEpatents

Islam, Zahirul; Das, Ritesh K.; Weinstein, Roy

2015-04-14

A method and a dual-stage trapped-flux magnet cryostat apparatus are provided for implementing enhanced measurements at high magnetic fields. The dual-stage trapped-flux magnet cryostat system includes a trapped-flux magnet (TFM). A sample, for example, a single crystal, is adjustably positioned proximate to the surface of the TFM, using a translation stage such that the distance between the sample and the surface is selectively adjusted. A cryostat is provided with a first separate thermal stage provided for cooling the TFM and with a second separate thermal stage provided for cooling sample.

Single-scan dual-tracer FLT+FDG PET tumor characterization.

PubMed

Kadrmas, Dan J; Rust, Thomas C; Hoffman, John M

2013-02-07

Rapid multi-tracer PET aims to image two or more tracers in a single scan, simultaneously characterizing multiple aspects of physiology and function without the need for repeat imaging visits. Using dynamic imaging with staggered injections, constraints on the kinetic behavior of each tracer are applied to recover individual-tracer measures from the multi-tracer PET signal. The ability to rapidly and reliably image both (18)F-fluorodeoxyglucose (FDG) and (18)F-fluorothymidine (FLT) would provide complementary measures of tumor metabolism and proliferative activity, with important applications in guiding oncologic treatment decisions and assessing response. However, this tracer combination presents one of the most challenging dual-tracer signal-separation problems--both tracers have the same radioactive half-life, and the injection delay is short relative to the half-life and tracer kinetics. This work investigates techniques for single-scan dual-tracer FLT+FDG PET tumor imaging, characterizing the performance of recovering static and dynamic imaging measures for each tracer from dual-tracer datasets. Simulation studies were performed to characterize dual-tracer signal-separation performance for imaging protocols with both injection orders and injection delays of 10-60 min. Better performance was observed when FLT was administered first, and longer delays before administration of FDG provided more robust signal-separation and recovery of the single-tracer imaging measures. An injection delay of 30 min led to good recovery (R > 0.96) of static image values (e.g. SUV), K(net), and K(1) as compared to values from separate, single-tracer time-activity curves. Recovery of higher order rate parameters (k(2), k(3)) was less robust, indicating that information regarding these parameters was harder to recover in the presence of statistical noise and dual-tracer effects. Performance of the dual-tracer FLT(0 min)+FDG(32 min) technique was further evaluated using PET/CT imaging studies in five patients with primary brain tumors where the data from separate scans of each tracer were combined to synthesize dual-tracer scans with known single-tracer components; results demonstrated similar dual-tracer signal recovery performance. We conclude that rapid dual-tracer FLT+FDG tumor imaging is feasible and can provide quantitative tumor imaging measures comparable to those from conventional separate-scan imaging.

Single-scan dual-tracer FLT+FDG PET tumor characterization

NASA Astrophysics Data System (ADS)

Kadrmas, Dan J.; Rust, Thomas C.; Hoffman, John M.

2013-02-01

Rapid multi-tracer PET aims to image two or more tracers in a single scan, simultaneously characterizing multiple aspects of physiology and function without the need for repeat imaging visits. Using dynamic imaging with staggered injections, constraints on the kinetic behavior of each tracer are applied to recover individual-tracer measures from the multi-tracer PET signal. The ability to rapidly and reliably image both 18F-fluorodeoxyglucose (FDG) and 18F-fluorothymidine (FLT) would provide complementary measures of tumor metabolism and proliferative activity, with important applications in guiding oncologic treatment decisions and assessing response. However, this tracer combination presents one of the most challenging dual-tracer signal-separation problems—both tracers have the same radioactive half-life, and the injection delay is short relative to the half-life and tracer kinetics. This work investigates techniques for single-scan dual-tracer FLT+FDG PET tumor imaging, characterizing the performance of recovering static and dynamic imaging measures for each tracer from dual-tracer datasets. Simulation studies were performed to characterize dual-tracer signal-separation performance for imaging protocols with both injection orders and injection delays of 10-60 min. Better performance was observed when FLT was administered first, and longer delays before administration of FDG provided more robust signal-separation and recovery of the single-tracer imaging measures. An injection delay of 30 min led to good recovery (R > 0.96) of static image values (e.g. SUV), Knet, and K1 as compared to values from separate, single-tracer time-activity curves. Recovery of higher order rate parameters (k2, k3) was less robust, indicating that information regarding these parameters was harder to recover in the presence of statistical noise and dual-tracer effects. Performance of the dual-tracer FLT(0 min)+FDG(32 min) technique was further evaluated using PET/CT imaging studies in five patients with primary brain tumors where the data from separate scans of each tracer were combined to synthesize dual-tracer scans with known single-tracer components; results demonstrated similar dual-tracer signal recovery performance. We conclude that rapid dual-tracer FLT+FDG tumor imaging is feasible and can provide quantitative tumor imaging measures comparable to those from conventional separate-scan imaging.

Single-scan dual-tracer FLT+FDG PET tumor characterization

PubMed Central

Kadrmas, Dan J; Rust, Thomas C; Hoffman, John M

2013-01-01

Rapid multi-tracer PET aims to image two or more tracers in a single scan, simultaneously characterizing multiple aspects of physiology and function without the need for repeat imaging visits. Using dynamic imaging with staggered injections, constraints on the kinetic behavior of each tracer are applied to recover individual-tracer measures from the multi-tracer PET signal. The ability to rapidly and reliably image both 18F-fluorodeoxyglucose (FDG) and 18F-fluorothymidine (FLT) would provide complementary measures of tumor metabolism and proliferative activity, with important applications in guiding oncologic treatment decisions and assessing response. However, this tracer combination presents one of the most challenging dual-tracer signal-separation problems—both tracers have the same radioactive half-life, and the injection delay is short relative to the half-life and tracer kinetics. This work investigates techniques for single-scan dual-tracer FLT+FDG PET tumor imaging, characterizing the performance of recovering static and dynamic imaging measures for each tracer from dual-tracer datasets. Simulation studies were performed to characterize dual-tracer signal-separation performance for imaging protocols with both injection orders and injection delays of 10–60 min. Better performance was observed when FLT was administered first, and longer delays before administration of FDG provided more robust signal-separation and recovery of the single-tracer imaging measures. An injection delay of 30 min led to good recovery (R > 0.96) of static image values (e.g. SUV), Knet, and K1 as compared to values from separate, single-tracer time-activity curves. Recovery of higher order rate parameters (k2, k3) was less robust, indicating that information regarding these parameters was harder to recover in the presence of statistical noise and dual-tracer effects. Performance of the dual-tracer FLT(0 min)+FDG(32 min) technique was further evaluated using PET/CT imaging studies in five patients with primary brain tumors where the data from separate scans of each tracer were combined to synthesize dual-tracer scans with known single-tracer components; results demonstrated similar dual-tracer signal recovery performance. We conclude that rapid dual-tracer FLT+FDG tumor imaging is feasible and can provide quantitative tumor imaging measures comparable to those from conventional separate-scan imaging. PMID:23296314

The effects of combined repetitive transcranial magnetic stimulation and transcranial direct current stimulation on motor function in patients with stroke.

PubMed

Kwon, Tae Gun; Park, Eunhee; Kang, Chung; Chang, Won Hyuk; Kim, Yun-Hee

2016-11-22

Both transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), when provided to stroke patients in combination with motor training, enhance therapeutic efficacy and motor function. However, the majority of previous studies have only examined a single treatment modality. The authors investigated the modulating influence of combination dual-mode brain stimulation upon bihemispheric stimulation with motor training in stroke patients. Twenty stroke patients with hemiparesis underwent five randomly arranged sessions of diverse combinations of rTMS and tDCS. We applied cathodal or anodal tDCS over the contralesional primary motor cortex (cM1) and 10 Hz rTMS over the ipsilesional primary motor cortex (iM1) in a simultaneous or preconditioning method including sham stimulation. Immediately after dual-mode stimulation, sequential hand motor training was performed for 5 minutes. The total pulses of rTMS and the duration of tDCS and motor training were the same for all sessions. Cortical excitability and sequential motor performance were evaluated before and after each session. Motor function and corticomotor excitability following simultaneous stimulation via cathodal tDCS over the cM1 combined with 10 Hz rTMS over the iM1 were significantly increased after the intervention, with significantly greater motor improvement than seen with other treatment conditions (P < 0.05). For the combination of bihemispheric rTMS and tDCS, simultaneous stimulation of cathodal tDCS and 10 Hz rTMS results in better motor performance in stroke patients than other combination methods. This result seemed to be related to effective modulation of interhemispheric imbalance of cortical excitability by dual-mode stimulation.

Dual-Energy Contrast-Enhanced Breast Tomosynthesis: Optimization of Beam Quality for Dose and Image Quality

PubMed Central

Samei, Ehsan; Saunders, Robert S.

2014-01-01

Dual-energy contrast-enhanced breast tomosynthesis is a promising technique to obtain three-dimensional functional information from the breast with high resolution and speed. To optimize this new method, this study searched for the beam quality that maximized image quality in terms of mass detection performance. A digital tomosynthesis system was modeled using a fast ray-tracing algorithm, which created simulated projection images by tracking photons through a voxelized anatomical breast phantom containing iodinated lesions. The single-energy images were combined into dual-energy images through a weighted log subtraction process. The weighting factor was optimized to minimize anatomical noise, while the dose distribution was chosen to minimize quantum noise. The dual-energy images were analyzed for the signal difference to noise ratio (SdNR) of iodinated masses. The fast ray-tracing explored 523,776 dual-energy combinations to identify which yields optimum mass SdNR. The ray-tracing results were verified using a Monte Carlo model for a breast tomosynthesis system with a selenium-based flat-panel detector. The projection images from our voxelized breast phantom were obtained at a constant total glandular dose. The projections were combined using weighted log subtraction and reconstructed using commercial reconstruction software. The lesion SdNR was measured in the central reconstructed slice. The SdNR performance varied markedly across the kVp and filtration space. Ray-tracing results indicated that the mass SdNR was maximized with a high-energy tungsten beam at 49 kVp with 92.5 μm of copper filtration and a low-energy tungsten beam at 49 kVp with 95 μm of tin filtration. This result was consistent with Monte Carlo findings. This mammographic technique led to a mass SdNR of 0.92 ± 0.03 in the projections and 3.68 ± 0.19 in the reconstructed slices. These values were markedly higher than those for non-optimized techniques. Our findings indicate that dual-energy breast tomosynthesis can be performed optimally at 49 kVp with alternative copper and tin filters, with reconstruction following weighted subtraction. The optimum technique provides best visibility of iodine against structured breast background in dual-energy contrast-enhanced breast tomosynthesis. PMID:21908902

Dual optical marker Raman characterization of strained GaN-channels on AlN using AlN/GaN/AlN quantum wells and {sup 15}N isotopes

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

Qi, Meng; Li, Guowang; Protasenko, Vladimir

2015-01-26

This work shows that the combination of ultrathin highly strained GaN quantum wells embedded in an AlN matrix, with controlled isotopic concentrations of Nitrogen enables a dual marker method for Raman spectroscopy. By combining these techniques, we demonstrate the effectiveness in studying strain in the vertical direction. This technique will enable the precise probing of properties of buried active layers in heterostructures, and can be extended in the future to vertical devices such as those used for optical emitters and for power electronics.

The effects of voice and manual control mode on dual task performance

NASA Technical Reports Server (NTRS)

Wickens, C. D.; Zenyuh, J.; Culp, V.; Marshak, W.

1986-01-01

Two fundamental principles of human performance, compatibility and resource competition, are combined with two structural dichotomies in the human information processing system, manual versus voice output, and left versus right cerebral hemisphere, in order to predict the optimum combination of voice and manual control with either hand, for time-sharing performance of a dicrete and continuous task. Eight right handed male subjected performed a discrete first-order tracking task, time-shared with an auditorily presented Sternberg Memory Search Task. Each task could be controlled by voice, or by the left or right hand, in all possible combinations except for a dual voice mode. When performance was analyzed in terms of a dual-task decrement from single task control conditions, the following variables influenced time-sharing efficiency in diminishing order of magnitude, (1) the modality of control, (discrete manual control of tracking was superior to discrete voice control of tracking and the converse was true with the memory search task), (2) response competition, (performance was degraded when both tasks were responded manually), (3) hemispheric competition, (performance degraded whenever two tasks were controlled by the left hemisphere) (i.e., voice or right handed control). The results confirm the value of predictive models invoice control implementation.

Does Combined Physical and Cognitive Training Improve Dual-Task Balance and Gait Outcomes in Sedentary Older Adults?

PubMed Central

Fraser, Sarah A.; Li, Karen Z.-H.; Berryman, Nicolas; Desjardins-Crépeau, Laurence; Lussier, Maxime; Vadaga, Kiran; Lehr, Lora; Minh Vu, Thien Tuong; Bosquet, Laurent; Bherer, Louis

2017-01-01

Everyday activities like walking and talking can put an older adult at risk for a fall if they have difficulty dividing their attention between motor and cognitive tasks. Training studies have demonstrated that both cognitive and physical training regimens can improve motor and cognitive task performance. Few studies have examined the benefits of combined training (cognitive and physical) and whether or not this type of combined training would transfer to walking or balancing dual-tasks. This study examines the dual-task benefits of combined training in a sample of sedentary older adults. Seventy-two older adults (≥60 years) were randomly assigned to one of four training groups: Aerobic + Cognitive training (CT), Aerobic + Computer lessons (CL), Stretch + CT and Stretch + CL. It was expected that the Aerobic + CT group would demonstrate the largest benefits and that the active placebo control (Stretch + CL) would show the least benefits after training. Walking and standing balance were paired with an auditory n-back with two levels of difficulty (0- and 1-back). Dual-task walking and balance were assessed with: walk speed (m/s), cognitive accuracy (% correct) and several mediolateral sway measures for pre- to post-test improvements. All groups demonstrated improvements in walk speed from pre- (M = 1.33 m/s) to post-test (M = 1.42 m/s, p < 0.001) and in accuracy from pre- (M = 97.57%) to post-test (M = 98.57%, p = 0.005).They also increased their walk speed in the more difficult 1-back (M = 1.38 m/s) in comparison to the 0-back (M = 1.36 m/s, p < 0.001) but reduced their accuracy in the 1-back (M = 96.39%) in comparison to the 0-back (M = 99.92%, p < 0.001). Three out of the five mediolateral sway variables (Peak, SD, RMS) demonstrated significant reductions in sway from pre to post test (p-values < 0.05). With the exception of a group difference between Aerobic + CT and Stretch + CT in accuracy, there were no significant group differences after training. Results suggest that there can be dual-task benefits from training but that in this sedentary sample Aerobic + CT training was not more beneficial than other types of combined training. PMID:28149274

Dual-color single-mode lasing in axially coupled organic nanowire resonators

PubMed Central

Zhang, Chunhuan; Zou, Chang-Ling; Dong, Haiyun; Yan, Yongli; Yao, Jiannian; Zhao, Yong Sheng

2017-01-01

Miniaturized lasers with multicolor output and high spectral purity are of crucial importance for yielding more compact and more versatile photonic devices. However, multicolor lasers usually operate in multimode, which largely restricts their practical applications due to the lack of an effective mode selection mechanism that is simultaneously applicable to multiple wavebands. We propose a mutual mode selection strategy to realize dual-color single-mode lasing in axially coupled cavities constructed from two distinct organic self-assembled single-crystal nanowires. The unique mode selection mechanism in the heterogeneously coupled nanowires was elucidated experimentally and theoretically. With each individual nanowire functioning as both the laser source and the mode filter for the other nanowire, dual-color single-mode lasing was successfully achieved in the axially coupled heterogeneous nanowire resonators. Furthermore, the heterogeneously coupled resonators provided multiple nanoscale output ports for delivering coherent signals with different colors, which could greatly contribute to increasing the integration level of functional photonic devices. These results advance the fundamental understanding of the lasing modulation in coupled cavity systems and offer a promising route to building multifunctional nanoscale lasers for high-level practical photonic integrations. PMID:28785731

Power combination of two phase-locked high power microwave beams from a new coaxial microwave source based on dual beams

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

Li, Yangmei; Zhang, Xiaoping, E-mail: plinafly@163.com; Zhang, Jiande

2014-10-15

The new coaxial high power microwave source based on dual beams has demonstrated two phase-locked output microwave beams generated by its two sub-sources. In order to achieve a single higher output power, we present a three-port waveguide-based power combiner to combine the two microwave beams. Particle-in-cell simulation results show that when the diode voltage is 675 kV and the guiding magnetic field is 0.8 T, a combined microwave with an average power of about 4.0 GW and a frequency of 9.74 GHz is generated; the corresponding power conversion efficiency is 29%. The combination effect of the combiner is further validated in the diodemore » voltage range from 675 kV to 755 kV as well as in the pulse regime. The simulations indicate that the maximum surface axial electric field strength of the electrodynamic structure is 720 kV/cm, which is relatively low corresponding to an output power of 4.0 GW. The stable combined output suggests the probability of long-pulse operation for the combined source.« less

Dual mTORC2/mTORC1 targeting results in potent suppressive effects on acute myeloid leukemia (AML) progenitors*

PubMed Central

Altman, Jessica K.; Sassano, Antonella; Kaur, Surinder; Glaser, Heather; Kroczynska, Barbara; Redig, Amanda J.; Russo, Suzanne; Barr, Sharon; Platanias, Leonidas C.

2011-01-01

Purpose To determine whether mTORC2 and RI-mTORC1 complexes are present in AML cells and to examine the effects of dual mTORC2/mTORC1 inhibition on primitive AML leukemic progenitors. Experimental Design Combinations of different experimental approaches were used, including immunoblotting to detect phosphorylated/activated forms of elements of the mTOR pathway in leukemic cell lines and primary AML blasts; cell proliferation assays; direct assessment of mRNA translation in polysomal fractions of leukemic cells; and clonogenic assays in methylcellulose to evaluate leukemic progenitor colony formation. Results mTORC2 complexes are active in AML cells and play critical roles in leukemogenesis. Rapamycin insensitive (RI) mTORC1 complexes are also formed and regulate the activity of the translational repressor 4E-BP1 in AML cells. OSI-027, blocks mTORC1 and mTORC2 activities and suppresses mRNA translation of cyclin D1 and other genes that mediate proliferative responses in AML cells. Moreover, OSI-027 acts as a potent suppressor of primitive leukemic precursors from AML patients and is much more effective than rapamycin in eliciting antileukemic effects in vitro. Conclusions Dual targeting of mTORC2 and mTORC1 results in potent suppressive effects on primitive leukemic progenitors from AML patients. Inhibition of the mTOR catalytic site with OSI-027 results in suppression of both mTORC2 and RI-mTORC1 complexes and elicits much more potent antileukemic responses than selective mTORC1 targeting with rapamycin. PMID:21415215

On the calibration and use of Dual Electron Sensors for NASA's Magnetospheric MultiScale mission

NASA Astrophysics Data System (ADS)

Avanov, L. A.; Gliese, U.; Pollock, C. J.; Barrie, A.; Mariano, A. J.; Tucker, C. J.; Jacques, A. D.; Zeuch, M.; Shields, N.; Christian, K. D.

2013-12-01

The scientific target of NASA's Magnetospheric MultiScale (MMS) mission is to study the fundamentally important phenomenon of magnetic reconnection. Theoretical models of this process predict a small (order of ten kilometers) size for the diffusion region where electrons are demagnetized at the dayside magnetopause. Yet, the region may typically sweep over the spacecraft at relatively high speeds of 50km/s. That is why Fast Plasma Investigation (FPI) instrument suite must have extremely high time resolution for measurements of the 3D particle distribution functions. The Dual Electron Spectrometers (DESs) provide fast (30ms) 3D electron velocity distributions, from 10eV to 30,000 eV, as part of the Fast Plasma Investigation (FPI) on NASA's Magnetospheric MultiScale (MMS) mission. This is accomplished by combining the measurements from eight different spectrometers (packaged in four dual sets) on each MMS spacecraft to produce each full distribution. This approach presents a new and challenging aspect to the calibration and operation of these instruments. The response uniformity among the spectrometer set, the consistency and reliability of their calibration in both sensitivity and their phase space selectivity (energy and angle), and the approach to handling any temporal evolution of these calibrated characteristics all assume enhanced importance in this application. In this paper, we will present brief descriptions of the spectrometers and our approach their ground calibration, trended results of those calibrations, and our plans to detect, track, and respond to any temporal evolution in instrument performance through the life of the mission.

Intramuscular Fentanyl and Ketorolac Associated with Superior Pain Control After Pediatric Bilateral Myringotomy and Tube Placement Surgery: A Retrospective Cohort Study.

PubMed

Stricker, Paul A; Muhly, Wallis T; Jantzen, Ellen C; Li, Yue; Jawad, Abbas F; Long, Alexander S; Polansky, Marcia; Cook-Sather, Scott D

2017-01-01

Bilateral myringotomy and pressure equalization tube insertion (BMT) is the most common surgery in children. Multiple anesthetic techniques for BMT have been proposed, but that which reliably promotes ideal recovery remains unclear. We sought to assess associations between anesthetic regimens that included single-agent (fentanyl or ketorolac) or dual-agent (fentanyl and ketorolac) analgesic therapy and the primary outcome of maximal postanesthesia care unit (PACU) pain score. Secondary outcomes included in-hospital rescue analgesic administration, recovery time, and emesis incidence. Principal analysis was conducted on a retrospective cohort of 3669 children aged 6 months to <7 years who underwent BMT over a 16-month period and received intraoperative fentanyl and/or ketorolac. Routine anesthetic care included preoperative oral midazolam, general anesthesia via a mask maintained with sevoflurane and N2O or air in O2, and intramuscular analgesic administration. Multivariable analyses were performed examining relationships between analgesic regimen with the following outcomes: maximum PACU Face, Legs, Activity, Cry, and Consolability (FLACC) score = 0 or 7 to 10, oxycodone administration, and time to discharge readiness. Demographic variables, midazolam exposure, and location (main hospital vs ambulatory surgery center) were included in the multivariable analyses as potential confounders. Associations with postoperative vomiting were studied separately in 2725 children from a subsequent, nonoverlapping 12-month period using similar inclusion criteria. Fentanyl and ketorolac dose-response relationships were evaluated for selected outcome variables. Maximum FLACC = 0, maximum FLACC score of 7 to 10, and oxycodone rescue were most strongly associated with dual-agent therapy versus single-agent ketorolac: odds ratios 4.89 (95% confidence interval [CI], 4.04-5.93), 0.13 (95% CI, 0.10-0.16), and 0.11 (98.3% CI, 0.09-0.14), respectively, P < .001 for each). Minor associations were found for age, Hispanic ethnicity, midazolam, and location, and none for sex or race. For subjects managed with higher dose fentanyl (≥1.5 µg/kg) and ketorolac (≥0.75 mg/kg), 90% had no demonstrable pain, agitation, or distress. Mean discharge readiness times were 21 ± 11 minutes (ketorolac), 26 ± 16 minutes (fentanyl), and 24 ± 14 minutes (dual) (P < .0001). Postoperative emesis incidences associated with ketorolac (2.7%) versus dual therapy (4.5%) were not different (P = .08). In this large retrospective pediatric BMT study, combination intramuscular fentanyl/ketorolac was strongly associated with superior PACU analgesia and reduced need for oxycodone rescue without clinically significant increases in recovery time or emesis incidence. Combination fentanyl at 1.5 to 2 µg/kg and 1 mg/kg ketorolac was associated with optimal outcomes. Dual therapy appears similarly effective in children of either European Caucasian or African ancestry or of Hispanic ethnicity.

CXCR4-using HIV variants in a cohort of Black men who have sex with men: HIV Prevention Trials Network 061

PubMed Central

Chen, Iris; Huang, Wei; Connor, Matthew B.; Frantzell, Arne; Cummings, Vanessa; Beauchamp, Geetha G.; Griffith, Sam; Fields, Sheldon D.; Scott, Hyman M.; Shoptaw, Steven; del Rio, Carlos; Magnus, Manya; Mannheimer, Sharon; Tieu, Hong-Van; Wheeler, Darrell P.; Mayer, Kenneth H.; Koblin, Beryl A.; Eshleman, Susan H.

2016-01-01

Objective To evaluate factors associated with HIV tropism among Black men who have sex with men (MSM) in the United States enrolled in a clinical study (HIV Prevention Trials Network 061). Methods HIV tropism was analyzed using a phenotypic assay (Trofile assay, Monogram Biosciences). Samples were analyzed from 43 men who were HIV infected at enrollment and reported either exclusive insertive intercourse or exclusive receptive intercourse; samples were also analyzed from 20 men who were HIV uninfected at enrollment and seroconverted during the study. Clonal analysis of individual viral variants was performed for seroconverters who had dual/mixed viruses. Results Dual/mixed viruses were detected in samples from 11 (26%) of the 43 HIV-infected men analyzed at the enrollment visit; HIV tropism did not differ between those reporting exclusive insertive vs. receptive intercourse. Dual/mixed viruses were also detected in five (25%) of the 20 seroconverters. Dual/mixed viruses were associated with lower CD4 cell counts. Seroconverters with dual/mixed viruses had dual-tropic viruses only or mixed populations of CCR5− and dual-tropic viruses. Conclusions Dual/mixed viruses were frequently detected among Black MSM in this study, including seroconverters. Further studies are needed to understand factors driving transmission and selection of CXCR4− and dual-tropic viruses among Black MSM. PMID:27300696

Determination of trace uranium by resonance fluorescence method coupled with photo-catalytic technology and dual cloud point extraction

NASA Astrophysics Data System (ADS)

Li, Jiekang; Li, Guirong; Han, Qian

2016-12-01

In this paper, two kinds of salophens (Sal) with different solubilities, Sal1 and Sal2, have been respectively synthesized, and they all can combine with uranyl to form stable complexes: [UO22 +-Sal1] and [UO22 +-Sal2]. Among them, [UO22 +-Sal1] was used as ligand to extract uranium in complex samples by dual cloud point extraction (dCPE), and [UO22 +-Sal2] was used as catalyst for the determination of uranium by photocatalytic resonance fluorescence (RF) method. The photocatalytic characteristic of [UO22 +-Sal2] on the oxidized pyronine Y (PRY) by potassium bromate which leads to the decrease of RF intensity of PRY were studied. The reduced value of RF intensity of reaction system (ΔF) is in proportional to the concentration of uranium (c), and a novel photo-catalytic RF method was developed for the determination of trace uranium (VI) after dCPE. The combination of photo-catalytic RF techniques and dCPE procedure endows the presented methods with enhanced sensitivity and selectivity. Under optimal conditions, the linear calibration curves range for 0.067 to 6.57 ng mL- 1, the linear regression equation was ΔF = 438.0 c (ng mL- 1) + 175.6 with the correlation coefficient r = 0.9981. The limit of detection was 0.066 ng mL- 1. The proposed method was successfully applied for the separation and determination of uranium in real samples with the recoveries of 95.0-103.5%. The mechanisms of the indicator reaction and dCPE are discussed.

Analysis of cytokinin nucleotides in coconut (Cocos nucifera L.) water using capillary zone electrophoresis-tandem mass spectrometry after solid-phase extraction.

PubMed

Ge, Liya; Yong, Jean Wan Hong; Tan, Swee Ngin; Yang, Xin Hao; Ong, Eng Shi

2006-11-10

A method based on solid-phase extraction (SPE) and capillary zone electrophoresis-tandem mass spectrometry (CZE-MS/MS) is described for the separation and determination of six cytokinin nucleotides in coconut water. The best CZE separation for the six cytokinin nucleotide standards was achieved using a 25 mM ammonium formate/formic acid buffer (pH 3.8) and 2% (v/v) methanol with an applied gradient separation voltage (25 kV for 32 min, and then a linear gradient to 30 kV in 5 min, finally 30 kV to the end of separation) in less than 60 min. MS/MS with multiple reaction monitoring (MRM) detection was carried out to obtain sufficient selectivity and sensitivity for the cytokinin nucleotides. The combined use of on-line sample stacking and CZE-MS/MS achieved limits of detection (LODs) in the range of 0.06-0.19 microM for the six cytokinin nucleotides at a signal-to-noise ratio of 3. Furthermore, a novel dual-step SPE procedure was developed for the pre-concentration and purification of cytokinin nucleotides using Oasis HLB and Oasis MAX cartridges. The recoveries of the cytokinin nucleotides after the dual-step SPE were in the range of 44-71%. The combination of off-line SPE, on-line sample stacking and CZE-MS/MS approach was successfully applied to screen for endogenous cytokinin nucleotides present in coconut water sample. trans-Zeatin riboside-5'-monophosphate (ZMP) was detected and quantified in coconut water by CZE-MS/MS after SPE and on-line sample stacking.

PIK3CA mutations enable targeting of a breast tumor dependency through mTOR-mediated MCL-1 translation

PubMed Central

Anderson, Grace R.; Wardell, Suzanne E.; Cakir, Merve; Crawford, Lorin; Leeds, Jim C.; Nussbaum, Daniel P.; Shankar, Pallavi S.; Soderquist, Ryan S.; Stein, Elizabeth M.; Tingley, Jennifer P.; Winter, Peter S.; Zieser-Misenheimer, Elizabeth K.; Alley, Holly M.; Yllanes, Alexander; Haney, Victoria; Blackwell, Kimberly L.; McCall, Shannon J.; McDonnell, Donald P.; Wood, Kris C.

2017-01-01

Therapies that efficiently induce apoptosis are likely to be required for durable clinical responses in patients with solid tumors. Using a pharmacological screening approach, we discovered that the combined inhibition of BCL-XL and the mTOR/4E-BP axis results in selective and synergistic induction of apoptosis in cellular and animal models of PIK3CA mutant breast cancers, including triple negative tumors. Mechanistically, inhibition of mTOR/4E-BP suppresses MCL-1 protein translation only in PIK3CA mutant tumors, creating a synthetic dependence on BCL-XL. This dual dependence on BCL-XL and MCL-1, but not on BCL-2, appears to be a fundamental property of diverse breast cancer cell lines, xenografts, and patient-derived tumors that is independent of molecular subtype or PIK3CA mutational status. Further, this dependence distinguishes breast cancers from normal breast epithelial cells, which are neither primed for apoptosis nor dependent on BCL-XL/MCL-1, suggesting a potential therapeutic window. By tilting the balance of pro- to anti-apoptotic signals in the mitochondria, dual inhibition of MCL-1 and BCL-XL also sensitizes breast cancer cells to standard of care cytotoxic and targeted chemotherapies. Together, these results suggest that patients with PIK3CA mutant breast cancers may benefit from combined treatment with inhibitors of BCL-XL and the mTOR/4E-BP axis, whereas alternative methods of inhibiting MCL-1 and BCL-XL may be effective in tumors lacking PIK3CA mutations. PMID:27974663

High/variable mixture ratio O2/H2 engine

NASA Technical Reports Server (NTRS)

Adams, A.; Parsley, R. C.

1988-01-01

Vehicle/engine analysis studies have identified the High/Dual Mixture Ratio O2/H2 Engine cycle as a leading candidate for an advanced Single Stage to Orbit (SSTO) propulsion system. This cycle is designed to allow operation at a higher than normal O/F ratio of 12 during liftoff and then transition to a more optimum O/F ratio of 6 at altitude. While operation at high mixture ratios lowers specific impulse, the resultant high propellant bulk density and high power density combine to minimize the influence of atmospheric drag and low altitude gravitational forces. Transition to a lower mixture ratio at altitude then provides improved specific impulse relative to a single mixture ratio engine that must select a mixture ratio that is balanced for both low and high altitude operation. This combination of increased altitude specific impulse and high propellant bulk density more than offsets the compromised low altitude performance and results in an overall mission benefit. Two areas of technical concern relative to the execution of this dual mixture ratio cycle concept are addressed. First, actions required to transition from high to low mixture ratio are examined, including an assessment of the main chamber environment as the main chamber mixture ratio passes through stoichiometric. Secondly, two approaches to meet a requirement for high turbine power at high mixture ratio condition are examined. One approach uses high turbine temperature to produce the power and requires cooled turbines. The other approach incorporates an oxidizer-rich preburner to increase turbine work capability via increased turbine mass flow.

Combination therapy for male erectile dysfunction and urinary incontinence.

PubMed

Zafirakis, Helen; Wang, Run; Westney, O Lenaine

2008-01-01

Urinary incontinence (UI) and erectile dysfunction (ED) are both very prevalent conditions. Insertion of an artificial urinary sphincter (AUS) and penile prosthesis (PP) is an effective and proven method of treatment for both conditions. With advancing age, as well as with increasing populations of patients radically treated for prostate cancer, the occurrence of both conditions found in the same patient is increasing. The purpose of this article was to analyze the available evidence for simultaneous surgical management of male ED and UI using prosthetic devices. The existing literature pertaining to dual implantation of AUS and PP was reviewed. The concomitant insertion of the PP with the male perineal sling was also considered. Concurrent ED and UI are increasingly seen in the post radical prostatectomy population, who are often younger and less willing to suffer with these conditions. Insertion of an AUS and PP, either simultaneously or as a two-stage procedure, appears to be a safe, efficacious and long-lasting method of treatment. The improvements in design of both the AUS and PP as well as the development of the single transverse scrotal incision have made simultaneous insertion of these prostheses possible. Dual implantation of the PP and male sling looks promising in a selected population. In conclusion, the insertion of the AUS and PP for the treatment of concurrent UI and ED is safe and effective. Simultaneous insertion of these prostheses in the same patient offers potential advantages in operative and recovery time and is associated with high patient satisfaction. Combination therapy should therefore be included in the arsenal of treatment of these conditions.

Antibacterial, anti-inflammatory, and bone-regenerative dual-drug-loaded calcium phosphate nanocarriers-in vitro and in vivo studies.

PubMed

Madhumathi, K; Rubaiya, Y; Doble, Mukesh; Venkateswari, R; Sampath Kumar, T S

2018-05-01

A dual local drug delivery system (DDS) composed of calcium phosphate bioceramic nanocarriers aimed at treating the antibacterial, anti-inflammatory, and bone-regenerative aspects of periodontitis has been developed. Calcium-deficient hydroxyapatite (CDHA, Ca/P = 1.61) and tricalcium phosphate (β-TCP) were prepared by microwave-accelerated wet chemical synthesis method. The phase purity of the nanocarriers was confirmed by x-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR), while the transmission electron microscopy (TEM) confirmed their nanosized morphology. CDHA was selected as carrier for the antibiotic (tetracycline) while TCP was chosen as the anti-inflammatory drug (ibuprofen) carrier. Combined drug release profile was studied in vitro from CDHA/TCP (CTP) system and compared with a HA/TCP (BCP) biphasic system. The tetracycline and ibuprofen release rate was 71 and 23% from CTP system as compared to 63 and 20% from BCP system. CTP system also showed a more controlled drug release profile compared to BCP system. Modeling of drug release kinetics from CTP system indicated that the release follows Higuchi model with a non-typical Fickian diffusion profile. In vitro biological studies showed the CTP system to be biocompatible with significant antibacterial and anti-inflammatory activity. In vivo implantation studies on rat cranial defects showed greater bone healing and new bone formation in the drug-loaded CTP system compared to control (no carrier) at the end of 12 weeks. The in vitro and in vivo results suggest that the combined drug delivery platform can provide a comprehensive management for all bone infections requiring multi-drug therapy.

Evidence for a neural dual-process account for adverse effects of cognitive control.

PubMed

Zink, Nicolas; Stock, Ann-Kathrin; Colzato, Lorenza; Beste, Christian

2018-06-09

Advantageous effects of cognitive control are well-known, but cognitive control may also have adverse effects, for example when it suppresses the implicit processing of stimulus-response (S-R) bindings that could benefit task performance. Yet, the neurophysiological and functional neuroanatomical structures associated with adverse effects of cognitive control are poorly understood. We used an extreme group approach to compare individuals who exhibit adverse effects of cognitive control to individuals who do not by combining event-related potentials (ERPs), source localization, time-frequency analysis and network analysis methods. While neurophysiological correlates of cognitive control (i.e. N2, N450, theta power and theta-mediated neuronal network efficiency) and task-set updating (P3) both reflect control demands and implicit information processing, differences in the degree of adverse cognitive control effects are associated with two independent neural mechanisms: Individuals, who show adverse behavioral effects of cognitive control, show reduced small-world properties and thus reduced efficiency in theta-modulated networks when they fail to effectively process implicit information. In contrast to this, individuals who do not display adverse control effects show enhanced task-set updating mechanism when effectively processing implicit information, which is reflected by the P3 ERP component and associated with the temporo-parietal junction (TPJ, BA 40) and medial frontal gyrus (MFG; BA 8). These findings suggest that implicit S-R contingencies, which benefit response selection without cognitive control, are always 'picked up', but may fail to be integrated with task representations to guide response selection. This provides evidence for a neurophysiological and functional neuroanatomical "dual-process" account of adverse cognitive control effects.

Neurophysiological processes and functional neuroanatomical structures underlying proactive effects of emotional conflicts.

PubMed

Schreiter, Marie Luise; Chmielewski, Witold; Beste, Christian

2018-07-01

There is a strong inter-relation of cognitive and emotional processes as evidenced by emotional conflict monitoring processes. In the cognitive domain, proactive effects of conflicts have widely been studied; i.e. effects of conflicts in the n-1 trial on trial n. Yet, the neurophysiological processes and associated functional neuroanatomical structures underlying such proactive effects during emotional conflicts have not been investigated. This is done in the current study combining EEG recordings with signal decomposition methods and source localization approaches. We show that an emotional conflict in the n-1 trial differentially influences processing of positive and negative emotions in trial n, but not the processing of conflicts in trial n. The dual competition framework stresses the importance of dissociable 'perceptual' and 'response selection' or cognitive control levels for interactive effects of cognition and emotion. Only once these coding levels were isolated in the neurophysiological data, processes explaining the behavioral effects were detectable. The data show that there is not only a close correspondence between theoretical propositions of the dual competition framework and neurophysiological processes. Rather, processing levels conceptualized in the framework operate in overlapping time windows, but are implemented via distinct functional neuroanatomical structures; the precuneus (BA31) and the insula (BA13). It seems that decoding of information in the precuneus, as well as the integration of information during response selection in the insula is more difficult when confronted with angry facial emotions whenever cognitive control resources have been highly taxed by previous conflicts. Copyright © 2018 Elsevier Inc. All rights reserved.

Bond strength of selected composite resin-cements to zirconium-oxide ceramic

PubMed Central

Fons-Font, Antonio; Amigó-Borrás, Vicente; Granell-Ruiz, María; Busquets-Mataix, David; Panadero, Rubén A.; Solá-Ruiz, Maria F.

2013-01-01

Objectives: The aim of this study was to evaluate bond strengths of zirconium-oxide (zirconia) ceramic and a selection of different composite resin cements. Study Design: 130 Lava TM cylinders were fabricated. The cylinders were sandblasted with 80 µm aluminium oxide or silica coated with CoJet Sand. Silane, and bonding agent and/or Clearfil Ceramic Primer were applied. One hundred thirty composite cement cylinders, comprising two dual-polymerizing (Variolink II and Panavia F) and two autopolymerizing (Rely X and Multilink) resins were bonded to the ceramic samples. A shear test was conducted, followed by an optical microscopy study to identify the location and type of failure, an electron microscopy study (SEM and TEM) and statistical analysis using the Kruskal-Wallis test for more than two independent samples and Mann-Whitney for two independent samples. Given the large number of combinations, Bonferroni correction was applied (α=0.001). Results: Dual-polymerizing cements provided better adhesion values (11.7 MPa) than the autopolymerizing (7.47 MPa) (p-value M-W<0.001). The worst techniques were Lava TM + sandblasting + Silane + Rely X; Lava TM + sandblasting + Silane + Multilink and Lava TM + CoJet + silane + Multilink. Adhesive failure (separation of cement and ceramic) was produced at a lesser force than cohesive failure (fracture of cement) (p-value M-W<0.001). Electron microscopy confirmed that the surface treatments modified the zirconium-oxide ceramic, creating a more rough and retentive surface, thus providing an improved micromechanical interlocking between the cement and the ceramic. Key words:Shear bond strength, silica coating, surface treatment, zirconia ceramics, phosphate monomer. PMID:22926485

Coupling effect and control strategies of the maglev dual-stage inertially stabilization system based on frequency-domain analysis.

PubMed

Lin, Zhuchong; Liu, Kun; Zhang, Li; Zeng, Delin

2016-09-01

Maglev dual-stage inertially stabilization (MDIS) system is a newly proposed system which combines a conventional two-axis gimbal assembly and a 5-DOF (degree of freedom) magnetic bearing with vernier tilting capacity to perform dual-stage stabilization for the LOS of the suspended optical instrument. Compared with traditional dual-stage system, maglev dual-stage system exhibits different characteristics due to the negative position stiffness of the magnetic forces, which introduces additional coupling in the dual stage control system. In this paper, the coupling effect on the system performance is addressed based on frequency-domain analysis, including disturbance rejection, fine stage saturation and coarse stage structural resonance suppression. The difference between various control strategies is also discussed, including pile-up(PU), stabilize-follow (SF) and stabilize-compensate (SC). A number of principles for the design of a maglev dual stage system are proposed. A general process is also suggested, which leads to a cost-effective design striking a balance between high performance and complexity. At last, a simulation example is presented to illustrate the arguments in the paper. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

Toward a New Theory for Selecting Instructional Visuals.

ERIC Educational Resources Information Center

Croft, Richard S.; Burton, John K.

This paper provides a rationale for the selection of illustrations and visual aids for the classroom. The theories that describe the processing of visuals are dual coding theory and cue summation theory. Concept attainment theory offers a basis for selecting which cues are relevant for any learning task which includes a component of identification…

Synchronous colonic tumours of dual pathology.

PubMed

Basu, S; Selvachandran, S N; Cade, D

2001-05-01

Synchronous colonic tumours of dual pathology are extremely rare. A review of the literature revealed that few cases have been reported to date. Because of their rarity and lack of specific symptoms, preoperative diagnosis is not easy and there is no protocol as yet for the ideal management of these cases. We present such a case which was treated by a combination of surgery and chemotherapy.

An O({radical}nL) primal-dual affine scaling algorithm for linear programming

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

Huang, Siming

1994-12-31

We present a new primal-dual affine scaling algorithm for linear programming. The search direction of the algorithm is a combination of classical affine scaling direction of Dikin and a recent new affine scaling direction of Jansen, Roos and Terlaky. The algorithm has an iteration complexity of O({radical}nL), comparing to O(nL) complexity of Jansen, Roos and Terlaky.

Dual-mode microwave system to enhance early detection of cancer

NASA Technical Reports Server (NTRS)

Carr, K. L.; El-Mahdi, A. M.; Shaeffer, J.

1981-01-01

A dual-mode microwave system has been developed that will permit early detection of cancer. The system combines the use of the passive microwave radiometer with an active transmitter. The active transmitter will provide localized heating to enhance early detection by taking advantage of the differential heating (i.e., tumor temperature with respect to surrounding tissue) associated with the thermal characteristics of tumors.

An Organizational Informatics Analysis of Colorectal, Breast, and Cervical Cancer Screening Clinical Decision Support and Information Systems within Community Health Centers

ERIC Educational Resources Information Center

Carney, Timothy Jay

2012-01-01

A study design has been developed that employs a dual modeling approach to identify factors associated with facility-level cancer screening improvement and how this is mediated by the use of clinical decision support. This dual modeling approach combines principles of (1) Health Informatics, (2) Cancer Prevention and Control, (3) Health Services…

Phase Grating Design for a Dual-Band Snapshot Imaging Spectrometer

NASA Astrophysics Data System (ADS)

Scholl, James F.; Dereniak, Eustace L.; Descour, Michael R.; Tebow, Christopher P.; Volin, Curtis E.

2003-01-01

Infrared spectral features have proved useful in the identification of threat objects. Dual-band focal-plane arrays (FPAs) have been developed in which each pixel consists of superimposed midwave and long-wave photodetectors [Dyer and Tidrow, Conference on Infrared Detectors and Focal Plane Arrays (SPIE, Bellingham, Wash., 1999), pp. 434 -440 . Combining dual-band FPAs with imaging spectrometers capable of interband hyperspectral resolution greatly improves spatial target discrimination. The computed-tomography imaging spectrometer (CTIS) ] [Descour and Dereniak, Appl. Opt. 34, 4817 -4826 (1995) has proved effective in producing hyperspectral images in a single spectral region. Coupling the CTIS with a dual-band detector can produce two hyperspectral data cubes simultaneously. We describe the design of two-dimensional, surface-relief, computer-generated hologram dispersers that permit image information in these two bands simultaneously.

Dual-energy KUB radiographic examination for the detection of renal calculus.

PubMed

Yen, Peggy; Bailly, Greg; Pringle, Christopher; Barnes, David

2014-08-01

The dual-energy radiographic technique has been proved to be clinically useful in the thorax. Herein, we attempt to apply this technique to the abdomen and pelvis in the context of renal colic. The visibility of renal calculi were assessed using various dual energy peak kilovoltage combination radiographs applied to standard phantoms. This technique demonstrates a higher than acceptable radiation dosage required to optimize the image quality and the optimized diagnostic quality is inferior to that of the standard Kidneys, Ureters, and Bladder radiograph. The dual-energy radiographic technique could not better identify the radiopaque renal calculi. Limiting technical considerations include the increased subcutaneous and peritoneal adipose tissue and the limited contrast between the soft tissue and underlying calculi. Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.

Compact dual-wavelength Nd:GdVO4 laser working at 1063 and 1065 nm.

PubMed

Wu, Bo; Jiang, Peipei; Yang, Dingzhong; Chen, Tao; Kong, Jian; Shen, Yonghang

2009-04-13

We report a compact diode-laser pumped Nd:GdVO(4) laser with stable dual-wavelength output at 1063 nm and 1065 nm simultaneously. Two types of resonant cavity configurations were presented to support the stable dual-wavelength operation of the laser. Using a polarization beam splitter(PBS) included T-shaped cavity, we obtained a total power output over 5 W in two orthogonal polarized beam directions with 4 W in sigma polarization (1065.5 nm) and 1 W in pi polarization (1063.1 nm). By combining a half-wave-plate with the PBS in the laser cavity, a new configuration favoring one beam direction dual-wavelength output with same polarization direction was realized. A phenomenon of further line splitting was observed in both 1065 nm and 1063 nm.

Dual-lasing channel quantum cascade laser based on scattering-assisted injection design.

PubMed

Wen, Boyu; Xu, Chao; Wang, Siyi; Wang, Kaixi; Tam, Man Chun; Wasilewski, Zbig; Ban, Dayan

2018-04-02

A dual lasing channel Terahertz Quantum Cascade laser (THz QCL) based on GaAs/Al 0.17 Ga 0.83 As material system is demonstrated. The device shows the lowest reported threshold current density (550A/cm 2 at 50K) of GaAs/Al x Ga 1-x As material system based scattering-assisted (SA) structures and operates up to a maximum lasing temperature of 144K. Dual lasing channel operation is investigated theoretically and experimentally. The combination of low frequency emission, dual lasing channel operation, low lasing threshold current density and high temperature performance make such devices ideal candidates for low frequency applications, and initiates the design strategy for achieving high-temperature performance terahertz quantum cascade laser with wide frequency coverage at low frequency.

Soliton microcomb range measurement

NASA Astrophysics Data System (ADS)

Suh, Myoung-Gyun; Vahala, Kerry J.

2018-02-01

Laser-based range measurement systems are important in many application areas, including autonomous vehicles, robotics, manufacturing, formation flying of satellites, and basic science. Coherent laser ranging systems using dual-frequency combs provide an unprecedented combination of long range, high precision, and fast update rate. We report dual-comb distance measurement using chip-based soliton microcombs. A single pump laser was used to generate dual-frequency combs within a single microresonator as counterpropagating solitons. We demonstrated time-of-flight measurement with 200-nanometer precision at an averaging time of 500 milliseconds within a range ambiguity of 16 millimeters. Measurements at distances up to 25 meters with much lower precision were also performed. Our chip-based source is an important step toward miniature dual-comb laser ranging systems that are suitable for photonic integration.

Removal of impacted esophageal foreign bodies with a dual-channel endoscope: 19 cases

PubMed Central

WANG, CHANGXIONG; CHEN, PING

2013-01-01

There have been few reports concerning the endoscopic removal of impacted esophageal foreign bodies from patients. The objective of this study was to evaluate the effectiveness of dual-channel endoscopy in managing foreign-body ingestions in patients. A total of 19 patients with foreign-body ingestions between September 2008 and July 2011 were selected from the Digestive Endoscope Center in Lishui, a typical middle-sized city in China. The patients underwent endoscopy following admission. The impacted foreign bodies were successfully removed from 18 patients without complications using a dual-channel endoscope. One patient underwent surgery for an ingested denture following the failure of the endoscopic removal method. This study demonstrates that dual-channel endoscopic management may be a useful option for removing ingested foreign bodies from the esophagus. PMID:23935752

Surface engineering on mesoporous silica chips for enriching low molecular weight phosphorylated proteins

NASA Astrophysics Data System (ADS)

Hu, Ye; Peng, Yang; Lin, Kevin; Shen, Haifa; Brousseau, Louis C., III; Sakamoto, Jason; Sun, Tong; Ferrari, Mauro

2011-02-01

Phosphorylated peptides and proteins play an important role in normal cellular activities, e.g., gene expression, mitosis, differentiation, proliferation, and apoptosis, as well as tumor initiation, progression and metastasis. However, technical hurdles hinder the use of common fractionation methods to capture phosphopeptides from complex biological fluids such as human sera. Herein, we present the development of a dual strategy material that offers enhanced capture of low molecular weight phosphoproteins: mesoporous silica thin films with precisely engineered pore sizes that sterically select for molecular size combined with chemically selective surface modifications (i.e. Ga3+, Ti4+ and Zr4+) that target phosphoroproteins. These materials provide high reproducibility (CV = 18%) and increase the stability of the captured proteins by excluding degrading enzymes, such as trypsin. The chemical and physical properties of the composite mesoporous thin films were characterized by X-ray diffraction, transmission electron microscopy, X-ray photoelectron spectroscopy, energy dispersive X-ray spectroscopy and ellipsometry. Using mass spectroscopy and biostatistics analysis, the enrichment efficiency of different metal ions immobilized on mesoporous silica chips was investigated. The novel technology reported provides a platform capable of efficiently profiling the serum proteome for biomarker discovery, forensic sampling, and routine diagnostic applications.Phosphorylated peptides and proteins play an important role in normal cellular activities, e.g., gene expression, mitosis, differentiation, proliferation, and apoptosis, as well as tumor initiation, progression and metastasis. However, technical hurdles hinder the use of common fractionation methods to capture phosphopeptides from complex biological fluids such as human sera. Herein, we present the development of a dual strategy material that offers enhanced capture of low molecular weight phosphoproteins: mesoporous silica thin films with precisely engineered pore sizes that sterically select for molecular size combined with chemically selective surface modifications (i.e. Ga3+, Ti4+ and Zr4+) that target phosphoroproteins. These materials provide high reproducibility (CV = 18%) and increase the stability of the captured proteins by excluding degrading enzymes, such as trypsin. The chemical and physical properties of the composite mesoporous thin films were characterized by X-ray diffraction, transmission electron microscopy, X-ray photoelectron spectroscopy, energy dispersive X-ray spectroscopy and ellipsometry. Using mass spectroscopy and biostatistics analysis, the enrichment efficiency of different metal ions immobilized on mesoporous silica chips was investigated. The novel technology reported provides a platform capable of efficiently profiling the serum proteome for biomarker discovery, forensic sampling, and routine diagnostic applications. Electronic supplementary information (ESI) available. See DOI: 10.1039/c0nr00720j

Liquid chromatography incorporating ultraviolet and electrochemical analyses for dual detection of zeranol and zearalenone metabolites in mouldy grains.

PubMed

Hsieh, Han-Yun; Shyu, Ching-Lin; Liao, Chen-Wei; Lee, Ren-Jye; Lee, Maw-Rong; Vickroy, Thomas W; Chou, Chi-Chung

2012-04-01

Zeranol (Z) is a semi-synthetic mycotoxin that is used in some countries as a growth-promoting agent in livestock. In view of the known oestrogenic actions by Z and certain Z analogues, significant concerns exist with regard to the presence of Z residues in human foods and the potential for untoward effects, including carcinogenicity within the reproductive system. In order to confirm that foods are free from harmful Z residues, regulators need a quick and reliable analytical method that can be used for routine confirmation of Z-positive samples identified by enzyme-linked immunosorbent assay (ELISA) screening. In this study the authors have developed and validated a simple and rapid high-performance liquid chromatography method incorporating ultraviolet (UV) absorbance (wavelength 274 nm) and electrochemical (EC) dual-mode detection for simultaneous determination of Z-related mycotoxins produced from mouldy grain matrices, including rice, soybean and corn flakes. Recoveries for all analytes were around 80% and the limits of detection ranged from 10 to 25 ng mL(-1) for UV and from 50 to 90 ng mL(-1) for EC detection with good accuracy and reproducibility. Differential profiles and occurrence rates of Z, β-zearalenol, β-zearalanol and α-zearalenol in naturally moulded grain matrices were observed, indicating different metabolite patterns and possibly grain-specific effects of mycotoxin exposure for humans and animals. The strength of this dual detection method lies in its selectivity characterised by a carbon screen-printed electrode such that aflatoxin interference is precluded. The combined dual detection technique affords quick and reliable semi-confirmative and quantitative information on multiple types of Z analogues in mouldy grains without the necessity of using expensive mass spectrometry. The method is considered a superior supplement to ELISA, which only screens total Z immunoreactivity. Copyright © 2011 Society of Chemical Industry.

Betahistine plus piracetam dual therapy versus betahistine monotherapy for peripheral vestibular vertigo: a confounder-corrected subanalysis of the OSVaLD study.

PubMed

Melnikov, Oleg A; Lilenko, Sergey V; Nauta, Jos; Ouwens, Mario J N M

2015-11-01

This subanalysis compared the efficacy of betahistine plus piracetam dual therapy versus betahistine monotherapy using data from OSVaLD, a 3 month, open-label, observational study conducted in 2272 patients with peripheral vestibular vertigo. Of the 1898 patients included in the original efficacy population, 1076 were from countries where betahistine plus piracetam dual therapy was prescribed to >1 patient; 114 of these 1076 patients (11%) received the dual therapy and 567 (53%) were treated with betahistine monotherapy; these patients were selected for analysis. Efficacy was assessed using the Dizziness Handicap Inventory (DHI) total and subscale scores. Propensity-score matching was used to correct potential differences in patient baseline characteristics between treatment groups. In addition, a subgroup analysis evaluated 103 patients treated with betahistine because of insufficient efficacy with their existing treatment. In the propensity-score matched, total-population evaluation, improvements in the DHI total and subscale scores were numerically greater in the betahistine plus piracetam group (n = 88) versus the betahistine group (n = 89) (DHI total, -42.9 vs. -37.6, respectively; DHI physical, -12.1 vs. -10.4; DHI emotional, -13.5 vs. -13.2) and statistically significant for the DHI functional score (-17.3 vs. -14.0, respectively, p = 0.01). The percentage of patients with no impairment at final visit was 27% with betahistine and 47% with betahistine plus piracetam; odds ratio: 2.3, 95% confidence interval: 1.3-2.4 (p = 0.007). Similar results were obtained in the subgroup analyses for patients whose current vertigo treatment was insufficient. The overall incidence of adverse events was low and similar in both groups, and there were no discontinuations due to drug-related adverse events. By using propensity-score matching, which controls for potential heterogeneity in patient baseline characteristics and small patient numbers, the results of this analysis suggest that combined betahistine and piracetam may be more effective than betahistine alone in patients with peripheral vestibular vertigo.

Dual Motor-Cognitive Virtual Reality Training Impacts Dual-Task Performance in Freezing of Gait.

PubMed

Killane, Isabelle; Fearon, Conor; Newman, Louise; McDonnell, Conor; Waechter, Saskia M; Sons, Kristian; Lynch, Timothy; Reilly, Richard B

2015-11-01

Freezing of gait (FOG), an episodic gait disturbance characterized by the inability to generate effective stepping, occurs in more than half of Parkinson's disease patients. It is associated with both executive dysfunction and attention and becomes most evident during dual tasking (performing two tasks simultaneously). This study examined the effect of dual motor-cognitive virtual reality training on dual-task performance in FOG. Twenty community dwelling participants with Parkinson's disease (13 with FOG, 7 without FOG) participated in a pre-assessment, eight 20-minute intervention sessions, and a post-assessment. The intervention consisted of a virtual reality maze (DFKI, Germany) through which participants navigated by stepping-in-place on a balance board (Nintendo, Japan) under time pressure. This was combined with a cognitive task (Stroop test), which repeatedly divided participants' attention. The primary outcome measures were pre- and post-intervention differences in motor (stepping time, symmetry, rhythmicity) and cognitive (accuracy, reaction time) performance during single- and dual-tasks. Both assessments consisted of 1) a single cognitive task 2) a single motor task, and 3) a dual motor-cognitive task. Following the intervention, there was significant improvement in dual-task cognitive and motor parameters (stepping time and rhythmicity), dual-task effect for those with FOG and a noteworthy improvement in FOG episodes. These improvements were less significant for those without FOG. This is the first study to show benefit of a dual motor-cognitive approach on dual-task performance in FOG. Advances in such virtual reality interventions for home use could substantially improve the quality of life for patients who experience FOG.

Dual practice in the health sector: review of the evidence

PubMed Central

Ferrinho, Paulo; Van Lerberghe, Wim; Fronteira, Inês; Hipólito, Fátima; Biscaia, André

2004-01-01

This paper reports on income generation practices among civil servants in the health sector, with a particular emphasis on dual practice. It first approaches the subject of public–private overlap. Thereafter it focuses on coping strategies in general and then on dual practice in particular. To compensate for unrealistically low salaries, health workers rely on individual coping strategies. Many clinicians combine salaried, public-sector clinical work with a fee-for-service private clientele. This dual practice is often a means by which health workers try to meet their survival needs, reflecting the inability of health ministries to ensure adequate salaries and working conditions. Dual practice may be considered present in most countries, if not all. Nevertheless, there is surprisingly little hard evidence about the extent to which health workers resort to dual practice, about the balance of economic and other motives for doing so, or about the consequences for the proper use of the scarce public resources dedicated to health. In this paper dual practice is approached from six different perspectives: (1) conceptual, regarding what is meant by dual practice; (2) descriptive, trying to develop a typology of dual practices; (3) quantitative, trying to determine its prevalence; (4) impact on personal income, the health care system and health status; (5) qualitative, looking at the reasons why practitioners so frequently remain in public practice while also working in the private sector and at contextual, personal life, institutional and professional factors that make it easier or more difficult to have dual practices; and (6) possible interventions to deal with dual practice. PMID:15509305

Combining presentation high-sensitivity cardiac troponin I and glucose measurements to rule-out an acute myocardial infarction in patients presenting to emergency department with chest pain.

PubMed

Greenslade, J H; Kavsak, P; Parsonage, W; Shortt, C; Than, M; Pickering, J W; Aldous, S; Cullen, L

2015-03-01

The use of high sensitivity troponin (hs-Tn) may enable early rule out of acute myocardial infarction (AMI) for patients presenting to the emergency department (ED) with chest pain. This study evaluated two approaches to the early rule out of AMI; a combination of a presentation hs-Tn <4ng/L and normal glucose at presentation (dual testing) and a presentation hs-Tn troponin below the limit of detection (LoD). We utilised prospectively collected data on adult patients presenting with suspected ACS in two EDs in Australia and New Zealand. Blood samples were taken on presentation and tested for glucose and high sensitivity troponin I. The primary endpoint was index AMI and the secondary endpoint was 30-day acute coronary syndrome (ACS). Sensitivity, specificity, positive and negative predictive values were used to assess the diagnostic accuracy of the dual testing and LoD approaches. Of the 1412 participants, 182 (12.9%) had index AMI. The LoD and the dual testing approach were 100% sensitive for index AMI. The specificity of the dual testing approach (25.2%) was slightly higher than that of the LoD (20.4%). Sensitivity for ACS was similar for the two approaches (96.5% for dual testing and 98.1% for the LoD). The dual testing and LoD approach identified all patients with index AMI and could be used to reduce the proportion of patients requiring lengthy assessment and inpatient admission. Further investigation is still required to rule out unstable angina pectoris in patients identified as low risk. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Group-based exercise combined with dual-task training improves gait but not vascular health in active older adults without dementia.

PubMed

Gregory, Michael A; Gill, Dawn P; Zou, Guangyong; Liu-Ambrose, Teresa; Shigematsu, Ryosuke; Fitzgerald, Clara; Hachinski, Vladimir; Shoemaker, Kevin; Petrella, Robert J

2016-01-01

Gait abnormalities and vascular disease risk factors are associated with cognitive impairment in aging. To determine the impact of group-based exercise and dual-task training on gait and vascular health, in active community-dwelling older adults without dementia. Participants [n=44, mean (SD) age: 73.5 (7.2) years, 68% female] were randomized to either intervention (exercise+dual-task; EDT) or control (exercise only; EO). Each week, for 26 weeks, both groups accumulated 50 or 75 min of aerobic exercise from group-based classes and 45 min of beginner-level square stepping exercise (SSE). Participants accumulating only 50 min of aerobic exercise were instructed to participate in an additional 25 min each week outside of class. The EDT group also answered cognitively challenging questions while performing SSE (i.e., dual-task training). The effect of the interventions on gait and vascular health was compared between groups using linear mixed effects models. At 26 weeks, the EDT group demonstrated increased dual-task (DT) gait velocity [difference between groups in mean change from baseline (95% CI): 0.29 m/s (0.16-0.43), p<0.001], DT step length [5.72 cm (2.19-9.24), p =0.002], and carotid intima-media thickness [0.10mm (0.003-0.20), p=0.04], as well as reduced DT stride time variability [8.31 coefficient of variation percentage points (-12.92 to -3.70), p<0.001], when compared to the EO group. Group-based exercise combined with dual-task training can improve DT gait characteristics in active older adults without dementia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Microstructural Developments Leading to New Advanced High Strength Sheet Steels: A Historical Assessment of Critical Metallographic Observations

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

Matlock, David K; Thomas, Larrin S; Taylor, Mark D

In the past 30+ years significant advancements have been made in the development of higher strength sheet steels with improved combinations of strength and ductility that have enabled important product improvements leading to safer, lighter weight, and more fuel efficient automobiles and in other applications. Properties of the primarily low carbon, low alloy steels are derived through careful control of time-temperature processing histories designed to produce multiphase ferritic based microstructures that include martensite and other constituents including retained austenite. The basis for these developments stems from the early work on dual-phase steels which was the subject of much interest. Inmore » response to industry needs, dual-phase steels have evolved as a unique class of advanced high strength sheet steels (AHSS) in which the thermal and mechanical processing histories have been specifically designed to produce constituent combinations for the purpose of simultaneously controlling strength and deformation behavior, i.e. stress-strain curve shapes. Improvements continue as enhanced dual-phase steels have recently been produced with finer microstructures, higher strengths, and better overall formability. Today, dual phase steels are the primary AHSS products used in vehicle manufacture, and several companies have indicated that the steels will remain as important design materials well into the future. In this presentation, fundamental results from the early work on dual-phase steels will be reviewed and assessed in light of recent steel developments. Specific contributions from industry/university cooperative research leading to product improvements will be highlighted. The historical perspective provided in the evolution of dual-phase steels represents a case-study that provides important framework and lessons to be incorporated in next generation AHSS products.« less

Simultaneous exposure of nematophagous fungi, entomopathogenic nematodes and entomopathogenic fungi can modulate belowground insect pest control.

PubMed

Bueno-Pallero, Francisco Ángel; Blanco-Pérez, Rubén; Dionísio, Lídia; Campos-Herrera, Raquel

2018-05-01

Entomopathogenic nematodes (EPNs) and fungi (EPF) are well known biological control agents (BCAs) against insect pests. Similarly, the nematophagous fungi (NF) are considered good BCA candidates for controlling plant parasitic nematodes. Because NF can employ EPNs as food and interact with EPF, we speculate that the simultaneous application of EPNs and EPF might result in higher insect mortality, whereas the triple species combination with NF will reduce the EPN and EPF activity by predation or inhibition. Here we evaluated single, dual (EPN + EPF, EPF + NF, EPN + NF) and triple (EPN + EPF + NF) combinations of one EPN, Steinernema feltiae (Rhabditida: Steinernematidae), one EPF, Beauveria bassiana (Hypocreales: Clavicipitaceae), and two NF, Arthrobotrys musiformis (Orbiliales: Orbiliaceae) and Purpureocillium lilacinum (Hypocreales: Ophiocordycipitaceae) under laboratory conditions. First, we showed that EPF reduced the growth rate of NF and vice versa when combined in both rich and limiting media, suggesting a negative interaction when combining both fungi. Three different fungal applications (contact with mycelia-conidia, immersion in conidial suspension, and injection of conidial suspension) were tested in single, dual and triple species combinations, evaluating Galleria mellonella (Lepidoptera: Pyralidae) larval mortality and time to kill. When mycelia was presented, the EPF appeared to be the dominant in combined treatments, whereas in immersion exposure was the EPN. In both types of exposure, NF alone did not produce any effect on larvae. However, when A. musiformis was injected, it produced larval mortalities >70% in the same time span as EPN. Overall, additive effects dominated the dual and triple combinations, with the exception of injection method, where synergisms occurred for both NF species combined with EPN + EPF. This study illustrates how differences in species combination and timing of fungal arrival can modulate the action of BCAs when augmented in the soil. Further studies are required to fine-tune these multitrophic interactions to provide successful, sustainable and resilient pest management in agroecosystems. Copyright © 2018 Elsevier Inc. All rights reserved.

The Association between High Neuroticism-Low Extraversion and Dual-Task Performance during Walking While Talking in Non-demented Older Adults

PubMed Central

LeMonda, Brittany C.; Mahoney, Jeannette R.; Verghese, Joe; Holtzer, Roee

2016-01-01

The Walking While Talking (WWT) dual-task paradigm is a mobility stress test that predicts major outcomes, including falls, frailty, disability, and mortality in aging. Certain personality traits, such as neuroticism, extraversion, and their combination, have been linked to both cognitive and motor outcomes. We examined whether individual differences in personality dimensions of neuroticism and extraversion predicted dual-task performance decrements (both motor and cognitive) on a WWT task in non-demented older adults. We hypothesized that the combined effect of high neuroticism-low extraversion would be related to greater dual-task costs in gait velocity and cognitive performance in non-demented older adults. Participants (N = 295; age range, = 65–95 years; female = 164) completed the Big Five Inventory and WWT task involving concurrent gait and a serial 7's subtraction task. Gait velocity was obtained using an instrumented walkway. The high neuroticism-low extraversion group incurred greater dual-task costs (i.e., worse performance) in both gait velocity {95% confidence interval (CI) [−17.68 to −3.07]} and cognitive performance (95% CI [−19.34 to −2.44]) compared to the low neuroticism-high extraversion group, suggesting that high neuroticism-low extraversion interferes with the allocation of attentional resources to competing task demands during the WWT task. Older individuals with high neuroticism-low extraversion may be at higher risk for falls, mobility decline and other adverse outcomes in aging. PMID:26527241

Daclatasvir/asunaprevir/beclabuvir fixed-dose combination in Japanese patients with HCV genotype 1 infection.

PubMed

Toyota, Joji; Karino, Yoshiyasu; Suzuki, Fumitaka; Ikeda, Fusao; Ido, Akio; Tanaka, Katsuaki; Takaguchi, Koichi; Naganuma, Atsushi; Tomita, Eiichi; Chayama, Kazuaki; Fujiyama, Shigetoshi; Inada, Yukiko; Yoshiji, Hitoshi; Watanabe, Hideaki; Ishikawa, Hiroki; Hu, Wenhua; McPhee, Fiona; Linaberry, Misti; Yin, Philip D; Swenson, Eugene Scott; Kumada, Hiromitsu

2017-03-01

DCV-TRIO, a fixed-dose combination of daclatasvir (pangenotypic NS5A inhibitor), asunaprevir (NS3/4A protease inhibitor), and beclabuvir (non-nucleoside NS5B inhibitor), has achieved high rates of sustained virologic response at post-treatment Week 12 (SVR12) in phase 3 studies. In this phase 3 study, DCV-TRIO for 12 weeks and daclatasvir plus asunaprevir (DUAL) for 24 weeks were studied in Japanese patients infected with HCV genotype 1 (99 % genotype 1b). SVR12 rates ≥95 % were achieved in both treatment-naive (N = 152) and interferon-experienced (N = 65) cohorts treated with DCV-TRIO for 12 weeks and were comparable across patient subgroups, including patients aged ≥65 years and those with cirrhosis. DUAL recipients (N = 75) had an SVR12 rate of 87 %. In the absence of baseline resistance-associated polymorphisms at positions NS5A-Y93H or -L31, SVR12 rates were 98 % with DCV-TRIO or DUAL. Among genotype 1b-infected patients with baseline Y93H or L31 polymorphisms, 35/38 (92 %) DCV-TRIO recipients, and 7/16 (44 %) DUAL recipients achieved SVR12. Adverse events, mostly liver related, led to treatment discontinuation in 10 % of DCV-TRIO recipients. In this group, SVR12 was achieved by 3/9 patients who discontinued before Week 4 and by 12/12 patients who completed ≥4 weeks of DCV-TRIO. Treatment-related serious adverse events occurred in 4 and 3 % of DCV-TRIO and DUAL recipients, respectively. Seven patients (9 %) discontinued DUAL due to adverse events. No deaths occurred. SVR12 was achieved by 96 % of Japanese patients with HCV genotype 1 infection after 12 weeks of treatment with the DCV-TRIO regimen. DCV-TRIO and DUAL exhibited comparable safety profiles.

Quantifying the combined effects of pronase and benzalkonium chloride in removing late-stage Listeria monocytogenes-Escherichia coli dual-species biofilms.

PubMed

Rodríguez-López, Pedro; Puga, Carmen H; Orgaz, Belén; Cabo, Marta L

2017-09-01

This work presents the assessment of the effectivity of a pronase (PRN)-benzalkonium chloride (BAC) sequential treatment in removing Listeria monocytogenes-Escherichia coli dual-species biofilms grown on stainless steel (SS) using fluorescence microscopy and plate count assays. The effects of PRN-BAC on the occupied area (OA) by undamaged cells in 168 h dual-species samples were determined using a first-order factorial design. Empirical equations significantly (r 2 = 0.927) described a negative individual effect of BAC and a negative interactive effect of PRN-BAC achieving OA reductions up to 46%. After treatment, high numbers of remaining attached and released viable and cultivable E. coli cells were detected in PRN-BAC combinations when low BAC concentrations were used. Therefore, at appropriate BAC doses, in addition to biofilm removal, sequential application of PRN and BAC represents an appealing strategy for pathogen control on SS surfaces while hindering the dispersion of live cells into the environment.

Design of two-DMD based zoom MW and LW dual-band IRSP using pixel fusion

NASA Astrophysics Data System (ADS)

Pan, Yue; Xu, Xiping; Qiao, Yang

2018-06-01

In order to test the anti-jamming ability of mid-wave infrared (MWIR) and long-wave infrared (LWIR) dual-band imaging system, a zoom mid-wave (MW) and long-wave (LW) dual-band infrared scene projector (IRSP) based on two-digital micro-mirror device (DMD) was designed by using a projection method of pixel fusion. Two illumination systems, which illuminate the two DMDs directly with Kohler telecentric beam respectively, were combined with projection system by a spatial layout way. The distances of projection entrance pupil and illumination exit pupil were also analyzed separately. MWIR and LWIR virtual scenes were generated respectively by two DMDs and fused by a dichroic beam combiner (DBC), resulting in two radiation distributions in projected image. The optical performance of each component was evaluated by ray tracing simulations. Apparent temperature and image contrast were demonstrated by imaging experiments. On the basis of test and simulation results, the aberrations of optical system were well corrected, and the quality of projected image meets test requirements.

Development in high-grade dual phase steels with low C and Si design

NASA Astrophysics Data System (ADS)

Zhu, Guo-hui; Zhang, Xue-hui; Mao, Wei-min

2009-12-01

Cold rolled dual phase steels with low C and Si addition were investigated in terms of combination of composition and processing in order to improve mechanical properties and workability including welding and galvanizing. Mo and Cr could be used as alloying elements to partially replace C and Si to assure enough hardening ability of the steels and also give solute-hardening. Mo addition is more effective than Cr addition in terms of obtaining the required volume fraction of martensite and mechanical strength. The ferrite grain was effectively refined by addition of Nb microalloying, which gives optimized mechanical properties. The experimental results show that it is possible to obtain the required mechanical properties of high grade 800 MPa dual phase steel, i.e., tensile strength > 780 MPa, elongation > 15%, and yield/tensile strength ratio < 0.6 in the condition of low carbon (C < 0.11 wt.%) and low silicon design (Si < 0.05 wt.%) through adequate combination of composition and processing.

Dual Sulfide-Disulfide Crosslinked Networks with Rapid and Room Temperature Self-Healability.

PubMed

An, So Young; Noh, Seung Man; Nam, Joon Hyun; Oh, Jung Kwon

2015-07-01

Polymer-based crosslinked networks with intrinsic self-repairing ability have emerged due to their built-in ability to repair physical damages. Here, novel dual sulfide-disulfide crosslinked networks (s-ssPxNs) are reported exhibiting rapid and room temperature self-healability within seconds to minutes, with no extra healing agents and no change under any environmental conditions. The method to synthesize these self-healable networks utilizes a combination of well-known crosslinking chemistry: photoinduced thiol-ene click-type radical addition, generating lightly sulfide-crosslinked polysulfide-based networks with excess thiols, and their oxidation, creating dynamic disulfide crosslinkages to yield the dual s-ssPxNs. The resulting s-ssPxN networks show rapid self-healing within 30 s to 30 min at room temperature, as well as self-healing elasticity with reversible viscoelastic properties. These results, combined with tunable self-healing kinetics, demonstrate the versatility of the method as a new means to synthesize smart multifunctional polymeric materials. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Information access in a dual-task context: testing a model of optimal strategy selection.

PubMed

Wickens, C D; Seidler, K S

1997-09-01

Pilots were required to access information from a hierarchical aviation database by navigating under single-task conditions (Experiment 1) and when this task was time-shared with an altitude-monitoring task of varying bandwidth and priority (Experiment 2). In dual-task conditions, pilots had 2 viewports available, 1 always used for the information task and the other to be allocated to either task. Dual-task strategy, inferred from the decision of which task to allocate to the 2nd viewport, revealed that allocation was generally biased in favor of the monitoring task and was only partly sensitive to the difficulty of the 2 tasks and their relative priorities. Some dominant sources of navigational difficulties failed to adaptively influence selection strategy. The implications of the results are to provide tools for jumping to the top of the database, to provide 2 viewports into the common database, and to provide training as to the optimum viewport management strategy in a multitask environment.

A novel electrochemical cytosensor for selective and highly sensitive detection of cancer cells using binding-induced dual catalytic hairpin assembly.

PubMed

Zhang, Ye; Luo, Shihua; Situ, Bo; Chai, Zhixin; Li, Bo; Liu, Jumei; Zheng, Lei

2018-04-15

Rare cancer cells in body fluid could be useful biomarkers for noninvasive diagnosis of cancer. However, detection of these rare cells is currently challenging. In this work, a binding-induced dual catalytic hairpin assembly (DCHA) electrochemical cytosensor was developed for highly selective and sensitive detection of cancer cells. The fuel probe, released by hybridization between the capture probe and catalytic hairpin assembly (CHA) products of target cell-responsive reaction, initiated dual CHA recycling, leading to multiple CHA products. Furthermore, the hybridization between fuel probe and capture probe decreased non-specific CHA products, improving the signal-to-noise ratio and detection sensitivity. Under the optimal conditions, the developed cytosensor was able to detect cells down to 30 cells mL -1 (S/N = 3) with a linear range from 50 to 100,000 cells mL -1 and was capable of distinguishing target cells from normal cells in clinical blood samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Selective impairment of masked priming in dual-task performance.

PubMed

Fischer, Rico; Kiesel, Andrea; Kunde, Wilfried; Schubert, Torsten

2011-03-01

This study investigated the impact of divided attention on masked priming. In a dual-task setting, two tasks had to be carried out in close temporal succession: a tone discrimination task and a masked priming task. The order of the tasks was varied between experiments, and attention was always allocated to the first task-that is, the first task was prioritized. The priming task was the second (nonprioritized) task in Experiment 1 and the first (prioritized) task in Experiment 2. In both experiments, "novel" prime stimuli associated with semantic processing were essentially ineffective. However, there was intact priming by another type of prime stimuli associated with response priming. Experiment 3 showed that all these prime stimuli can reveal significant priming effects during a task-switching paradigm in which both tasks were performed consecutively. We conclude that dual-task specific interference processes (e.g., the simultaneous coordination of multiple stimulus-response rules) selectively impair priming that is assumed to rely on semantic processing.

Information access in a dual-task context: testing a model of optimal strategy selection

NASA Technical Reports Server (NTRS)

Wickens, C. D.; Seidler, K. S.

1997-01-01

Pilots were required to access information from a hierarchical aviation database by navigating under single-task conditions (Experiment 1) and when this task was time-shared with an altitude-monitoring task of varying bandwidth and priority (Experiment 2). In dual-task conditions, pilots had 2 viewports available, 1 always used for the information task and the other to be allocated to either task. Dual-task strategy, inferred from the decision of which task to allocate to the 2nd viewport, revealed that allocation was generally biased in favor of the monitoring task and was only partly sensitive to the difficulty of the 2 tasks and their relative priorities. Some dominant sources of navigational difficulties failed to adaptively influence selection strategy. The implications of the results are to provide tools for jumping to the top of the database, to provide 2 viewports into the common database, and to provide training as to the optimum viewport management strategy in a multitask environment.

Polysaccharide nano-vesicular multidrug carriers for synergistic killing of cancer cells

NASA Astrophysics Data System (ADS)

Pramod, P. S.; Shah, Ruchira; Chaphekar, Sonali; Balasubramanian, Nagaraj; Jayakannan, Manickam

2014-09-01

Multi-drug delivery based on polymer nano-scaffolds is an essential protocol to be developed for better administration of anticancer drugs to enhance their therapeutic efficacies against cancer cells. Here, we report dual delivery polysaccharide nano-vesicles that are capable of loading and delivering both water soluble and water insoluble drugs together in a single polymer scaffold. The selective rupture of the nano-vesicular assembly under intracellular enzyme conditions allowed the simultaneous delivery of a hydrophobic drug camptothecin (CPT) and hydrophilic drug doxorubicin (DOX) supporting their synergistic killing of breast and colon cancer cells. The polysaccharide nano-vesicles have allowed us to address a few important questions regarding the need for multiple drug administration in cancer cells including (a) the role of simultaneous drug release, (b) antagonistic versus synergistic effects of drug combinations and (c) how these are affected by the ratio of drugs. Further, evaluation of the role of caveolae in endocytosis of these polymer scaffolds was also made. The vesicular scaffolds were found to preserve and deliver DOX resulting in 50-60% better killing of cancer cells than the free drug. Additionally, dual loaded nano-vesicles when compared to drug cocktails with individual drugs in separate nano-vesicles (at comparable molar ratios) suggest the relative drug concentration following release and mode of delivery to be both important in cancer cell killing. Results from these experiments have revealed newly developed polysaccharide nano-vesicles loaded with DOX and CPT drugs as potential candidates for improved breast cancer cell killing. Thus, these custom-designed polysaccharide nano-vesicles provide a new perspective on multi-anticancer drug delivery systems and their efficacy.Multi-drug delivery based on polymer nano-scaffolds is an essential protocol to be developed for better administration of anticancer drugs to enhance their therapeutic efficacies against cancer cells. Here, we report dual delivery polysaccharide nano-vesicles that are capable of loading and delivering both water soluble and water insoluble drugs together in a single polymer scaffold. The selective rupture of the nano-vesicular assembly under intracellular enzyme conditions allowed the simultaneous delivery of a hydrophobic drug camptothecin (CPT) and hydrophilic drug doxorubicin (DOX) supporting their synergistic killing of breast and colon cancer cells. The polysaccharide nano-vesicles have allowed us to address a few important questions regarding the need for multiple drug administration in cancer cells including (a) the role of simultaneous drug release, (b) antagonistic versus synergistic effects of drug combinations and (c) how these are affected by the ratio of drugs. Further, evaluation of the role of caveolae in endocytosis of these polymer scaffolds was also made. The vesicular scaffolds were found to preserve and deliver DOX resulting in 50-60% better killing of cancer cells than the free drug. Additionally, dual loaded nano-vesicles when compared to drug cocktails with individual drugs in separate nano-vesicles (at comparable molar ratios) suggest the relative drug concentration following release and mode of delivery to be both important in cancer cell killing. Results from these experiments have revealed newly developed polysaccharide nano-vesicles loaded with DOX and CPT drugs as potential candidates for improved breast cancer cell killing. Thus, these custom-designed polysaccharide nano-vesicles provide a new perspective on multi-anticancer drug delivery systems and their efficacy. Electronic supplementary information (ESI) available: Synthesis scheme, DLS histogram, FE-SEM image, AFM image, TEM image of DEX-PDP-5, AFM image of VDOX+CPT, AFM image of VDOX, characterization of VCPT, characterization of VRHO, DOX nuclear localization, characterization of dual drug loaded vesicles, fluorescent microscopic image of VDOX-CPT, cumulative drug release profile from dual drug loaded vesicles, rate constant determination, and cumulative release profile of DOX and CPT from VDOX+CPT (1 : 4). See DOI: 10.1039/c4nr03514c

New therapeutic options for the metabolic syndrome: what's next?

PubMed

Flordellis, Christodoulos S; Ilias, Ioannis; Papavassiliou, Athanasios G

2005-08-01

The metabolic syndrome (MSX), characterized by obesity, insulin resistance, dyslipidemia and hypertension, increases the risk of cardiovascular morbidity and mortality. It has recently been hypothesized that MSX and type 2 diabetes are caused by triglyceride and long-chain fatty acid accumulation in liver, muscle, pancreatic islets and selected brain areas. This lipocentric approach is integrated with analysis of inflammation associated with end-organ damage, including the vascular wall. Genes and proteins contributing to insulin resistance, beta cell dysfunction and vascular wall damage have been identified. Transcription factors and coactivators, including peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator-1 are crucial in mediating insulin resistance and accelerating vascular wall inflammation, and represent promising therapeutic targets. New pharmacological strategies include dual PPARalpha/gamma agonists, drugs with pleiotropic effects or combination therapies.

The effect of direct renin inhibition alone and in combination with ACE inhibition on endothelial function, arterial stiffness, and renal function in type 1 diabetes.

PubMed

Cherney, David Z I; Scholey, James W; Jiang, Shan; Har, Ronnie; Lai, Vesta; Sochett, Etienne B; Reich, Heather N

2012-11-01

Diabetes is associated with renin-angiotensin system (RAS) activation, leading to renal and systemic vascular dysfunction that contribute to end-organ injury and significant morbidity. RAS blockade with ACE inhibitors reduces, but does not abolish, RAS effects. Accordingly, our aim was to determine if direct renin inhibition alone, and in combination with an ACE inhibitor, corrects early hemodynamic abnormalities associated with type 1 diabetes. Arterial stiffness (augmentation index), flow-mediated vasodilatation (FMD), and renal hemodynamic function (inulin and paraaminohippurate clearance) were measured at baseline under clamped euglycemic and hyperglycemic conditions (n = 21). Measures were repeated after 4 weeks of aliskiren therapy and again after aliskiren plus ramipril. Blood pressure-lowering effects of aliskiren were similar during clamped euglycemia and hyperglycemia. Combination therapy augmented this effect under both glycemic conditions (P = 0.0005). Aliskiren reduced arterial stiffness under clamped euglycemic and hyperglycemic conditions, and the effects were augmented by dual RAS blockade (-3.4 ± 11.2 to -8.0 ± 11.5 to -14.3 ± 8.4%, respectively, during euglycemia, P = 0.0001). During clamped euglycemia, aliskiren increased FMD; dual therapy exaggerated this effect (5.1 ± 3.3 to 7.5 ± 3.0 to 10.8 ± 3.5%, repeated-measures ANOVA, P = 0.0001). Aliskiren monotherapy caused renal vasodilatation during clamped hyperglycemia only. In contrast, dual therapy augmented renal vasodilatory effects during clamped euglycemia and hyperglycemia. In patients with uncomplicated type 1 diabetes, aliskiren-based dual RAS blockade is associated with greater arterial compliance, FMD, and renal vasodilatation.

Trispecific antibodies for CD16A-directed NK cell engagement and dual-targeting of tumor cells.

PubMed

Gantke, Thorsten; Weichel, Michael; Herbrecht, Carmen; Reusch, Uwe; Ellwanger, Kristina; Fucek, Ivica; Eser, Markus; Müller, Thomas; Griep, Remko; Molkenthin, Vera; Zhukovsky, Eugene A; Treder, Martin

2017-09-01

Bispecific antibodies that redirect the lytic activity of cytotoxic immune effector cells, such as T- and NK cells, onto tumor cells have emerged as a highly attractive and clinically validated treatment modality for hematological malignancies. Advancement of this therapeutic concept into solid tumor indications, however, is hampered by the scarcity of targetable antigens that are surface-expressed on tumor cells but demonstrate only limited expression on healthy tissues. To overcome this limitation, the concept of dual-targeting, i.e. the simultaneous targeting of two tumor-expressed surface antigens with limited co-expression on non-malignant cells, with multispecific antibodies has been proposed to increase tumor selectivity of antibody-induced effector cell cytotoxicity. Here, a novel CD16A (FcγRIIIa)-directed trispecific, tetravalent antibody format, termed aTriFlex, is described, that is capable of redirecting NK cell cytotoxicity to two surface-expressed antigens. Using a BCMA/CD200-based in vitro model system, the potential use of aTriFlex antibodies for dual-targeting and selective induction of NK cell-mediated target cell lysis was investigated. Bivalent bispecific target cell binding was found to result in significant avidity gains and up to 17-fold increased in vitro potency. These data suggest trispecific aTriFlex antibodies may support dual-targeting strategies to redirect NK cell cytotoxicity with increased selectivity to enable targeting of solid tumor antigens. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Gait performance is not influenced by working memory when walking at a self-selected pace.

PubMed

Grubaugh, Jordan; Rhea, Christopher K

2014-02-01

Gait performance exhibits patterns within the stride-to-stride variability that can be indexed using detrended fluctuation analysis (DFA). Previous work employing DFA has shown that gait patterns can be influenced by constraints, such as natural aging or disease, and they are informative regarding a person's functional ability. Many activities of daily living require concurrent performance in the cognitive and gait domains; specifically working memory is commonly engaged while walking, which is considered dual-tasking. It is unknown if taxing working memory while walking influences gait performance as assessed by DFA. This study used a dual-tasking paradigm to determine if performance decrements are observed in gait or working memory when performed concurrently. Healthy young participants (N = 16) performed a working memory task (automated operation span task) and a gait task (walking at a self-selected speed on a treadmill) in single- and dual-task conditions. A second dual-task condition (reading while walking) was included to control for visual attention, but also introduced a task that taxed working memory over the long term. All trials involving gait lasted at least 10 min. Performance in the working memory task was indexed using five dependent variables (absolute score, partial score, speed error, accuracy error, and math error), while gait performance was indexed by quantifying the mean, standard deviation, and DFA α of the stride interval time series. Two multivariate analyses of variance (one for gait and one for working memory) were used to examine performance in the single- and dual-task conditions. No differences were observed in any of the gait or working memory dependent variables as a function of task condition. The results suggest the locomotor system is adaptive enough to complete a working memory task without compromising gait performance when walking at a self-selected pace.

Enhancing Targeted Genomic DNA Editing in Chicken Cells Using the CRISPR/Cas9 System

PubMed Central

Wang, Ling; Yang, Likai; Guo, Yijie; Du, Weili; Yin, Yajun; Zhang, Tao; Lu, Hongzhao

2017-01-01

The CRISPR/Cas9 system has enabled highly efficient genome targeted editing for various organisms. However, few studies have focused on CRISPR/Cas9 nuclease-mediated chicken genome editing compared with mammalian genomes. The current study combined CRISPR with yeast Rad52 (yRad52) to enhance targeted genomic DNA editing in chicken DF-1 cells. The efficiency of CRISPR/Cas9 nuclease-induced targeted mutations in the chicken genome was increased to 41.9% via the enrichment of the dual-reporter surrogate system. In addition, the combined effect of CRISPR nuclease and yRad52 dramatically increased the efficiency of the targeted substitution in the myostatin gene using 50-mer oligodeoxynucleotides (ssODN) as the donor DNA, resulting in a 36.7% editing efficiency after puromycin selection. Furthermore, based on the effect of yRad52, the frequency of exogenous gene integration in the chicken genome was more than 3-fold higher than that without yRad52. Collectively, these results suggest that ssODN is an ideal donor DNA for targeted substitution and that CRISPR/Cas9 combined with yRad52 significantly enhances chicken genome editing. These findings could be extensively applied in other organisms. PMID:28068387

Combined antitumor gene therapy with herpes simplex virus-thymidine kinase and short hairpin RNA specific for mammalian target of rapamycin.

PubMed

Woo, Ha-Na; Lee, Won Il; Kim, Ji Hyun; Ahn, Jeonghyun; Han, Jeong Hee; Lim, Sue Yeon; Lee, Won Woo; Lee, Heuiran

2015-12-01

A proof-of-concept study is presented using dual gene therapy that employed a small hairpin RNA (shRNA) specific for mammalian target of rapamycin (mTOR) and a herpes simplex virus-thymidine kinase (HSV-TK) gene to inhibit the growth of tumors. Recombinant adeno-associated virus (rAAV) vectors containing a mutant TK gene (sc39TK) were transduced into HeLa cells, and the prodrug ganciclovir (GCV) was administered to establish a suicide gene-therapy strategy. Additionally, rAAV vectors expressing an mTOR-targeted shRNA were employed to suppress mTOR-dependent tumor growth. GCV selectively induced death in tumor cells expressing TK, and the mTOR-targeted shRNA altered the cell cycle to impair tumor growth. Combining the TK-GCV system with mTOR inhibition suppressed tumor growth to a greater extent than that achieved with either treatment alone. Furthermore, HSV-TK expression and mTOR inhibition did not mutually interfere with each other. In conclusion, gene therapy that combines the TK-GCV system and mTOR inhibition shows promise as a novel strategy for cancer therapy.

Targeted estrogen delivery reverses the metabolic syndrome

PubMed Central

Finan, Brian; Yang, Bin; Ottaway, Nickki; Stemmer, Kerstin; Müller, Timo D; Yi, Chun-Xia; Habegger, Kirk; Schriever, Sonja C; García-Cáceres, Cristina; Kabra, Dhiraj G; Hembree, Jazzminn; Holland, Jenna; Raver, Christine; Seeley, Randy J; Hans, Wolfgang; Irmler, Martin; Beckers, Johannes; de Angelis, Martin Hrabě; Tiano, Joseph P; Mauvais-Jarvis, Franck; Perez-Tilve, Diego; Pfluger, Paul; Zhang, Lianshan; Gelfanov, Vasily; DiMarchi, Richard D; Tschöp, Matthias H

2013-01-01

We report the development of a new combinatorial approach that allows for peptide-mediated selective tissue targeting of nuclear hormone pharmacology while eliminating adverse effects in other tissues. Specifically, we report the development of a glucagon-like peptide-1 (GLP-1)-estrogen conjugate that has superior sex-independent efficacy over either of the individual hormones alone to correct obesity, hyperglycemia and dyslipidemia in mice. The therapeutic benefits are driven by pleiotropic dual hormone action to improve energy, glucose and lipid metabolism, as shown by loss-of-function models and genetic action profiling. Notably, the peptide-based targeting strategy also prevents hallmark side effects of estrogen in male and female mice, such as reproductive endocrine toxicity and oncogenicity. Collectively, selective activation of estrogen receptors in GLP-1–targeted tissues produces unprecedented efficacy to enhance the metabolic benefits of GLP-1 agonism. This example of targeting the metabolic syndrome represents the discovery of a new class of therapeutics that enables synergistic co-agonism through peptide-based selective delivery of small molecules. Although our observations with the GLP-1–estrogen conjugate justify translational studies for diabetes and obesity, the multitude of other possible combinations of peptides and small molecules may offer equal promise for other diseases. PMID:23142820

Light output function and assembly of the time-of-flight enhanced diagnostics neutron spectrometer plastic scintillators for background reduction by double kinematic selection at EAST

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

Peng, X. Y.; Chen, Z. J.; Zhang, X.

The 2.5 MeV neutron spectrometer TOFED (Time-Of-Flight Enhanced Diagnostics) has been constructed to perform advanced neutron emission spectroscopy diagnosis of deuterium plasmas on EAST. The instrument has a double-ring structure which, in combination with pulse shape digitization, allows for a dual kinematic selection in the time-of-flight/recoil proton energy (tof/E{sub p}) space, thus improving the spectrometer capability to resolve fast ion signatures in the neutron spectrum, in principle up to a factor ≈100. The identification and separation of features from the energetic ions in the neutron spectrum depends on the detailed knowledge of the instrument response function, both in terms ofmore » the light output function of the scintillators and the effect of undesired multiple neutron scatterings in the instrument. This work presents the determination of the light output function of the TOFED plastic scintillator detectors and their geometrical assembly. Results from dedicated experiments with γ-ray sources and quasi-monoenergetic neutron beams are presented. Implications on the instrument capability to perform background suppression based on double kinematic selection are discussed.« less

Application of different spectrophotometric methods for simultaneous determination of elbasvir and grazoprevir in pharmaceutical preparation

NASA Astrophysics Data System (ADS)

Attia, Khalid A. M.; El-Abasawi, Nasr M.; El-Olemy, Ahmed; Abdelazim, Ahmed H.

2018-01-01

The first three UV spectrophotometric methods have been developed of simultaneous determination of two new FDA approved drugs namely; elbasvir and grazoprevir in their combined pharmaceutical dosage form. These methods include simultaneous equation, partial least squares with and without variable selection procedure (genetic algorithm). For simultaneous equation method, the absorbance values at 369 (λmax of elbasvir) and 253 nm (λmax of grazoprevir) have been selected for the formation of two simultaneous equations required for the mathematical processing and quantitative analysis of the studied drugs. Alternatively, the partial least squares with and without variable selection procedure (genetic algorithm) have been applied in the spectra analysis because the synchronous inclusion of many unreal wavelengths rather than by using a single or dual wavelength which greatly increases the precision and predictive ability of the methods. Successfully assay of the drugs in their pharmaceutical formulation has been done by the proposed methods. Statistically comparative analysis for the obtained results with the manufacturing methods has been performed. It is noteworthy to mention that there was no significant difference between the proposed methods and the manufacturing one with respect to the validation parameters.

Evolving methods to combine cognitive and physical training for individuals with mild cognitive impairment: study protocol for a randomized controlled study.

PubMed

Lee, Ya-Yun; Wu, Ching-Yi; Teng, Ching-Hung; Hsu, Wen-Chuin; Chang, Ku-Chou; Chen, Poyu

2016-10-28

Nonpharmacologic interventions, such as cognitive training or physical exercise, are effective in improving cognitive functions for older adults with mild cognitive impairment (MCI). Some researchers have proposed that combining physical exercise with cognitive training may augment the benefits of cognition. However, strong evidence is lacking regarding whether a combined therapy is superior to a single type of training for older adults with MCI. Moreover, which combination approach - combining physical exercise with cognitive training sequentially or simultaneously - is more advantageous for cognitive improvement is not yet clear. This proposed study is designed to clarify these questions. This study is a single-blinded, multicenter, randomized controlled trial. Eighty individuals with MCI will be recruited and randomly assigned to cognitive training (COG), physical exercise training (PE), sequential training (SEQ), and dual-task training (DUAL) groups. The intervention programs will be 90 min/day, 2-3 days/week, for a total of 36 training sessions. The participants in the SEQ group will first perform 45 min of physical exercise followed by 45 min of cognitive training, whereas those in the DUAL group will perform physical exercise and cognitive training simultaneously. Participants will be assessed at baseline, after the intervention, and at 6-month follow-up. The primary cognitive outcome tests will include the Montreal Cognitive Assessment and the color-naming Stroop test. Other outcomes will include assessments that evaluate the cognitive, physical, and daily functions of older adults with MCI. The results of this proposed study will provide important information regarding the feasibility and intervention effects of combining physical exercise and cognitive training for older individuals with MCI. ClinicalTrials.gov Identifier: NCT02512627 , registered on 20 July 2015.

Combination of three angiogenic growth factors has synergistic effects on sprouting of endothelial cell/mesenchymal stem cell-based spheroids in a 3D matrix.

PubMed

Kim, Sook Kyoung; Lee, Jaeyeon; Song, Myeongjin; Kim, Mirim; Hwang, Soon Jung; Jang, Hwanseok; Park, Yongdoo

2016-11-01

Combinations of angiogenic growth factors have been shown to have synergistic effects on angiogenesis and natural wound healing in various animal models. Each growth factor has unique roles during angiogenesis; vascular endothelial growth factor (VEGF) plays a key role during the initial step of angiogenesis, whereas PDGF functions in the maturation of blood vessels. We used a combination of three angiogenic growth factors to increase angiogenesis in vitro and in vivo. We chose VEGF as a basic factor and added platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) to induce angiogenesis in three in vitro and in vivo models: 3D angiogenesis assay, 3D co-culture, and matrigel plug implantation assay. Cell proliferation was significantly higher in co-cultured cells treated with PDGF + VEGF + FGF than in the control, single, or dual combination groups. mRNA expression of α-smooth muscle actin (α-SMA), von Willebrand factor (vWF), and CD105 was higher in the triple group (PDGF + VEGF + FGF) than in control, single, or dual combination groups. In the PDGF + VEGF + FGF group, the length and number of branches of spheroids was also significantly higher than in the control, single, or dual combination groups. Furthermore, in a nude mouse model, α-SMA expression was significantly higher in the PDGF + VEGF + FGF group than in other groups. In conclusion, the addition of PDGF and FGF to VEGF showed synergistic effects on angiogenesis in vitro and in vivo. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1535-1543, 2016. © 2015 Wiley Periodicals, Inc.

A dual Lewis base activation strategy for enantioselective carbene-catalyzed annulations.

PubMed

Izquierdo, Javier; Orue, Ane; Scheidt, Karl A

2013-07-24

A dual activation strategy integrating N-heterocyclic carbene (NHC) catalysis and a second Lewis base has been developed. NHC-bound homoenolate equivalents derived from α,β-unsaturated aldehydes combine with transient reactive o-quinone methides in an enantioselective formal [4 + 3] fashion to access 2-benzoxopinones. The overall approach provides a general blueprint for the integration of carbene catalysis with additional Lewis base activation modes.

A dual-user teleoperation system with Online Authority Adjustment for haptic training.

PubMed

Fei Liu; Leleve, Arnaud; Eberard, Damien; Redarce, Tanneguy

2015-08-01

This paper introduces a dual-user teleoperation system for hands-on medical training. A shared control based architecture is presented for authority management. In this structure, the combination of control signals is obtained using a dominance factor. Its main improvement is Online Authority Adjustment (OAA): the authority can be adjusted manually/automatically during the training progress. Experimental results are provided to validate the performances of the system.

Dual-eligibles with Mental Disorders and Medicare Part D: How are they faring?

PubMed Central

Donohue, Julie M.; Huskamp, Haiden A.; Zuvekas, Samuel H.

2009-01-01

In 2006, 6 million beneficiaries who were dually eligible for Medicare and Medicaid switched from Medicaid to Medicare Part D coverage of their prescription drugs. This change led to a significant expansion of Medicare’s role in financing psychotropic medications for this group. A reduction in the number of plans serving dual-eligibles and an increase in utilization restrictions for some psychotropics since 2006 raises concerns about medication access for dual-eligibles with mental disorders and point to potential problems with adverse selection. To improve access to medication for this population, Medicare might consider changes to the enrollment and risk-sharing systems. PMID:19414883

Dual Energy Method for Breast Imaging: A Simulation Study.

PubMed

Koukou, V; Martini, N; Michail, C; Sotiropoulou, P; Fountzoula, C; Kalyvas, N; Kandarakis, I; Nikiforidis, G; Fountos, G

2015-01-01

Dual energy methods can suppress the contrast between adipose and glandular tissues in the breast and therefore enhance the visibility of calcifications. In this study, a dual energy method based on analytical modeling was developed for the detection of minimum microcalcification thickness. To this aim, a modified radiographic X-ray unit was considered, in order to overcome the limited kVp range of mammographic units used in previous DE studies, combined with a high resolution CMOS sensor (pixel size of 22.5 μm) for improved resolution. Various filter materials were examined based on their K-absorption edge. Hydroxyapatite (HAp) was used to simulate microcalcifications. The contrast to noise ratio (CNR tc ) of the subtracted images was calculated for both monoenergetic and polyenergetic X-ray beams. The optimum monoenergetic pair was 23/58 keV for the low and high energy, respectively, resulting in a minimum detectable microcalcification thickness of 100 μm. In the polyenergetic X-ray study, the optimal spectral combination was 40/70 kVp filtered with 100 μm cadmium and 1000 μm copper, respectively. In this case, the minimum detectable microcalcification thickness was 150 μm. The proposed dual energy method provides improved microcalcification detectability in breast imaging with mean glandular dose values within acceptable levels.

Laparoscopic Transcystic Treatment Biliary Calculi by Laser Lithotripsy

PubMed Central

Jin, Lan; Zhang, Zhongtao

2016-01-01

Background and Objectives: Laparoscopic transcystic common bile duct exploration (LTCBDE) is a complex procedure requiring expertise in laparoscopic and choledochoscopic skills. The purpose of this study was to investigate the safety and feasibility of treating biliary calculi through laparoscopic transcystic exploration of the CBD via an ultrathin choledochoscope combined with dual-frequency laser lithotripsy. Methods: From August 2011 through September 2014, 89 patients at our hospital were treated for cholecystolithiasis with biliary calculi. Patients underwent laparoscopic cholecystectomy and exploration of the CBD via the cystic duct and the choledochoscope instrument channel. A dual-band, dual-pulse laser lithotripsy system was used to destroy the calculi. Two intermittent laser emissions (intensity, 0.12 J; pulse width 1.2 μs; and pulse frequency, 10 Hz) were applied during each contact with the calculi. The stones were washed out by water injection or removed by a stone-retrieval basket. Results: Biliary calculi were removed in 1 treatment in all 89 patients. No biliary tract injury or bile leakage was observed. Follow-up examination with type-B ultrasonography or magnetic resonance cholangiopancreatography 3 months after surgery revealed no instances of retained-calculi–related biliary tract stenosis. Conclusion: The combined use of laparoscopic transcystic CBD exploration by ultrathin choledochoscopy and dual-frequency laser lithotripsy offers an accurate, convenient, safe, effective method of treating biliary calculi. PMID:27904308

Dual Energy Method for Breast Imaging: A Simulation Study

PubMed Central

2015-01-01

Dual energy methods can suppress the contrast between adipose and glandular tissues in the breast and therefore enhance the visibility of calcifications. In this study, a dual energy method based on analytical modeling was developed for the detection of minimum microcalcification thickness. To this aim, a modified radiographic X-ray unit was considered, in order to overcome the limited kVp range of mammographic units used in previous DE studies, combined with a high resolution CMOS sensor (pixel size of 22.5 μm) for improved resolution. Various filter materials were examined based on their K-absorption edge. Hydroxyapatite (HAp) was used to simulate microcalcifications. The contrast to noise ratio (CNRtc) of the subtracted images was calculated for both monoenergetic and polyenergetic X-ray beams. The optimum monoenergetic pair was 23/58 keV for the low and high energy, respectively, resulting in a minimum detectable microcalcification thickness of 100 μm. In the polyenergetic X-ray study, the optimal spectral combination was 40/70 kVp filtered with 100 μm cadmium and 1000 μm copper, respectively. In this case, the minimum detectable microcalcification thickness was 150 μm. The proposed dual energy method provides improved microcalcification detectability in breast imaging with mean glandular dose values within acceptable levels. PMID:26246848

Implantable chemothermal brachytherapy seeds: A synergistic approach to brachytherapy using polymeric dual drug delivery and hyperthermia for malignant solid tumor ablation.

PubMed

Aguilar, Ludwig Erik; Thomas, Reju George; Moon, Myeong Ju; Jeong, Yong Yeon; Park, Chan Hee; Kim, Cheol Sang

2018-08-01

Chemothermal brachytherapy seeds have been developed using a combination of polymeric dual drug chemotherapy and alternating magnetic field induced hyperthermia. The synergistic effect of chemotherapy and hyperthermia brachytherapy has been investigated in a way that has never been performed before, with an in-depth analysis of the cancer cell inhibition property of the new system. A comprehensive in vivo study on athymic mice model with SCC7 tumor has been conducted to determine optimal arrays and specifications of the chemothermal seeds. Dual drug chemotherapy has been achieved via surface deposition of polydopamine that carries bortezomib, and also via loading an acidic pH soluble hydrogel that contains 5-Fluorouracil inside the chemothermal seed; this increases the drug loading capacity of the chemothermal seed, and creates dual drug synergism. An external alternating magnetic field has been utilized to induce hyperthermia conditions, using the inherent ferromagnetic property of the nitinol alloy used as the seed casing. The materials used in this study were fully characterized using FESEM, H 1 NMR, FT-IR, and XPS to validate their properties. This new approach to experimental cancer treatment is a pilot study that exhibits the potential of thermal brachytherapy and chemotherapy as a combined treatment modality. Copyright © 2018 Elsevier B.V. All rights reserved.

The Monitoring and Affinity Purification of Proteins Using Dual Tags with Tetracysteine Motifs

NASA Astrophysics Data System (ADS)

Giannone, Richard J.; Liu, Yie; Wang, Yisong

Identification and characterization of protein-protein interaction networks is essential for the elucidation of biochemical mechanisms and cellular function. Affinity purification in combination with liquid chromatography-tandem mass spectrometry (LC-MS/MS) has emerged as a very powerful tactic for the identification of specific protein-protein interactions. In this chapter, we describe a comprehensive methodology that uses our recently developed dual-tag affinity purification system for the enrichment and identification of mammalian protein complexes. The protocol covers a series of separate but sequentially related techniques focused on the facile monitoring and purification of a dual-tagged protein of interest and its interacting partners via a system built with tetracysteine motifs and various combinations of affinity tags. Using human telomeric repeat binding factor 2 (TRF2) as an example, we demonstrate the power of the system in terms of bait protein recovery after dual-tag affinity purification, detection of bait protein subcellular localization and expression, and successful identification of known and potentially novel TRF2 interacting proteins. Although the protocol described here has been optimized for the identification and characterization of TRF2-associated proteins, it is, in principle, applicable to the study of any other mammalian protein complexes that may be of interest to the research community.

Enhanced efficacy of synergistic combinations of antimicrobial peptides with caspofungin versus Candida albicans in insect and murine models of systemic infection.

PubMed

MacCallum, D M; Desbois, A P; Coote, P J

2013-08-01

The objective of this study was to determine whether combinations of antimicrobial peptides (AMPs) with caspofungin display enhanced antifungal activity versus Candida albicans in vitro and in vivo. Three conventional AMPs that satisfied criteria favouring their potential development as novel antifungals were selected for investigation. Colistin sulphate was also included as a cyclic peptide antibiotic used in the clinic. Minimum inhibitory concentrations (MICs) were determined for each antifungal agent and checkerboard assays were used to determine fractional inhibitory concentration index (FICI) values for dual combinations of AMPs or colistin with caspofungin. Viability assays were performed for the same combinations in order to investigate fungicidal interactions. Synergistic antifungal combinations were then tested for efficacy in vivo and compared to monotherapies in wax moth larva and murine models of systemic C. albicans infection. In combination with caspofungin, each of the AMPs [hMUC7-12, DsS3(1-16), hLF(1-11)] and colistin were synergistic and candidacidal in vitro. The treatment of infected wax moth larvae with combinations of caspofungin with hMUC7-12, DsS3(1-16) or colistin resulted in significant enhancements in survival compared to treatment with monotherapies. Notably, the treatment of C. albicans-infected mice with a combination of caspofungin and DsS3(1-16) resulted in the enhancement of survival compared to groups treated with just the individual agents. This study demonstrates that combination therapies containing caspofungin and AMPs or colistin merit further development as potential novel treatments for C. albicans infections.

Mechanistic switch in dual gold catalysis of diynes: C(sp(3))-H activation through bifurcation--vinylidene versus carbene pathways.

PubMed

Hansmann, Max M; Rudolph, Matthias; Rominger, Frank; Hashmi, A Stephen K

2013-02-25

The other side of the mountain: Changing the framework of diyne systems opens up new cyclization modes for dual gold catalysis. Instead of a 5-endo cyclization and gold vinylidenes a 6-endo cyclization gives rise to gold-stabilized carbenes as key intermediates for selective C-H insertions. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Executive Function Is Necessary for Perspective Selection, Not Level-1 Visual Perspective Calculation: Evidence from a Dual-Task Study of Adults

ERIC Educational Resources Information Center

Qureshi, Adam W.; Apperly, Ian A.; Samson, Dana

2010-01-01

Previous research suggests that perspective-taking and other "theory of mind" processes may be cognitively demanding for adult participants, and may be disrupted by concurrent performance of a secondary task. In the current study, a Level-1 visual perspective task was administered to 32 adults using a dual-task paradigm in which the secondary task…

Dual-polarization airborne lidar for freshwater fisheries management and research

NASA Astrophysics Data System (ADS)

Roddewig, Michael R.; Pust, Nathan J.; Churnside, James H.; Shaw, Joseph A.

2017-03-01

The design of a compact, dual-polarization, nonscanning lidar system intended to fly in a small, single-engine aircraft for airborne study of freshwater marine ecosystems and mapping of fish schools in mountain lakes is discussed. Design trade-offs are presented with special attention paid to selecting the field of view and telescope aperture diameter. Example results and a comparison with a similar existing lidar system are presented.

Dual-Selective and Dual-Enhanced SERS Nanoprobes Strategy for Circulating Hepatocellular Carcinoma Cells Detection.

PubMed

Pang, Yuanfeng; Wang, Chongwen; Xiao, Rui; Sun, Zhiwei

2018-05-11

The detection of hepatocellular carcinoma (HCC) circulating tumor cells (CTCs) from a blood sample can be a very powerful noninvasive approach for the early detection and therapy of liver cancer. However, the extreme rarity of tumor cells in blood containing billions of other cells makes the capture and identification of CTCs with sufficient sensitivity and specificity a real challenge. Here, a magnetically assisted surface-enhanced Raman scattering (SERS) biosensor for HCC CTC detection is reported for the first time. The biosensor consists of two basic elements: anti-ASGPR antibody-Fe 3 O 4 @Ag magnetic nanoparticles and anti-GPC3 antibody-Au@Ag@DTNB nanorods. According to the dual-selectivity of the anti-ASGPR and anti-GPC3 antibodies and the dual-enhancement SERS signal of the MNPs silver shell and the Au@Ag NRs SERS tags, a limit of detection of 1 cell mL -1 for HCC CTC in human peripheral blood samples with a linear relationship from 1 to 100 cells mL -1 can be obtained. The system shows good performance in real serum, which suggests it may be a promising tool for HCC clinical diagnosis. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enhancing venetoclax activity in acute myeloid leukemia by co-targeting MCL1.

PubMed

Teh, T-C; Nguyen, N-Y; Moujalled, D M; Segal, D; Pomilio, G; Rijal, S; Jabbour, A; Cummins, K; Lackovic, K; Blombery, P; Thompson, E; Ekert, P G; Lessene, G; Glaser, S P; Huang, D C S; Roberts, A W; Guthridge, M A; Wei, A H

2018-02-01

Targeted therapies are frequently combined with standard cytotoxic drugs to enhance clinical response. Targeting the B-cell lymphoma 2 (BCL-2) family of proteins is an attractive option to combat chemoresistance in leukemia. Preclinical and clinical studies indicate modest single-agent activity with selective BCL-2 inhibitors (for example, venetoclax). We show that venetoclax synergizes with cytarabine and idarubicin to increase antileukemic efficacy in a TP53-dependent manner. Although TP53 deficiency impaired sensitivity to combined venetoclax and chemotherapy, higher-dose idarubicin was able to suppress MCL1 and induce cell death independently of TP53. Consistent with an MCL1-specific effect, cell death from high-dose idarubicin was dependent on pro-apoptotic Bak. Combining higher-dose idarubicin with venetoclax was able to partially overcome resistance in Bak-deficient cells. Using inducible vectors and venetoclax to differentially target anti-apoptotic BCL-2 family members, BCL-2 and MCL1 emerged as critical and complementary proteins regulating cell survival in acute myeloid leukemia. Dual targeting of BCL-2 and MCL1, but not either alone, prolonged survival of leukemia-bearing mice. In conclusion, our findings support the further investigation of venetoclax in combination with standard chemotherapy, including intensified doses of idarubicin. Venetoclax should also be investigated in combination with direct inhibitors of MCL1 as a chemotherapy-free approach in the future.

A technique for pole-zero placement for dual-input control systems. [computer simulation of CH-47 helicopter longitudinal dynamics

NASA Technical Reports Server (NTRS)

Reid, G. F.

1976-01-01

A technique is presented for determining state variable feedback gains that will place both the poles and zeros of a selected transfer function of a dual-input control system at pre-determined locations in the s-plane. Leverrier's algorithm is used to determine the numerator and denominator coefficients of the closed-loop transfer function as functions of the feedback gains. The values of gain that match these coefficients to those of a pre-selected model are found by solving two systems of linear simultaneous equations. The algorithm has been used in a computer simulation of the CH-47 helicopter to control longitudinal dynamics.

Multi-species trace gas analysis with dual-wavelength quantum cascade laser

NASA Astrophysics Data System (ADS)

Jágerská, Jana; Tuzson, Béla; Looser, Herbert; Jouy, Pierre; Hugi, Andreas; Mangold, Markus; Soltic, Patrik; Faist, Jérôme; Emmenegger, Lukas

2015-04-01

Simultaneous detection of multiple gas species using mid-IR laser spectroscopy is highly appealing for a large variety of applications ranging from air quality monitoring, medical breath analysis to industrial process control. However, state-of-the-art distributed-feedback (DFB) mid-IR lasers are usually tunable only within a narrow spectral range, which generally leads to one-laser-one-compound measurement strategy. Thus, multi-species detection involves several lasers and elaborate beam combining solutions [1]. This makes them bulky, costly, and highly sensitive to optical alignment, which limits their field deployment. In this paper, we explore an alternative measurement concept based on a dual-wavelength quantum cascade laser (DW-QCL) [2]. Such a laser can emit at two spectrally distinct wavelengths using a succession of two DFB gratings with different periodicities and a common waveguide to produce one output beam. The laser design was optimized for NOx measurements and correspondingly emits single-mode at 5.26 and 6.25 μm. Electrical separation of the respective laser sections makes it possible to address each wavelength independently. Thereby, it is possible to detect NO and NO2 species with one laser using the same optical path, without any beam combining optics, i.e. in a compact and cost-efficient single-path optical setup. Operated in a time-division multiplexed mode, the spectrometer reaches detection limits at 100 s averaging of 0.5 and 1.5 ppb for NO2 and NO, respectively. The performance of the system was validated against the well-established chemiluminescence detection while measuring the NOx emissions on an automotive test-bench, as well as monitoring the pollution at a suburban site. [1] B. Tuzson, K. Zeyer, M. Steinbacher, J. B. McManus, D. D. Nelson, M. S. Zahniser, and L. Emmenegger, 'Selective measurements of NO, NO2 and NOy in the free troposphere using quantum cascade laser spectroscopy,' Atmospheric Measurement Techniques 6, 927-936 (2013). [2] J. Jágerská, P. Jouy, A. Hugi, B. Tuzson, H. Looser, M. Mangold, M. Beck, L. Emmenegger, and J. Faist, 'Dual-wavelength quantum cascade laser for trace gas spectroscopy,' Applied Physics Letters 105, 161109-161109-4 (2014).

Investigation of a tubular dual-stator flux-switching permanent-magnet linear generator for free-piston energy converter

NASA Astrophysics Data System (ADS)

Sui, Yi; Zheng, Ping; Tong, Chengde; Yu, Bin; Zhu, Shaohong; Zhu, Jianguo

2015-05-01

This paper describes a tubular dual-stator flux-switching permanent-magnet (PM) linear generator for free-piston energy converter. The operating principle, topology, and design considerations of the machine are investigated. Combining the motion characteristic of free-piston Stirling engine, a tubular dual-stator PM linear generator is designed by finite element method. Some major structural parameters, such as the outer and inner radii of the mover, PM thickness, mover tooth width, tooth width of the outer and inner stators, etc., are optimized to improve the machine performances like thrust capability and power density. In comparison with conventional single-stator PM machines like moving-magnet linear machine and flux-switching linear machine, the proposed dual-stator flux-switching PM machine shows advantages in higher mass power density, higher volume power density, and lighter mover.

Dual-modality imaging

NASA Astrophysics Data System (ADS)

Hasegawa, Bruce; Tang, H. Roger; Da Silva, Angela J.; Wong, Kenneth H.; Iwata, Koji; Wu, Max C.

2001-09-01

In comparison to conventional medical imaging techniques, dual-modality imaging offers the advantage of correlating anatomical information from X-ray computed tomography (CT) with functional measurements from single-photon emission computed tomography (SPECT) or with positron emission tomography (PET). The combined X-ray/radionuclide images from dual-modality imaging can help the clinician to differentiate disease from normal uptake of radiopharmaceuticals, and to improve diagnosis and staging of disease. In addition, phantom and animal studies have demonstrated that a priori structural information from CT can be used to improve quantification of tissue uptake and organ function by correcting the radionuclide data for errors due to photon attenuation, partial volume effects, scatter radiation, and other physical effects. Dual-modality imaging therefore is emerging as a method of improving the visual quality and the quantitative accuracy of radionuclide imaging for diagnosis of patients with cancer and heart disease.

A unified material decomposition framework for quantitative dual- and triple-energy CT imaging.

PubMed

Zhao, Wei; Vernekohl, Don; Han, Fei; Han, Bin; Peng, Hao; Yang, Yong; Xing, Lei; Min, James K

2018-04-21

Many clinical applications depend critically on the accurate differentiation and classification of different types of materials in patient anatomy. This work introduces a unified framework for accurate nonlinear material decomposition and applies it, for the first time, in the concept of triple-energy CT (TECT) for enhanced material differentiation and classification as well as dual-energy CT (DECT). We express polychromatic projection into a linear combination of line integrals of material-selective images. The material decomposition is then turned into a problem of minimizing the least-squares difference between measured and estimated CT projections. The optimization problem is solved iteratively by updating the line integrals. The proposed technique is evaluated by using several numerical phantom measurements under different scanning protocols. The triple-energy data acquisition is implemented at the scales of micro-CT and clinical CT imaging with commercial "TwinBeam" dual-source DECT configuration and a fast kV switching DECT configuration. Material decomposition and quantitative comparison with a photon counting detector and with the presence of a bow-tie filter are also performed. The proposed method provides quantitative material- and energy-selective images examining realistic configurations for both DECT and TECT measurements. Compared to the polychromatic kV CT images, virtual monochromatic images show superior image quality. For the mouse phantom, quantitative measurements show that the differences between gadodiamide and iodine concentrations obtained using TECT and idealized photon counting CT (PCCT) are smaller than 8 and 1 mg/mL, respectively. TECT outperforms DECT for multicontrast CT imaging and is robust with respect to spectrum estimation. For the thorax phantom, the differences between the concentrations of the contrast map and the corresponding true reference values are smaller than 7 mg/mL for all of the realistic configurations. A unified framework for both DECT and TECT imaging has been established for the accurate extraction of material compositions using currently available commercial DECT configurations. The novel technique is promising to provide an urgently needed solution for several CT-based diagnostic and therapy applications, especially for the diagnosis of cardiovascular and abdominal diseases where multicontrast imaging is involved. © 2018 American Association of Physicists in Medicine.

Physiology and silviculture of black walnut for combined timber and nut production

Treesearch

J. W. Van Sambeek; George Rink

1981-01-01

Research literature was reviewed for evidence supporting the management of black walnut plantations for combined timber and nut production. The silviculture of the species is discussed in relation to dual cropping. Stimulation and phenology of flowering and fruiting are reviewed.

Pharmacokinetic drug evaluation of saxagliptin plus dapagliflozin for the treatment of type 2 diabetes.

PubMed

Scheen, André J

2017-05-01

Combining a dipeptidyl peptidase-4 inhibitor and a sodium-glucose cotransporter type 2 inhibitor is an attractive option to treat hyperglycaemia in type 2 diabetes. Areas covered: The saxagliptin plus dapagliflozin combination is carefully analysed, focusing on: 1) pharmacokinetic properties, 2) pharmacodynamics data, and 3) results of randomised controlled trials (dual combination versus either monotherapy, sequential therapy saxagliptin added to dapagliflozin or dapagliflozin added to saxagliptin). Expert opinion: Pharmacokinetic findings demonstrate the absence of drug-drug interaction and the bioequivalence of the FDC compared with separated tablets. Pharmacodynamic observations confirm a complementary mode of action of the two agents. Dual saxagliptin-dapagliflozin therapy is more potent than either monotherapy. It may be used as an initial combination, although this approach remains debatable and should probably be reserved in case of high glycated hemoglobin, or a stepwise strategy, according to a personalized approach. The developed saxagliptin-dapagliflozin FDC may simplify anti-hyperglycemic therapy and improve drug compliance.

Dual-telescope multi-channel thermal-infrared radiometer for outer planet fly-by missions

NASA Astrophysics Data System (ADS)

Aslam, Shahid; Amato, Michael; Bowles, Neil; Calcutt, Simon; Hewagama, Tilak; Howard, Joseph; Howett, Carly; Hsieh, Wen-Ting; Hurford, Terry; Hurley, Jane; Irwin, Patrick; Jennings, Donald E.; Kessler, Ernst; Lakew, Brook; Loeffler, Mark; Mellon, Michael; Nicoletti, Anthony; Nixon, Conor A.; Putzig, Nathaniel; Quilligan, Gerard; Rathbun, Julie; Segura, Marcia; Spencer, John; Spitale, Joseph; West, Garrett

2016-11-01

The design of a versatile dual-telescope thermal-infrared radiometer spanning the spectral wavelength range 8-200 μm, in five spectral pass bands, for outer planet fly-by missions is described. The dual-telescope design switches between a narrow-field-of-view and a wide-field-of-view to provide optimal spatial resolution images within a range of spacecraft encounters to the target. The switchable dual-field-of-view system uses an optical configuration based on the axial rotation of a source-select mirror along the optical axis. The optical design, spectral performance, radiometric accuracy, and retrieval estimates of the instrument are discussed. This is followed by an assessment of the surface coverage performance at various spatial resolutions by using the planned NASA Europa Mission 13-F7 fly-by trajectories as a case study.

Dual-Telescope Multi-Channel Thermal-Infrared Radiometer for Outer Planet Fly-By Missions

NASA Technical Reports Server (NTRS)

Aslam, Shahid; Amato, Michael; Bowles, Neil; Calcutt, Simon; Hewagama, Tilak; Howard, Joseph; Howett, Carly; Hsieh, Wen-Ting; Hurford, Terry; Hurley, Jane;

Are factors related to dual-task performance in people with Parkinson's disease dependent on the type of dual task?

PubMed

Strouwen, Carolien; Molenaar, Esther A L M; Keus, Samyra H J; Münks, Liesbeth; Heremans, Elke; Vandenberghe, Wim; Bloem, Bastiaan R; Nieuwboer, Alice

2016-02-01

Impaired dual-task performance significantly impacts upon functional mobility in people with Parkinson's disease (PD). The aim of this study was to identify determinants of dual-task performance in people with PD in three different dual tasks to assess their possible task-dependency. We recruited 121 home-dwelling patients with PD (mean age 65.93 years; mean disease duration 8.67 years) whom we subjected to regular walking (control condition) and to three dual-task conditions: walking combined with a backwards Digit Span task, an auditory Stroop task and a Mobile Phone task. We measured dual-task gait velocity using the GAITRite mat and dual-task reaction times and errors on the concurrent tasks as outcomes. Motor, cognitive and descriptive variables which correlated to dual-task performance (p < 0.20) were entered into a stepwise forward multiple linear regression model. Single-task gait velocity and executive function, tested by the alternating intake test, was significantly associated with gait velocity during the Digit Span (R(2) = 0.65; p < 0.001), the Stroop (R(2) = 0.73; p < 0.001) and the Mobile Phone task (R(2) = 0.62; p < 0.001). In addition, disease severity proved correlated to gait velocity during the Stroop task. Age was a surplus determinant of gait velocity while using a mobile phone. Single-task gait velocity and executive function as measured by a verbal fluency switching task were independent determinants of dual-task gait performance in people with PD. In contrast to expectation, these factors were the same across different tasks, supporting the robustness of the findings. Future study needs to determine whether these factors predict dual-task abnormalities prospectively. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of gas flow rate on the etch characteristics of a low- k sicoh film with an amorphous carbon mask in dual-frequency CF4/C4F8/Ar capacitively-coupled plasmas

NASA Astrophysics Data System (ADS)

Kwon, Bong-Soo; Lee, Hea-Lim; Lee, Nae-Eung; Kim, Chang-Young; Choi, Chi Kyu

2013-01-01

Highly selective nanoscale etching of a low-dielectric constant (low- k) organosilicate (SiCOH) layer using a mask pattern of chemical-vapor-deposited (CVD) amorphous carbon layer (ACL) was carried out in CF4/C4F8/Ar dual-frequency superimposed capacitively-coupled plasmas. The etching characteristics of the SiCOH layers, such as the etch rate, etch selectivity, critical dimension (CD), and line edge roughness (LER) during the plasma etching, were investigated by varying the C4F8 flow rate. The C4F8 gas flow rate primarily was found to control the degree of polymerization and to cause variations in the selectivity, CD and LER of the patterned SiCOH layer. Process windows for ultra-high etch selectivity of the SiCOH layer to the CVD ACL are formed due to the disproportionate degrees of polymerization on the SiCOH and the ACL surfaces.

Anisotropic selective etching between SiGe and Si

NASA Astrophysics Data System (ADS)

Ishii, Yohei; Scott-McCabe, Ritchie; Yu, Alex; Okuma, Kazumasa; Maeda, Kenji; Sebastian, Joseph; Manos, Jim

2018-06-01

In Si/SiGe dual-channel FinFETs, it is necessary to simultaneously control the etched amounts of SiGe and Si. However, the SiGe etch rate is higher than the Si etch rate in not only halogen plasmas but also physical sputtering. In this study, we found that hydrogen plasma selectively etches Si over SiGe. The result shows that the selectivity of Si over SiGe can be up to 38 with increasing Ge concentration in SiGe. Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) results indicate that hydrogen selectively bonds with Si rather than with Ge in SiGe. During the etching, hydrogen-induced Si surface segregation is also observed. It is also observed that the difference in etched amount between SiGe and Si can be controlled from positive to negative values even in Si/SiGe dual-channel fin patterning while maintaining the vertical profiles. Furthermore, no plasma-induced lattice damage was observed by transmission electron microscopy for both Si and SiGe fin sidewalls.

The cytoplasmic prolyl-tRNA synthetase of the malaria parasite is a dual-stage target of febrifugine and its analogs.

PubMed

Herman, Jonathan D; Pepper, Lauren R; Cortese, Joseph F; Estiu, Guillermina; Galinsky, Kevin; Zuzarte-Luis, Vanessa; Derbyshire, Emily R; Ribacke, Ulf; Lukens, Amanda K; Santos, Sofia A; Patel, Vishal; Clish, Clary B; Sullivan, William J; Zhou, Huihao; Bopp, Selina E; Schimmel, Paul; Lindquist, Susan; Clardy, Jon; Mota, Maria M; Keller, Tracy L; Whitman, Malcolm; Wiest, Olaf; Wirth, Dyann F; Mazitschek, Ralph

2015-05-20

The emergence of drug resistance is a major limitation of current antimalarials. The discovery of new druggable targets and pathways including those that are critical for multiple life cycle stages of the malaria parasite is a major goal for developing next-generation antimalarial drugs. Using an integrated chemogenomics approach that combined drug resistance selection, whole-genome sequencing, and an orthogonal yeast model, we demonstrate that the cytoplasmic prolyl-tRNA (transfer RNA) synthetase (PfcPRS) of the malaria parasite Plasmodium falciparum is a biochemical and functional target of febrifugine and its synthetic derivative halofuginone. Febrifugine is the active principle of a traditional Chinese herbal remedy for malaria. We show that treatment with febrifugine derivatives activated the amino acid starvation response in both P. falciparum and a transgenic yeast strain expressing PfcPRS. We further demonstrate in the Plasmodium berghei mouse model of malaria that halofuginol, a new halofuginone analog that we developed, is active against both liver and asexual blood stages of the malaria parasite. Halofuginol, unlike halofuginone and febrifugine, is well tolerated at efficacious doses and represents a promising lead for the development of dual-stage next-generation antimalarials. Copyright © 2015, American Association for the Advancement of Science.

Isotherm ranking and selection using thirteen literature datasets involving hydrophobic organic compounds.

PubMed

Matott, L Shawn; Jiang, Zhengzheng; Rabideau, Alan J; Allen-King, Richelle M

2015-01-01

Numerous isotherm expressions have been developed for describing sorption of hydrophobic organic compounds (HOCs), including "dual-mode" approaches that combine nonlinear behavior with a linear partitioning component. Choosing among these alternative expressions for describing a given dataset is an important task that can significantly influence subsequent transport modeling and/or mechanistic interpretation. In this study, a series of numerical experiments were undertaken to identify "best-in-class" isotherms by refitting 10 alternative models to a suite of 13 previously published literature datasets. The corrected Akaike Information Criterion (AICc) was used for ranking these alternative fits and distinguishing between plausible and implausible isotherms for each dataset. The occurrence of multiple plausible isotherms was inversely correlated with dataset "richness", such that datasets with fewer observations and/or a narrow range of aqueous concentrations resulted in a greater number of plausible isotherms. Overall, only the Polanyi-partition dual-mode isotherm was classified as "plausible" across all 13 of the considered datasets, indicating substantial statistical support consistent with current advances in sorption theory. However, these findings are predicated on the use of the AICc measure as an unbiased ranking metric and the adoption of a subjective, but defensible, threshold for separating plausible and implausible isotherms. Copyright © 2015 Elsevier B.V. All rights reserved.

No Significant Endothelial Apoptosis in the Radiation-Induced Gastrointestinal Syndrome

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

Schuller, Bradley W.; Rogers, Arlin B.; Cormier, Kathleen S.

2007-05-01

Purpose: This report addresses the incidence of vascular endothelial cell apoptosis in the mouse small intestine in relation to the radiation-induced gastrointestinal (GI) syndrome. Methods and Materials: Nonanesthetized mice received whole-body irradiation at doses above and below the threshold for death from the GI syndrome with 250 kVp X-rays, {sup 137}Cs gamma rays, epithermal neutrons alone, or a unique approach for selective vascular irradiation using epithermal neutrons in combination with boronated liposomes that are restricted to the blood. Both terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining for apoptosis and dual-fluorescence staining for apoptosis and endothelial cells were carriedmore » out in jejunal cross-sections at 4 h postirradiation. Results: Most apoptotic cells were in the crypt epithelium. The number of TUNEL-positive nuclei per villus was low (1.62 {+-} 0.03, mean {+-} SEM) for all irradiation modalities and showed no dose-response as a function of blood vessel dose, even as the dose crossed the threshold for death from the GI syndrome. Dual-fluorescence staining for apoptosis and endothelial cells verified the TUNEL results and identified the apoptotic nuclei in the villi as CD45-positive leukocytes. Conclusion: These data do not support the hypothesis that vascular endothelial cell apoptosis is the cause of the GI syndrome.« less

Toward Fourier interferometry fluorescence excitation/emission imaging of malignant cells combined with photoacoustic microscopy

NASA Astrophysics Data System (ADS)

Kohen, Elli; Hirschberg, Joseph G.; Berry, John P.; Ozkutuk, Nuri; Ornek, Ceren; Monti, Marco; Leblanc, Roger M.; Schachtschabel, Dietrich O.; Haroon, Sumaira

2003-10-01

Dual excitation fluorescence imaging has been used as a first step towards multi-wavelength excitation/emission fluorescence spectral imaging. Target cells are transformed keratinocytes, and other osteosarcoma, human breast and color cancer cells. Mitochondrial membrane potential probes, e.g. TMRM (tetramethylrhodamine methyl ester), Mitotracker Green (Molecular Probes, Inc., Eugene OR,USA; a recently synthesized mitochondrial oxygen probe, [PRE,P1"- pyrene butyl)-2-rhodamine ester] allow dual excitation in the UV plus in teh blue-green spectral regions. Also, using the natural endogenous probe NAD(P)H, preliminary results indicate mitochondrial responses to metabolic challenges (e.g. glucose addition), plus changes in mitochonrial distribution and morphology. In terms of application to biomedicine (for diagnostiscs, prognostsics and drug trials) three parameters have been selected in addition to the natural probe NAD(P)H, i.e. vital fluorescence probing of mitochondria, lysosomes and Golgi apparatus. It is hoped that such a multiparameter approach will allow malignant cell characterization and grading. A new area being introduced is the use of similar methodology for biotechnical applications such as the study of the hydrogen-producing alga Chlamydomonas Reinhardtii, and possible agricultural applications, such as Saccharomyces yeast for oenology. Complementation by Photoacoustic Microscopy is also contemplated, to study the internal conversion component which follows the excitation by photons.

Physicians' engagement in dual practices and the effects on labor supply in public hospitals: results from a register-based study.

PubMed

Johannessen, Karl-Arne; Hagen, Terje P

2014-07-10

Physician dual practice, a combination of public and private practice, has attracted attention due to fear of reduced work supply and a lack of key personnel in the public system, increase in low priority treatments, and conflicts of interest for physicians who may be competing for their own patients when working for private suppliers. In this article, we analyze both choice of dual practice among hospital physicians and the dual practices' effect on work supply in public hospitals. The sample consisted of 12,399 Norwegian hospital physicians working in public hospitals between 2001 and 2009. We linked hospital registry data on salaries and hospital working hours with data from national income and other registries covering non-hospital income, including income from dual work, cohabiting status, childbirths and socioeconomic characteristics. Our dataset also included hospital variables describing i.e. workload. We estimated odds ratio for choosing dual practice and the effects of dual practice on public working hours using different versions of mixed models. The percentage of physicians engaged in dual practice fell from 35.1% for men and 17.6% for women in 2001 to 25.0% and 14.2%, respectively, in 2009. For both genders, financial debt and interest payments were positively correlated and having a newborn baby was negatively correlated with engaging in dual practice. Larger family size and being cohabitating increased the odds ratio of dual practice among men but reduced it for women. The most significant internal hospital factor for choosing dual practice was high wages for extended working hours, which significantly reduced the odds ratio for dual practice. The total working hours in public hospitals were similar for both those who did and did not engage in dual practice; however, dual practice reduced public working hours in some specialties. Economic factors followed by family variables are significant elements influencing dual practice. Although our findings indicate that engagement in dual practice by public hospital physicians in a well-regulated market may increase the total labor supply, this may vary significantly between medical specialties.

Physicians’ engagement in dual practices and the effects on labor supply in public hospitals: results from a register-based study

PubMed Central

2014-01-01

Background Physician dual practice, a combination of public and private practice, has attracted attention due to fear of reduced work supply and a lack of key personnel in the public system, increase in low priority treatments, and conflicts of interest for physicians who may be competing for their own patients when working for private suppliers. In this article, we analyze both choice of dual practice among hospital physicians and the dual practices’ effect on work supply in public hospitals. Methods The sample consisted of 12,399 Norwegian hospital physicians working in public hospitals between 2001 and 2009. We linked hospital registry data on salaries and hospital working hours with data from national income and other registries covering non-hospital income, including income from dual work, cohabiting status, childbirths and socioeconomic characteristics. Our dataset also included hospital variables describing i.e. workload. We estimated odds ratio for choosing dual practice and the effects of dual practice on public working hours using different versions of mixed models. Results The percentage of physicians engaged in dual practice fell from 35.1% for men and 17.6% for women in 2001 to 25.0% and 14.2%, respectively, in 2009. For both genders, financial debt and interest payments were positively correlated and having a newborn baby was negatively correlated with engaging in dual practice. Larger family size and being cohabitating increased the odds ratio of dual practice among men but reduced it for women. The most significant internal hospital factor for choosing dual practice was high wages for extended working hours, which significantly reduced the odds ratio for dual practice. The total working hours in public hospitals were similar for both those who did and did not engage in dual practice; however, dual practice reduced public working hours in some specialties. Conclusion Economic factors followed by family variables are significant elements influencing dual practice. Although our findings indicate that engagement in dual practice by public hospital physicians in a well-regulated market may increase the total labor supply, this may vary significantly between medical specialties. PMID:25011448

Comparison of pulsed dye laser versus combined pulsed dye laser and Nd:YAG laser in the treatment of inflammatory acne vulgaris.

PubMed

Salah El Din, Manal Mohamed; Samy, Nevien Ahmed; Salem, Amira Eid

2017-06-01

Both pulsed dye laser and combined 585/1064-nm (sequential dual-wavelength PDL and Nd:YAG) laser improves inflammatory skin disorders including acne vulgaris. To compare the efficacy of 585-nm pulsed dye laser versus sequential dual-wavelength PDL and Nd:YAG in treatment of acne vulgaris. Thirty patients with acne vulgaris were treated by PDL alone on half of the face while contra lateral half was treated by combined 585/1064 nm laser. The study showed that inflammatory acne lesions count was significantly reduced by 82.5% (p 0.0001) on PDL sides and by 83.5% (p 0.00001) on combined 585/1064-nm side after 8 weeks, while reduction of non-inflammatory acne lesions was observed at 8 weeks by 58.4% and 71.5% respectively. However, difference between the two modalities was not statistically significant. PDL and combined PDL/Nd:YAG laser treatment were found to be an effective, safe and well-tolerated treatment option for inflammatory and non-inflammatory acne vulgaris.

Safety and efficacy of neratinib in combination with weekly paclitaxel and trastuzumab in women with metastatic HER2‑positive breast cancer: an NSABP Foundation Research Program phase I study.

PubMed

Jankowitz, Rachel C; Abraham, Jame; Tan, Antoinette R; Limentani, Steven A; Tierno, Marni B; Adamson, Laura M; Buyse, Marc; Wolmark, Norman; Jacobs, Samuel A

2013-12-01

Neratinib is an oral, small-molecule inhibitor that irreversibly binds to pan-HER (ErbB) receptor tyrosine kinases. Studies suggest that dual anti-HER therapies utilized in breast cancer patients are more efficacious than single agents in both the metastatic and neoadjuvant settings. In this phase I study, neratinib was combined with trastuzumab and paclitaxel in metastatic HER2-positive patients. Twenty-one patients entered this dose-escalation study to determine the maximum-tolerated dose, safety, and efficacy of neratinib (120 up to 240 mg/day) with trastuzumab (4 mg/kg IV loading dose, then 2 mg/kg IV weekly), and paclitaxel (80 mg/m(2) IV days 1, 8, and 15 of a 28-day cycle) in women with HER2-positive metastatic breast cancer previously treated with anti-HER agent(s) and a taxane. The recommended phase II dose of neratinib with trastuzumab and paclitaxel was 200 mg/day. Common grade 3/4 adverse events were diarrhea (38 %), dehydration (14 %), electrolyte imbalance (19 %), and fatigue (19 %). With mandated primary diarrheal prophylaxis, ≥grade 3 diarrhea was not observed. Objective responses, complete (CR) and partial (PR), occurred in eight patients (38 %), with a clinical benefit of CR + PR+ stable disease (SD) ≥24 weeks in 11 patients (52 %). Median time-to-disease progression was 3.7 months. Dual anti-HER blockade with neratinib and trastuzumab resulted in significant clinical benefit despite prior exposure to trastuzumab, lapatinib, T-DM1, a taxane, and multiple lines of chemotherapy. In selected populations, inhibiting multiple ErbB-family receptors may be more advantageous than single-agent inhibition. Based on favorable tolerance and efficacy, this three-drug combination will be further assessed in a randomized phase II neoadjuvant trial (NSABP FB-7:NCT01008150).

Analysis of space systems for the space disposal of nuclear waste follow-on study. Volume 2. Technical report

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

None

1982-01-01

Some of the conclusions reached as a result of this study are summarized. Waste form parameters for the reference cermet waste form are available only by analogy. Detail design of the waste payload would require determination of actual waste form properties. The billet configuration constraints for the cermet waste form limit the packing efficiency to slightly under 75% net volume. The effect of this packing inefficiency in reducing the net waste form per waste payload can be seen graphically. The cermet waste form mass per unit mass of waste payload is lower than that of the iodine waste form evenmore » though the cermet has a higher density (6.5 versus 5.5). This is because the lead iodide is cast achieving almost 100% efficiency in packing. This inefficiency in the packing of the cermet results in a 20% increase in number of flights which increases both cost and risk. Alternative systems for waste mixes requiring low flight rates (technetium-99, iodine-129) can make effective use of the existing 65K space transportation system in either single- or dual-launch scenarios. A comprehensive trade study would be required to select the optimum orbit transfer system for low-launch-rate systems. This study was not conducted as part of the present effort due to selection of the cermet waste form as the reference for the study. Several candidates look attractive for both single- and dual-launch systems (see sec. 4.4), but due to the relatively small number of missions, a comprehensive comparison of life cycle costs including DDT and E would be required to select the best system. The reference system described in sections 5.0, 6.0, 7.0, and 8.0 offers the best combination of cost, risk, and alignment with ongoing NASA technology development efforts for disposal of the reference cermet waste form.« less

Neuroticism related differences in the functional neuroanatomical correlates of multitasking. An fMRI study.

PubMed

Szameitat, Andre J; Saylik, Rahmi; Parton, Andrew

2016-12-02

It is known that neuroticism impairs cognitive performance mostly in difficult tasks, but not so much in easier tasks. One pervasive situation of this type is multitasking, in which the combination of two simple tasks creates a highly demanding dual-task, and consequently high neurotics show higher dual-task costs than low neurotics. However, the functional neuroanatomical correlates of these additional performance impairments in high neurotics are unknown. To test for this, we assessed brain activity by means of functional magnetic resonance imaging (fMRI) in 17 low and 15 high neurotics while they were performing a demanding dual-task and the less demanding component tasks as single-tasks. Behavioural results showed that performance (response times and error rates) was lower in the dual-task than in the single-tasks (dual-task costs), and that these dual-task costs were significantly higher in high neurotics. Imaging data showed that high neurotics showed less dual-task specific activation in lateral (mainly middle frontal gyrus) and medial prefrontal cortices. We conclude that high levels of neuroticism impair behavioural performance in demanding tasks, and that this impairment is accompanied by reduced activation of the task-associated brain areas. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Monoamine Reuptake Inhibitors in Parkinson's Disease

PubMed Central

Huot, Philippe; Fox, Susan H.; Brotchie, Jonathan M.

2015-01-01

The motor manifestations of Parkinson's disease (PD) are secondary to a dopamine deficiency in the striatum. However, the degenerative process in PD is not limited to the dopaminergic system and also affects serotonergic and noradrenergic neurons. Because they can increase monoamine levels throughout the brain, monoamine reuptake inhibitors (MAUIs) represent potential therapeutic agents in PD. However, they are seldom used in clinical practice other than as antidepressants and wake-promoting agents. This review article summarises all of the available literature on use of 50 MAUIs in PD. The compounds are divided according to their relative potency for each of the monoamine transporters. Despite wide discrepancy in the methodology of the studies reviewed, the following conclusions can be drawn: (1) selective serotonin transporter (SERT), selective noradrenaline transporter (NET), and dual SERT/NET inhibitors are effective against PD depression; (2) selective dopamine transporter (DAT) and dual DAT/NET inhibitors exert an anti-Parkinsonian effect when administered as monotherapy but do not enhance the anti-Parkinsonian actions of L-3,4-dihydroxyphenylalanine (L-DOPA); (3) dual DAT/SERT inhibitors might enhance the anti-Parkinsonian actions of L-DOPA without worsening dyskinesia; (4) triple DAT/NET/SERT inhibitors might exert an anti-Parkinsonian action as monotherapy and might enhance the anti-Parkinsonian effects of L-DOPA, though at the expense of worsening dyskinesia. PMID:25810948

An efficient platform for genetic selection and screening of gene switches in Escherichia coli

PubMed Central

Muranaka, Norihito; Sharma, Vandana; Nomura, Yoko; Yokobayashi, Yohei

2009-01-01

Engineered gene switches and circuits that can sense various biochemical and physical signals, perform computation, and produce predictable outputs are expected to greatly advance our ability to program complex cellular behaviors. However, rational design of gene switches and circuits that function in living cells is challenging due to the complex intracellular milieu. Consequently, most successful designs of gene switches and circuits have relied, to some extent, on high-throughput screening and/or selection from combinatorial libraries of gene switch and circuit variants. In this study, we describe a generic and efficient platform for selection and screening of gene switches and circuits in Escherichia coli from large libraries. The single-gene dual selection marker tetA was translationally fused to green fluorescent protein (gfpuv) via a flexible peptide linker and used as a dual selection and screening marker for laboratory evolution of gene switches. Single-cycle (sequential positive and negative selections) enrichment efficiencies of >7000 were observed in mock selections of model libraries containing functional riboswitches in liquid culture. The technique was applied to optimize various parameters affecting the selection outcome, and to isolate novel thiamine pyrophosphate riboswitches from a complex library. Artificial riboswitches with excellent characteristics were isolated that exhibit up to 58-fold activation as measured by fluorescent reporter gene assay. PMID:19190095

Evaluating Drug Cost per Response with SGLT2 Inhibitors in Patients with Type 2 Diabetes Mellitus.

PubMed

Lopez, Janice M S; Macomson, Brian; Ektare, Varun; Patel, Dipen; Botteman, Marc

2015-09-01

The sodium-glucose cotransporter 2 (SGLT2) inhibitors, which include canagliflozin, dapagliflozin, and empagliflozin, represent a new class of antihyperglycemic agents. Few studies have assessed their cost per response, with "cost per response" being the total cost of a select drug, divided by the resulting change in glycated hemoglobin (HbA1c) levels. To examine the drug cost of SGLT2 inhibitors per a reduction in placebo-adjusted 1% HbA1c in patients with type 2 diabetes mellitus who received treatment during 26 weeks with canagliflozin, dapagliflozin, or empagliflozin. The drug cost per response for each of the 3 agents individually was assessed based on data from a subset of clinical trials discussed in the prescribing information for each drug that were all placebo-controlled studies evaluating each drug as monotherapy, dual therapy (combined with metformin), and triple therapy (combined with metformin and a sulfonylurea) in patients with uncontrolled, type 2 diabetes mellitus. The US 2015 wholesale acquisition cost for each drug was used to calculate each drug's treatment costs over 26 weeks. The average cost per response for each drug was defined as the prescription drug cost of each SGLT2 inhibitor, divided by the average, placebo-adjusted HbA1c reduction at 26 weeks. The drug cost per unit dose was the same for canagliflozin (100 mg or 300 mg), dapagliflozin (5 mg or 10 mg), and empagliflozin (10 mg or 25 mg), at $11.43. The drug cost per placebo-adjusted 1% HbA1c reduction varied by agent and by dose, as a result of the differences in the treatment responses for each of the 3 drugs. The costs per response for canagliflozin 100 mg as monotherapy, dual therapy, and triple therapy regimens ranged from $2286 to $3355, and for canagliflozin 300 mg, from $1793 to $2702. The costs per response for dapagliflozin 5 mg as monotherapy and dual therapy (triple therapy was not available at the time of the study) ranged from $4161 to $5201; the cost for dapagliflozin 10 mg ranged from $2972 to $4161. The costs per response for empagliflozin 10 mg ranged from $2972 to $3467 across the monotherapy, dual therapy, and triple therapy regimens; the cost for empagliflozin 25 mg ranged from $2311 to $3467. Simple analyses, such as the drug cost per placebo-adjusted 1% reduction in HbA1c, may be useful when considering the addition of antihyperglycemic agents to the health plan's formulary.

Dual PI3K/mTOR inhibitors, GSK2126458 and PKI-587, suppress tumor progression and increase radiosensitivity in nasopharyngeal carcinoma.

PubMed

Liu, Tongxin; Sun, Quanquan; Li, Qi; Yang, Hua; Zhang, Yuqin; Wang, Rong; Lin, Xiaoshan; Xiao, Dong; Yuan, Yawei; Chen, Longhua; Wang, Wei

2015-02-01

Although combined chemoradiotherapy has provided considerable improvements for nasopharyngeal carcinoma (NPC), recurrence and metastasis are still frequent. The PI3K/Akt/mTOR pathway plays a critical role in tumor formation and tumor cell survival after radiation-induced DNA damage. In the present study, we evaluated whether inhibition of PI3K/mTOR by two novel dual inhibitors, GSK2126458 and PKI-587, could suppress tumor progression and sensitize NPC cells to radiation. Four NPC cell lines (CNE-1, CNE-2, 5-8F, and 6-10B) were used to analyze the effects of GSK216458 and PKI-587 on cell proliferation, migration, invasion, clonogenic survival, amount of residual γ-H2AX foci, cell cycle, and apoptosis after radiation. A 5-8F xenograft model was used to evaluate the in vivo effects of the two compounds in combination with ionizing radiation (IR). Both GSK216458 and PKI-587 effectively inhibited cell proliferation and motility in NPC cells and suppressed phosphorylation of Akt, mTOR, S6, and 4EBP1 proteins in a concentration- and time-dependent manner. Moreover, both compounds sensitized NPC cells to IR by increasing DNA damage, enhancing G2-M cell-cycle delay, and inducing apoptosis. In vivo, the combination of IR with GSK2126458 or PKI-587 significantly inhibited tumor growth. Antitumor effect was correlated with induction of apoptosis and suppression of the phosphorylation of mTOR, Akt, and 4EBP1. These new findings suggest the usefulness of PI3K/mTOR dual inhibition for antitumor and radiosensitizing. The combination of IR with a dual PI3K/mTOR inhibitor, GSK2126458 or PKI-587, might be a promising therapeutic strategy for NPC. ©2014 American Association for Cancer Research.

Influence of Sequential vs. Simultaneous Dual-Task Exercise Training on Cognitive Function in Older Adults.

PubMed

Tait, Jamie L; Duckham, Rachel L; Milte, Catherine M; Main, Luana C; Daly, Robin M

2017-01-01

Emerging research indicates that exercise combined with cognitive training may improve cognitive function in older adults. Typically these programs have incorporated sequential training, where exercise and cognitive training are undertaken separately. However, simultaneous or dual-task training, where cognitive and/or motor training are performed simultaneously with exercise, may offer greater benefits. This review summary provides an overview of the effects of combined simultaneous vs. sequential training on cognitive function in older adults. Based on the available evidence, there are inconsistent findings with regard to the cognitive benefits of sequential training in comparison to cognitive or exercise training alone. In contrast, simultaneous training interventions, particularly multimodal exercise programs in combination with secondary tasks regulated by sensory cues, have significantly improved cognition in both healthy older and clinical populations. However, further research is needed to determine the optimal characteristics of a successful simultaneous training program for optimizing cognitive function in older people.

An NLRA Transducer for Dual Use Bone Conduction Audio and Haptic Communication. Summary Report

DTIC Science & Technology

2016-12-30

VIBRANT COMPOSITES INC. 1 A16-019 Phase 1 Summary Report Vibrant Composites Inc. December 30, 2016 I. ABSTRACT A combined transducer capable of bone ...transducer core capable of both precise haptic communication and high fidelity bone conduction audio. The transducer design leverages Micro-Multilayer...head-mounted system. In this Phase I SBIR, Vibrant Composites has delivered functional dual-mode bone conduction and vibrotactile transducer prototypes

Optical levitation particle delivery system for a dual beam fiber optic trap.

PubMed

Gauthier, R C; Frangioudakis, A

2000-01-01

We combine a radiation-pressure-based levitation system with a dual fiber, laser trapping system to demonstrate the potential of delivering single particles into the fiber trap. The forces versus position and the trajectory of the particle subjected to the laser beams are examined with an enhanced ray optics model. A sequence of video images taken from the experimental apparatus demonstrates the principle of particle delivery, trapping, and further manipulation.

Can machine learning complement traditional medical device surveillance? A case study of dual-chamber implantable cardioverter–defibrillators

PubMed Central

Ross, Joseph S; Bates, Jonathan; Parzynski, Craig S; Akar, Joseph G; Curtis, Jeptha P; Desai, Nihar R; Freeman, James V; Gamble, Ginger M; Kuntz, Richard; Li, Shu-Xia; Marinac-Dabic, Danica; Masoudi, Frederick A; Normand, Sharon-Lise T; Ranasinghe, Isuru; Shaw, Richard E; Krumholz, Harlan M

2017-01-01

Background Machine learning methods may complement traditional analytic methods for medical device surveillance. Methods and results Using data from the National Cardiovascular Data Registry for implantable cardioverter–defibrillators (ICDs) linked to Medicare administrative claims for longitudinal follow-up, we applied three statistical approaches to safety-signal detection for commonly used dual-chamber ICDs that used two propensity score (PS) models: one specified by subject-matter experts (PS-SME), and the other one by machine learning-based selection (PS-ML). The first approach used PS-SME and cumulative incidence (time-to-event), the second approach used PS-SME and cumulative risk (Data Extraction and Longitudinal Trend Analysis [DELTA]), and the third approach used PS-ML and cumulative risk (embedded feature selection). Safety-signal surveillance was conducted for eleven dual-chamber ICD models implanted at least 2,000 times over 3 years. Between 2006 and 2010, there were 71,948 Medicare fee-for-service beneficiaries who received dual-chamber ICDs. Cumulative device-specific unadjusted 3-year event rates varied for three surveyed safety signals: death from any cause, 12.8%–20.9%; nonfatal ICD-related adverse events, 19.3%–26.3%; and death from any cause or nonfatal ICD-related adverse event, 27.1%–37.6%. Agreement among safety signals detected/not detected between the time-to-event and DELTA approaches was 90.9% (360 of 396, k=0.068), between the time-to-event and embedded feature-selection approaches was 91.7% (363 of 396, k=−0.028), and between the DELTA and embedded feature selection approaches was 88.1% (349 of 396, k=−0.042). Conclusion Three statistical approaches, including one machine learning method, identified important safety signals, but without exact agreement. Ensemble methods may be needed to detect all safety signals for further evaluation during medical device surveillance. PMID:28860874

Comparative study between recent methods manipulating ratio spectra and classical methods based on two-wavelength selection for the determination of binary mixture of antazoline hydrochloride and tetryzoline hydrochloride.

PubMed

Abdel-Halim, Lamia M; Abd-El Rahman, Mohamed K; Ramadan, Nesrin K; El Sanabary, Hoda F A; Salem, Maissa Y

2016-04-15

A comparative study was developed between two classical spectrophotometric methods (dual wavelength method and Vierordt's method) and two recent methods manipulating ratio spectra (ratio difference method and first derivative of ratio spectra method) for simultaneous determination of Antazoline hydrochloride (AN) and Tetryzoline hydrochloride (TZ) in their combined pharmaceutical formulation and in the presence of benzalkonium chloride as a preservative without preliminary separation. The dual wavelength method depends on choosing two wavelengths for each drug in a way so that the difference in absorbance at those two wavelengths is zero for the other drug. While Vierordt's method, is based upon measuring the absorbance and the absorptivity values of the two drugs at their λ(max) (248.0 and 219.0 nm for AN and TZ, respectively), followed by substitution in the corresponding Vierordt's equation. Recent methods manipulating ratio spectra depend on either measuring the difference in amplitudes of ratio spectra between 255.5 and 269.5 nm for AN and 220.0 and 273.0 nm for TZ in case of ratio difference method or computing first derivative of the ratio spectra for each drug then measuring the peak amplitude at 250.0 nm for AN and at 224.0 nm for TZ in case of first derivative of ratio spectrophotometry. The specificity of the developed methods was investigated by analyzing different laboratory prepared mixtures of the two drugs. All methods were applied successfully for the determination of the selected drugs in their combined dosage form proving that the classical spectrophotometric methods can still be used successfully in analysis of binary mixture using minimal data manipulation rather than recent methods which require relatively more steps. Furthermore, validation of the proposed methods was performed according to ICH guidelines; accuracy, precision and repeatability are found to be within the acceptable limits. Statistical studies showed that the methods can be competitively applied in quality control laboratories. Copyright © 2016 Elsevier B.V. All rights reserved.

A fluoride-sensing receptor based on 2,2'-bis(indolyl)methane by dual-function of colorimetry and fluorescence.

PubMed

Wei, Wei; Shao, Shi Jun; Guo, Yong

2015-10-05

A compound based on 2,2'-bis(indolyl)methane containing nitro group was studied as a new anion receptor. It could recognize selectively F(-) by an increasing fluorescence signal and a visible color change from colorless to blue. The introduction of nitro group induced the spectral dual-function related to the deprotonation of N-H protons. Copyright © 2015 Elsevier B.V. All rights reserved.

Reduced auditory processing capacity during vocalization in children with Selective Mutism.

PubMed

Arie, Miri; Henkin, Yael; Lamy, Dominique; Tetin-Schneider, Simona; Apter, Alan; Sadeh, Avi; Bar-Haim, Yair

2007-02-01

Because abnormal Auditory Efferent Activity (AEA) is associated with auditory distortions during vocalization, we tested whether auditory processing is impaired during vocalization in children with Selective Mutism (SM). Participants were children with SM and abnormal AEA, children with SM and normal AEA, and normally speaking controls, who had to detect aurally presented target words embedded within word lists under two conditions: silence (single task), and while vocalizing (dual task). To ascertain specificity of auditory-vocal deficit, effects of concurrent vocalizing were also examined during a visual task. Children with SM and abnormal AEA showed impaired auditory processing during vocalization relative to children with SM and normal AEA, and relative to control children. This impairment is specific to the auditory modality and does not reflect difficulties in dual task per se. The data extends previous findings suggesting that deficient auditory processing is involved in speech selectivity in SM.

Phenformin-Induced Mitochondrial Dysfunction Sensitizes Hepatocellular Carcinoma for Dual Inhibition of mTOR.

PubMed

Veiga, Sonia Rosa; Ge, Xuemei; Mercer, Carol A; Hernández-Alvarez, María Isabel; Thomas, Hala Elnakat; Hernández-Losa, Javier; Ramón Y Cajal, Santiago; Zorzano, Antonio; Thomas, George; Kozma, Sara C

2018-04-24

Hepatocellular carcinoma (HCC) ranks second in cancer mortality and has limited therapeutic options. We recently described the synergistic effect of allosteric and ATP-site competitive inhibitors against the mammalian target of rapamycin (mTOR) for the treatment of HCC. However, such inhibitors induce glycemia and increase mitochondrial efficiency. Here we determined whether the mitochondrial complex I inhibitor Phenformin could reverse both side effects, impose an energetic-stress on cancer cells and suppress the growth of HCC. Human HCC cell lines were used in vitro to access the signaling and energetic impact of mTOR inhibitors and Phenformin, either alone or in combination. Next, the therapeutic utility of these drugs alone or in combination was investigated pre-clinically in human orthotopic tumors implanted in mice, by analyzing their impact on the tumor burden and overall survival. We found Phenformin caused mitochondrial dysfunction and fragmentation, inducing a compensatory shift to glycolysis. In contrast, dual inhibition of mTOR impaired cell growth and glycolysis, while increasing mitochondrial fusion and efficiency. In a mouse model of human HCC, dual inhibition of mTOR, together with Phenformin, was highly efficacious in controlling tumor burden. However, more striking, pretreatment with Phenformin sensitized tumors to dual inhibition of mTOR, leading to a dramatic improvement in survival. Treatment of HCC cells in vitro with the biguanide Phenformin causes a metabolic shift to glycolysis, mitochondrial dysfunction and fragmentation, and dramatically sensitizes orthotopic liver tumors to dual inhibition of mTOR. We therefore propose this therapeutic approach should be tested clinically in HCC. Copyright ©2018, American Association for Cancer Research.