Science.gov

Sample records for dual functional lithium-lead

  1. Volumetric Properties of Lithium-Lead Melts

    NASA Astrophysics Data System (ADS)

    Khairulin, R. A.; Abdullaev, R. N.; Stankus, S. V.; Agazhanov, A. S.; Savchenko, I. V.

    2017-02-01

    The density of liquid lithium and lithium-lead alloys (10.02 at.% Pb, 14.98 at.% Pb, 18.06 at.% Pb, 20.02 at.% Pb, 22.24 at.% Pb, 23.09 at.% Pb, 25.10 at.% Pb, 30.15 at.% Pb, 38.21 at.% Pb, 40.11 at.% Pb, 43.08 at.% Pb, 46.65 at.% Pb, 50.15 at.% Pb, 60.23 at.% Pb, 70.01 at.% Pb, 83.00 at.% Pb, and 84.30 at.% Pb) has been measured using the gamma-ray attenuation technique over the temperature range from the liquidus line to 1050 K. The position of the liquidus curve in the Li-Pb phase diagram has been clarified. The compositional dependencies of molar volume and volumetric thermal expansion coefficient of the Li-Pb liquid system have been constructed and discussed.

  2. Dual function conducting polymer diodes

    DOEpatents

    Heeger, Alan J.; Yu, Gang

    1996-01-01

    Dual function diodes based on conjugated organic polymer active layers are disclosed. When positively biased the diodes function as light emitters. When negatively biased they are highly efficient photodiodes. Methods of preparation and use of these diodes in displays and input/output devices are also disclosed.

  3. Unraveling Executive Functioning in Dual Diagnosis

    PubMed Central

    Duijkers, Judith C. L. M.; Vissers, Constance Th. W. M.; Egger, Jos I. M.

    2016-01-01

    In mental health, the term dual-diagnosis is used for the co-occurrence of Substance Use Disorder (SUD) with another mental disorder. These co-occurring disorders can have a shared cause, and can cause/intensify each other’s expression. Forming a threat to health and society, dual-diagnosis is associated with relapses in addiction-related behavior and a destructive lifestyle. This is due to a persistent failure to control impulses and the maintaining of inadequate self-regulatory behavior in daily life. Thus, several aspects of executive functioning like inhibitory, shifting and updating processes seem impaired in dual-diagnosis. Executive (dys-)function is currently even seen as a shared underlying key component of most mental disorders. However, the number of studies on diverse aspects of executive functioning in dual-diagnosis is limited. In the present review, a systematic overview of various aspects of executive functioning in dual-diagnosis is presented, striving for a prototypical profile of patients with dual-diagnosis. Looking at empirical results, inhibitory and shifting processes appear to be impaired for SUD combined with schizophrenia, bipolar disorder or cluster B personality disorders. Studies involving updating process tasks for dual-diagnosis were limited. More research that zooms in to the full diversity of these executive functions is needed in order to strengthen these findings. Detailed insight in the profile of strengths and weaknesses that underlies one’s behavior and is related to diagnostic classifications, can lead to tailor-made assessment and indications for treatment, pointing out which aspects need attention and/or training in one’s self-regulative abilities. PMID:27445939

  4. Affine Riesz bases and the dual function

    NASA Astrophysics Data System (ADS)

    Terekhin, P. A.

    2016-09-01

    This paper is concerned with systems of functions on the unit interval which are generated by dyadic dilations and integer translations of a given function. Similar systems have a wide range of applications in the theory of wavelets, in nonlinear, and in particular, in greedy approximations, in the representation of functions by series, in problems in numerical analysis, and so on. Conditions, and in some particular cases, criteria for the generating function are given for the system to be Besselian, to form a Riesz basis or to be an orthonormal system, and separately, to be complete. For this purpose, the concept of the dual function of the generating function of a system is introduced and studied. Some of the conditions given below are easy to verify in practice, as is demonstrated by examples. Bibliography: 25 titles.

  5. Dual and Feller-Reuter-Riley transition functions

    NASA Astrophysics Data System (ADS)

    Li, Yangrong

    2006-01-01

    In this paper, we investigate duality and Feller-Reuter-Riley (FRR) property of continuous-time Markov chains (CTMCs). A criterion of dual q-functions is given in terms of their q-matrices. For a dual q-matrix Q, a necessary and sufficient conditions for the minimal Q-function to be a FRR transition function are also given. Finally, by using dual technique, we give a criterion of FRR Q-functions when Q is monotone.

  6. Dual functional selenium-substituted hydroxyapatite

    PubMed Central

    Wang, Yanhua; Ma, Jun; Zhou, Lei; Chen, Jin; Liu, Yonghui; Qiu, Zhiye; Zhang, Shengmin

    2012-01-01

    Hydroxyapatite (HA) doped with trace elements has attracted much attention recently owing to its excellent biological functions. Herein, we use a facile co-precipitation method to incorporate selenium into HA by adding sodium selenite during synthesis. The obtained selenium-substituted HA products are needle-like nanoparticles which have  size and crystallinity that are similar to those of the pure HA nanoparticles (HANs) when the selenium content is low. HANs are found to have the ability to induce the apoptosis of osteosarcoma cells, and the anti-tumour effects are enhanced after incorporation of selenium. Meanwhile, the nanoparticles can also support the growth of bone marrow stem cells. Furthermore, the flow cytometric results indicate that the apoptosis induction of osteosarcoma cells is caused by the increased reactive oxygen species and decreased mitochondrial membrane potential. These results show that the selenium-substituted HANs are potentially promising bone graft materials in osteosarcoma treatment due to their dual functions of supporting normal cell growth and inducing tumour cell apoptosis. PMID:23741613

  7. Enrichment of orange emission of Er3+ ion with Sn4+ ion as sensitizer in lithium lead phosphate glass system

    NASA Astrophysics Data System (ADS)

    Rajanikanth, P.; Gandhi, Y.; Veeraiah, N.

    2015-10-01

    Lithium lead phosphate glasses doped with 1.0 mol% of Er2O3 and mixed with varying concentrations of SnO2 (from 0 to 7.0 mol%) have been synthesized. Optical absorption and luminescence spectra of the prepared glasses were recorded at ambient temperature. The radiative lifetimes were measured from the luminescence decay profiles recorded at room temperature. Similar studies have also been carried out for the SnO2 singly doped glasses. The absorption and luminescence spectra of Er3+ ions doped glasses were characterized using Judd-Ofelt theory. The radiative parameters viz., transition probability A, branching ratio β and the radiative lifetime τ of principal emission transitions of these glasses have been evaluated. The energy transfer mechanism between Sn4+ and Er3+ in co-doped glasses has been explored as a function of SnO2 concentration with the help of rate equations. The results indicated a significant enhancement in the intensity of orange emission 4G11/2 → 4I11/2 of Er3+ ions due to co-doping with SnO2. The results were further analyzed with IR spectral data and ac conductivity studies. The analysis pointed out that about 3.0 mol% of SnO2 is the most favorable concentration for getting the highest quantum efficiency of orange emission and for the maximum energy transfer with low non-radiative transition probabilities.

  8. Dual Functional Star Polymers for Lubricants

    SciTech Connect

    Cosimbescu, Lelia; Robinson, Joshua W.; Zhou, Yan; Qu, Jun

    2016-09-12

    Star-shaped poly(alkyl methacrylate)s (PAMAs) with a 3-arm architecture were designed, prepared and their performance as a dual additive (viscosity index improver and friction modifier) for engine oils was evaluated. Furthermore, the structure-property relationships between macromolecular structure and lubricant performance were studied. Several co-polymers of dodecylmethacrylate with polar methacrylates in various amounts and various topologies, were synthesized as model compounds. Star polymers with a polar content of at least 10% effectively reduced the friction coefficient in both mixed and boundary lubrication regime only in block or tapered block topology. However, a polar content of 20% was efficient in reducing friction in both random and block topologies.

  9. Dual functional star polymers for lubricants

    SciTech Connect

    Cosimbescu, Lelia; Robinson, Joshua W.; Zhou, Yan; Qu, Jun

    2016-09-12

    Star-shaped poly(alkyl methacrylate)s (PAMAs) with a three arm architecturewere designed, prepared and their performance as a dual additive (viscosity index improver and friction modifier) for engine oils was evaluated. Furthermore, the structure property relationships between the macromolecular structure and lubricant performance were studied, such as molecular weight and polarity effects on the viscosity index. Several copolymers of dodecylmethacrylate with polar methacrylates in various amounts and various topologies, were synthesized as model compounds. Star polymers with a polar content of at least 10% in a block or tapered block topology effectively reduced the friction coefficient in both mixed and boundary lubrication regimes. Furthermore, a polar content of 20% was efficient in reducing friction in both random and block topologies.

  10. Dual functional star polymers for lubricants

    DOE PAGES

    Cosimbescu, Lelia; Robinson, Joshua W.; Zhou, Yan; ...

    2016-09-12

    Star-shaped poly(alkyl methacrylate)s (PAMAs) with a three arm architecturewere designed, prepared and their performance as a dual additive (viscosity index improver and friction modifier) for engine oils was evaluated. Furthermore, the structure property relationships between the macromolecular structure and lubricant performance were studied, such as molecular weight and polarity effects on the viscosity index. Several copolymers of dodecylmethacrylate with polar methacrylates in various amounts and various topologies, were synthesized as model compounds. Star polymers with a polar content of at least 10% in a block or tapered block topology effectively reduced the friction coefficient in both mixed and boundary lubricationmore » regimes. Furthermore, a polar content of 20% was efficient in reducing friction in both random and block topologies.« less

  11. Dual-modality imaging of function and physiology

    NASA Astrophysics Data System (ADS)

    Hasegawa, Bruce H.; Iwata, Koji; Wong, Kenneth H.; Wu, Max C.; Da Silva, Angela; Tang, Hamilton R.; Barber, William C.; Hwang, Andrew B.; Sakdinawat, Anne E.

    2002-04-01

    Dual-modality imaging is a technique where computed tomography or magnetic resonance imaging is combined with positron emission tomography or single-photon computed tomography to acquire structural and functional images with an integrated system. The data are acquired during a single procedure with the patient on a table viewed by both detectors to facilitate correlation between the structural and function images. The resulting data can be useful for localization for more specific diagnosis of disease. In addition, the anatomical information can be used to compensate the correlated radionuclide data for physical perturbations such as photon attenuation, scatter radiation, and partial volume errors. Thus, dual-modality imaging provides a priori information that can be used to improve both the visual quality and the quantitative accuracy of the radionuclide images. Dual-modality imaging systems also are being developed for biological research that involves small animals. The small-animal dual-modality systems offer advantages for measurements that currently are performed invasively using autoradiography and tissue sampling. By acquiring the required data noninvasively, dual-modality imaging has the potential to allow serial studies in a single animal, to perform measurements with fewer animals, and to improve the statistical quality of the data.

  12. Study on hydrogen isotopes permeation in fluidized state of liquid lithium-lead

    SciTech Connect

    Yoshimura, S.; Yoshimura, R.; Okada, M.; Fukada, S.; Edao, Y.

    2015-03-15

    Lithium-lead (Li-Pb) is one of the most promising candidate materials for the liquid blanket of fusion reactors. Hydrogen transfer under a fluidized condition of Li-Pb is investigated experimentally to design a Li-Pb blanket system. Li-Pb eutectic alloy flows inside a Ni tube in the experimental system, where H{sub 2} permeates into and out of the forced Li-Pb flow. The overall H{sub 2} permeation rate is analyzed using a mass balance model. Hydrogen atoms diffuse in Ni and Li-Pb. The steady-state H{sub 2} permeation rate obtained by this experiment is smaller than the result of the calculation model. A resistance factor is introduced to the present analysis in order to evaluate the influence of other H{sub 2} transfer mechanisms, such as diffusion in Li-Pb and dissolution reaction between Ni and Li-Pb. The contribution of the resistance to the overall H{sub 2} permeation rate becomes large when the flow rate of Li-Pb is low. This is because the boundary layer thickness between Ni and Li-Pb affects the overall H{sub 2} permeation rate. When the flow velocity of Li-Pb increases, the thickness of the boundary layer becomes thin, and the driving force of H{sub 2} permeation through the Ni wall becomes bigger. (authors)

  13. Polymeric blends for sensor and actuation dual functionality

    NASA Technical Reports Server (NTRS)

    St. Clair, Terry L. (Inventor); Harrison, Joycelyn S. (Inventor); Su, Ji (Inventor); Ounaies, Zoubeida (Inventor)

    2004-01-01

    The invention described herein supplies a new class of electroactive polymeric blend materials which offer both sensing and actuation dual functionality. The blend comprises two components, one component having a sensing capability and the other component having an actuating capability. These components should be co-processable and coexisting in a phase separated blend system. Specifically, the materials are blends of a sensing component selected from the group consisting of ferroelectric, piezoelectric, pyroelectric and photoelectric polymers and an actuating component that responds to an electric field in terms of dimensional change. Said actuating component includes, but is not limited to, electrostrictive graft elastomers, dielectric electroactive elastomers, liquid crystal electroactive elastomers and field responsive polymeric gels. The sensor functionality and actuation functionality are designed by tailoring the relative fraction of the two components. The temperature dependence of the piezoelectric response and the mechanical toughness of the dual functional blends are also tailored by the composition adjustment.

  14. Colored dual-functional photovoltaic cells

    NASA Astrophysics Data System (ADS)

    Lee, Kyu-Tae; Lee, Jae Yong; Xu, Ting; Park, Hui Joon; Guo, L. Jay

    2016-06-01

    In this article, we review our recent efforts on multi-functional photovoltaic (PV) cells that can produce desired reflective, transmissive, or neutral colors, by controlling light interaction with semiconductors and electrode structures in a desired manner. The PV cells integrated with plasmonic color filtering schemes using subwavelength gratings, and other approaches exploiting photonic resonances in an optical nanocavity consisting of highly absorbing semiconductor media are described. For further enhancement of optical and electrical performance characteristics of the multi-functional PV cells, possible difficulties and the outlook for future work are discussed.

  15. Balancing the Dual Functions of Portfolio Assessment

    ERIC Educational Resources Information Center

    Lam, Ricky; Lee, Icy

    2010-01-01

    While research on portfolio assessment (PA) has focused largely on the summative aspects of writing assessment, not much has been done to find out its formative potential. Drawing upon student questionnaires and student and teacher interview data, this paper aims to explore the formative functions of PA and, specifically, how the formative…

  16. Bacterial cells carrying synthetic dual-function operon survived starvation.

    PubMed

    Matsumoto, Yuki; Ito, Yoichiro; Tsuru, Saburo; Ying, Bei-Wen; Yomo, Tetsuya

    2011-01-01

    A synthetic dual-function operon with a bistable structure was designed and successfully integrated into the bacterial genome. Bistability was generated by the mutual inhibitory structure comprised of the promoters P(tet) and P(lac) and the repressors LacI and TetR. Dual function essential for cell growth was introduced by replacing the genes (i.e., hisC and leuB) encoding proteins involved in the biosynthesis of histidine and leucine from their native chromosomal locations to the synthetic operon. Both colony formation and population dynamics of the cells carrying this operon showed that the cells survived starvation and the newly formed population transited between the two stable states, representing the induced hisC and leuB levels, in accordance with the nutritional status. The results strongly suggested that the synthetic design of proto-operons sensitive to external perturbations is practical and functional in native cells.

  17. 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.

  18. Design of the helium cooled lithium lead breeding blanket in CEA: from TBM to DEMO

    NASA Astrophysics Data System (ADS)

    Aiello, G.; Aubert, J.; Forest, L.; Jaboulay, J.-C.; Li Puma, A.; Boccaccini, L. V.

    2017-04-01

    The helium cooled lithium lead (HCLL) blanket concept was originally developed in CEA at the beginning of 2000: it is one of the two European blanket concepts to be tested in ITER in the form of a test blanket module (TBM) and one of the four blanket concepts currently being considered for the DEMOnstration reactor that will follow ITER. The TBM is a highly optimized component for the ITER environment that will provide crucial information for the development of the DEMO blanket, but its design needs to be adapted to the DEMO reactor. With respect to the TBM design, reduction of the steel content in the breeding zone (BZ) is sought in order to maximize tritium breeding reactions. Different options are being studied, with the potential of reaching tritium breeding ratio (TBR) values up to 1.21. At the same time, the design of the back supporting structure (BSS), which is a DEMO specific component that has to support the blanket modules inside the vacuum vessel (VV), is ongoing with the aim of maximizing the shielding power and minimizing pumping power. This implies a re-engineering of the modules’ attachment system. Design changes however, will have an impact on the manufacturing and assembly sequences that are being developed for the HCLL-TBM. Due to the differences in joint configurations, thicknesses to be welded, heat dissipation and the various technical constraints related to the accessibility of the welding tools and implementation of non-destructive examination (NDE), the manufacturing procedure should be adapted and optimized for DEMO design. Laser welding instead of TIG could be an option to reduce distortions. The time-of-flight diffraction (TOFD) technique is being investigated for NDE. Finally, essential information expected from the HCLL-TBM program that will be needed to finalize the DEMO design is discussed.

  19. Dual-Functional Antifogging/Antimicrobial Polymer Coating.

    PubMed

    Zhao, Jie; Ma, Li; Millians, William; Wu, Tiehang; Ming, Weihua

    2016-04-06

    Dual-functional antifogging/antimicrobial polymer coatings were prepared by forming a semi-interpenetrating polymer network (SIPN) of partially quaternized poly(2-(dimethylamino)ethyl methacrylate-co-methyl methacrylate) and polymerized ethylene glycol dimethacrylate network. The excellent antifogging behavior of the smooth coating was mainly attributed to the hydrophilic/hydrophobic balance of the partially quaternized copolymer, while the covalently bonded, hydrophobic quaternary ammonium compound (5 mol % in the copolymer) rendered the coating strongly antimicrobial, as demonstrated by the total kill against both Gram-positive Staphylococcus epidermidis and Gram-negative Escherichia coli. The antimicrobial action of the SIPN coating was based on contact killing, without leaching of bactericidal species, as revealed by a zone-of-inhibition test. This type of dual-functional coating may find unique applications where both antimicrobial and antifogging properties are desired.

  20. Dual-functional photocatalysis for hydrogen evolution from industrial wastewaters.

    PubMed

    Lin, Zhaoyong; Li, Lihua; Yu, Lili; Li, Weijia; Yang, Guowei

    2017-03-22

    Realization of hydrogen economy requires an environmental and economic method for hydrogen (H2) evolution. Dual-functional photocatalysis, that is, producing H2 from industrial wastewaters, may be the most ideal. However, it seems almost impossible to achieve dual-functional photocatalysis because of the difficulty in the simultaneous existence of photocatalytic pollutant degradation (PDR) and H2 evolution reactions (HER) in one system. All previous designs show that either HER or PDR is inhibited due to the insufficient management of the photo-generated electrons (e(-)) and holes (h(+)). To overcome this issue, we consider that both PDR and HER could be improved simultaneously by employing a suitable photocatalyst whose main active species in PDR are h(+). In this case, e(-) and h(+) can play their own roles in accomplishing HER and PDR, respectively, via the charge spatial separation in the selected photocatalyst. Herein, Cu2O polyhedrons are constructed as a proof-of-concept example. A favorable dual-functional photocatalytic performance is achieved by the Cu2O cubooctahedrons. Furthermore, an appropriate pollutant concentration is significant for the optimization of both HER and PDR performances due to the competition between H atom adsorption and pollutant molecule adsorption on the surfaces of the photocatalyst. This advance provides the H2 evolution technology with a more environmental and economic method.

  1. Dual-Language Education for Low-Income Children: Preliminary Evidence of Benefits for Executive Function

    ERIC Educational Resources Information Center

    Esposito, Alena G.; Baker-Ward, Lynne

    2013-01-01

    This investigation is an initial examination of possible enhancement of executive function through a dual-language (50:50) education model. The ethnically diverse, low-income sample of 120 children from Grades K, 2, and 4 consisted of approximately equal numbers of children enrolled in dual-language and traditional classrooms. Dual-language…

  2. Dual-functional electrospun poly(2-hydroxyethyl methacrylate).

    PubMed

    Zhang, Bo; Lalani, Reza; Cheng, Fang; Liu, Qingsheng; Liu, Lingyun

    2011-12-01

    Poly(2-hydroxyethyl methacrylate) (pHEMA) has been widely used in many biomedical applications due to its well-known biocompatibility. For tissue engineering applications, porous scaffolds that mimic fibrous structures of natural extracellular matrix and possess high surface-area-to-volume ratios are highly desirable. So far, a systematic approach to control diameter and morphology of pHEMA fibers has not been reported and potential applications of pHEMA fibers have barely been explored. In this work, pHEMA was synthesized and processed into fibrous scaffolds using an electrospinning approach. Fiber diameters from 270 nm to 3.6 μm were achieved by controlling polymer solution concentration and electrospinning flow rate. Post-electrospinning thermal treatment significantly improves integrity of the electrospun membranes in water. The pHEMA microfibrous membranes exhibited water absorption up to 280% (w/w), whereas the pHEMA hydrogel only absorbed 70% water. Fibrinogen adsorption experiments demonstrate that the electrospun pHEMA fibers highly resist nonspecific protein adsorption. Hydroxyl groups on electrospun pHEMA fibers were further activated for protein immobilization. A bovine serum albumin (BSA) binding capacity as high as 120 mg BSA/g membrane was realized at an intermediate fiber diameter. The pHEMA fibrous scaffolds functionalized with collagen I significantly promoted fibroblast adhesion, spreading, and proliferation. We conclude that the electrospun pHEMA fibers are dual functional, that is, they resist nonspecific protein adsorption meanwhile abundant hydroxyl groups on fibers allow effective conjugation of biomolecules in a nonfouling background. High water absorption and dual functionality of the electrospun pHEMA fibers may lead to a number of potential applications such as wound dressings, tissue scaffolds, and affinity membranes.

  3. Development of a chemical kinetic measurement apparatus and the determination of the reaction rate constants for lithium-lead/water interaction

    SciTech Connect

    Biney, P.O.

    1993-04-01

    An experimental set-up for accurate measurement of hydrogen generation rate in Lithium-Lead (Li[sub 17]Pb[sub 83]) Steam or water interactions has been designed. The most important features of the design include a pneumatic actuated quick opening and closing high temperature all stainless steel valve used to control the reaction time and the placement of most measuring devices below a water line to minimize leakage of the hydrogen collected. A PC based data acquisition and control system provides remote process sequencing, acquisition and control of all major components of the set-up. Initial tests indicate that the first design objective of maintaining leakproof gas collection chamber has been achieved. Initial pressure tests indicated that the pressure drop over a time span of 30 minutes was within the tolerance of the pressure transducer used to measure the pressure (within 0.690 kPa) at a nominal system pressure of 685 kPa. The experimental system hardware, data acquisition and control programs and data analysis program have been completed, tested and are currently functional.

  4. Electrical/optical dual-function redox potential transistor

    PubMed Central

    Li, Shunpu; Wang, Wensi; Xu, Ju; Chu, Daping; Shen, Z. John; Roy, Saibal

    2013-01-01

    We demonstrate a new type of transistors, the electrical/optical “dual-function redox-potential transistors”, which is solution processable and environmentally stable. This device consists of vertically staked electrodes that act as gate, emitter and collector. It can perform as a normal transistor, whilst one electrode which is sensitised by dye enables to generate photocurrent when illuminated. Solution processable oxide-nanoparticles were used to form various functional layers, which allow an electrolyte to penetrate through and, consequently, the current between emitter and collector can be controlled by the gate potential modulated distribution of ions. The result here shows that the device performs with high ON-current under low driving voltage (<1 V), while the transistor performance can readily be controlled by photo-illumination. Such device with combined optical and electrical functionalities allows single device to perform the tasks that are usually done by a circuit/system with multiple optical and electrical components, and it is promising for various applications. PMID:24310311

  5. Mental Health and Psychological Functioning of Dual-Career Families.

    ERIC Educational Resources Information Center

    Gilbert, Lucia Albino; Rachlin, Vicki

    1987-01-01

    Identifies key issues in the psychosocial development of women and men that are important to understanding dual-career marriages. Describes life as a dual career family considering rewards, sources of stress, and factors that promote effective coping. Addresses pertinent metaissues--concepts of equity and the nature of society. Offers…

  6. An immunostimulatory dual-functional nanocarrier that improves cancer immunochemotherapy

    PubMed Central

    Chen, Yichao; Xia, Rui; Huang, Yixian; Zhao, Wenchen; Li, Jiang; Zhang, Xiaolan; Wang, Pengcheng; Venkataramanan, Raman; Fan, Jie; Xie, Wen; Ma, Xiaochao; Lu, Binfeng; Li, Song

    2016-01-01

    Immunochemotherapy combines a chemotherapeutic agent with an immune-modulating agent and represents an attractive approach to improve cancer therapy. However, the success of immunochemotherapy is hampered by the lack of a strategy to effectively co-deliver the two therapeutics to the tumours. Here we report the development of a dual-functional, immunostimulatory nanomicellar carrier that is based on a prodrug conjugate of PEG with NLG919, an indoleamine 2,3-dioxygenase (IDO) inhibitor currently used for reversing tumour immune suppression. An Fmoc group, an effective drug-interactive motif, is also introduced into the carrier to improve the drug loading capacity and formulation stability. We show that PEG2k-Fmoc-NLG alone is effective in enhancing T-cell immune responses and exhibits significant antitumour activity in vivo. More importantly, systemic delivery of paclitaxel (PTX) using the PEG2k-Fmoc-NLG nanocarrier leads to a significantly improved antitumour response in both breast cancer and melanoma mouse models. PMID:27819653

  7. Transport properties of lithium- lead-vanadium-telluride glass and glass ceramics

    SciTech Connect

    Sathish, M.; Eraiah, B.

    2014-04-24

    Glasses with the chemical composition 35Li{sub 2}O-(45-x)V{sub 2}O{sub 5−}20PbO-xTeO{sub 2} (where x = 2.5, 5, 7.5, 10, 15 mol %) have prepared by conventional melt quenching method. The electrical conductivity of Li{sup +} ion conducting lead vanadium telluride glass samples has been carried out both as a function of temperature and frequency in the temperature range 503K-563K and over frequencies 40 Hz to 10 MHz. The electronic conduction has been observed in the present systems. When these samples annealed around 400°C for 2hour become the glass ceramic, which also shows increase tendency of conductivity. SEM confines glass and glass ceramic nature of the prepared samples.

  8. The Role of Control Functions in Mentalizing: Dual-Task Studies of Theory of Mind and Executive Function

    ERIC Educational Resources Information Center

    Bull, Rebecca; Phillips, Louise H.; Conway, Claire A.

    2008-01-01

    Conflicting evidence has arisen from correlational studies regarding the role of executive control functions in Theory of Mind. The current study used dual-task manipulations of executive functions (inhibition, updating and switching) to investigate the role of these control functions in mental state and non-mental state tasks. The "Eyes"…

  9. Functional mathematical model of dual pathway AV nodal conduction.

    PubMed

    Climent, A M; Guillem, M S; Zhang, Y; Millet, J; Mazgalev, T N

    2011-04-01

    Dual atrioventricular (AV) nodal pathway physiology is described as two different wave fronts that propagate from the atria to the His bundle: one with a longer effective refractory period [fast pathway (FP)] and a second with a shorter effective refractory period [slow pathway (SP)]. By using His electrogram alternance, we have developed a mathematical model of AV conduction that incorporates dual AV nodal pathway physiology. Experiments were performed on five rabbit atrial-AV nodal preparations to develop and test the presented model. His electrogram alternances from the inferior margin of the His bundle were used to identify fast and slow wave front propagations. The ability to predict AV conduction time and the interaction between FP and SP wave fronts have been analyzed during regular and irregular atrial rhythms (e.g., atrial fibrillation). In addition, the role of dual AV nodal pathway wave fronts in the generation of Wenckebach periodicities has been illustrated. Finally, AV node ablative modifications have been evaluated. The model accurately reproduced interactions between FP and SP during regular and irregular atrial pacing protocols. In all experiments, specificity and sensitivity higher than 85% were obtained in the prediction of the pathway responsible for conduction. It has been shown that, during atrial fibrillation, the SP ablation significantly increased the mean HH interval (204 ± 39 vs. 274 ± 50 ms, P < 0.05), whereas FP ablation did not produce significant slowing of ventricular rate. The presented mathematical model can help in understanding some of the intriguing AV node mechanisms and should be considered as a step forward in the studies of AV nodal conduction.

  10. Polynomial dual energy inverse functions for bone Calcium/Phosphorus ratio determination and experimental evaluation.

    PubMed

    Sotiropoulou, P; Fountos, G; Martini, N; Koukou, V; Michail, C; Kandarakis, I; Nikiforidis, G

    2016-12-01

    An X-ray dual energy (XRDE) method was examined, using polynomial nonlinear approximation of inverse functions for the determination of the bone Calcium-to-Phosphorus (Ca/P) mass ratio. Inverse fitting functions with the least-squares estimation were used, to determine calcium and phosphate thicknesses. The method was verified by measuring test bone phantoms with a dedicated dual energy system and compared with previously published dual energy data. The accuracy in the determination of the calcium and phosphate thicknesses improved with the polynomial nonlinear inverse function method, introduced in this work, (ranged from 1.4% to 6.2%), compared to the corresponding linear inverse function method (ranged from 1.4% to 19.5%).

  11. Embedding dual function into molecular motors through collective motion.

    PubMed

    Saito, Nen; Kaneko, Kunihiko

    2017-03-10

    Protein motors, such as kinesins and dyneins, bind to a microtubule and travel along it in a specific direction. Previously, it was thought that the directionality for a given motor was constant in the absence of an external force. However, the directionality of the kinesin-5 Cin8 was recently found to change as the number of motors that bind to the same microtubule is increased. Here, we introduce a simple mechanical model of a microtubule-sliding assay in which multiple motors interact with the filament. We show that, due to the collective phenomenon, the directionality of the motor changes (e.g., from minus- to plus- end directionality), depending on the number of motors. This is induced by a large diffusive component in the directional walk and by the subsequent frustrated motor configuration, in which multiple motors pull the filament in opposite directions, similar to a game of tug-of-war. A possible role of the dual-directional motors for the mitotic spindle formation is also discussed. Our framework provides a general mechanism to embed two conflicting tasks into a single molecular machine, which works context-dependently.

  12. Embedding dual function into molecular motors through collective motion

    PubMed Central

    Saito, Nen; Kaneko, Kunihiko

    2017-01-01

    Protein motors, such as kinesins and dyneins, bind to a microtubule and travel along it in a specific direction. Previously, it was thought that the directionality for a given motor was constant in the absence of an external force. However, the directionality of the kinesin-5 Cin8 was recently found to change as the number of motors that bind to the same microtubule is increased. Here, we introduce a simple mechanical model of a microtubule-sliding assay in which multiple motors interact with the filament. We show that, due to the collective phenomenon, the directionality of the motor changes (e.g., from minus- to plus- end directionality), depending on the number of motors. This is induced by a large diffusive component in the directional walk and by the subsequent frustrated motor configuration, in which multiple motors pull the filament in opposite directions, similar to a game of tug-of-war. A possible role of the dual-directional motors for the mitotic spindle formation is also discussed. Our framework provides a general mechanism to embed two conflicting tasks into a single molecular machine, which works context-dependently. PMID:28281683

  13. TRICHLOROETHYLENE SORPTION AND OXIDATION USING A DUAL FUNCTION SORBENT/CATALYST IN A FALLING FURNACE REACTOR

    EPA Science Inventory

    A dual function medium (Cr-ZSM-5), capable of physisorbing trichloroethylene (TCE) at ambient temperature and catalytically oxidizing it at elevated temperature (-350 degrees C) was utilized in a novel continuous falling furnace reactor system to store and periodically destroy t...

  14. 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.

  15. Dual functions of perirhinal cortex in fear conditioning.

    PubMed

    Kent, Brianne A; Brown, Thomas H

    2012-10-01

    The present review examines the role of perirhinal cortex (PRC) in Pavlovian fear conditioning. The focus is on rats, partly because so much is known, behaviorally and neurobiologically, about fear conditioning in these animals. In addition, the neuroanatomy and neurophysiology of rat PRC have been described in considerable detail at the cellular and systems levels. The evidence suggests that PRC can serve at least two types of mnemonic functions in Pavlovian fear conditioning. The first function, termed "stimulus unitization," refers to the ability to treat two or more separate items or stimulus elements as a single entity. Supporting evidence for this perceptual function comes from studies of context conditioning as well as delay conditioning to discontinuous auditory cues. In a delay paradigm, the conditional stimulus (CS) and unconditional stimulus (US) overlap temporally and co-terminate. The second PRC function entails a type of "transient memory." Supporting evidence comes from studies of trace cue conditioning, where there is a temporal gap or trace interval between the CS offset and the US onset. For learning to occur, there must be a transient CS representation during the trace interval. We advance a novel neurophysiological mechanism for this transient representation. These two hypothesized functions of PRC are consistent with inferences based on non-aversive forms of learning.

  16. Dual Functions of Perirhinal Cortex in Fear Conditioning

    PubMed Central

    Kent, Brianne A.; Brown, Thomas H.

    2012-01-01

    The present review examines the role of perirhinal cortex (PRC) in Pavlovian fear conditioning. The focus is on rats, partly because so much is known, behaviorally and neurobiologically, about fear conditioning in these animals. In addition, the neuroanatomy and neurophysiology of rat PRC have been described in considerable detail at the cellular and systems levels. The evidence suggests that PRC can serve at least two types of mnemonic functions in Pavlovian fear conditioning. The first function, termed "stimulus unitization," refers to the ability to treat two or more separate items or stimulus elements as a single entity. Supporting evidence for this perceptual function comes from studies of context conditioning as well as delay conditioning to discontinuous auditory cues. In a delay paradigm, the conditional stimulus (CS) and unconditional stimulus (US) overlap temporally and co-terminate. The second PRC function entails a type of "transient memory." Supporting evidence comes from studies of trace cue conditioning, where there is a temporal gap or trace interval between the CS offset and the US onset. For learning to occur, there must be a transient CS representation during the trace interval. We advance a novel neurophysiological mechanism for this transient representation. These two hypothesized functions of PRC are consistent with inferences based on non-aversive forms of learning. PMID:22903623

  17. Dual function of the selenoprotein PHGPx during sperm maturation.

    PubMed

    Ursini, F; Heim, S; Kiess, M; Maiorino, M; Roveri, A; Wissing, J; Flohé, L

    1999-08-27

    The selenoprotein phospholipid hydroperoxide glutathione peroxidase (PHGPx) changes its physical characteristics and biological functions during sperm maturation. PHGPx exists as a soluble peroxidase in spermatids but persists in mature spermatozoa as an enzymatically inactive, oxidatively cross-linked, insoluble protein. In the midpiece of mature spermatozoa, PHGPx protein represents at least 50 percent of the capsule material that embeds the helix of mitochondria. The role of PHGPx as a structural protein may explain the mechanical instability of the mitochondrial midpiece that is observed in selenium deficiency.

  18. Potential Benefits of Exergaming for Cognition and Dual-Task Function in Older Adults: A Systematic Review.

    PubMed

    Ogawa, Elisa F; You, Tongjian; Leveille, Suzanne G

    2016-04-01

    This paper provides a systematic review of current research findings using exergaming as a treatment for improving cognition and dual-task function in older adults. A literature search was conducted to collect exergaming intervention studies that were either randomized controlled or uncontrolled studies. Of the seven identified studies (five randomized controlled studies and two uncontrolled studies), three studies focused on cognitive function alone, two studies focused on dual-task function alone, and two studies measured both cognitive function and dual-task function. Current evidence supports that exergaming improves cognitive function and dual-task function, which potentially leads to fall prevention. However, it is unclear whether exergaming, which involves both cognitive input and physical exercise, has additional benefits compared with traditional physical exercise alone. Further studies should include traditional exercise as a control group to identify these potential, additional benefits.

  19. Dual-functional ROMP-based betaines: effect of hydrophilicity and backbone structure on nonfouling properties.

    PubMed

    Colak, Semra; Tew, Gregory N

    2012-01-10

    Foundational materials for nonfouling coatings were designed and synthesized from a series of novel dual-functional zwitterionic polymers, Poly[NRZI], which were easily obtained via ring-opening metathesis polymerization (ROMP) followed by a single step transformation of the cationic precursor, Poly[NR(+)], to the zwitterion, Poly[NRZI]. The resulting unique dual-functional structure contained the anion and the cation within the same repeat unit but on separate side chains, enabling the hydrophilicity of the system to be tuned at the repeat unit level. These dual-functional zwitterionic polymers were specifically designed to investigate the impact of structural changes, including the backbone, hydrophilicity, and charge, on the overall nonfouling properties. To evaluate the importance of backbone structure, and as a direct comparison to previously studied methacrylate-based betaines, norbornene-based carbo- and sulfobetaines (Poly[NCarboZI] and Poly[NSulfoZI]) as well as a methacrylate-based sulfobetaine (Poly[MASulfoZI]) were synthesized. These structures contain the anion-cation pairs on the same side chain. Nonfouling coatings were prepared from copolymers, composed of the zwitterionic/cationic precursor monomer and an ethoxysilane-containing monomer. The coatings were evaluated by using protein adsorption studies, which clearly indicated that the overall hydrophilicity has a major influence on the nonfouling character of the materials. The most hydrophilic coating, from the oligoethylene glycol (OEG)-containing dual-functional betaine, Poly[NOEGZI-co-NSi], showed the best resistance to nonspecific protein adsorption (Γ(FIB) = 0.039 ng/mm(2)). Both norbornene-based polymers systems, Poly[NSulfoZI] and Poly[NCarboZI], were more hydrophilic and thus more resistant to protein adsorption than the methacrylate-based Poly[MASulfoZI]. Comparing the protein resistance of the dual-functional zwitterionic coatings, Poly[NRZI-co-NSi], to that of their cationic

  20. Dual Function of Sox1 in Telencephalic Progenitor Cells

    PubMed Central

    Kan, Lixin; Jalali, Ali; Zhao, Li-Ru; Zhou, Xiaojing; McGuire, Tammy; Kazanis, Ilias; Episkopou, Vasso; Bassuk, Alexander G.; Kessler, John A.

    2012-01-01

    The transcription factor, Sox1 has been implicated in the maintenance of neural progenitor cell status, but accumulating evidence suggests that this is only part of its function. This study examined the role of Sox1 expression in proliferation, lineage commitment, and differentiation by telencephalic neural progenitor cells in vitro and in vivo, and further clarified the pattern of Sox1 expression in postnatal and adult mouse brain. Telencephalic neural progenitor cells isolated from Sox1 null embryos formed neurospheres normally, but were specifically deficient in neuronal differentiation. Conversely, overexpression of Sox1 in the embryonic telencephalon in vivo both expanded the progenitor pool and biased neural progenitor cells towards neuronal lineage commitment. Sox1 mRNA and protein were found to be persistently expressed in the postnatal and adult brain in both differentiated and neurogenic regions. Importantly, in differentiated regions Sox1 co-labeled only with neuronal markers. These observations, coupled with previous studies, suggest that Sox1 expression by early embryonic progenitor cells initially helps to maintain the cells in cell cycle, but that continued expression subsequently promotes neuronal lineage commitment. PMID:17719572

  1. Dual functional AuNRs@MnMEIOs nanoclusters for magnetic resonance imaging and photothermal therapy.

    PubMed

    Chuang, Yao-Chen; Lin, Chia-Jung; Lo, Shih-Feng; Wang, Jei-Lin; Tzou, Shey-Cherng; Yuan, Shyng-Shiou; Wang, Yun-Ming

    2014-05-01

    A novel dual functional theranosis platform is developed based on manganese magnetism-engineered iron oxide (MnMEIO) and gold nanorods (AuNRs) to combine magnetic resonance (MR) imaging and photothermal therapy in one nanocluster. The platform showed improved T2-weighted MR imaging and exhibited a near-infrared (NIR) induced temperature elevation due to the unique characteristics of AuNRs@MnMEIOs nanoclusters. The obtained dual functional spherical-shaped nanoclusters showed low cytotoxicity, and high cellular uptake efficiency. The AuNRs@MnMEIOs nanoclusters also demonstrated a 1.9 and 2.2 folds r2 relaxivity value higher than those of monodispersed MnMEIO and Resovist. In addition, in vivo MR imaging study found that the contrast enhancements were - 70.4 ± 4.3% versus - 7.5 ± 3.0% in Her-2/neu overexpression tumors as compared to the control tumors. More importantly, NIR laser irradiation to the tumor site resulted in outstanding photothermal therapeutic efficacy and without damage to the surrounding tissue. In additional, the prepared dual functional AuNRs@MnMEIOs display high stability and furthermore disperse even in the presence of external magnet, showing that AuNRs@MnMEIOs nanoclusters can be manipulated by an external magnetic field. Therefore, such nanoclusters combined MR imaging and photothermal therapeutic functionality can be developed as a promising nanosystem for effective cancer diagnosis and therapy.

  2. Dual representation for the generating functional of the Feynman path-integral

    NASA Astrophysics Data System (ADS)

    Matone, Marco

    2016-09-01

    The generating functional for scalar theories admits a representation which is dual with respect to the one introduced by Schwinger, interchanging the role of the free and interacting terms. It maps ∫ V (δJ) and JΔJ to δϕc Δδϕc and ∫ V (ϕc), respectively, with ϕc = ∫ JΔ and Δ the Feynman propagator. Comparing the Schwinger representation with its dual version one gets a little known relation that we prove to be a particular case of a more general operatorial relation. We then derive a new representation of the generating functional T [ϕc ] = W [ J ] expressed in terms of covariant derivatives acting on 1

  3. Development of a chemical kinetic measurement apparatus and the determination of the reaction rate constants for lithium-lead/water interaction. Technical status progress report, October 1, 1991--March 15, 1993

    SciTech Connect

    Biney, P.O.

    1993-04-01

    An experimental set-up for accurate measurement of hydrogen generation rate in Lithium-Lead (Li{sub 17}Pb{sub 83}) Steam or water interactions has been designed. The most important features of the design include a pneumatic actuated quick opening and closing high temperature all stainless steel valve used to control the reaction time and the placement of most measuring devices below a water line to minimize leakage of the hydrogen collected. A PC based data acquisition and control system provides remote process sequencing, acquisition and control of all major components of the set-up. Initial tests indicate that the first design objective of maintaining leakproof gas collection chamber has been achieved. Initial pressure tests indicated that the pressure drop over a time span of 30 minutes was within the tolerance of the pressure transducer used to measure the pressure (within 0.690 kPa) at a nominal system pressure of 685 kPa. The experimental system hardware, data acquisition and control programs and data analysis program have been completed, tested and are currently functional.

  4. Dual-functional composite with anticoagulant and antibacterial properties based on heparinized silk fibroin and chitosan.

    PubMed

    Wang, Jianglin; Hu, Wei; Liu, Qun; Zhang, Shengmin

    2011-07-01

    Heparinized biomaterials exhibit great anticoagulant properties. However, they promote proliferation of Staphylococcus aureus (S. aureus) and therefore cause infection within the bloodstream upon implantation in vivo. In the present study, an interesting dual-functional composite with anticoagulant and antibacterial properties based on heparinized silk fibroin and chitosan was synthesized. First, heparin was grafted onto the silk fibroin by covalent immobilization with N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide (EDC) and N-hydroxysuccinimide (NHS). All data gathered from Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and elemental analysis (EA) indicated that the heparin was successfully immobilized onto the silk fibroin. The dual-functional composite of heparinized silk fibroin and chitosan was then fabricated by a blending method. The anticoagulant activity of the heparinized materials was evaluated using the prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT). The results showed that both heparinized silk fibroin and the composite material exhibited better hemocompatibility in comparison with single silk fibroin or chitosan. The antibacterial property of the materials was investigated by the pour-plate method. Results further suggested that the composite antibacterial property with respect to S. aureus was significantly enhanced. The dual-functionality of the composite material may supply a potential choice in blood contact devices.

  5. Using Dual Regression to Investigate Network Shape and Amplitude in Functional Connectivity Analyses

    PubMed Central

    Nickerson, Lisa D.; Smith, Stephen M.; Öngür, Döst; Beckmann, Christian F.

    2017-01-01

    Independent Component Analysis (ICA) is one of the most popular techniques for the analysis of resting state FMRI data because it has several advantageous properties when compared with other techniques. Most notably, in contrast to a conventional seed-based correlation analysis, it is model-free and multivariate, thus switching the focus from evaluating the functional connectivity of single brain regions identified a priori to evaluating brain connectivity in terms of all brain resting state networks (RSNs) that simultaneously engage in oscillatory activity. Furthermore, typical seed-based analysis characterizes RSNs in terms of spatially distributed patterns of correlation (typically by means of simple Pearson's coefficients) and thereby confounds together amplitude information of oscillatory activity and noise. ICA and other regression techniques, on the other hand, retain magnitude information and therefore can be sensitive to both changes in the spatially distributed nature of correlations (differences in the spatial pattern or “shape”) as well as the amplitude of the network activity. Furthermore, motion can mimic amplitude effects so it is crucial to use a technique that retains such information to ensure that connectivity differences are accurately localized. In this work, we investigate the dual regression approach that is frequently applied with group ICA to assess group differences in resting state functional connectivity of brain networks. We show how ignoring amplitude effects and how excessive motion corrupts connectivity maps and results in spurious connectivity differences. We also show how to implement the dual regression to retain amplitude information and how to use dual regression outputs to identify potential motion effects. Two key findings are that using a technique that retains magnitude information, e.g., dual regression, and using strict motion criteria are crucial for controlling both network amplitude and motion-related amplitude

  6. Using Dual Regression to Investigate Network Shape and Amplitude in Functional Connectivity Analyses.

    PubMed

    Nickerson, Lisa D; Smith, Stephen M; Öngür, Döst; Beckmann, Christian F

    2017-01-01

    Independent Component Analysis (ICA) is one of the most popular techniques for the analysis of resting state FMRI data because it has several advantageous properties when compared with other techniques. Most notably, in contrast to a conventional seed-based correlation analysis, it is model-free and multivariate, thus switching the focus from evaluating the functional connectivity of single brain regions identified a priori to evaluating brain connectivity in terms of all brain resting state networks (RSNs) that simultaneously engage in oscillatory activity. Furthermore, typical seed-based analysis characterizes RSNs in terms of spatially distributed patterns of correlation (typically by means of simple Pearson's coefficients) and thereby confounds together amplitude information of oscillatory activity and noise. ICA and other regression techniques, on the other hand, retain magnitude information and therefore can be sensitive to both changes in the spatially distributed nature of correlations (differences in the spatial pattern or "shape") as well as the amplitude of the network activity. Furthermore, motion can mimic amplitude effects so it is crucial to use a technique that retains such information to ensure that connectivity differences are accurately localized. In this work, we investigate the dual regression approach that is frequently applied with group ICA to assess group differences in resting state functional connectivity of brain networks. We show how ignoring amplitude effects and how excessive motion corrupts connectivity maps and results in spurious connectivity differences. We also show how to implement the dual regression to retain amplitude information and how to use dual regression outputs to identify potential motion effects. Two key findings are that using a technique that retains magnitude information, e.g., dual regression, and using strict motion criteria are crucial for controlling both network amplitude and motion-related amplitude effects

  7. Integrated rate-dependent and dual pathway AV nodal functions: principles and assessment framework.

    PubMed

    Billette, Jacques; Tadros, Rafik

    2014-01-15

    The atrioventricular (AV) node conducts slowly and has a long refractory period. These features sustain the filtering of atrial impulses and hence are often modulated to optimize ventricular rate during supraventricular tachyarrhythmias. The AV node is also the site of a clinically common reentrant arrhythmia. Its function is assessed for a variety of purposes from its responses to a premature protocol (S1S2, test beats introduced at different cycle lengths) repeatedly performed at different basic rates and/or to an incremental pacing protocol (increasingly faster rates). Puzzlingly, resulting data and interpretation differ with protocols as well as with chosen recovery and refractory indexes, and are further complicated by the presence of built-in fast and slow pathways. This problem applies to endocavitary investigations of arrhythmias as well as to many experimental functional studies. This review supports an integrated framework of rate-dependent and dual pathway AV nodal function that can account for these puzzling characteristics. The framework was established from AV nodal responses to S1S2S3 protocols that, compared with standard S1S2 protocols, allow for an orderly quantitative dissociation of the different factors involved in changes in AV nodal conduction and refractory indexes under rate-dependent and dual pathway function. Although largely based on data from experimental studies, the proposed framework may well apply to the human AV node. In conclusion, the rate-dependent and dual pathway properties of the AV node can be integrated within a common functional framework the contribution of which to individual responses can be quantitatively determined with properly designed protocols and analytic tools.

  8. Dynamic Changes in Brain Functional Connectivity during Concurrent Dual-Task Performance

    PubMed Central

    Cocchi, Luca; Zalesky, Andrew; Toepel, Ulrike; Whitford, Thomas J.; De-Lucia, Marzia; Murray, Micah M.; Carter, Olivia

    2011-01-01

    This study investigated the spatial, spectral, temporal and functional proprieties of functional brain connections involved in the concurrent execution of unrelated visual perception and working memory tasks. Electroencephalography data was analysed using a novel data-driven approach assessing source coherence at the whole-brain level. Three connections in the beta-band (18–24 Hz) and one in the gamma-band (30–40 Hz) were modulated by dual-task performance. Beta-coherence increased within two dorsofrontal-occipital connections in dual-task conditions compared to the single-task condition, with the highest coherence seen during low working memory load trials. In contrast, beta-coherence in a prefrontal-occipital functional connection and gamma-coherence in an inferior frontal-occipitoparietal connection was not affected by the addition of the second task and only showed elevated coherence under high working memory load. Analysis of coherence as a function of time suggested that the dorsofrontal-occipital beta-connections were relevant to working memory maintenance, while the prefrontal-occipital beta-connection and the inferior frontal-occipitoparietal gamma-connection were involved in top-down control of concurrent visual processing. The fact that increased coherence in the gamma-connection, from low to high working memory load, was negatively correlated with faster reaction time on the perception task supports this interpretation. Together, these results demonstrate that dual-task demands trigger non-linear changes in functional interactions between frontal-executive and occipitoparietal-perceptual cortices. PMID:22140572

  9. Characterizing individual differences in functional connectivity using dual-regression and seed-based approaches.

    PubMed

    Smith, David V; Utevsky, Amanda V; Bland, Amy R; Clement, Nathan; Clithero, John A; Harsch, Anne E W; McKell Carter, R; Huettel, Scott A

    2014-07-15

    A central challenge for neuroscience lies in relating inter-individual variability to the functional properties of specific brain regions. Yet, considerable variability exists in the connectivity patterns between different brain areas, potentially producing reliable group differences. Using sex differences as a motivating example, we examined two separate resting-state datasets comprising a total of 188 human participants. Both datasets were decomposed into resting-state networks (RSNs) using a probabilistic spatial independent component analysis (ICA). We estimated voxel-wise functional connectivity with these networks using a dual-regression analysis, which characterizes the participant-level spatiotemporal dynamics of each network while controlling for (via multiple regression) the influence of other networks and sources of variability. We found that males and females exhibit distinct patterns of connectivity with multiple RSNs, including both visual and auditory networks and the right frontal-parietal network. These results replicated across both datasets and were not explained by differences in head motion, data quality, brain volume, cortisol levels, or testosterone levels. Importantly, we also demonstrate that dual-regression functional connectivity is better at detecting inter-individual variability than traditional seed-based functional connectivity approaches. Our findings characterize robust-yet frequently ignored-neural differences between males and females, pointing to the necessity of controlling for sex in neuroscience studies of individual differences. Moreover, our results highlight the importance of employing network-based models to study variability in functional connectivity.

  10. Dual-Functional Hydrazide-Reactive and Anhydride-Containing Oligomeric Hydrogel Building Blocks.

    PubMed

    Kascholke, Christian; Loth, Tina; Kohn-Polster, Caroline; Möller, Stephanie; Bellstedt, Peter; Schulz-Siegmund, Michaela; Schnabelrauch, Matthias; Hacker, Michael C

    2017-03-13

    Biomimetic hydrogels are advanced biomaterials that have been developed following different synthetic routes. Covalent postfabrication functionalization is a promising strategy to achieve efficient matrix modification decoupled of general material properties. To this end, dual-functional macromers were synthesized by free radical polymerization of maleic anhydride with diacetone acrylamide (N-(1,1-dimethyl-3-oxobutyl)acrylamide) and pentaerythritol diacrylate monostearate. Amphiphilic oligomers (Mn < 7.5 kDa) with anhydride contents of 7-20% offered cross-linking reactivity to yield rigid hydrogels with gelatinous peptides (E = 4-13 kPa) and good cell adhesion properties. Mildly reactive methyl ketones as second functionality remained intact during hydrogel formation and potential of covalent matrix modification was shown using hydrazide and hydrazine model compounds. Successful secondary dihydrazide cross-linking was demonstrated by an increase of hydrogel stiffness (>40%). Efficient hydrazide/hydrazine immobilization depending on solution pH, hydrogel ketone content as well as ligand concentration for bioconjugation was shown and reversibility of hydrazone formation was indicated by physiologically relevant hydrazide release over 7 days. Proof-of-concept experiments with hydrazido-functionalized hyaluronan demonstrated potential for covalent aECM immobilization. The presented dual-functional macromers have perspective as reactive hydrogel building blocks for various biomedical applications.

  11. Continuous Dual Resetting of the Immune Repertoire as a Basic Principle of the Immune System Function

    PubMed Central

    2017-01-01

    Idiopathic chronic inflammatory conditions (ICIC) such as allergy, asthma, chronic obstructive pulmonary disease, and various autoimmune conditions are a worldwide health problem. Understanding the pathogenesis of ICIC is essential for their successful therapy and prevention. However, efforts are hindered by the lack of comprehensive understanding of the human immune system function. In line with those efforts, described here is a concept of stochastic continuous dual resetting (CDR) of the immune repertoire as a basic principle that governs the function of immunity. The CDR functions as a consequence of system's thermodynamically determined intrinsic tendency to acquire new states of inner equilibrium and equilibrium against the environment. Consequently, immune repertoire undergoes continuous dual (two-way) resetting: against the physiologic continuous changes of self and against the continuously changing environment. The CDR-based dynamic concept of immunity describes mechanisms of self-regulation, tolerance, and immunosenescence, and emphasizes the significance of immune system's compartmentalization in the pathogenesis of ICIC. The CDR concept's relative simplicity and concomitantly documented congruency with empirical, clinical, and experimental data suggest it may represent a plausible theoretical framework to better understand the human immune system function. PMID:28246613

  12. Continuous Dual Resetting of the Immune Repertoire as a Basic Principle of the Immune System Function.

    PubMed

    Balzar, Silvana

    2017-01-01

    Idiopathic chronic inflammatory conditions (ICIC) such as allergy, asthma, chronic obstructive pulmonary disease, and various autoimmune conditions are a worldwide health problem. Understanding the pathogenesis of ICIC is essential for their successful therapy and prevention. However, efforts are hindered by the lack of comprehensive understanding of the human immune system function. In line with those efforts, described here is a concept of stochastic continuous dual resetting (CDR) of the immune repertoire as a basic principle that governs the function of immunity. The CDR functions as a consequence of system's thermodynamically determined intrinsic tendency to acquire new states of inner equilibrium and equilibrium against the environment. Consequently, immune repertoire undergoes continuous dual (two-way) resetting: against the physiologic continuous changes of self and against the continuously changing environment. The CDR-based dynamic concept of immunity describes mechanisms of self-regulation, tolerance, and immunosenescence, and emphasizes the significance of immune system's compartmentalization in the pathogenesis of ICIC. The CDR concept's relative simplicity and concomitantly documented congruency with empirical, clinical, and experimental data suggest it may represent a plausible theoretical framework to better understand the human immune system function.

  13. The Dual Role of Oxygen Functions in Coal Pretreatment and Liquefaction: Crosslinking and Cleavage Reactions

    SciTech Connect

    Michael Serio; Erik Kroo; Sylvie Charpenay; Peter Solomon

    1993-09-30

    The overall objective of this project was to elucidate and model the dual role of oxygen functions in thermal pretreatment and liquefaction of low rank coals through the application of analytical techniques and theoretical models. The project was an integrated study of model polymers representative of coal structures, raw coals of primarily low rank, and selectively modified coals in order to provide specific information relevant to the reactions of real coals. The investigations included liquefaction experiments in microautoclave reactors, along with extensive analysis of intermediate solid, liquid and gaseous products. Attempts were made to incorporate the results of experiments on the different systems into a liquefaction model.

  14. Single active-layer structured dual-function devices using hybrid polymer-quantum dots.

    PubMed

    Son, Dong-Ick; Park, Dong-Hee; Ie, Sang-Yub; Choi, Won-Kook; Choi, Ji-Won; Li, Fushan; Kim, Tae-Whan

    2008-10-01

    We demonstrate hybrid polymer-quantum dot dual-function devices with a single active-layer structure consisting of CdSe/ZnS semiconductor quantum dots dispersed with poly N-vinylcarbazole (PVK) and 1,3,5-tirs-(N-phenylbenzimidazol-2-yl) benzene (TPBi) fabricated on an indium-tin-oxide (ITO)/glass substrate by using a simple spin-coating technique. The dual-function devices are composed of light-emitting diodes (LED) on the top side and nonvolatile organic bistable memory devices (OBD) on the bottom side and can show electroluminescence (EL) along with electrical bistability concurrently. Both the functionality of LEDs and OBDs can be successfully achieved by adding an electron transport layer (ETL) TPBi to the OBD to attain an LED in which the lowest unoccupied molecular orbital (LUMO) level of TPBi is positioned at the energy level between the conduction band of CdSe/ZnS and the LiF/Al electrode. Through transmission electron microscopy (TEM) study, it is revealed that CdSe/ZnS QDs distributed on the interface of the hole transport layer (HTL) and ETL significantly take part in the electroluminescence process rather than those existing at the outer surface of the ETL.

  15. Development of a patch type embedded cardiac function monitoring system using dual microprocessor for arrhythmia detection in heart disease patient.

    PubMed

    Jang, Yongwon; Noh, Hyung Wook; Lee, I B; Jung, Ji-Wook; Song, Yoonseon; Lee, Sooyeul; Kim, Seunghwan

    2012-01-01

    A patch type embedded cardiac function monitoring system was developed to detect arrhythmias such as PVC (Premature Ventricular Contraction), pause, ventricular fibrillation, and tachy/bradycardia. The overall system is composed of a main module including a dual processor and a Bluetooth telecommunication module. The dual microprocessor strategy minimizes power consumption and size, and guarantees the resources of embedded software programs. The developed software was verified with standard DB, and showed good performance.

  16. Dual function of MG53 in membrane repair and insulin signaling

    PubMed Central

    Tan, Tao; Ko, Young-Gyu; Ma, Jianjie

    2016-01-01

    MG53 is a member of the TRIM-family protein that acts as a key component of the cell membrane repair machinery. MG53 is also an E3-ligase that ubiquinates insulin receptor substrate-1 and controls insulin signaling in skeletal muscle cells. Since its discovery in 2009, research efforts have been devoted to translate this basic discovery into clinical applications in human degenerative and metabolic diseases. This review article highlights the dual function of MG53 in cell membrane repair and insulin signaling, the mechanism that underlies the control of MG53 function, and the therapeutic value of targeting MG53 function in regenerative medicine. [BMB Reports 2016; 49(8): 414-423] PMID:27174502

  17. Upper-Extremity Dual-Task Function: An Innovative Method to Assess Cognitive Impairment in Older Adults

    PubMed Central

    Toosizadeh, Nima; Najafi, Bijan; Reiman, Eric M.; Mager, Reine M.; Veldhuizen, Jaimeson K.; O’Connor, Kathy; Zamrini, Edward; Mohler, Jane

    2016-01-01

    Background: Difficulties in orchestrating simultaneous tasks (i.e., dual-tasking) have been associated with cognitive impairments in older adults. Gait tests have been commonly used as the motor task component for dual-task assessments; however, many older adults have mobility impairments or there is a lack of space in busy clinical settings. We assessed an upper-extremity function (UEF) test as an alternative motor task to study the dual-task motor performance in older adults. Methods: Older adults (≥65 years) were recruited, and cognitive ability was measured using the Montreal cognitive assessment (MoCA). Participants performed repetitive elbow flexion with their maximum pace, once single-task, and once while counting backward by one (dual-task). Single- and dual-task gait tests were also performed with normal speed. Three-dimensional kinematics was measured both from upper-extremity and lower-extremity using wearable sensors to determine UEF and gait parameters. Parameters were compared between the cognitively impaired and healthy groups using analysis of variance tests, while controlling for age, gender, and body mass index (BMI). Correlations between UEF and gait parameters for dual-task and dual-task cost were assessed using linear regression models. Results: Sixty-seven older adults were recruited (age = 83 ± 10 years). Based on MoCA, 10 (15%) were cognitively impaired. While no significant differences were observed in the single-task condition, within the dual-task condition, the cognitively impaired group showed significantly less arm flexion speed (62%, d = 1.51, p = 0.02) and range of motion (27%, d = 0.93, p = 0.04), and higher speed variability (88%, d = 1.82, p < 0.0001) compared to the cognitively intact group, when adjusted with age, gender, and BMI. Significant correlations were observed between UEF speed parameters and gait stride velocity for dual-task condition (r = 0.55, p < 0.0001) and dual-task cost (r = 0.28, p = 0.03). Conclusion: We

  18. Dual functionalized graphene oxide serves as a carrier for delivering oligohistidine- and biotin-tagged biomolecules into cells.

    PubMed

    Jana, Batakrishna; Mondal, Goutam; Biswas, Atanu; Chakraborty, Indrani; Saha, Abhijit; Kurkute, Prashant; Ghosh, Surajit

    2013-11-01

    A versatile method of dual chemical functionalization of graphene oxide (GO) with Tris-[nitrilotris(acetic acid)] (Tris-NTA) and biotin for cellular delivery of oligohistidine- and biotin-tagged biomolecules is reported. Orthogonally functionalized GO surfaces with Tris-NTA and biotin to obtain a dual-functionalized GO (DFGO) are prepared and characterized by various spectroscopic and microscopic techniques. Fluorescence microscopic images reveal that DFGO surfaces are capable of binding oligohistidine-tagged biomolecules/proteins and avidin/biotin-tagged biomolecules/proteins orthogonally. The DFGO nanoparticles are non-cytotoxic in nature and can deliver oligohistidine- and biotin-tagged biomolecules simultaneously into the cell.

  19. AMDE-1 Is a Dual Function Chemical for Autophagy Activation and Inhibition

    PubMed Central

    Li, Min; Yang, Zuolong; Vollmer, Laura L.; Gao, Ying; Fu, Yuanyuan; Liu, Cui; Chen, Xiaoyun; Liu, Peiqing; Vogt, Andreas; Yin, Xiao-Ming

    2015-01-01

    Autophagy is the process by which cytosolic components and organelles are delivered to the lysosome for degradation. Autophagy plays important roles in cellular homeostasis and disease pathogenesis. Small chemical molecules that can modulate autophagy activity may have pharmacological value for treating diseases. Using a GFP-LC3-based high content screening assay we identified a novel chemical that is able to modulate autophagy at both initiation and degradation levels. This molecule, termed as Autophagy Modulator with Dual Effect-1 (AMDE-1), triggered autophagy in an Atg5-dependent manner, recruiting Atg16 to the pre-autophagosomal site and causing LC3 lipidation. AMDE-1 induced autophagy through the activation of AMPK, which inactivated mTORC1 and activated ULK1. AMDE-1did not affect MAP kinase, JNK or oxidative stress signaling for autophagy induction. Surprisingly, treatment with AMDE-1 resulted in impairment in autophagic flux and inhibition of long-lived protein degradation. This inhibition was correlated with a reduction in lysosomal degradation capacity but not with autophagosome-lysosome fusion. Further analysis indicated that AMDE-1 caused a reduction in lysosome acidity and lysosomal proteolytic activity, suggesting that it suppressed general lysosome function. AMDE-1 thus also impaired endocytosis-mediated EGF receptor degradation. The dual effects of AMDE-1 on autophagy induction and lysosomal degradation suggested that its net effect would likely lead to autophagic stress and lysosome dysfunction, and therefore cell death. Indeed, AMDE-1 triggered necroptosis and was preferentially cytotoxic to cancer cells. In conclusion, this study identified a new class of autophagy modulators with dual effects, which can be explored for potential uses in cancer therapy. PMID:25894744

  20. Musical training, bilingualism, and executive function: a closer look at task switching and dual-task performance.

    PubMed

    Moradzadeh, Linda; Blumenthal, Galit; Wiseheart, Melody

    2015-07-01

    This study investigated whether musical training and bilingualism are associated with enhancements in specific components of executive function, namely, task switching and dual-task performance. Participants (n = 153) belonging to one of four groups (monolingual musician, bilingual musician, bilingual non-musician, or monolingual non-musician) were matched on age and socioeconomic status and administered task switching and dual-task paradigms. Results demonstrated reduced global and local switch costs in musicians compared with non-musicians, suggesting that musical training can contribute to increased efficiency in the ability to shift flexibly between mental sets. On dual-task performance, musicians also outperformed non-musicians. There was neither a cognitive advantage for bilinguals relative to monolinguals, nor an interaction between music and language to suggest additive effects of both types of experience. These findings demonstrate that long-term musical training is associated with improvements in task switching and dual-task performance.

  1. Dual-functional polymeric waveguide with optical amplification and electro-optic modulation

    NASA Astrophysics Data System (ADS)

    An, Dechang; Yue, ZuZhou; Chen, Ray T.

    1997-12-01

    Optical amplification and electro-optic modulation have been observed simultaneously in one polymeric material photo-lime gel which has been used as a volume holographic material to produce dichromated gelatin (DCG) films. In this paper, the dual functions were achieved by doping neodymium chloride hexahydrate (NdCl3(DOT)6H2O) and chlorophenol red (C19H12Cl2O5S). The optimized doping concentrations of Nd+3 and chlorophenol red were 6.7 X 1019/cm3 and 23% respectively. We observed a gain of 3.8 dB at 1.04 micrometers and an electro-optic coefficient of 30 pm/V at 633 nm. The experimental results confirms that the co-doping process does not degrade the respective functions of Nd+3 for optical amplification and chlorophenol red for electro-optic modulation.

  2. A hierarchical polymer brush coating with dual-function antibacterial capability.

    PubMed

    Yan, Shunjie; Song, Lingjie; Luan, Shifang; Xin, Zhirong; Du, Shanshan; Shi, Hengchong; Yuan, Shuaishuai; Yang, Yuming; Yin, Jinghua

    2017-01-01

    Bacterial infections are problematic in many healthcare-associated devices. Antibacterial surfaces integrating the strength of bacteria repellent and bactericidal functions exhibit an encouraging efficacy in tackling this problem. Herein, a hierarchical dual-function antibacterial polymer brush coating that integrates an antifouling bottom layer with a bactericidal top layer is facilely constructed via living photograft polymerization. Excellent resistance to bacterial attachment is correlated with the antifouling components, and good bactericidal activity is afforded by the bactericidal components, and therefore the hierarchical coating shows an excellent long-term antibacterial capability. In addition, due to the presence of the hydrophilic background layer, the hierarchical surface has the greatly improved biocompatibility, as shown by the suppression of platelet adhesion and activation, the inhibition of erythrocyte adhesion and damage, and low toxicity against mammalian cells. The hierarchical polymer brush system provides the basis for the development of long-term antibacterial and biocompatible surfaces.

  3. 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

  4. The dual roles of functional groups in the photoluminescence of graphene quantum dots.

    PubMed

    Wang, Shujun; Cole, Ivan S; Zhao, Dongyuan; Li, Qin

    2016-04-14

    The photoluminescent properties of graphene nanoparticle (named graphene quantum dots) have attracted significant research attention in recent years owing to their profound application potential. However, the photoluminescence (PL) origin of this class of nanocarbons is still unclear. In this paper, combining direct experimental evidence enabled by a facile size-tunable oxygenated graphene quantum dots (GQDs) synthesis method and theoretical calculations, the roles of the aromatic core, functional groups and disordered structures (i.e. defects and sp(3) carbon) in the PL of oxygenated GQDs are elucidated in detail. In particular, we found that the functional groups on GQDs play dual roles in the overall emission: (1) they enable π* → n and σ* → n transitions, resulting in a molecular type of PL, spectrally invariable with change of particle size or excitation energy; (2) similar to defects and sp(3) carbon, functional groups also induce structural deformation to the aromatic core, leading to mid-gap states or, in other words, energy traps, causing π* → mid-gap states → π transitions. Therefore, functional groups contribute to both the blue edge and the red shoulder of GQDs' PL spectra. The new insights on the role of functional groups in PL of fluorescent nanocarbons will enable better designs of this new class of materials.

  5. [Post-translational ligation and function of dual-vector transferred split CFTR gene].

    PubMed

    Zhu, Fu-Xiang; Liu, Ze-Long; Qu, Hui-Ge; Chi, Xiao-Yan

    2010-01-01

    The mutation of cystic fibrosis transmembrane conductance regulator (CFTR) gene leads to an autosomal recessive genetic disorder cystic fibrosis (CF). The gene therapy for CF using adeno-associated virus (AAV) vectors delivering CFTR gene is restricted by the contents limitation of AAV vectors. In this study the split CFTR genes severed at its regulatory domain were delivered by a dual-vector system with an intein-mediated protein trans-splicing as a technique to investigate the post-translational ligation of CFTR half proteins and its function as a chloride ion channel. A pair of eukaryotic expression vectors was constructed by breaking the human CFTR cDNA before Ser712 codon and fusing with Ssp DnaB intein coding sequences. After co-transfection into baby hamster kidney (BHK) cells followed by transient expression, patch clamps were carried out to record the chloride current of whole-cell and the activity of a single channel, and the ligation of two halves of CFTR was observed by Western blotting. The results showed that the intein-fused half genes co-transfected cells displayed a high whole cell chloride current and activity of a single channel indicating the functional recovery of chloride channel, and an intact CFTR protein band was figured out by CFTR-specific antibodies indicating that intein can efficiently ligate the separately expressed half CFTR proteins. The data demonstrated that protein splicing strategy could be used as a strategy in delivering CFTR gene by two vectors, encouraging our ongoing research program on dual AAV vector system based gene transfer in gene therapy for cystic fibrosis.

  6. Effects of Gait Self-Efficacy and Lower-Extremity Physical Function on Dual-Task Performance in Older Adults.

    PubMed

    Ehlers, Diane K; Banducci, Sarah E; Daugherty, Ana M; Fanning, Jason; Awick, Elizabeth A; Porter, Gwenndolyn C; Burzynska, Agnieszka; Shen, Sa; Kramer, Arthur F; McAuley, Edward

    2017-01-01

    Objectives. Despite evidence of self-efficacy and physical function's influences on functional limitations in older adults, few studies have examined relationships in the context of complex, real-world tasks. The present study tested the roles of self-efficacy and physical function in predicting older adults' street-crossing performance in single- and dual-task simulations. Methods. Lower-extremity physical function, gait self-efficacy, and street-crossing success ratio were assessed in 195 older adults (60-79 years old) at baseline of a randomized exercise trial. During the street-crossing task, participants walked on a self-propelled treadmill in a virtual reality environment. Participants crossed the street without distraction (single-task trials) and conversed on a cell phone (dual-task trials). Structural equation modeling was used to test hypothesized associations independent of demographic and clinical covariates. Results. Street-crossing performance was better on single-task trials when compared with dual-task trials. Direct effects of self-efficacy and physical function on success ratio were observed in dual-task trials only. The total effect of self-efficacy was significant in both conditions. The indirect path through physical function was evident in the dual-task condition only. Conclusion. Physical function can predict older adults' performance on high fidelity simulations of complex, real-world tasks. Perceptions of function (i.e., self-efficacy) may play an even greater role. The trial is registered with United States National Institutes of Health ClinicalTrials.gov (ID: NCT01472744; Fit & Active Seniors Trial).

  7. Effects of Gait Self-Efficacy and Lower-Extremity Physical Function on Dual-Task Performance in Older Adults

    PubMed Central

    Banducci, Sarah E.; Daugherty, Ana M.; Fanning, Jason; Awick, Elizabeth A.; Porter, Gwenndolyn C.; Burzynska, Agnieszka; Shen, Sa; Kramer, Arthur F.; McAuley, Edward

    2017-01-01

    Objectives. Despite evidence of self-efficacy and physical function's influences on functional limitations in older adults, few studies have examined relationships in the context of complex, real-world tasks. The present study tested the roles of self-efficacy and physical function in predicting older adults' street-crossing performance in single- and dual-task simulations. Methods. Lower-extremity physical function, gait self-efficacy, and street-crossing success ratio were assessed in 195 older adults (60–79 years old) at baseline of a randomized exercise trial. During the street-crossing task, participants walked on a self-propelled treadmill in a virtual reality environment. Participants crossed the street without distraction (single-task trials) and conversed on a cell phone (dual-task trials). Structural equation modeling was used to test hypothesized associations independent of demographic and clinical covariates. Results. Street-crossing performance was better on single-task trials when compared with dual-task trials. Direct effects of self-efficacy and physical function on success ratio were observed in dual-task trials only. The total effect of self-efficacy was significant in both conditions. The indirect path through physical function was evident in the dual-task condition only. Conclusion. Physical function can predict older adults' performance on high fidelity simulations of complex, real-world tasks. Perceptions of function (i.e., self-efficacy) may play an even greater role. The trial is registered with United States National Institutes of Health ClinicalTrials.gov (ID: NCT01472744; Fit & Active Seniors Trial). PMID:28255557

  8. A novel high-power dual-band coupled-line Gysel power divider with impedance-transforming functions.

    PubMed

    Wang, Weimin; Wu, Yongle; Liu, Yuanan

    2014-01-01

    A novel coupled-line structure is proposed to design dual-band and high-power Gysel power dividers with inherent impedance-transforming functions. Based on traditional even- and odd-mode technique, the analytical design methods in closed-form formula are obtained and the accurate electrical parameters analysis is presented. Due to the usage of coupled-line sections, more design-parameter freedom and a wider frequency-ratio operation range for this kind of dual-band Gysel powder divider are obtained. Several numerical examples are designed and calculated to demonstrate flexible dual-band applications with different impedance-transforming functions. A practical microstrip power divider operating at 2 GHz and 3.2 GHz is designed, fabricated, and measured. The good agreement between the calculated and measured results verifies our proposed circuit structure and analytical design approach.

  9. A Novel High-Power Dual-Band Coupled-Line Gysel Power Divider with Impedance-Transforming Functions

    PubMed Central

    Wang, Weimin; Liu, Yuanan

    2014-01-01

    A novel coupled-line structure is proposed to design dual-band and high-power Gysel power dividers with inherent impedance-transforming functions. Based on traditional even- and odd-mode technique, the analytical design methods in closed-form formula are obtained and the accurate electrical parameters analysis is presented. Due to the usage of coupled-line sections, more design-parameter freedom and a wider frequency-ratio operation range for this kind of dual-band Gysel powder divider are obtained. Several numerical examples are designed and calculated to demonstrate flexible dual-band applications with different impedance-transforming functions. A practical microstrip power divider operating at 2 GHz and 3.2 GHz is designed, fabricated, and measured. The good agreement between the calculated and measured results verifies our proposed circuit structure and analytical design approach. PMID:24764768

  10. Onsite-effects of dual-hemisphere versus conventional single-hemisphere transcranial direct current stimulation: A functional MRI study.

    PubMed

    Kwon, Yong Hyun; Jang, Sung Ho

    2012-08-25

    We performed functional MRI examinations in six right-handed healthy subjects. During functional MRI scanning, transcranial direct current stimulation was delivered with the anode over the right primary sensorimotor cortex and the cathode over the left primary sensorimotor cortex using dual-hemispheric transcranial direct current stimulation. This was compared to a cathode over the left supraorbital area using conventional single-hemispheric transcranial direct current stimulation. Voxel counts and blood oxygenation level-dependent signal intensities in the right primary sensorimotor cortex regions were estimated and compared between the two transcranial direct current stimulation conditions. Our results showed that dual-hemispheric transcranial direct current stimulation induced greater cortical activities than single-hemispheric transcranial direct current stimulation. These findings suggest that dual-hemispheric transcranial direct current stimulation may provide more effective cortical stimulation than single-hemispheric transcranial direct current stimulation.

  11. HMGB1, IL-1α, IL-33 and S100 proteins: dual-function alarmins

    PubMed Central

    Bertheloot, Damien; Latz, Eicke

    2017-01-01

    Our immune system is based on the close collaboration of the innate and adaptive immune systems for the rapid detection of any threats to the host. Recognition of pathogen-derived molecules is entrusted to specific germline-encoded signaling receptors. The same receptors have now also emerged as efficient detectors of misplaced or altered self-molecules that signal tissue damage and cell death following, for example, disruption of the blood supply and subsequent hypoxia. Many types of endogenous molecules have been shown to provoke such sterile inflammatory states when released from dying cells. However, a group of proteins referred to as alarmins have both intracellular and extracellular functions which have been the subject of intense research. Indeed, alarmins can either exert beneficial cell housekeeping functions, leading to tissue repair, or provoke deleterious uncontrolled inflammation. This group of proteins includes the high-mobility group box 1 protein (HMGB1), interleukin (IL)-1α, IL-33 and the Ca2+-binding S100 proteins. These dual-function proteins share conserved regulatory mechanisms, such as secretory routes, post-translational modifications and enzymatic processing, that govern their extracellular functions in time and space. Release of alarmins from mesenchymal cells is a highly relevant mechanism by which immune cells can be alerted of tissue damage, and alarmins play a key role in the development of acute or chronic inflammatory diseases and in cancer development. PMID:27569562

  12. Dual functions of a small regulatory subunit in the mitochondrial calcium uniporter complex

    PubMed Central

    Tsai, Ming-Feng; Phillips, Charles B; Ranaghan, Matthew; Tsai, Chen-Wei; Wu, Yujiao; Williams, Carole; Miller, Christopher

    2016-01-01

    Mitochondrial Ca2+ uptake, a process crucial for bioenergetics and Ca2+ signaling, is catalyzed by the mitochondrial calcium uniporter. The uniporter is a multi-subunit Ca2+-activated Ca2+ channel, with the Ca2+ pore formed by the MCU protein and Ca2+-dependent activation mediated by MICU subunits. Recently, a mitochondrial inner membrane protein EMRE was identified as a uniporter subunit absolutely required for Ca2+ permeation. However, the molecular mechanism and regulatory purpose of EMRE remain largely unexplored. Here, we determine the transmembrane orientation of EMRE, and show that its known MCU-activating function is mediated by the interaction of transmembrane helices from both proteins. We also reveal a second function of EMRE: to maintain tight MICU regulation of the MCU pore, a role that requires EMRE to bind MICU1 using its conserved C-terminal polyaspartate tail. This dual functionality of EMRE ensures that all transport-competent uniporters are tightly regulated, responding appropriately to a dynamic intracellular Ca2+ landscape. DOI: http://dx.doi.org/10.7554/eLife.15545.001 PMID:27099988

  13. A Dual-Organic-Transistor-Based Tactile-Perception System with Signal-Processing Functionality.

    PubMed

    Zang, Yaping; Shen, Hongguang; Huang, Dazhen; Di, Chong-An; Zhu, Daoben

    2017-02-22

    Organic-device-based tactile-perception systems can open up new opportunities for the next generation of intelligent products. To meet the critical requirements of artificial perception systems, the efficient construction of organic smart elements with integrated sensing and signal processing functionalities is highly desired, but remains a challenge. This study presents a dual-organic-transistor-based tactile-perception element (DOT-TPE) with biomimetic functionality by the construction of organic synaptic transistors with integrated sensing transistors. The unique geometry of the DOT-TPE permits instantaneous sensing of pressure stimuli and synapse-like processing of an electric signal in a single element. More importantly, these organic-transistor-based tactile-perception elements can be built into arrays to serve as bionic tactile-perception systems. The combined biomimetic functionality of tactile-perception systems, together with their promising features of flexibility and large-area fabrication, makes this work represent a step forward toward novel e-skin devices for artificial intelligence.

  14. Evaluation of pulmonary function using single-breath-hold dual-energy computed tomography with xenon

    PubMed Central

    Kyoyama, Hiroyuki; Hirata, Yusuke; Kikuchi, Satoshi; Sakai, Kosuke; Saito, Yuriko; Mikami, Shintaro; Moriyama, Gaku; Yanagita, Hisami; Watanabe, Wataru; Otani, Katharina; Honda, Norinari; Uematsu, Kazutsugu

    2017-01-01

    Abstract Xenon-enhanced dual-energy computed tomography (xenon-enhanced CT) can provide lung ventilation maps that may be useful for assessing structural and functional abnormalities of the lung. Xenon-enhanced CT has been performed using a multiple-breath-hold technique during xenon washout. We recently developed xenon-enhanced CT using a single-breath-hold technique to assess ventilation. We sought to evaluate whether xenon-enhanced CT using a single-breath-hold technique correlates with pulmonary function testing (PFT) results. Twenty-six patients, including 11 chronic obstructive pulmonary disease (COPD) patients, underwent xenon-enhanced CT and PFT. Three of the COPD patients underwent xenon-enhanced CT before and after bronchodilator treatment. Images from xenon-CT were obtained by dual-source CT during a breath-hold after a single vital-capacity inspiration of a xenon–oxygen gas mixture. Image postprocessing by 3-material decomposition generated conventional CT and xenon-enhanced images. Low-attenuation areas on xenon images matched low-attenuation areas on conventional CT in 21 cases but matched normal-attenuation areas in 5 cases. Volumes of Hounsfield unit (HU) histograms of xenon images correlated moderately and highly with vital capacity (VC) and total lung capacity (TLC), respectively (r = 0.68 and 0.85). Means and modes of histograms weakly correlated with VC (r = 0.39 and 0.38), moderately with forced expiratory volume in 1 second (FEV1) (r = 0.59 and 0.56), weakly with the ratio of FEV1 to FVC (r = 0.46 and 0.42), and moderately with the ratio of FEV1 to its predicted value (r = 0.64 and 0.60). Mode and volume of histograms increased in 2 COPD patients after the improvement of FEV1 with bronchodilators. Inhalation of xenon gas caused no adverse effects. Xenon-enhanced CT using a single-breath-hold technique depicted functional abnormalities not detectable on thin-slice CT. Mode, mean, and volume of HU histograms of xenon images

  15. Does extending the dual-task functional exercises workout improve postural balance in individuals with ID?

    PubMed

    Mikolajczyk, Edyta; Jankowicz-Szymanska, Agnieszka

    2015-03-01

    Maintaining postural balance, overcoming visual and motor coordination disorders and experiencing problems with low general fitness - typical of intellectually disabled individuals - adversely affect the performance quality of their activities of daily living (ADLs). Physical fitness and postural balance can be improved by taking part in special intervention programs. Our study was designed to test whether extending the dual-task intervention program (combining ADLs with balance exercises on unstable surfaces) from 12 to 24 weeks additionally improved postural balance in individuals with intellectual disability (ID). We also attempted to assess whether the effects of the above intervention program were still noticeable after 8 weeks of holidays, in which participants did not take any rehabilitation exercises. A total of 34 adolescents, aged 14-16 years (15.06±0.9), with moderate ID took part in our study. The experimental group (E) consisted of 17 individuals, who continued the intervention program originated 3 months earlier, and the control group (C) comprised the same number of participants. Postural balance was assessed on a stabilometric platform Alfa. Having extended the workout period by another 12 weeks, we noticed that the path length of the center of pressure (COP) covered by participants on tests with their eyes open and closed significantly shortened. After a lapse of 8 weeks from the completion of the program, the experimental group revealed a statistically significant decrease in the velocity along the medio-lateral (M/L) and anterior-posterior (A/P) axes. The remaining variables stayed at the same level and the control group did not demonstrate any statistically significant changes. Dual-task exercises, in which enhancing functional tasks of daily living is combined with a parallel stimulation of balance reactions, may improve static balance in persons with ID.

  16. Musical Training, Bilingualism, and Executive Function: A Closer Look at Task Switching and Dual-Task Performance

    ERIC Educational Resources Information Center

    Moradzadeh, Linda; Blumenthal, Galit; Wiseheart, Melody

    2015-01-01

    This study investigated whether musical training and bilingualism are associated with enhancements in specific components of executive function, namely, task switching and dual-task performance. Participants (n = 153) belonging to one of four groups (monolingual musician, bilingual musician, bilingual non-musician, or monolingual non-musician)…

  17. Two new native ß-glucosidases from Clavispora NRRL Y-50464 confer its dual function as cellobiose fermenting ethanologenic yeast

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Clavispora NRRL Y-50464, a dual functional cellobiose fermenting and ethanologenic yeast strain, is a candidate biocatalyst for lower cost lignocellulose-to-ethanol production using simultaneous saccharification and fermentation. A ß-glucosidase BGL1 protein from this strain was recently reported an...

  18. Structure reveals function of the dual variable domain immunoglobulin (DVD-Ig™) molecule.

    PubMed

    Jakob, Clarissa G; Edalji, Rohinton; Judge, Russell A; DiGiammarino, Enrico; Li, Yingchun; Gu, Jijie; Ghayur, Tariq

    2013-01-01

    Several bispecific antibody-based formats have been developed over the past 25 years in an effort to produce a new generation of immunotherapeutics that target two or more disease mechanisms simultaneously. One such format, the dual-variable domain immunoglobulin (DVD-Ig™), combines the target binding domains of two monoclonal antibodies via flexible naturally occurring linkers, which yields a tetravalent IgG - like molecule. We report the structure of an interleukin (IL)12-IL18 DVD-Ig™ Fab (DFab) fragment with IL18 bound to the inner variable domain (VD) that reveals the remarkable flexibility of the DVD-Ig™ molecule and how the DVD-Ig™ format can function to bind four antigens simultaneously. An understanding of how the inner variable domain retains function is of critical importance for designing DVD-Ig™ molecules, and for better understanding of the flexibility of immunoglobulin variable domains and linkers, which may aid in the design of improved bi- and multi-specific biologics in general.

  19. A trilayer separator with dual function for high performance lithium-sulfur batteries

    NASA Astrophysics Data System (ADS)

    Song, Rensheng; Fang, Ruopian; Wen, Lei; Shi, Ying; Wang, Shaogang; Li, Feng

    2016-01-01

    In this article, we propose a trilayer graphene/polypropylene/Al2O3 (GPA) separator with dual function for high performance lithium-sulfur (Li-S) batteries. Graphene is coated on one side of polypropylene (PP) separator, which functions as a conductive layer and an electrolyte reservoir that allows for rapid electron and ion transport. Then Al2O3 particles are coated on the other side to further enhance thermal stability and safety of the graphene coated polypropylene (GCP) separator, which are touched with lithium metal anode in the Li-S battery. The GPA separator shows good thermal stability after heating at 157 °C for 10 min while both GCP and PP separators showing an obvious shrinkage about 10%. The initial discharge specific capacity of Li-S coin cell with a GPA separator could reach 1067.7 mAh g-1 at 0.2C. After 100 discharge/charge cycles, it can still deliver a reversible capacity of as high as 804.4 mAh g-1 with 75% capacity retention. The pouch cells further confirm that the trilayer design has great promise towards practical applications.

  20. Designing Dual-functionalized Gels for Self-reconfiguration and Autonomous Motion

    NASA Astrophysics Data System (ADS)

    Kuksenok, Olga; Balazs, Anna C.

    2015-04-01

    Human motion is enabled by the concerted expansion and contraction of interconnected muscles that are powered by inherent biochemical reactions. One of the challenges in the field of biomimicry is eliciting this form of motion from purely synthetic materials, which typically do not generate internalized reactions to drive mechanical action. Moreover, for practical applications, this bio-inspired motion must be readily controllable. Herein, we develop a computational model to design a new class of polymer gels where structural reconfigurations and internalized reactions are intimately linked to produce autonomous motion, which can be directed with light. These gels contain both spirobenzopyran (SP) chromophores and the ruthenium catalysts that drive the oscillatory Belousov-Zhabotinsky (BZ) reaction. Importantly, both the SP moieties and the BZ reaction are photosensitive. When these dual-functionalized gels are exposed to non-uniform illumination, the localized contraction of the gel (due to the SP moieties) in the presence of traveling chemical waves (due to the BZ reaction) leads to new forms of spontaneous, self-sustained movement, which cannot be achieved by either of the mono-functionalized networks.

  1. Designing Dual-functionalized Gels for Self-reconfiguration and Autonomous Motion

    SciTech Connect

    Kuksenok, Olga; Balazs, Anna C.

    2015-04-30

    Human motion is enabled by the concerted expansion and contraction of interconnected muscles that are powered by inherent biochemical reactions. One of the challenges in the field of biomimicry is eliciting this form of motion from purely synthetic materials, which typically do not generate internalized reactions to drive mechanical action. Moreover, for practical applications, this bio-inspired motion must be readily controllable. Herein, we develop a computational model to design a new class of polymer gels where structural reconfigurations and internalized reactions are intimately linked to produce autonomous motion, which can be directed with light. These gels contain both spirobenzopyran (SP) chromophores and the ruthenium catalysts that drive the oscillatory Belousov-Zhabotinsky (BZ) reaction. Importantly, both the SP moieties and the BZ reaction are photosensitive. When these dual-functionalized gels are exposed to non-uniform illumination, the localized contraction of the gel (due to the SP moieties) in the presence of traveling chemical waves (due to the BZ reaction) leads to new forms of spontaneous, self-sustained movement, which cannot be achieved by either of the mono-functionalized networks.

  2. Designing Dual-functionalized Gels for Self-reconfiguration and Autonomous Motion

    DOE PAGES

    Kuksenok, Olga; Balazs, Anna C.

    2015-04-30

    Human motion is enabled by the concerted expansion and contraction of interconnected muscles that are powered by inherent biochemical reactions. One of the challenges in the field of biomimicry is eliciting this form of motion from purely synthetic materials, which typically do not generate internalized reactions to drive mechanical action. Moreover, for practical applications, this bio-inspired motion must be readily controllable. Herein, we develop a computational model to design a new class of polymer gels where structural reconfigurations and internalized reactions are intimately linked to produce autonomous motion, which can be directed with light. These gels contain both spirobenzopyran (SP)more » chromophores and the ruthenium catalysts that drive the oscillatory Belousov-Zhabotinsky (BZ) reaction. Importantly, both the SP moieties and the BZ reaction are photosensitive. When these dual-functionalized gels are exposed to non-uniform illumination, the localized contraction of the gel (due to the SP moieties) in the presence of traveling chemical waves (due to the BZ reaction) leads to new forms of spontaneous, self-sustained movement, which cannot be achieved by either of the mono-functionalized networks.« less

  3. 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.

  4. Functional test of FOOTPRINT pedotransfer functions for the dual-permeability model MACRO

    NASA Astrophysics Data System (ADS)

    Moeys, J.; Jarvis, N. J.; Stenemo, F.; Hollis, J. M.; Dubus, I. G.; Larsbo, M.; Brown, C. D.; Bromilow, R.; Coquet, Y.; Vachier, P.

    2009-04-01

    Our ability to assess and predict pollution risks for surface waters and groundwater across larger areas (e.g. catchment and regional scales) relies on our capacity to estimate soil physical and hydrological properties and crop characteristics that are generally required as model parameters. ‘Pedotransfer' functions (PTF) can be used to estimate model parameters from more easily available soil survey data. The EU-FP6 European project FOOTPRINT (www.eu-footprint.org) has supported the development of a full set of PTF's to completely parameterise the pesticide fate model MACRO from only easily available site and soil data for a range of European agronomic, climatic and pedological scenarios The work presented here aimed at assessing the performance of the parameterisation procedures developed in the FOOTPRINT project for MACRO, from a functional point of view. We present a comparison of measured and simulated tracer leaching in medium- to long-term (2 months to 2 years) experiments driven by natural-transient rainfall conditions on 41 lysimeters, representing 15 soil types, located in Sweden, UK and France. For each experiment, the only information used to parameterize the model was a soil profile description, in which each horizon is characterized by its thickness, FAO master horizon type, texture class, organic carbon content and bulk density and knowledge of the tillage (till, no-till, harrowed) and cropping practices (crop type, and sowing dates). The average depth of the lysimeters was 1 meter, each profile containing an average of 4.6 horizons. The soil properties covered a large range of textures (1 to 78% clay), organic matter contents (0 to 29%) and bulk densities (550 to 1870 kg.m-3). Simulations were first conducted without any calibration of parameters. In a second step, we conducted simulations where two crop parameters were optimized (root depth and root water uptake efficiency), in order to estimate the impact of errors in the simulated water balance

  5. Creating conditional dual fluorescence labeled transgenic animals for studying function of small noncoding RNAs.

    PubMed

    Yang, Kun; Gao, Yun; Yang, Mingfu; Xu, Zuoshang; Chen, Qian

    2017-01-01

    Because the function of most noncoding (nc) RNAs is unknown, Cre-lox transgenic mice are useful tools to determine their functions in a tissue or developmental stage-specific manner. However, the technology faces challenges because expression of ncRNA-transgene lacks protein product. No antibody or peptide-tag can be used to trace ncRNA expression in mouse tissues in real time. Furthermore, transgene integration at different locus or orientations in the genome may result in recombination of genomic fragments in the Cre-lox system. Establishing a reliable method that can be used to determine the precise copy number and orientation of the transgene is critical to the field. We developed a fast and straightforward method to determine ncRNA-transgene copy number, orientation, and insertion site in the genome. Furthermore, upon tissue-specific expression of ncRNA, a Cre-loxP-mediated dual-fluorescence expression system facilitates fluorescence signal switching from green to red, which enables real-time monitoring of ncRNA expression by fluorescence signals. As proof of concept, we demonstrate that after microRNA (miRNA)-Flox mice crossed with Col2a1-Cre mice, miRNA transgene expression could be detected successfully by red fluorescence signals in various cartilaginous tissues. This method of creating small ncRNA transgenic mice facilitates both tissue-specific ncRNA expression and real-time visualization of its expression. It is particularly suitable for in vivo studies of the functional roles and lineage tracing of small ncRNA.

  6. Dual functions of autophagy in the response of breast tumor cells to radiation

    PubMed Central

    Bristol, Molly L.; Di, Xu; Beckman, Matthew J.; Wilson, Eden N.; Henderson, Scott C.; Maiti, Aparna; Fan, Zhen; Gewirtz, David A.

    2012-01-01

    In MCF-7 breast tumor cells, ionizing radiation promoted autophagy that was cytoprotective; pharmacological or genetic interference with autophagy induced by radiation resulted in growth suppression and/or cell killing (primarily by apoptosis). The hormonally active form of vitamin D, 1,25D3, also promoted autophagy in irradiated MCF-7 cells, sensitized the cells to radiation and suppressed the proliferative recovery that occurs after radiation alone. 1,25D3 enhanced radiosensitivity and promoted autophagy in MCF-7 cells that overexpress Her-2/neu as well as in p53 mutant Hs578t breast tumor cells. In contrast, 1,25D3 failed to alter radiosensitivity or promote autophagy in the BT474 breast tumor cell line with low-level expression of the vitamin D receptor. Enhancement of MCF-7 cell sensitivity to radiation by 1,25D3 was not attenuated by a genetic block to autophagy due largely to the promotion of apoptosis via the collateral suppression of protective autophagy. However, MCF-7 cells were protected from the combination of 1,25D3 with radiation using a concentration of chloroquine that produced minimal sensitization to radiation alone. The current studies are consistent with the premise that while autophagy mediates a cytoprotective function in irradiated breast tumor cells, promotion of autophagy can also confer radiosensitivity by vitamin D (1,25D3). As both cytoprotective and cytotoxic autophagy can apparently be expressed in the same experimental system in response to radiation, this type of model could be utilized to distinguish biochemical, molecular and/or functional differences in these dual functions of autophagy. PMID:22498493

  7. Chemically modified inulin microparticles serving dual function as a protein antigen delivery vehicle and immunostimulatory adjuvant.

    PubMed

    Gallovic, Matthew D; Montjoy, Douglas G; Collier, Michael A; Do, Clement; Wyslouzil, Barbara E; Bachelder, Eric M; Ainslie, Kristy M

    2016-03-01

    To develop a new subunit vaccine adjuvant, we chemically modified a naturally-occurring, immunostimulatory inulin polysaccharide to produce an acid-sensitive biopolymer (acetalated inulin, Ace-IN). Various hydrophobic Ace-IN polymers were formed into microparticles (MPs) by oil-in-water emulsions followed by solvent evaporation These Ace-IN MPs possessed tunable degradation characteristics that, unlike polyesters used in FDA-approved microparticulate formulations, had only pH-neutral hydrolytic byproducts. Macrophages were passively targeted with cytocompatible Ace-IN MPs. TNF-α production by macrophages treated with Ace-IN MPs could be altered by adjusting the polymers' chemistry. Mice immunized with Ace-IN MPs encapsulating a model ovalbumin (OVA) antigen showed higher production of anti-OVA IgG antibody levels relative to soluble antigen. The antibody titers were also comparable to an alum-based formulation. This proof-of-concept establishes the potential for chemically-modified inulin MPs to simultaneously enable dual functionality as a stimuli-controlled antigen delivery vehicle and immunostimulatory adjuvant.

  8. Dual-Functional Nanoparticles Targeting CXCR4 and Delivering Antiangiogenic siRNA Ameliorate Liver Fibrosis.

    PubMed

    Liu, Chun-Hung; Chan, Kun-Ming; Chiang, Tsaiyu; Liu, Jia-Yu; Chern, Guann-Gen; Hsu, Fu-Fei; Wu, Yu-Hsuan; Liu, Ya-Chi; Chen, Yunching

    2016-07-05

    The progression of liver fibrosis, an intrinsic response to chronic liver injury, is associated with hepatic hypoxia, angiogenesis, abnormal inflammation, and significant matrix deposition, leading to the development of cirrhosis and hepatocellular carcinoma (HCC). Due to the complex pathogenesis of liver fibrosis, antifibrotic drug development has faced the challenge of efficiently and specifically targeting multiple pathogenic mechanisms. Therefore, CXCR4-targeted nanoparticles (NPs) were formulated to deliver siRNAs against vascular endothelial growth factor (VEGF) into fibrotic livers to block angiogenesis during the progression of liver fibrosis. AMD3100, a CXCR4 antagonist that was incorporated into the NPs, served dual functions: it acted as a targeting moiety and suppressed the progression of fibrosis by inhibiting the proliferation and activation of hepatic stellate cells (HSCs). We demonstrated that CXCR4-targeted NPs could deliver VEGF siRNAs to fibrotic livers, decrease VEGF expression, suppress angiogenesis and normalize the distorted vessels in the fibrotic livers in the carbon tetrachloride (CCl4) induced mouse model. Moreover, blocking SDF-1α/CXCR4 by CXCR4-targeted NPs in combination with VEGF siRNA significantly prevented the progression of liver fibrosis in CCl4-treated mice. In conclusion, the multifunctional CXCR4-targeted NPs delivering VEGF siRNAs provide an effective antifibrotic therapeutic strategy.

  9. Dual function of MDM2 and MDMX toward the tumor suppressors p53 and RB

    PubMed Central

    Hernández-Monge, Jesús; Rousset-Roman, Adriana Berenice; Medina-Medina, Ixaura; Olivares-Illana, Vanesa

    2016-01-01

    The orchestrated crosstalk between the retinoblastoma (RB) and p53 pathways contributes to preserving proper homeostasis within the cell. The deregulation of one or both pathways is a common factor in the development of most types of human cancer. The proto-oncoproteins MDMX and MDM2 are the main regulators of the well- known tumor suppressor p53 protein. Under normal conditions, MDM2 and MDMX inhibit p53, either via repression of its transcriptional activity by protein-protein interaction, or via polyubiquitination as a result of MDM2-E3 ubiquitin ligase activity, for which MDM2 needs to dimerize with MDMX. Under genotoxic stress conditions, both become positive regulators of p53. The ATM-dependent phosphorylation of MDM2 and MDMX allow them to bind p53 mRNA, these interactions promote p53 translation. MDM2 and MDMX are also being revealed as effective regulators of the RB protein. MDM2 is able to degrade RB by two different mechanisms, that is, by ubiquitin dependent and independent pathways. MDMX enhances the ability of MDM2 to bind and degrade RB protein. However, MDMX also seems to stabilize RB through interaction and competition with MDM2. Here, we will contextualize the findings that suggest that the MDM2 and MDMX proteins have a dual function on both p53 and RB. PMID:28050229

  10. Dual functions of polyvinyl alcohol (PVA): fabricating particles and electrospinning nanofibers applied in controlled drug release

    NASA Astrophysics Data System (ADS)

    Qin, Xiao-Hong; Wu, De-Qun; Chu, Chih-Chang

    2013-01-01

    The fabrication of submicron size microsphere from 8-Phe-4 poly(ester amide) (PEA) using polyvinyl alcohol (PVA) as the emulsion was reported. The biodegradable microspheres were prepared by an oil-in-water emulsion/solvent evaporation technique, and PVA was used as the emulsion. Furthermore, the emulsion PVA was electrospun into nanofibrous mats, and 8-Phe-4 PEA microspheres were entrapped in the resultant mats. The dual functions of PVA to fabricate ideal nanofibrous mats which can entrap microspheres in them and to obtain 8-Phe-4 microspheres as emulsion in their potential application were demonstrated. The anti-cancer drug doxorubicin (DOX) was encapsulated in the 8-Phe-4 amino acid-based PEA microspheres and the entrapment efficiency is almost 100 %. At the same time, the DOX can be controlled released in PBS solution and in α-chymotrypsin solution. The cytotoxicity of PVA, PVA mats-entrapped 8-Phe-4 microspheres and PVA mats-entrapped DOX-loaded 8-Phe-4 microspheres, was investigated. Hela cells were used to test the cytotoxicity of the DOX that released from the PVA mats-entrapped DOX-loaded 8-Phe-4 microspheres for 2 days, and the cell viability is below 30 % when the 8-Phe-4 microspheres concentration is 1 mg/mL. It demonstrated that the PVA mats-entrapped DOX-loaded 8-Phe-4 microspheres have a potential biomedical application.

  11. Dual function of MDM2 and MDMX toward the tumor suppressors p53 and RB.

    PubMed

    Hernández-Monge, Jesús; Rousset-Roman, Adriana Berenice; Medina-Medina, Ixaura; Olivares-Illana, Vanesa

    2016-09-01

    The orchestrated crosstalk between the retinoblastoma (RB) and p53 pathways contributes to preserving proper homeostasis within the cell. The deregulation of one or both pathways is a common factor in the development of most types of human cancer. The proto-oncoproteins MDMX and MDM2 are the main regulators of the well- known tumor suppressor p53 protein. Under normal conditions, MDM2 and MDMX inhibit p53, either via repression of its transcriptional activity by protein-protein interaction, or via polyubiquitination as a result of MDM2-E3 ubiquitin ligase activity, for which MDM2 needs to dimerize with MDMX. Under genotoxic stress conditions, both become positive regulators of p53. The ATM-dependent phosphorylation of MDM2 and MDMX allow them to bind p53 mRNA, these interactions promote p53 translation. MDM2 and MDMX are also being revealed as effective regulators of the RB protein. MDM2 is able to degrade RB by two different mechanisms, that is, by ubiquitin dependent and independent pathways. MDMX enhances the ability of MDM2 to bind and degrade RB protein. However, MDMX also seems to stabilize RB through interaction and competition with MDM2. Here, we will contextualize the findings that suggest that the MDM2 and MDMX proteins have a dual function on both p53 and RB.

  12. Dual-Functionalized Double Carbon Shells Coated Silicon Nanoparticles for High Performance Lithium-Ion Batteries.

    PubMed

    Chen, Shuangqiang; Shen, Laifa; van Aken, Peter A; Maier, Joachim; Yu, Yan

    2017-03-15

    To address the challenge of huge volume change and unstable solid electrolyte interface (SEI) of silicon in cycles, causing severe pulverization, this paper proposes a "double-shell" concept. This concept is designed to perform dual functions on encapsulating volume change of silicon and stabilizing SEI layer in cycles using double carbon shells. Double carbon shells coated Si nanoparticles (DCS-Si) are prepared. Inner carbon shell provides finite inner voids to allow large volume changes of Si nanoparticles inside of inner carbon shell, while static outer shell facilitates the formation of stable SEI. Most importantly, intershell spaces are preserved to buffer volume changes and alleviate mechanical stress from inner carbon shell. DCS-Si electrodes display a high rechargeable specific capacity of 1802 mAh g(-1) at a current rate of 0.2 C, superior rate capability and good cycling performance up to 1000 cycles. A full cell of DCS-Si//LiNi0.45 Co0.1 Mn1.45 O4 exhibits an average discharge voltage of 4.2 V, a high energy density of 473.6 Wh kg(-1) , and good cycling performance. Such double-shell concept can be applied to synthesize other electrode materials with large volume changes in cycles by simultaneously enhancing electronic conductivity and controlling SEI growth.

  13. The pheromone frontalin and its dual function in the invasive bark beetle Dendroctonus valens.

    PubMed

    Liu, Zhudong; Xu, Bingbing; Miao, Zhenwang; Sun, Jianghua

    2013-07-01

    The red turpentine beetle, Dendroctonus valens LeConte, is one of the most destructive invasive forest pests in China, having killed more than 6 million pines since its first outbreak in 1999. Little is known about D. valens pheromone biology and no aggregation pheromone has yet been identified. Analysis by gas chromatograph/mass spectrometer of volatiles collected from live beetles in China showed that female beetles produce frontalin and males do not. Olfactory assays in the laboratory showed that males were attracted to frontalin at a wide range of concentrations, whereas females were attracted to it at a narrow range of concentrations. In field trials, 3-carene, a monoterpene kairomone from a pine tree selected to host the beetles attracted both sexes, and when frontalin was added, the total number of beetles captured increased by almost 200%. However, increasing concentrations of frontalin significantly decreased the percentage of female beetles trapped. These results suggest a new role of frontalin as an aggregation pheromone in addition to a female-produced sex pheromone, which was previously shown in a North American population. The dual functions of the pheromone frontalin produced by D. valens females, as well as its ecological significance for overcoming host resistance, are discussed.

  14. Targeting the mitochondrial genome via a dual function MITO-Porter: evaluation of mtDNA levels and mitochondrial function.

    PubMed

    Yamada, Yuma; Harashima, Hideyoshi

    2015-01-01

    Genetic mutations and defects in mitochondrial DNA (mtDNA) are associated with certain types of mitochondrial dysfunction, ultimately resulting in the occurrence of a variety of human diseases. For an effective mitochondrial gene therapy, it will be necessary to deliver therapeutic agents to the innermost mitochondrial space (the mitochondrial matrix), which contains the mtDNA pool. We recently developed a MITO-Porter, a liposome-based nano-carrier that delivers cargo to mitochondria via a membrane-fusion mechanism. Using propidium iodide, as a probe to detect mtDNA, we were able to confirm that the MITO-Porter delivered cargoes to mitochondrial matrices in living cells. More recently, we constructed a Dual Function (DF)-MITO-Porter, a liposome-based nanocarrier for mitochondrial delivery via a stepwise process. In this chapter, we describe the methodology used to deliver bioactive molecules to the mitochondrial matrix using the above DF-MITO-Porter, and the evaluation of mtDNA levels and mitochondrial activities in living cells.

  15. Smart dual-functional warhead for folate receptor-specific activatable imaging and photodynamic therapy.

    PubMed

    Kim, Jisu; Tung, Ching-Hsuan; Choi, Yongdoo

    2014-09-21

    A smart dual-targeted theranostic agent becomes highly fluorescent and phototoxic only when its linker is cleaved by tumor-associated lysosomal enzyme cathepsin B after internalization into folate receptor-positive cancer cells.

  16. Dual effect of local anesthetics on the function of excitable rod outer segment disk membrane

    SciTech Connect

    Mashimo, T.; Abe, K.; Yoshiya, I.

    1986-04-01

    The effects of local anesthetics and a divalent cation, Ca2+, on the function of rhodopsin were estimated from the measurements of light-induced proton uptake. The light-induced proton uptake by rhodopsin in the rod outer segment disk membrane was enhanced at lower pH (4) but depressed at higher pHs (6 to 8) by the tertiary amine local anesthetics lidocaine, bupivacaine, tetracaine, and dibucaine. The order of local anesthetic-induced depression of the proton uptake followed that of their clinical anesthetic potencies. The depression of the proton uptake versus the concentration of the uncharged form of local anesthetic nearly describes the same curve for small and large dose of added anesthetic. Furthermore, a neutral local anesthetic, benzocaine, depressed the proton uptake at all pHs between 4 and 7. These results indicate that the depression of the proton uptake is due to the effect of only the uncharged form. It is hypothesized that the uncharged form of local anesthetics interacts hydrophobically with the rhodopsin in the disk membrane. The dual effect of local anesthetics on the proton uptake, on the other hand, suggests that the activation of the function of rhodopsin may be caused by the charged form. There was no significant change in the light-induced proton uptake by rhodopsin when 1 mM of Ca2+ was introduced into the disk membrane at varying pHs in the absence or presence of local anesthetics. This fact indicates that Ca2+ ion does not influence the diprotonating process of metarhodopsin; neither does it interfere with the local anesthetic-induced changes in the rhodopsin molecule.

  17. A dual RF resonator system for high-field functional magnetic resonance imaging of small animals.

    PubMed

    Ludwig, R; Bodgdanov, G; King, J; Allard, A; Ferris, C F

    2004-01-30

    A new apparatus has been developed that integrates an animal restrainer arrangement for small animals with an actively tunable/detunable dual radio-frequency (RF) coil system for in vivo anatomical and functional magnetic resonance imaging of small animals at 4.7 T. The radio-frequency coil features an eight-element microstrip line configuration that, in conjunction with a segmented outer copper shield, forms a transversal electromagnetic (TEM) resonator structure. Matching and active tuning/detuning is achieved through fixed/variable capacitors and a PIN diode for each resonator element. These components along with radio-frequency chokes (RFCs) and blocking capacitors are placed on two printed circuit boards (PCBs) whose copper coated ground planes form the front and back of the volume coil and are therefore an integral part of the resonator structure. The magnetic resonance signal response is received with a dome-shaped single-loop surface coil that can be height-adjustable with respect to the animal's head. The conscious animal is immobilized through a mechanical arrangement that consists of a Plexiglas body tube and a head restrainer. This restrainer has a cylindrical holder with a mouthpiece and position screws to receive and restrain the head of the animal. The apparatus is intended to perform anatomical and functional magnetic resonance imaging in conscious animals such as mice, rats, hamsters, and marmosets. Cranial images acquired from fully conscious rats in a 4.7 T Bruker 40 cm bore animal scanner underscore the feasibility of this approach and bode well to extend this system to the imaging of other animals.

  18. Combining bifunctional chelator with (3 + 2)-cycloaddition approaches: synthesis of dual-function technetium complexes.

    PubMed

    Braband, Henrik; Imstepf, Sebastian; Benz, Michael; Spingler, Bernhard; Alberto, Roger

    2012-04-02

    A new concept for the synthesis of dual-functionalized technetium (Tc) compounds is presented, on the basis of the reactivity of fac-{Tc(VII)O(3)}(+) complexes. The concept combines the "classical" bifunctional chelator (BFC) approach with the new ligand centered labeling strategy of fac-{TcO(3)}(+) complexes with alkenes ((3 + 2)-cycloaddition approach). To evidence this concept, fac-{(99)TcO(3)}(+) model complexes containing functionalized 1,4,7-triazacyclononane (tacn) derivatives N-benzyl-2-(1,4,7-triazonan-1-yl)acetamide (tacn-ba) and 2,2',2″-(1,4,7-triazonane-1,4,7-triyl)triacetic acid (nota·3H) were synthesized and characterized. Whereas [(99)TcO(3)(tacn-ba)](+) [2](+) can be synthesized following a established oxidation procedure starting from the Tc(V) complex [(99)TcO(glyc)(tacn-ba)](+) [1](+), a new synthetic pathway for the synthesis of [(99)TcO(3)(nota)](2-) [5](2-) had to be developed, starting from [(99)Tc(nota·3H)(CO)(3)](+) [4](+) and using sodium perborate tetrahydrate (NaBO(3)·4H(2)O) as oxidizing reagent. While [(99)TcO(3)(nota)](2-) [5](2-) is a very attractive candidate for the development of trisubstituted novel multifunctional radioprobes, (3 + 2)-cycloaddition reactions of [(99)TcO(3)(tacn-ba)](+) [2](+) with 4-vinylbenzenesulfonate (styrene-SO(3)(-)) demonstrated the suitability of monosubstituted tacn derivatives for the new mixed "BFC-(3 + 2)-cycloaddition" approach. Kinetic studies of this reaction lead to the conclusion that the alteration of the electronic structure of the nitrogen donors by, e.g., alkylation can be used to tune the rate of the (3 + 2)-cycloaddition.

  19. Copper-doped titanium dioxide nanoparticles as dual-functional labels for fabrication of electrochemical immunosensors.

    PubMed

    Zhang, Sen; Ma, Hongmin; Yan, Liangguo; Cao, Wei; Yan, Tao; Wei, Qin; Du, Bin

    2014-09-15

    Constructions of versatile electroactive labels are key issues in the development of electrochemical immunosensors. In this study, copper-doped titanium dioxide nanoparticle (Cu@TiO2) was synthesized and used as labels for fabrication of sandwich-type electrochemical immunosensors on glassy carbon electrode (GCE). Due to the presence of copper ions, Cu@TiO2 shows a strong response current when coupled to an electrode. The prepared nanocomposite also shows high electrocatalytic activity towards reduction of hydrogen peroxide (H2O2). The dual functionality of Cu@TiO2 enables the fabrication of immunosensor using different detection modes, that is, square wave voltammetry (SWV) or chronoamperometry (CA). While Cu@TiO2 was used as labels of secondary antibodies (Ab2), carboxyl functionalized graphene oxide (CFGO) was used as electrode materials to immobilize primary antibodies (Ab1). Using human immunoglobulin G (IgG) as a model analyte, the immunosensor shows high sensitivity, acceptable stability and good reproducibility for both detection modes. Under optimal conditions, a linear range from 0.1 pg/mL to 100 ng/mL with a detection limit of 0.052 pg/mL was obtained for SWV analysis. For CA analysis, a wider linear range from 0.01 pg/mL to 100 ng/mL and a lower detection limit of 0.0043 pg/mL were obtained. The proposed metal ion-based enzyme-free and noble metal-free immunosensor may have promising applications in clinical diagnoses and many other fields.

  20. Dependence of light-emitting and photovoltaic properties of dual-function organic diodes on carrier-transporting layers

    NASA Astrophysics Data System (ADS)

    Lee, Ho-Nyeon; Choi, Mun Soo

    2013-10-01

    Dual-function photovoltaic organic light-emitting diodes (PVOEDs) have been investigated in this work. The PVOLEDs emit light when forward biased and generate electricity when backward biased. This dual function is based on the half-gap junction composed of 5,6,11,12-tetraphenylnaphthacene (rubrene) and C 60. The device structure was optimized through experiments using various organic materials for the electron-transporting layer (ETL) and electron-injection layer (EIL). Through this work, 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline (BCP), C 60 and LiF were selected as the ETL, electron-accepting layer and EIL, respectively. Using this device structure, we obtained a current efficiency of 0.27 cd/A for the light-emitting mode and a power-conversion efficiency of 1.95% for the photovoltaic mode.

  1. Dual AAV therapy ameliorates exercise-induced muscle injury and functional ischemia in murine models of Duchenne muscular dystrophy.

    PubMed

    Zhang, Yadong; Yue, Yongping; Li, Liang; Hakim, Chady H; Zhang, Keqing; Thomas, Gail D; Duan, Dongsheng

    2013-09-15

    Neuronal nitric oxide synthase (nNOS) membrane delocalization contributes to the pathogenesis of Duchenne muscular dystrophy (DMD) by promoting functional muscle ischemia and exacerbating muscle injury during exercise. We have previously shown that supra-physiological expression of nNOS-binding mini-dystrophin restores normal blood flow regulation and prevents functional ischemia in transgenic mdx mice, a DMD model. A critical next issue is whether systemic dual adeno-associated virus (AAV) gene therapy can restore nNOS-binding mini-dystrophin expression and mitigate muscle activity-related functional ischemia and injury. Here, we performed systemic gene transfer in mdx and mdx4cv mice using a pair of dual AAV vectors that expressed a 6 kb nNOS-binding mini-dystrophin gene. Vectors were packaged in tyrosine mutant AAV-9 and co-injected (5 × 10(12) viral genome particles/vector/mouse) via the tail vein to 1-month-old dystrophin-null mice. Four months later, we observed 30-50% mini-dystrophin positive myofibers in limb muscles. Treatment ameliorated histopathology, increased muscle force and protected against eccentric contraction-induced injury. Importantly, dual AAV therapy successfully prevented chronic exercise-induced muscle force drop. Doppler hemodynamic assay further showed that therapy attenuated adrenergic vasoconstriction in contracting muscle. Our results suggest that partial transduction can still ameliorate nNOS delocalization-associated functional deficiency. Further evaluation of nNOS binding mini-dystrophin dual AAV vectors is warranted in dystrophic dogs and eventually in human patients.

  2. Evaluation of bishexadecyltrimethyl ammonium palladium tetrachloride based dual functional colloidal carrier as an antimicrobial and anticancer agent.

    PubMed

    Kaur, Gurpreet; Kumar, Sandeep; Dilbaghi, Neeraj; Kaur, Baljinder; Kant, Ravi; Guru, Santosh Kumar; Bhushan, Shashi; Jaglan, Sundeep

    2016-04-21

    We have developed a dual function carrier using bishexadecyltrimethyl ammonium palladium tetrachloride, which has anticancer as well as antibacterial activity, using a ligand insertion method with a simple and easy work procedure. The complex is prepared by a simple and cost effective method using hexadecyltrimethyl ammonium chloride and palladium chloride under controlled stoichiometry. Herein, we report the aggregation (self assembly) of the metallosurfactant having palladium as a counter ion, in aqueous medium along with its binding affinity with bovine serum albumin. The palladium surfactant has exhibited excellent antimicrobial efficacy against fungus and bacteria (both Gram-positive and Gram-negative bacteria). Cytotoxicity of palladium surfactant against cancerous (Human leukemia HL-60, pancreatic MIA-Pa-Ca-2 and prostate cancer PC-3) and healthy cells (fR2 human breast epithelial cells) was also evaluated using MTT assay. The present dual functional moiety shows a low IC50 value and has potential to be used as an anticancer agent. Our dual function carrier which itself possesses antimicrobial and anticancer activity represents a simple and effective system and can also be utilized as a drug carrier in the future.

  3. The dual-functional capability of cytokine-induced killer cells and application in tumor immunology.

    PubMed

    Zhang, Qiang; Liu, Xiao-yan; Zhang, Teng; Zhang, Xin-feng; Zhao, Lin; Long, Fei; Liu, Zhuang-kai; Wang, En-hua

    2015-05-01

    Cytokine-induced killer (CIK) cells represent a heterogeneous cell population, including a large majority of CD3+CD56+ cells, a relatively minor fractions of typical T cells (CD3+CD56-), and natural killer (NK) cells (CD3-CD56+). In order to elucidate the tumor killing mechanism of these three subpopulations of CIK cells, this review summarized the concordances and differences among CD3+CD56+ CIK cells, CD3-CD56+ NK cells and CD3+CD56- T cells to the following aspects: the effects of cell surface molecules, mechanisms of tumor killing, and clinical applications of these cells in immunotherapy. NK cells can be classified into CD56brightCD16- NK cells, which produce cytokines in response to monokine co-stimulation, and the CD56dimCD16+ NK cells, which contribute to lysing susceptible target. Also, the immunity of NK cells is mainly regulated by several immune-receptors, such as ACR, ICR, NCR and KIRs. T cells require TCR and co-stimulatory molecules for initiation of T cell activation. The CD3+CD56+ CIK cells co-express with T-cell marker CD3 and NK cell marker CD56 to appear the most potent cytotoxicity and high impact on adoptive cellular immunotherapy. These CIK subpopulations share some similar tumor killing mechanisms. LFA-1 not only mediates the binding of NK cells to target cells through its ligand ICAM-1 to localize actin accumulation but also acts as a co-stimulatory receptor on NK cells. LFA-1 also functions as co-stimulatory receptor for T cells to transmit intracellular signals from the TCR to LFA-1. Furthermore, cytotoxic effect of CD3+CD56+ CIK cells is blocked by antibodies directly against LFA-1 and its counter receptor, ICAM-1. Clinically, antibody-dependent cell-mediated cytotoxicity (ADCC) is shown in both NK cells and T cells for tumor killing while dendritic cells are another main regulator for the activation of three subpopulations. In summary, CD3+CD56+ CIK cells have dual-functional capability as T-cell subsets which acquire NK cells function

  4. Inhibition of bacterial adhesion and biofilm formation by dual functional textured and nitric oxide releasing surfaces.

    PubMed

    Xu, Li-Chong; Wo, Yaqi; Meyerhoff, Mark E; Siedlecki, Christopher A

    2017-03-15

    In separate prior studies, physical topographic surface modification or nitric oxide (NO) release has been demonstrated to each be an effective approach to inhibit and control bacterial adhesion and biofilm formation on polymeric surfaces. Such approaches can prevent biomaterial-associated infection without causing the antibiotic resistance of the strain. In this work, both techniques were successfully integrated and applied to a polyurethane (PU) biomaterial surface that bears ordered pillar topographies (400/400nm and 500/500nm patterns) at the top surface and a S-nitroso-N-acetylpenicillamine (SNAP, NO donor) doped sub-layer in the middle, via a soft lithography two-stage replication process. Upon placing the SNAP textured PU films into PBS at 37°C, the decomposition of SNAP within polymer film initiates NO release with a lifetime of up to 10days at flux levels >0.5×10(-10)molmin(-1)cm(-2) for a textured polyurethane layer containing 15wt% SNAP. The textured surface reduces the accessible surface area and the opportunity of bacteria-surface interaction, while the NO release from the same surface further inhibits bacterial growth and biofilm formation. Such dual functionality surfaces are shown to provide a synergistic effect on inhibition of Staphylococcus epidermidis bacterial adhesion that is significantly greater than the inhibition of bacterial adhesion achieved by either single treatment approach alone. Longer term experiments to observe biofilm formation demonstrate that the SNAP doped-textured PU surface can inhibit the biofilm formation for >28d and provide a practical approach to improve the biocompatibility of current biomimetic biomaterials and thereby reduce the risk of pathogenic infection.

  5. Dual Sensory Loss and Depressive Symptoms: The Importance of Hearing, Daily Functioning, and Activity Engagement

    PubMed Central

    Kiely, Kim M.; Anstey, Kaarin J.; Luszcz, Mary A.

    2013-01-01

    Background: The association between dual sensory loss (DSL) and mental health has been well established. However, most studies have relied on self-report data and lacked measures that would enable researchers to examine causal pathways between DSL and depression. This study seeks to extend this research by examining the effects of DSL on mental health, and identify factors that explain the longitudinal associations between sensory loss and depressive symptoms. Methods: Piecewise linear-mixed models were used to analyze 16-years of longitudinal data collected on up to five occasions from 1611 adults (51% men) aged between 65 and 103 years. Depressive symptoms were assessed by the Centre for Epidemiological Studies Depression (CES-D). Vision loss (VL) was defined by corrected visual acuity >0.3 logMAR in the better eye, blindness, or glaucoma. Hearing loss (HL) was defined by pure-tone average (PTA) >25 dB in the better hearing ear. Analyses were adjusted for socio-demographics, medical conditions, lifestyle behaviors, activities of daily living (ADLs), cognitive function, and social engagement. Results: Unadjusted models indicated that higher levels of depressive symptoms were associated with HL (B = 1.16, SE = 0.33) and DSL (B = 2.15, SE = 0.39) but not VL. Greater rates of change in depressive symptoms were also evident after the onset of HL (B = 0.16, SE = 0.06, p < 0.01) and DSL (B = 0.30, SE = 0.09, p < 0.01). The associations between depressive symptoms and sensory loss were explained by difficulties with ADLs, and social engagement. Conclusion: Vision and HL are highly prevalent among older adults and their co-occurrence may compound their respective impacts on health, functioning, and activity engagement, thereby exerting strong effects on the mental health and wellbeing of those affected. There is therefore a need for rehabilitation programs to be sensitive to the combined effects of sensory loss on individuals

  6. The pesticin receptor of Yersinia enterocolitica: a novel virulence factor with dual function.

    PubMed

    Rakin, A; Saken, E; Harmsen, D; Heesemann, J

    1994-07-01

    The iron-repressible outer membrane protein FyuA of Yersinia enterocolitica operates as a receptor with dual function: (i) as a receptor for the Y. pestis bacteriocin pesticin, and (ii) as a receptor for yersiniabactin, a siderophore that is produced by mouse-virulent Y. enterocolitica strains of biogroup IB. Cloning of the FyuA-encoding gene was achieved by mobilization of a genomic cosmid library of the pesticin-sensitive and mouse-virulent Y. enterocolitica O:8 strain WA into the pesticin-resistant WA fyuA mutant and subsequent in vivo selection of transconjugants for the ability to survive and multiply in mice (phenotype mouse virulence). The reisolated transconjugants which survived in mice for 3 d harboured a unique cosmid and phenotypically were pesticin sensitive. From this cosmid a 2650 bp SalI-PstI fragment conferring pesticin sensitivity was subcloned. Sequencing of this DNA fragment revealed a single open reading frame of 2022 bp, which encodes a deduced polypeptide of 673 amino acids with a predicted molecular mass of 73,677 Da. Cleavage of a putative signal sequence composed of 22 amino acids should lead to a mature protein of 651 amino acids with a molecular mass of 71,368 Da. The open reading frame is preceded by a sequence which shares homology with the postulated consensus Fur iron-repressor protein-binding site. FyuA shows homology to other iron-regulated TonB-dependent outer membrane proteins with receptor functions (e.g. BtuB, CirA, FepA, IutA, FhuA, FoxA, FcuA). On the basis of multiple alignment of amino acid sequences of FyuA and other TonB-dependent receptors, a phylogenetic tree was constructed, demonstrating that FyuA probably belongs to the citrate subfamily or represents a new subfamily of TonB-dependent receptors. Moreover, by complementation of the WA fyuA mutant by the cloned fyuA gene, yersiniabactin uptake and mouse virulence were restored. These studies demonstrate that the cloned pesticin/yersiniabactin receptor FyuA of Y

  7. Inhibition of HIV Virus by Neutralizing Vhh Attached to Dual Functional Liposomes Encapsulating Dapivirine

    NASA Astrophysics Data System (ADS)

    Wang, Scarlet Xiaoyan; Michiels, Johan; Ariën, Kevin K.; New, Roger; Vanham, Guido; Roitt, Ivan

    2016-07-01

    efficacy in reducing viral replication in vitro. Thus, dual function liposomes may lead to a novel strategy for the prophylaxis of HIV/AIDS by combining the neutralizing activity of Vhh with antiviral effects of high drug concentrations.

  8. State of charge modeling of lithium-ion batteries using dual exponential functions

    NASA Astrophysics Data System (ADS)

    Kuo, Ting-Jung; Lee, Kung-Yen; Huang, Chien-Kang; Chen, Jau-Horng; Chiu, Wei-Li; Huang, Chih-Fang; Wu, Shuen-De

    2016-05-01

    A mathematical model is developed by fitting the discharging curve of LiFePO4 batteries and used to investigate the relationship between the state of charge and the closed-circuit voltage. The proposed mathematical model consists of dual exponential terms and a constant term which can fit the characteristics of dual equivalent RC circuits closely, representing a LiFePO4 battery. One exponential term presents the stable discharging behavior and the other one presents the unstable discharging behavior and the constant term presents the cut-off voltage.

  9. A Concise Access to C2-Symmetric Chiral 4-Pyrrolidinopyridine Catalysts with Dual Functional Side Chains.

    PubMed

    Mishiro, Kenji; Takeuchi, Hironori; Furuta, Takumi; Kawabata, Takeo

    2016-07-01

    A practical method was developed for the preparation of a diastereomeric library of C2-symmetric chiral 4-pyrrolidinopyridine catalysts with dual amide side chains. Use of a racemic precursor is the key to the concise production of catalysts with diverse stereochemisty.

  10. Function, Type, and Distribution of Teacher Questions in Dual-Language Preschool Read Alouds

    ERIC Educational Resources Information Center

    Gort, Mileidis; Pontier, Ryan W.; Sembiante, Sabrina F.

    2012-01-01

    This exploratory study investigated the nature and distribution of dual-language preschool teachers' questions across parallel Spanish- and English-medium read-aloud activities. The notions of comprehensible input (Krashen, 1985) and language output (Swain, 1985), along with a reciprocal interaction model of teaching (Cummins, 2000), guided our…

  11. Using the Time-Lagged Function of Dual-Aperture Scintillometer Measurements to Obtain the Crosswind

    NASA Astrophysics Data System (ADS)

    van Dinther, D.; Hartogensis, O.

    2013-12-01

    In this study the so-called crosswind (U⊥), the wind component perpendicular on a path, is determined from scintillometer measurements. A scintillometer is a device consisting of a transmitter and receiver, typically spaced a few hundred meters to a few kilometers apart. The dual-aperture scintillometer used in this study consists of two transmitters and two receivers installed next to each other. The transmitters emit light with a certain intensity which is refracted by the eddies in the atmosphere. The eddy field in between the transmitters and receivers constantly changes leading to intensity fluctuations of the light at the receivers side, which gives the scintillometer signal. The driving phenomenon of the changing eddy field is wind. The scintillometer path is ~ 100 m and the spacing in between the apertures is ~ 10 cm therefore the eddy field is mainly changed due to U⊥. A scintillometer obtains a path averaged U⊥, which for some applications (e.g. at airports) is an advantage compared to other wind measurement devices. Applying Taylor's frozen turbulence assumption the signals of the two scintillometers should be the same except for a small time shift between the two signals, from which U⊥ can be determined. This time shift can be obtained from the time-lagged-correlation function of the two signals (r12 (τ)). Four methods were used to obtain U⊥; the peak method, the Briggs method, the zero-slope method, and the correlation method. The last one is a new method introduced in this study, which obtains U⊥ by comparing r12 (τ) of a measurement to r12 (τ) of Lawrence et al. (1972) theoretical model. U⊥ values obtained from the scintillometer were validated against sonic anemometer measurements. The best results were obtained by the zero-slope method and the correlation method. The zero-slope method gave the best results for low U⊥ values (< 2 m s-1), while the correlation method gave the best results for high U⊥ values (> 2 m s-1). The

  12. Functional analysis of liverworts in dual symbiosis with Glomeromycota and Mucoromycotina fungi under a simulated Palaeozoic CO2 decline

    PubMed Central

    Field, Katie J; Rimington, William R; Bidartondo, Martin I; Allinson, Kate E; Beerling, David J; Cameron, Duncan D; Duckett, Jeffrey G; Leake, Jonathan R; Pressel, Silvia

    2016-01-01

    Most land plants form mutualistic associations with arbuscular mycorrhizal fungi of the Glomeromycota, but recent studies have found that ancient plant lineages form mutualisms with Mucoromycotina fungi. Simultaneous associations with both fungal lineages have now been found in some plants, necessitating studies to understand the functional and evolutionary significance of these tripartite associations for the first time. We investigate the physiology and cytology of dual fungal symbioses in the early-diverging liverworts Allisonia and Neohodgsonia at modern and Palaeozoic-like elevated atmospheric CO2 concentrations under which they are thought to have evolved. We found enhanced carbon cost to liverworts with simultaneous Mucoromycotina and Glomeromycota associations, greater nutrient gain compared with those symbiotic with only one fungal group in previous experiments and contrasting responses to atmospheric CO2 among liverwort–fungal symbioses. In liverwort–Mucoromycotina symbioses, there is increased P-for-C and N-for-C exchange efficiency at 440 p.p.m. compared with 1500 p.p.m. CO2. In liverwort–Glomeromycota symbioses, P-for-C exchange is lower at ambient CO2 compared with elevated CO2. No characteristic cytologies of dual symbiosis were identified. We provide evidence of a distinct physiological niche for plant symbioses with Mucoromycotina fungi, giving novel insight into why dual symbioses with Mucoromycotina and Glomeromycota fungi persist to the present day. PMID:26613340

  13. Functional analysis of liverworts in dual symbiosis with Glomeromycota and Mucoromycotina fungi under a simulated Palaeozoic CO2 decline.

    PubMed

    Field, Katie J; Rimington, William R; Bidartondo, Martin I; Allinson, Kate E; Beerling, David J; Cameron, Duncan D; Duckett, Jeffrey G; Leake, Jonathan R; Pressel, Silvia

    2016-06-01

    Most land plants form mutualistic associations with arbuscular mycorrhizal fungi of the Glomeromycota, but recent studies have found that ancient plant lineages form mutualisms with Mucoromycotina fungi. Simultaneous associations with both fungal lineages have now been found in some plants, necessitating studies to understand the functional and evolutionary significance of these tripartite associations for the first time. We investigate the physiology and cytology of dual fungal symbioses in the early-diverging liverworts Allisonia and Neohodgsonia at modern and Palaeozoic-like elevated atmospheric CO2 concentrations under which they are thought to have evolved. We found enhanced carbon cost to liverworts with simultaneous Mucoromycotina and Glomeromycota associations, greater nutrient gain compared with those symbiotic with only one fungal group in previous experiments and contrasting responses to atmospheric CO2 among liverwort-fungal symbioses. In liverwort-Mucoromycotina symbioses, there is increased P-for-C and N-for-C exchange efficiency at 440 p.p.m. compared with 1500 p.p.m. CO2. In liverwort-Glomeromycota symbioses, P-for-C exchange is lower at ambient CO2 compared with elevated CO2. No characteristic cytologies of dual symbiosis were identified. We provide evidence of a distinct physiological niche for plant symbioses with Mucoromycotina fungi, giving novel insight into why dual symbioses with Mucoromycotina and Glomeromycota fungi persist to the present day.

  14. Evolutionarily Conserved Dual Lysine Motif Determines the Non-Chaperone Function of Secreted Hsp90alpha in Tumor Progression

    PubMed Central

    Sahu, Divya; Hou, Yingping; Tsen, Fred; Tong, Chang; O’Brien, Kathryn; Situ, Alan J.; Schmidt, Thomas; Chen, Mei; Ying, Qilong; Ulmer, Tobias S.; Woodley, David T.; Li, Wei

    2016-01-01

    Both intracellular and extracellular heat shock protein-90 (Hsp90) family proteins (α and β) have been shown to support tumor progression. The tumor-promoting activity of the intracellular Hsp90 proteins is attributed to their N-terminal ATPase-driven chaperone function. What determines the extracellular function of secreted Hsp90 was unclear. Here we show that knocking out Hsp90α nullifies tumor cell abilities to migrate, invade and metastasize without affecting cell survival and growth. Knocking out Hsp90β leads to cell death. Extracellular supplementation with recombinant Hsp90α, but not Hsp90β, protein recovers the tumorigenicity of Hsp90α-knockout cells. Sequential mutagenesis identifies two evolutionarily conserved lysine residues, lys-270 and lys-277, in Hsp90α subfamily that determine the extracellular Hsp90α function. Hsp90β subfamily lacks the dual lysine motif and does not show the same extracellular function. Substitutions of gly-262 and thr-269 in Hsp90β with lysines convert Hsp90β to act as Hsp90α outside the cells. Monoclonal antibody, 1G6-D7, against the dual lysine region of secreted Hsp90α blocks de novo tumor formation and significantly inhibits expansion of already formed tumors. This study suggests an alternative therapeutic approach to selectively target the extracellular Hsp90α to the conventional approach targeting the ATPase of intracellular Hsp90α and Hsp90β in cancer. PMID:27721406

  15. Effect of dual modification of sonication and γ-irradiation on physicochemical and functional properties of lentil (Lens culinaris L.) starch.

    PubMed

    Majeed, Toiba; Wani, Idrees Ahmed; Hussain, Peerzada Rashid

    2017-03-21

    Starch isolated from lentil was subjected to two treatments namely sonication and, a dual treatment of sonication and irradiation at a dose of 5kGy. Lentil yielded 26.12±1.56g starch/100g of lentil. Chemical composition of native starch revealed 7.83±0.28% moisture, 0.23±0.30% protein, 0.35±0.05% fat and 0.10±0.00% ash. The results revealed that pasting properties of lentil starch were not affected upon sonication. However, these decreased significantly (p≤0.05) upon dual treatments. Amylose content of native starch was 31.16±1.80g/100g which showed a decrease upon sonication and dual treatments. Sonication and dual treatments (sonication and irradiation) decreased hunter 'L' value while 'a' and 'b' values showed an increase. Syneresis decreased more or less insignificantly upon sonication. However, a significant decrease in syneresis was observed after 120h storage following dual treatments. Sonication did not decrease the functional properties significantly while as dual treatment induced a significant decrease in functional properties. FT-IR analysis revealed a decrease in the intensities of OH, CH and OC stretches and CH2 bending upon sonication and dual treatments.

  16. Walking in School-Aged Children in a Dual-Task Paradigm Is Related to Age But Not to Cognition, Motor Behavior, Injuries, or Psychosocial Functioning

    PubMed Central

    Hagmann-von Arx, Priska; Manicolo, Olivia; Lemola, Sakari; Grob, Alexander

    2016-01-01

    Age-dependent gait characteristics and associations with cognition, motor behavior, injuries, and psychosocial functioning were investigated in 138 typically developing children aged 6.7–13.2 years (M = 10.0 years). Gait velocity, normalized velocity, and variability were measured using the walkway system GAITRite without an additional task (single task) and while performing a motor or cognitive task (dual task). Assessment of children’s cognition included tests for intelligence and executive functions; parents reported on their child’s motor behavior, injuries, and psychosocial functioning. Gait variability (an index of gait regularity) decreased with increasing age in both single- and dual-task walking. Dual-task gait decrements were stronger when children walked in the motor compared to the cognitive dual-task condition and decreased with increasing age in both dual-task conditions. Gait alterations from single- to dual-task conditions were not related to children’s cognition, motor behavior, injuries, or psychosocial functioning. PMID:27014158

  17. Determination of liquid's molecular interference function based on X-ray diffraction and dual-energy CT in security screening.

    PubMed

    Zhang, Li; YangDai, Tianyi

    2016-08-01

    A method for deriving the molecular interference function (MIF) of an unknown liquid for security screening is presented. Based on the effective atomic number reconstructed from dual-energy computed tomography (CT), equivalent molecular formula of the liquid is estimated. After a series of optimizations, the MIF and a new effective atomic number are finally obtained from the X-ray diffraction (XRD) profile. The proposed method generates more accurate results with less sensitivity to the noise and data deficiency of the XRD profile.

  18. Staining-free gel electrophoresis-based multiplex enzyme assay using DNA and peptide dual-functionalized gold nanoparticles.

    PubMed

    Zhao, Wenting; Yao, Chunlei; Luo, Xiaoteng; Lin, Li; Hsing, I-Ming

    2012-04-01

    We report a simple staining-free gel electrophoresis method to simultaneously probe protease and nuclease. Utilizing gold nanoparticles (Au-NPs) dual-functionalized with DNA and peptide, the presence and concentration of nuclease and protease are determined concurrently from the relative position and intensity of the bands in the staining-free gel electrophoresis. The use of Au-NPs eliminates the need for staining processes and enables naked eye detection, while a mononucleotide-mediated approach facilitates the synthesis of DNA/peptide conjugated Au-NPs and simplifies the operation procedures. Multiplex detection and quantification of DNase I and trypsin are successfully demonstrated.

  19. The dual functions of WLIM1a in cell elongation and secondary wall formation in developing cotton fibers.

    PubMed

    Han, Li-Bo; Li, Yuan-Bao; Wang, Hai-Yun; Wu, Xiao-Min; Li, Chun-Li; Luo, Ming; Wu, Shen-Jie; Kong, Zhao-Sheng; Pei, Yan; Jiao, Gai-Li; Xia, Gui-Xian

    2013-11-01

    LIN-11, Isl1 and MEC-3 (LIM)-domain proteins play pivotal roles in a variety of cellular processes in animals, but plant LIM functions remain largely unexplored. Here, we demonstrate dual roles of the WLIM1a gene in fiber development in upland cotton (Gossypium hirsutum). WLIM1a is preferentially expressed during the elongation and secondary wall synthesis stages in developing fibers. Overexpression of WLIM1a in cotton led to significant changes in fiber length and secondary wall structure. Compared with the wild type, fibers of WLIM1a-overexpressing plants grew longer and formed a thinner and more compact secondary cell wall, which contributed to improved fiber strength and fineness. Functional studies demonstrated that (1) WLIM1a acts as an actin bundler to facilitate elongation of fiber cells and (2) WLIM1a also functions as a transcription factor to activate expression of Phe ammonia lyase-box genes involved in phenylpropanoid biosynthesis to build up the secondary cell wall. WLIM1a localizes in the cytosol and nucleus and moves into the nucleus in response to hydrogen peroxide. Taken together, these results demonstrate that WLIM1a has dual roles in cotton fiber development, elongation, and secondary wall formation. Moreover, our study shows that lignin/lignin-like phenolics may substantially affect cotton fiber quality; this finding may guide cotton breeding for improved fiber traits.

  20. Dual-function photonic integrated circuit for frequency octo-tupling or single-side-band modulation.

    PubMed

    Hasan, Mehedi; Maldonado-Basilio, Ramón; Hall, Trevor J

    2015-06-01

    A dual-function photonic integrated circuit for microwave photonic applications is proposed. The circuit consists of four linear electro-optic phase modulators connected optically in parallel within a generalized Mach-Zehnder interferometer architecture. The photonic circuit is arranged to have two separate output ports. A first port provides frequency up-conversion of a microwave signal from the electrical to the optical domain; equivalently single-side-band modulation. A second port provides tunable millimeter wave carriers by frequency octo-tupling of an appropriate amplitude RF carrier. The circuit exploits the intrinsic relative phases between the ports of multi-mode interference couplers to provide substantially all the static optical phases needed. The operation of the proposed dual-function photonic integrated circuit is verified by computer simulations. The performance of the frequency octo-tupling and up-conversion functions is analyzed in terms of the electrical signal to harmonic distortion ratio and the optical single side band to unwanted harmonics ratio, respectively.

  1. Dual-functional Lipid-like Nanoparticles for Delivery of mRNA and MRI Contrast Agent†

    PubMed Central

    Luo, X.; Li, B.; Zhang, X.; Zhao, W.; Bratasz, A.; Deng, B.; McComb, D. W.

    2017-01-01

    Multi-functional nanomaterials possess unique properties, facilitating both therapeutic and diagnostic applications among others. Herein, we developed dual-functional lipid-like nanoparticles for simultaneous delivery of mRNA and magnetic resonance imaging (MRI) contrast agent in order to express functional proteins and provide real-time visualization. TT3-Gd18 LLNs was identified as a lead formulation, which was able to encapsulate 91% of mRNA and 74% of Gd. This formulation showed comparable or slightly higher delivery efficiency of mRNA compared to the initial TT3 LLNs. Moreover, strong MRI signal was observed in cell pellets treated with TT3-Gd18 LLNs. More importantly, TT3-Gd18 LLNs demonstrated efficient delivery of mRNA and Gd contrast agent in vivo. PMID:28067926

  2. Dual-functional Polyurea Microcapsules for Chronic Wound Care Dressings: Sustained Drug Delivery and Non-leaching Infection Control

    NASA Astrophysics Data System (ADS)

    He, Wei

    A new design of dual-functional polyurea microcapsules was proposed for chronic wound dressings to provide both non-leaching infection control and sustained topical drug delivery functionalities. Quaternary ammonium functionalized polyurea microcapsules (MCQs) were synthesized under mild conditions through an interfacial crosslinking reaction between branched polyethylenimine (PEI) and 2,4-toluene diisocyanate (TDI) in a dimethylformamide/cyclohexane emulsion. An in-situ modification method was developed to endow non-leaching surface antimicrobial properties to MCQs via bonding antimicrobial surfactants to surface isocyanate residues on the polyurea shells. The resultant robust MCQs with both non-leaching antimicrobial properties and sustained drug releasing properties have potential applications in medical textiles, such as chronic wound dressings, for infection control and drug delivery.

  3. Manganese (II) Chelate Functionalized Copper Sulfide Nanoparticles for Efficient Magnetic Resonance/Photoacoustic Dual-Modal Imaging Guided Photothermal Therapy

    PubMed Central

    Liu, Renfa; Jing, Lijia; Peng, Dong; Li, Yong; Tian, Jie; Dai, Zhifei

    2015-01-01

    The integration of diagnostic and therapeutic functionalities into one nanoplatform shows great promise in cancer therapy. In this research, manganese (II) chelate functionalized copper sulfide nanoparticles were successfully prepared using a facile hydrothermal method. The obtained ultrasmall nanoparticles exhibit excellent photothermal effect and photoaoustic activity. Besides, the high loading content of Mn(II) chelates makes the nanoparticles attractive T1 contrast agent in magnetic resonance imaging (MRI). In vivo photoacoustic imaging (PAI) results showed that the nanoparticles could be efficiently accumulated in tumor site in 24 h after systematic administration, which was further validated by MRI tests. The subsequent photothermal therapy of cancer in vivo was achieved without inducing any observed side effects. Therefore, the copper sulfide nanoparticles functionalized with Mn(II) chelate hold great promise as a theranostic nanomedicine for MR/PA dual-modal imaging guided photothermal therapy of cancer. PMID:26284144

  4. Manganese (II) Chelate Functionalized Copper Sulfide Nanoparticles for Efficient Magnetic Resonance/Photoacoustic Dual-Modal Imaging Guided Photothermal Therapy.

    PubMed

    Liu, Renfa; Jing, Lijia; Peng, Dong; Li, Yong; Tian, Jie; Dai, Zhifei

    2015-01-01

    The integration of diagnostic and therapeutic functionalities into one nanoplatform shows great promise in cancer therapy. In this research, manganese (II) chelate functionalized copper sulfide nanoparticles were successfully prepared using a facile hydrothermal method. The obtained ultrasmall nanoparticles exhibit excellent photothermal effect and photoaoustic activity. Besides, the high loading content of Mn(II) chelates makes the nanoparticles attractive T1 contrast agent in magnetic resonance imaging (MRI). In vivo photoacoustic imaging (PAI) results showed that the nanoparticles could be efficiently accumulated in tumor site in 24 h after systematic administration, which was further validated by MRI tests. The subsequent photothermal therapy of cancer in vivo was achieved without inducing any observed side effects. Therefore, the copper sulfide nanoparticles functionalized with Mn(II) chelate hold great promise as a theranostic nanomedicine for MR/PA dual-modal imaging guided photothermal therapy of cancer.

  5. Functional Results of Intercondylar Fractures of the Humerus Fixed with Dual Y-Plate; A Technical Note  

    PubMed Central

    Mahapatra, Swagat; Abraham, Vineet Thomas

    2017-01-01

    Objective: To evaluate and report the functional results of surgical management of intercondylar fractures of the humerus in adults using a novel dual plating technique. Methods: A total number of 60 patients with Riseborough and Radin type II, III, and IV intercondylar humerus fractures were operated with open reduction through a Trans-olecranon approach and internal fixation using two plates in inverted-Y configuration. Patients were followed for 3 weeks, 3 and 6 months were evaluated using the Mayo Elbow performance score and Quick-DASH score. Results: There were 50(83.33%)men and 10 (16.67%)women with mean age of 34.9 ± 12.63 years. 63.3% of the cases were following Motor vehicle accident and rest following fall. The right upper limb was more commonly affected than the left side. Riseborough and Radin type II fractures accounted for 3.33% of cases; type III fractures accounted for 50% of cases and type IV accounted for 46.67%. Excellent to Good results were seen in almost 80% of cases as per the Mayo Elbow performance score at 6-month follow-up. Quick-DASH scores for the series at 6-month follow-up was on average of 15.96 ± 9.92. Conclusion: Dual plating in inverted Y configuration offers a reliable fixation, which permits early mobilization and good functional outcome. PMID:28246622

  6. Targeted Delivery of Anticancer Agents via a Dual Function Nanocarrier with an Interfacial Drug-Interactive Motif

    PubMed Central

    2015-01-01

    We have developed a dual-function drug carrier, polyethylene glycol (PEG)-derivatized farnesylthiosalicylate (FTS). Here we report that incorporation of a drug-interactive motif (Fmoc) into PEG5k–FTS2 led to further improvement in both drug loading capacity and formulation stability. Doxorubicin (DOX) formulated in PEG5k–Fmoc–FTS2 showed sustained release kinetics slower than those of DOX loaded in PEG5k–FTS2. The maximum tolerated dose of DOX- or paclitaxel (PTX)-loaded PEG5k–Fmoc–FTS2 was significantly higher than that of the free drug. Pharmacokinetics and biodistribution studies showed that DOX/PEG5k–Fmoc–FTS2 mixed micelles were able to retain DOX in the bloodstream for a significant amount of time and efficiently deliver the drug to tumor sites. More importantly, drug (DOX or PTX)-loaded PEG5k–Fmoc–FTS2 led to superior antitumor activity over other treatments including drugs formulated in PEG5k–FTS2 in breast cancer and prostate cancer models. Our improved dual function carrier with a built-in drug-interactive motif represents a simple and effective system for targeted delivery of anticancer agents. PMID:25325795

  7. Dual Functional Polymer Interlayer for Facilitating Ion Transport and Reducing Charge Recombination in Dye-Sensitized Solar Cells.

    PubMed

    Wang, Ying-Chiao; Li, Shao-Sian; Wen, Cheng-Yen; Chen, Liang-Yih; Ho, Kuo-Chuan; Chen, Chun-Wei

    2016-12-14

    Dye-sensitized solar cells (DSSCs) present low-cost alternatives to conventional wafer-based inorganic solar cells and have remarkable power conversion efficiency. To further enhance performance, we propose a new DSSC architecture with a novel dual-functional polymer interlayer that prevents charge recombination and facilitates ionic conduction, as well as maintaining dye loading and regeneration. Poly(vinylidene fluoride-trifluoroethylene) (p(VDF-TrFE)) was coated on the outside of a dye-sensitized TiO2 photoanode by a simple solution process that did not sacrifice the amount of adsorbed dye molecules in the DSSC device. Light-intensity-modulated photocurrent and photovoltage spectroscopy revealed that the proposed p(VDF-TrFE)-coated anode yielded longer electron lifetime and improved the injection of photogenerated electrons into TiO2, thereby reducing the electron transport time. Comparative cyclic voltammetry and UV-visible absorption spectroscopy based on a ferrocene-ferrocenium external standard material demonstrated that p(VDF-TrFE) enhanced the power conversion efficiency from 7.67% to 9.11%. This dual functional p(VDF-TrFE) interlayer is a promising candidate for improving the performance of DSSCs and can also be employed in other electrochemical devices.

  8. Solenoid assembly with beam focusing and radiation shielding functions for the 9/6 MeV dual energy linac

    NASA Astrophysics Data System (ADS)

    Cha, Sungsu; Kim, Yujong; Ju, Jinsik; Joo, Youngwoo; Lee, Byeong-No; Lee, Soo Min; Kim, Jae Hyun; Buaphad, Pikad; Lee, Byung Cheol; Cha, Hyungki; Ha, Jang Ho; Park, Hyung Dal; Song, Ki Beak; Lee, Seung Hyun; Kim, Heesoo

    2016-09-01

    The Korea Atomic Energy Research Institute (KAERI) has been developing a Container Inspection System (CIS) by using a dual-energy (9/6 MeV) S-band (= 2856 MHz) electron linear accelerator. The key components of the CIS are the electron linear accelerator (including an electron gun, an accelerating structure, an RF power source, cooling chillers, vacuum pumps, magnet power supplies, and two solenoid magnets with beam focusing and shielding functions), a tungsten target for X-ray generation, an X-ray collimator, a detector array, and a container moving system. Generally, in accelerators, beam focusing is mainly done by solenoids operating in the region of a few MeV to keep the shape of transverse beam symmetrically round so as to reduce the loss of electrons, which increases the beam current and the beam power. In addition, a specially-designed component is needed to protect against the radiation due to the lost electrons. In this paper, we describe the design, fabrication, and optimization of two specially- designed solenoids with focusing and radiation shielding functions for a dual-energy S-band electron linear accelerator for a CIS.

  9. Computerized Dual-Task Testing of Gait and Visuospatial Cognitive Functions; Test-Retest Reliability and Validity

    PubMed Central

    Szturm, Tony J.; Sakhalkar, Vedant S.; Kanitkar, Anuprita; Nankar, Mayur

    2017-01-01

    The common occurrence of age decline in mobility and cognition does cause a decrease in the level of physical activity and an increased falls risk. Consequently, dual -task (DT) assessment that simultaneously addresses both mobility skills and cognitive functions are important because, continued difficulties and fall injuries will have a sizable impact in this population. The first objective of the present study was to assess test-retest reliability of a computerized DT treadmill walking protocol and concurrent outcome measures of gait and visuospatial executive function in a group of healthy older adults. Secondly, discriminative validity was evaluated by examining the effect of DT conditions (single task vs. dual-task) on; (a) spatiotemporal gait measures (average and coefficient of variation) and (b) visuomotor and visuospatial executive performance measures. Twenty-five community-dwelling individuals median age 65 (range 61–67) were recruited from a Fitness Facility. Participants performed a computerized visuomotor tracking task and a visuospatial executive game task in standing and while treadmill walking. Testing was conducted on two occasions, 1 week apart. Moderate to high test-retest reliability (ICC values of 0.65–0.88) were observed for spatiotemporal gait variables. No significant differences between the group means were observed between test periods in any gait variable. Moderate test-retest reliability (ICC values of 0.6–0.65) was observed for measures of visuomotor and visuospatial executive performance during treadmill walking. Significant DT effects were observed for both spatiotemporal gait variables and visuospatial executive performance measures. This study demonstrates the reliability and reproducibility of the computer-based assessment tool for dual task treadmill walking. The high to moderate ICC values and the lack of systematic errors in the measures indicate that this tool has the ability to repeatedly record reliable data from

  10. ``Green'' functionalization of magnetic nanoparticles via tea polyphenol for magnetic resonance/fluorescent dual-imaging

    NASA Astrophysics Data System (ADS)

    Jiang, Wen; Lai, Kuilin; Liu, Kexia; Xia, Rui; Gao, Fabao; Wu, Yao; Gu, Zhongwei

    2014-01-01

    Tea polyphenol serves as an environmentally friendly ligand-exchange molecule to synthesize multifunctional metal-doped superparamagnetic iron oxide nanoparticles via a catechol-metal coordination interaction. The resultant particles not only exhibit excellent hydrophilicity and protein adsorption resistance, but also are applicable as magnetic resonance/fluorescent dual-imaging probes due to their high T2 relaxivity, autofluorescence and large cellular uptake.Tea polyphenol serves as an environmentally friendly ligand-exchange molecule to synthesize multifunctional metal-doped superparamagnetic iron oxide nanoparticles via a catechol-metal coordination interaction. The resultant particles not only exhibit excellent hydrophilicity and protein adsorption resistance, but also are applicable as magnetic resonance/fluorescent dual-imaging probes due to their high T2 relaxivity, autofluorescence and large cellular uptake. Electronic supplementary information (ESI) available: Additional information and figures (Fig. S1-S7), including experimental sections, characterization of the products, protein corona analysis, cytotoxicity and cellular uptake quantification. See DOI: 10.1039/c3nr05003c

  11. A dual-route account for access to grammatical gender: evidence from functional MRI.

    PubMed

    Heim, Stefan; Alter, Kai; Friederici, Angela D

    2005-12-01

    Research investigating the neural correlates of grammatical gender processing has provided contradictory evidence with respect to activation in the left inferior frontal gyrus (IFG). A possible account for these discrepancies is a dual-route model proposing explicit vs implicit access to the gender information. In this event-related fMRI experiment, we investigated this issue by taking into account different processing strategies reported by the subjects. The participants performed two tasks, a gender judgement of German nouns and a non-lexical baseline task (spacing of consonant letter strings). Depending on the reported strategy (silent production of the definite determiner or direct access to the gender information), different patterns of activation in the left IFG were observed. Direct access to gender information yielded activation in the inferior tip of BA 44, whereas the verbalisation strategy elicited activation in the superior portion of BA 44, BA 45/47, and the fronto-median wall. These results speak in favour of a dual-route account for modelling the access to grammatical gender information during language comprehension.

  12. Analysis of Genotoxic and Cytotoxic Responses Induced by Simulated Space Radiation Qualities by Use of Recombinant Bacteria Carrying a Dual-Function Dual-Reporter Construct

    NASA Astrophysics Data System (ADS)

    Baumstark-Khan, Christa; Hellweg, Christine; Zahoor, Ahmed; Testard, Isabelle; Reitz, Guenther

    Along with the long-term space exploration come various potential health risks due to unique physical factors of the space environment. Space radiation is one of the primary environmental hazards associated with space flight. In order to deal with space-related risk radiation exposure must be properly characterised and quantified, and biological effects of charged particles have to be analysed in ground based research, especially as astronauts are subjected to a differing radiation quality in space than they receive on Earth. For risk assessment, the mutagenic potential of the heavy ion component of the galactic cosmic radiation is of major concern for tumour induction as radiation late effects. The recombinant SWITCH test is based on TA1535 Salmonella typhimurium cells transformed with a dual-function dual-reporter vector harbouring (a) the genes for bioluminescence production from Photobacterium leiognathi under the control of a DNA-damage inducible promoter and (b) the gene for green fluorescent protein from the jellyfish Aequorea victoria under the control of a constitutive promoter. Suchlike genetically modified organism report on the presence of genotoxic conditions by dose dependent increase of bioluminescence induction and on the presence of cytotoxic conditions by dose dependent decrease in GFP fluorescence. By this, it is possible to analyse bacterial inactivation and mutation induction by ionizing radiation in parallel in the same cell within short time. Experiments with heavy ions have been performed with the SWITCH test at GANIL with the following accelerated heavy ions: 35 MeV/u (72 keV/µm) and 75 MeV/u (37 keV/µm) carbon, 95 MeV/u argon (377 keV/µm), 95 MeV/u neon (98 keV/µm), 75 MeV/u nickel (967 keV/µm) and 29 MeV/u lead (10238 keV/µm). The results obtained clearly show that the numbers of hits (particles per cm2 ) necessary to inactivate the bacteria (cytotoxicity) depend on LET. The higher the ionisation capacity of the accelerated ion, the

  13. Dual function armchair graphene nanoribbon-based spin-photodetector: Optical spin-valve and light helicity detector

    SciTech Connect

    Ostovari, Fatemeh; Moravvej-Farshi, Mohammad Kazem

    2014-08-18

    We show an armchair graphene nanoribbon channel connected between asymmetric ferromagnetic source-drain structure—i.e., p-type Co/Au/graphene source and n-type Co/Cu/graphene drain—can operate as dual function spin-photodetector, under zero external biases at room temperature. It can function as an optical spin-valve with magnetoresistance of greater than 60% and responsivity as high as 25.12 A/mW, when irradiated by an un-polarized light of energy ∼3.03 eV. Under a circularly polarized illumination, this optical spin-valve can also operate as a light helicity detector. The calculated magnetoresistances for right and left circularly polarized lights are both greater than 60%.

  14. Dual functional, polymeric self-assembled monolayers as a facile platform for construction of patterns of biomolecules.

    PubMed

    Park, Sangjin; Lee, Kyung-Bok; Choi, Insung S; Langer, Robert; Jon, Sangyong

    2007-10-23

    We report a facile approach to the construction of patterns of biomolecules based on polymeric self-assembled monolayers (pSAMs) that possess dual functions: "bio-reactive (post-functionalizable)" and "bio-inert (anti-biofouling)" properties. To prepare pSAMs on Si/SiO2 wafers were synthesized new random copolymers by radical polymerization of poly(ethylene glycol) methyl ether methacrylate (PEGMA), 3-(trimethoxysilyl)propyl methacrylate (TMSMA), and N-acryloxysuccinimide (NAS), and referred to as poly(TMSMA-r-PEGMA-r-NAS). Poly(TMSMA-r-PEGMA-r-NAS) was designed to play triple roles: "surface-reactive", "bio-reactive", and "bio-inert" ones. The pSAMs of poly(TMSMA-r-PEGMA-r-NAS) were formed on Si/SiO2 wafers with 1 h incubation of the substrates in the polymer solution, which showed approximately a 1 nm-thick film as measured by ellipsometry. After the formation of the pSAMs, the feasibility of the pSAMs as a dual functional surface (bio-inert and bio-reactive properties) was examined. The ability of the pSAMs to block nonspecific adsorption of proteins was evaluated against bovine serum albumin as a model protein. High-resolution N(1s) X-ray photoelectron spectroscopy (XPS) analysis on the protein adsorption revealed that significant reduction up to approximately 97% was observed compared to the unmodified Si/SiO2 wafer. In addition, micropatterns of streptavidin with high signal-to-noise ratios were achieved using microcontact printing (microCP) of NH2-bearing biotin onto the pSAMs of poly(TMSMA-r-PEGMA-r-NAS) on glass slides, which suggests that other biomolecules could also be efficiently immobilized onto the pSAMs with high specificity while minimizing nonspecific adsorption. On the other hand, the surface density of both bio-reactive and anti-biofouling functionality could be tailored by simply changing initial feed ratios of each monomer in the polymer synthesis: different molar ratios of the bio-reactive group (NAS: 33%, 20%, and 10%, respectively) were

  15. Tetralogy of Fallot Cardiac Function Evaluation and Intelligent Diagnosis Based on Dual-Source Computed Tomography Cardiac Images.

    PubMed

    Cai, Ken; Rongqian, Yang; Li, Lihua; Xie, Zi; Ou, Shanxing; Chen, Yuke; Dou, Jianhong

    2016-05-01

    Tetralogy of Fallot (TOF) is the most common complex congenital heart disease (CHD) of the cyanotic type. Studies on ventricular functions have received an increasing amount of attention as the development of diagnosis and treatment technology for CHD continues to advance. Reasonable options for imaging examination and accurate assessment of preoperative and postoperative left ventricular functions of TOF patients are important in improving the cure rate of TOF radical operation, therapeutic evaluation, and judgment prognosis. Therefore, with the aid of dual-source computed tomography (DSCT), cardiac images with high temporal resolution and high definition, we measured the left ventricular time-volume curve using image data and calculating the left ventricular function parameters to conduct the preliminary evaluation on TOF patients. To comprehensively evaluate the cardiac function, the segmental ventricular wall function parameters were measured, and the measurement results were mapped to a bull's eye diagram to realize the standardization of segmental ventricular wall function evaluation. Finally, we introduced a new clustering method based on auto-regression model parameters and combined this method with Euclidean distance measurements to establish an intelligent diagnosis of TOF. The results of this experiment show that the TOF evaluation and the intelligent diagnostic methods proposed in this article are feasible.

  16. From ATP to PTP and Back: A Dual Function for the Mitochondrial ATP Synthase.

    PubMed

    Bernardi, Paolo; Di Lisa, Fabio; Fogolari, Federico; Lippe, Giovanna

    2015-05-22

    Mitochondria not only play a fundamental role in heart physiology but are also key effectors of dysfunction and death. This dual role assumes a new meaning after recent advances on the nature and regulation of the permeability transition pore, an inner membrane channel whose opening requires matrix Ca(2+) and is modulated by many effectors including reactive oxygen species, matrix cyclophilin D, Pi (inorganic phosphate), and matrix pH. The recent demonstration that the F-ATP synthase can reversibly undergo a Ca(2+)-dependent transition to form a channel that mediates the permeability transition opens new perspectives to the field. These findings demand a reassessment of the modifications of F-ATP synthase that take place in the heart under pathological conditions and of their potential role in determining the transition of F-ATP synthase from and energy-conserving into an energy-dissipating device.

  17. Design and Functional Validation of a Mechanism for Dual-Spinning CubeSats

    NASA Technical Reports Server (NTRS)

    Peters, Eric; Dave, Pratik; Kingsbury, Ryan; Marinan, Anne; Wise, Evan; Pong, Chris; Prinkey, Meghan; Cahoy, Kerri; Miller, David W.; Sklair, Devon

    2014-01-01

    The mission of the Micro-sized Microwave Atmospheric Satellite (MicroMAS) is to collect useful atmospheric images using a miniature passive microwave radiometer payload hosted on a low-cost CubeSat platform. In order to collect this data, the microwave radiometer payload must rotate to scan the ground-track perpendicular to the satellite's direction of travel. A custom motor assembly was developed to facilitate the rotation of the payload while allowing the spacecraft bus to remained fixed in the local-vertical, local-horizontal (LVLH) frame for increased pointing accuracy. This paper describes the mechanism used to enable this dual-spinning operation for CubeSats, and the lessons learned during the design, fabrication, integration, and testing phases of the mechanism's development lifecycle.

  18. Dual-modality brain PET-CT image segmentation based on adaptive use of functional and anatomical information.

    PubMed

    Xia, Yong; Eberl, Stefan; Wen, Lingfeng; Fulham, Michael; Feng, David Dagan

    2012-01-01

    Dual medical imaging modalities, such as PET-CT, are now a routine component of clinical practice. Medical image segmentation methods, however, have generally only been applied to single modality images. In this paper, we propose the dual-modality image segmentation model to segment brain PET-CT images into gray matter, white matter and cerebrospinal fluid. This model converts PET-CT image segmentation into an optimization process controlled simultaneously by PET and CT voxel values and spatial constraints. It is innovative in the creation and application of the modality discriminatory power (MDP) coefficient as a weighting scheme to adaptively combine the functional (PET) and anatomical (CT) information on a voxel-by-voxel basis. Our approach relies upon allowing the modality with higher discriminatory power to play a more important role in the segmentation process. We compared the proposed approach to three other image segmentation strategies, including PET-only based segmentation, combination of the results of independent PET image segmentation and CT image segmentation, and simultaneous segmentation of joint PET and CT images without an adaptive weighting scheme. Our results in 21 clinical studies showed that our approach provides the most accurate and reliable segmentation for brain PET-CT images.

  19. Dual therapeutic functions of F-5 fragment in burn wounds: preventing wound progression and promoting wound healing in pigs

    PubMed Central

    Bhatia, Ayesha; O’Brien, Kathryn; Chen, Mei; Wong, Alex; Garner, Warren; Woodley, David T.; Li, Wei

    2016-01-01

    Burn injuries are a leading cause of morbidity including prolonged hospitalization, disfigurement, and disability. Currently there is no Food and Drug Administration-approved burn therapeutics. A clinical distinction of burn injuries from other acute wounds is the event of the so-called secondary burn wound progression within the first week of the injury, in which a burn expands horizontally and vertically from its initial boundary to a larger area. Therefore, an effective therapeutics for burns should show dual abilities to prevent the burn wound progression and thereafter promote burn wound healing. Herein we report that topically applied F-5 fragment of heat shock protein-90α is a dual functional agent to promote burn wound healing in pigs. First, F-5 prevents burn wound progression by protecting the surrounding cells from undergoing heat-induced caspase 3 activation and apoptosis with increased Akt activation. Accordingly, F-5–treated burn and excision wounds show a marked decline in inflammation. Thereafter, F-5 accelerates burn wound healing by stimulating the keratinocyte migration-led reepithelialization, leading to wound closure. This study addresses a topical agent that is capable of preventing burn wound progression and accelerating burn wound healing. PMID:27382602

  20. Dual-responsive and Multi-functional Plasmonic Hydrogel Valves and Biomimetic Architectures Formed with Hydrogel and Gold Nanocolloids

    NASA Astrophysics Data System (ADS)

    Song, Ji Eun; Cho, Eun Chul

    2016-10-01

    We present a straightforward approach with high moldability for producing dual-responsive and multi-functional plasmonic hydrogel valves and biomimetic architectures that reversibly change volumes and colors in response to temperature and ion variations. Heating of a mixture of hybrid colloids (gold nanoparticles assembled on a hydrogel colloid) and hydrogel colloids rapidly induces (within 30 min) the formation of hydrogel architectures resembling mold shapes (cylinder, fish, butterfly). The biomimetic fish and butterfly display reversible changes in volumes and colors with variations of temperature and ionic conditions in aqueous solutions. The cylindrical plasmonic valves installed in flow tubes rapidly control water flow rate in on-off manner by responding to these stimuli. They also report these changes in terms of their colors. Therefore, the approach presented here might be helpful in developing new class of biomimetic and flow control systems where liquid conditions should be visually notified (e.g., glucose or ion concentration changes).

  1. Dual-responsive and Multi-functional Plasmonic Hydrogel Valves and Biomimetic Architectures Formed with Hydrogel and Gold Nanocolloids

    PubMed Central

    Song, Ji Eun; Cho, Eun Chul

    2016-01-01

    We present a straightforward approach with high moldability for producing dual-responsive and multi-functional plasmonic hydrogel valves and biomimetic architectures that reversibly change volumes and colors in response to temperature and ion variations. Heating of a mixture of hybrid colloids (gold nanoparticles assembled on a hydrogel colloid) and hydrogel colloids rapidly induces (within 30 min) the formation of hydrogel architectures resembling mold shapes (cylinder, fish, butterfly). The biomimetic fish and butterfly display reversible changes in volumes and colors with variations of temperature and ionic conditions in aqueous solutions. The cylindrical plasmonic valves installed in flow tubes rapidly control water flow rate in on-off manner by responding to these stimuli. They also report these changes in terms of their colors. Therefore, the approach presented here might be helpful in developing new class of biomimetic and flow control systems where liquid conditions should be visually notified (e.g., glucose or ion concentration changes). PMID:27703195

  2. Targeted Aucore-Agshell nanorods as a dual-functional contrast agent for photoacoustic imaging and photothermal therapy

    PubMed Central

    Shi, Yiwen; Peng, Dong; Wang, Kun; Chai, Xinyu; Ren, Qiushi; Tian, Jie; Zhou, Chuanqing

    2016-01-01

    Optimizing contrast enhancement is essential for producing specific signals in biomedical imaging and therapy. The potential of using Aucore-Agshell nanorods (Au@Ag NRs) as a dual-functional theranostic contrast agent is demonstrated for effective cancer imaging and treatments. Due to its strong NIR absorption and high efficiency of photothermal conversion, effects of both photoacoustic tomography (PAT) and photothermal therapy (PTT) are enhanced significantly. The PAT signal grows by 45.3% and 82% in the phantom and in vivo experiments, respectively, when compared to those using Au NRs. In PTT, The maximum increase of tissue temperature treated with Au@Ag NRs is 22.8 °C, twice that with Au NRs. Results of the current study show the feasibility of using Au@Ag NRs for synergetic PAT with PTT. And it will enhance the potential application on real-time PAT guided PTT, which will greatly benefit the customized PTT treatment of cancer. PMID:27231624

  3. Dual-Function Metal-Organic Framework as a Versatile Catalyst for Detoxifying Chemical Warfare Agent Simulants.

    PubMed

    Liu, Yangyang; Moon, Su-Young; Hupp, Joseph T; Farha, Omar K

    2015-12-22

    The nanocrystals of a porphyrin-based zirconium(IV) metal-organic framework (MOF) are used as a dual-function catalyst for the simultaneous detoxification of two chemical warfare agent simulants at room temperature. Simulants of nerve agent (such as GD, VX) and mustard gas, dimethyl 4-nitrophenyl phosphate and 2-chloroethyl ethyl sulfide, have been hydrolyzed and oxidized, respectively, to nontoxic products via a pair of pathways catalyzed by the same MOF. Phosphotriesterase-like activity of the Zr6-containing node combined with photoactivity of the porphyrin linker gives rise to a versatile MOF catalyst. In addition, bringing the MOF crystals down to the nanoregime leads to acceleration of the catalysis.

  4. CD44 Receptor Targeting and Endosomal pH-Sensitive Dual Functional Hyaluronic Acid Micelles for Intracellular Paclitaxel Delivery.

    PubMed

    Liu, Yanhua; Zhou, Chengming; Wang, Wenping; Yang, Jianhong; Wang, Hao; Hong, Wei; Huang, Yu

    2016-12-05

    A novel CD44 receptor targeting and endosome pH-sensitive dual functional hyaluronic acid-deoxycholic acid-histidine (HA-DOCA-His) micellar system was designed for intracellular paclitaxel (PTX) delivery. The HA-DOCA-His micelles exhibited desirable endosome pH (5.0-6.0)-induced aggregation and deformation behavior verified by size distribution, critical micellar concentration, and zeta potential changes. The HA-DOCA-His micelles presented excellent encapsulation efficiency and loading capacity of 90.0% and 18.9% for PTX, respectively. The PTX release from HA-DOCA-His micelles was pH-dependent, with more rapid PTX release at pH 6.0 and 5.0 than those at pH 7.4 and 6.5. The cellular uptake performance of HA-DOCA-His micelles was enhanced comparing with pH-insensitive HA-DOCA micelles by qualitative and quantitative measurements. HA-DOCA-His micelles could be taken up via CD44-receptor mediated endocytosis, transported into endosomes, and triggered drug release to cytoplasm. In vitro cytotoxicity study exhibited PTX-loaded HA-DOCA-His micelles were more active in tumor cell growth inhibition in MCF-7 cells at pH 5.8 than those at pH 6.8 and pH 7.4. A superior antitumor efficacy was demonstrated with HA-DOCA-His micelles in a MCF-7 breast tumor model. These indicated that the dual functional HA-DOCA-His micelles combined targeted intracellular delivery and endosomal release strategies could be developed as a promising nanocarrier for anticancer efficacy improvement of PTX.

  5. Fabrication of quantum dot/silica core-shell particles immobilizing Au nanoparticles and their dual imaging functions

    NASA Astrophysics Data System (ADS)

    Kobayashi, Yoshio; Matsudo, Hiromu; Li, Ting-ting; Shibuya, Kyosuke; Kubota, Yohsuke; Oikawa, Takahiro; Nakagawa, Tomohiko; Gonda, Kohsuke

    2016-03-01

    The present work proposes preparation methods for quantum dot/silica (QD/SiO2) core-shell particles that immobilize Au nanoparticles (QD/SiO2/Au). A colloid solution of QD/SiO2 core-shell particles with an average size of 47.0 ± 6.1 nm was prepared by a sol-gel reaction of tetraethyl orthosilicate in the presence of the QDs with an average size of 10.3 ± 2.1 nm. A colloid solution of Au nanoparticles with an average size of 17.9 ± 1.3 nm was prepared by reducing Au3+ ions with sodium citrate in water at 80 °C. Introduction of amino groups to QD/SiO2 particle surfaces was performed using (3-aminopropyl)-triethoxysilane (QD/SiO2-NH2). The QD/SiO2/Au particles were fabricated by mixing the Au particle colloid solution and the QD/SiO2-NH2 particle colloid solution. Values of radiant efficiency and computed tomography for the QD/SiO2/Au particle colloid solution were 2.23 × 107 (p/s/cm2/sr)/(μW/cm2) at a QD concentration of 8 × 10-7 M and 1180 ± 314 Hounsfield units and an Au concentration of 5.4 × 10-2 M. The QD/SiO2/Au particle colloid solution was injected into a mouse chest wall. Fluorescence emitted from the colloid solution could be detected on the skin covering the chest wall. The colloid solution could also be X-ray-imaged in the chest wall. Consequently, the QD/SiO2/Au particle colloid solution was found to have dual functions, i.e., fluorescence emission and X-ray absorption in vivo, which makes the colloid solution suitable to function as a contrast agent for dual imaging processes.

  6. Nuclear receptor Nurr1 agonists enhance its dual functions and improve behavioral deficits in an animal model of Parkinson's disease.

    PubMed

    Kim, Chun-Hyung; Han, Baek-Soo; Moon, Jisook; Kim, Deog-Joong; Shin, Joon; Rajan, Sreekanth; Nguyen, Quoc Toan; Sohn, Mijin; Kim, Won-Gon; Han, Minjoon; Jeong, Inhye; Kim, Kyoung-Shim; Lee, Eun-Hye; Tu, Yupeng; Naffin-Olivos, Jacqueline L; Park, Chang-Hwan; Ringe, Dagmar; Yoon, Ho Sup; Petsko, Gregory A; Kim, Kwang-Soo

    2015-07-14

    Parkinson's disease (PD), primarily caused by selective degeneration of midbrain dopamine (mDA) neurons, is the most prevalent movement disorder, affecting 1-2% of the global population over the age of 65. Currently available pharmacological treatments are largely symptomatic and lose their efficacy over time with accompanying severe side effects such as dyskinesia. Thus, there is an unmet clinical need to develop mechanism-based and/or disease-modifying treatments. Based on the unique dual role of the nuclear orphan receptor Nurr1 for development and maintenance of mDA neurons and their protection from inflammation-induced death, we hypothesize that Nurr1 can be a molecular target for neuroprotective therapeutic development for PD. Here we show successful identification of Nurr1 agonists sharing an identical chemical scaffold, 4-amino-7-chloroquinoline, suggesting a critical structure-activity relationship. In particular, we found that two antimalarial drugs, amodiaquine and chloroquine stimulate the transcriptional function of Nurr1 through physical interaction with its ligand binding domain (LBD). Remarkably, these compounds were able to enhance the contrasting dual functions of Nurr1 by further increasing transcriptional activation of mDA-specific genes and further enhancing transrepression of neurotoxic proinflammatory gene expression in microglia. Importantly, these compounds significantly improved behavioral deficits in 6-hydroxydopamine lesioned rat model of PD without any detectable signs of dyskinesia-like behavior. These findings offer proof of principle that small molecules targeting the Nurr1 LBD can be used as a mechanism-based and neuroprotective strategy for PD.

  7. Dual growth factor releasing multi-functional nanofibers for wound healing.

    PubMed

    Xie, Zhiwei; Paras, Christian B; Weng, Hong; Punnakitikashem, Primana; Su, Lee-Chun; Vu, Khanh; Tang, Liping; Yang, Jian; Nguyen, Kytai T

    2013-12-01

    The objective of this research is to develop a dual growth factor-releasing nanoparticle-in-nanofiber system for wound healing applications. In order to mimic and promote the natural healing procedure, chitosan and poly(ethylene oxide) were electrospun into nanofibrous meshes as mimics of extracellular matrix. Vascular endothelial growth factor (VEGF) was loaded within nanofibers to promote angiogenesis in the short term. In addition, platelet-derived growth factor-BB (PDGF-BB) encapsulated poly(lactic-co-glycolic acid) nanoparticles were embedded inside nanofibers to generate a sustained release of PDGF-BB for accelerated tissue regeneration and remodeling. In vitro studies revealed that our nanofibrous composites delivered VEGF quickly and PDGF-BB in a relayed manner, supported fibroblast growth and exhibited anti-bacterial activities. A preliminary in vivo study performed on normal full thickness rat skin wound models demonstrated that nanofiber/nanoparticle scaffolds significantly accelerated the wound healing process by promoting angiogenesis, increasing re-epithelialization and controlling granulation tissue formation. For later stages of healing, evidence also showed quicker collagen deposition and earlier remodeling of the injured site to achieve a faster full regeneration of skin compared to the commercial Hydrofera Blue® wound dressing. These results suggest that our nanoparticle-in-nanofiber system could provide a promising treatment for normal and chronic wound healing.

  8. Analysis of competition between transformation pathways in the functioning of biotic abstract dual automata.

    PubMed

    Popa, Radu; Cimpoiasu, Vily M

    2013-05-01

    Properties of avenues of transformation and their mutualism with forms of organization in dynamic systems are essential for understanding the evolution of prebiotic order. We have analyzed competition between two avenues of transformation in an A↔B system, using the simulation approach called BiADA (Biotic Abstract Dual Automata). We discuss means of avoiding common pitfalls of abstract system modeling and benefits of BiADA-based simulations. We describe the effect of the availability of free energy, energy sink magnitude, and autocatalysis on the evolution of energy flux and order in the system. Results indicate that prebiotic competition between avenues of transformation was more stringent in energy-limited environments. We predict that in such conditions the efficiency of autocatalysis during competition between alternative system states will increase for systems with forms of organization having short half-lives and thus information that is time-sensitive to energy starvation. Our results also offer a potential solution to Manfred Eigen's error catastrophe dilemma. In the conditions discussed above, the exponential growth of quasi species is curbed through the removal of less competitive "genetic" variants via energy starvation. We propose that one of the most important achievements (and selective edges) of a dynamic network during competition in energy-limited or energy-variable environments was the capacity to correlate the internal energy flux and the need for free energy with the availability of free energy in the environment.

  9. Synthesis of highly active and dual-functional electrocatalysts for methanol oxidation and oxygen reduction reactions

    NASA Astrophysics Data System (ADS)

    Zhao, Qi; Zhang, Geng; Xu, Guangran; Li, Yingjun; Liu, Baocang; Gong, Xia; Zheng, Dafang; Zhang, Jun; Wang, Qin

    2016-12-01

    The promising Pt-based ternary catalyst is crucial for polymer electrolyte membrane fuel cells (PEMFCs) due to improving catalytic activity and durability for both methanol oxidation reaction and oxygen reduction reaction. In this work, a facile strategy is used for the synthesis ternary RuMPt (M = Fe, Co, Ni, and Cu) nanodendrities catalysts. The ternary RuMPt alloys exhibit enhanced specific and mass activity, positive half-wave potential, and long-term stability, compared with binary Pt-based alloy and the commercial Pt/C catalyst, which is attributed to the high electron density and upshifting of the d-band center for Pt atoms, and synergistic catalytic effects among Pt, M, and Ru atoms by introducing a transition metal. Impressively, the ternary RuCoPt catalyst exhibits superior mass activity (801.59 mA mg-1) and positive half-wave potential (0.857 V vs. RHE) towards MOR and ORR, respectively. Thus, the RuMPt nanocomposite is a very promising material to be used as dual electrocatalyst in the application of PEMFCs.

  10. Dual-Compartment Neurofluidic System for Electrophysiological Measurements in Physically Segregated and Functionally Connected Neuronal Cell Culture

    PubMed Central

    Kanagasabapathi, Thirukumaran T.; Ciliberti, Davide; Martinoia, Sergio; Wadman, Wytse J.; Decré, Michel M. J.

    2011-01-01

    We developed a dual-compartment neurofluidic system with inter-connecting microchannels to connect neurons from their respective compartments, placed on a planar microelectrode arrays. The design and development of the compartmented microfluidic device for neuronal cell culture, protocol for sustaining long-term cultures, and neurite growth through microchannels in such a closed compartment device are presented. Using electrophysiological measurements of spontaneous network activity in the compartments and selective pharmacological manipulation of cells in one compartment, the biological origin of network activity and the fluidic isolation between the compartments are demonstrated. The connectivity between neuronal populations via the microchannels and the crossing-over of neurites are verified using transfection experiments and immunofluorescence staining. In addition to the neurite cross-over to the adjacent compartment, functional connectivity between cells in both the compartments is verified using cross-correlation (CC) based techniques. Bidirectional signal propagation between the compartments is demonstrated using functional connectivity maps. CC analysis and connectivity maps demonstrate that the two neuronal populations are not only functionally connected within each compartment but also with each other and a well connected functional network was formed between the compartments despite the physical barrier introduced by the microchannels. PMID:22025913

  11. Dual-channel in-situ optical imaging system for quantifying lipid uptake and lymphatic pump function

    NASA Astrophysics Data System (ADS)

    Kassis, Timothy; Kohan, Alison B.; Weiler, Michael J.; Nipper, Matthew E.; Cornelius, Rachel; Tso, Patrick; Brandon Dixon, J.

    2012-08-01

    Nearly all dietary lipids are transported from the intestine to venous circulation through the lymphatic system, yet the mechanisms that regulate this process remain unclear. Elucidating the mechanisms involved in the functional response of lymphatics to changes in lipid load would provide valuable insight into recent implications of lymphatic dysfunction in lipid related diseases. Therefore, we sought to develop an in situ imaging system to quantify and correlate lymphatic function as it relates to lipid transport. The imaging platform provides the capability of dual-channel imaging of both high-speed bright-field video and fluorescence simultaneously. Utilizing post-acquisition image processing algorithms, we can quantify correlations between vessel pump function, lymph flow, and lipid concentration of mesenteric lymphatic vessels in situ. All image analysis is automated with customized LabVIEW virtual instruments; local flow is measured through lymphocyte velocity tracking, vessel contraction through measurements of the vessel wall displacement, and lipid uptake through fluorescence intensity tracking of an orally administered fluorescently labelled fatty acid analogue, BODIPY FL C16. This system will prove to be an invaluable tool for scientists studying intestinal lymphatic function in health and disease, and those investigating strategies for targeting the lymphatics with orally delivered drugs to avoid first pass metabolism.

  12. Evaluation of mitochondrial function and membrane integrity by dual fluorescent staining for assessment of sperm status in rats.

    PubMed

    Kato, Masashi; Makino, Sachiko; Kimura, Hitoshi; Ota, Takao; Furuhashi, Tadakazu; Nagamura, Yoichi

    2002-02-01

    Dual fluorescent staining (DFS) with calcein acetoxy methyl ester (CAM), which labels the cellular esterase activity that is a major component of energy metabolism in cellular mitochondria, and with ethidium homodimer-1 (EthD-1) was used to evaluate mitochondrial function and membrane integrity in rat spermatozoa. The spermatozoa stained by DFS could be classified into three different populations microscopically when excited at 490 nm after 60 min incubation. 1) Spermatozoa, which were stained with CAM alone and had maintained either mitochondrial function or membrane integrity, were identified as live during incubation. 2) Spermatozoa, which were stained with EthD-1 alone and had lost either mitochondrial function or membrane integrity, were identified as already dead at the beginning of incubation. 3) Spermatozoa, which were stained with both CAM and EthD-1 and had maintained mitochondrial function with membrane breached, were identified as having died during incubation. Two toxicological tests, an in vitro triton X-100 experiment and an in vivo nitrobenzene experiment, were done. All spermatozoa were immobilized and lost either mitochondrial function or membrane integrity by 1.0% triton X-100 treatment. Almost no motile sperm were found at 0.1% in the triton X-100 group and in the groups treated with 60 and 40 mg/kg/day of nitrobenzene, and these spermatozoa maintained their mitochondrial function but had their membrane breached. In conclusion, the DFS procedure, which uses CAM and EthD-1, can clearly and visually identify the population of viable and dead spermatozoa simultaneously by fluorescence microscopy in rats. This is a useful technique to characterize sperm status, which is determined by the mitochondrial function assessed by CAM and membrane integrity evaluated by EthD-1.

  13. Chromate (CrO(4)(2-)) and copper (Cu2+) adsorption by dual-functional ion exchange resins made from agricultural by-products.

    PubMed

    Marshall, Wayne E; Wartelle, Lynda H

    2006-07-01

    Ion exchange resins commonly have a single functionality for either cations or anions. Resins that have a dual functionality for both cations and anions are uncommon. The objective of this study was to create dual-functional ion exchange resins derived from soybean hulls, sugarcane bagasse and corn stover. Dual-functional resins were prepared by two separate two-step processes. In the first two-step process, by-products were reacted with a solution of citric acid in order to impart additional negative charge, and then reacted with the cross-linking reagent dimethyloldihydroxyethylene urea (DMDHEU) and a quaternary amine (choline chloride) to add positive charge to the lignocellulosic material. In the second two-step process, the order of reaction was reversed, with positive charge added first, followed by the addition of negative charge. These combined reactions added both cationic and anionic character to the by-products as evidenced by the increased removal from solution of copper (Cu(2+)) cation and the chromate (CrO(4)(2-)) anion compared to unmodified by-products. The order of reaction appeared to slightly favor the functionality that was added last. That is, if negative charge was added last, the resulting resin sequestered more copper ion than a comparable resin where the negative charge was added first and vice-versa. Cu(2+) and CrO(4)(2-) were used as marker ions in a solution that contained both competing cations and anions. The dual-functional resins adsorbed as much as or more of the marker ions compared to commercial cation or anion exchange resins used for comparison. None of the commercial resins exhibited dual-functional properties to the same extent as the by-product-based resins.

  14. Kub5-Hera, the human Rtt103 homolog, plays dual functional roles in transcription termination and DNA repair.

    PubMed

    Morales, Julio C; Richard, Patricia; Rommel, Amy; Fattah, Farjana J; Motea, Edward A; Patidar, Praveen L; Xiao, Ling; Leskov, Konstantin; Wu, Shwu-Yuan; Hittelman, Walter N; Chiang, Cheng-Ming; Manley, James L; Boothman, David A

    2014-04-01

    Functions of Kub5-Hera (In Greek Mythology Hera controlled Artemis) (K-H), the human homolog of the yeast transcription termination factor Rtt103, remain undefined. Here, we show that K-H has functions in both transcription termination and DNA double-strand break (DSB) repair. K-H forms distinct protein complexes with factors that repair DSBs (e.g. Ku70, Ku86, Artemis) and terminate transcription (e.g. RNA polymerase II). K-H loss resulted in increased basal R-loop levels, DSBs, activated DNA-damage responses and enhanced genomic instability. Significantly lowered Artemis protein levels were detected in K-H knockdown cells, which were restored with specific K-H cDNA re-expression. K-H deficient cells were hypersensitive to cytotoxic agents that induce DSBs, unable to reseal complex DSB ends, and showed significantly delayed γ-H2AX and 53BP1 repair-related foci regression. Artemis re-expression in K-H-deficient cells restored DNA-repair function and resistance to DSB-inducing agents. However, R loops persisted consistent with dual roles of K-H in transcription termination and DSB repair.

  15. Functional dual hydrophilic dendrimer-modified metal-organic framework for the selective enrichment of N-glycopeptides.

    PubMed

    Wang, Yanan; Wang, Jiaxi; Gao, Mingxia; Zhang, Xiangmin

    2017-04-08

    Analysis of protein glycosylation remains a significant challenge due to the low abundance of glycoproteins or N-glycopeptides. Here we have synthesized an amino-functionalized metal-organic framework (MOF) MIL-101(Cr)-NH2 whose surface is grafted with a hydrophilic dendrimer poly(amidoamine) (PAMAM) for N-glycopeptide enrichment based on the hydrophilic interactions. The selected substrate MOF MIL-101(Cr) owns high surface area which provides nice support for peptide adsorption. In addition, the MOF displayed a good hydrophilic property after being modified with amino groups. Most importantly, the grafted hydrophilic dendrimer PAMAM was firstly applied in the post-synthetic modification (PSM) of MOFs. And this functionalization route using macromolecular dendrimer opens a new perspective in MOFs design. Owing to its long dendritic chains and abundant amino groups, our material displayed dual hydrophilic property. In the enrichment of standard glycoprotein horseradish peroxidase (HRP) digestion, the functional MOF material was shown to have low detection limit (1 fmol/μL) and good selectivity when the concentration of nonglycopeptides was 100 fold higher than the target N-glycopeptides. All the results proved that MIL-101(Cr)-NH2 @PAMAM has great potential in the glycoproteome analysis. This article is protected by copyright. All rights reserved.

  16. Dual-function sRNA encoded peptide SR1P modulates moonlighting activity of B. subtilis GapA

    PubMed Central

    Gimpel, Matthias; Brantl, Sabine

    2016-01-01

    ABSTRACT SR1 is a dual-function sRNA from B. subtilis that acts as a base-pairing regulatory RNA and as a peptide-encoding mRNA. Both functions of SR1 are highly conserved. Previously, we uncovered that the SR1 encoded peptide SR1P binds the glycolytic enzyme GapA resulting in stabilization of gapA mRNA. Here, we demonstrate that GapA interacts with RNases Y and J1, and this interaction was RNA-independent. About 1% of GapA molecules purified from B. subtilis carry RNase J1 and about 2% RNase Y. In contrast to the GapA/RNase Y interaction, the GapA/RNaseJ1 interaction was stronger in the presence of SR1P. GapA/SR1P-J1/Y displayed in vitro RNase activity on known RNase J1 substrates. Moreover, the RNase J1 substrate SR5 has altered half-lives in a ΔgapA strain and a Δsr1 strain, suggesting in vivo functions of the GapA/SR1P/J1 interaction. Our results demonstrate that the metabolic enzyme GapA moonlights in recruiting RNases while GapA bound SR1P promotes binding of RNase J1 and enhances its activity. PMID:27449348

  17. Peroxiredoxin 1 (Prx1) is a dual function enzyme by possessing Cys-independent catalase-like activity.

    PubMed

    Sun, Cen-Cen; Dong, Wei-Ren; Shao, Tong; Li, Jiang-Yuan; Zhao, Jing; Nie, Li; Xiang, Li-Xin; Zhu, Guan; Shao, Jian-Zhong

    2017-02-20

    Peroxiredoxin (Prx) was previously known as a Cys-dependent thioredoxin. However, we unexpected observed that Prx1 from the green spotted puffer fish Tetraodon nigroviridis (TnPrx1) was able to reduce H2O2 in a manner independent on the Cys peroxidation and reductants. This study aimed to validate the novel function for Prx1, delineate the biochemical features and explore its antioxidant role in cells. We have confirmed that Prx1 from the puffer fish and humans truly possesses a catalase-like activity that is independent of Cys residues and reductants, but dependent on iron. We have identified that the GVL motif was essential to the catalase-like (CAT) activity of Prx1, but not to the Cys-dependent thioredoxin peroxidase (POX) activity, and generated mutants lacking POX and/or CAT activities for individual functional validation. We discovered that the TnPrx1 POX and CAT activities possessed different kinetic features in reducing H2O2 The overexpression of wild-type TnPrx1 and mutants differentially regulated the intracellular levels of reactive oxygen species (ROS) and the phosphorylation of p38 in HEK-293T cells treated with H2O2 Prx1 is a dual function enzyme by acting as POX and CAT with varied affinities towards ROS. This study extends our knowledge on Prx1 and provides new opportunities to further study the biological roles of this family of antioxidants.

  18. Enhancing functional production of a chaperone-dependent lipase in Escherichia coli using the dual expression cassette plasmid

    PubMed Central

    2012-01-01

    into the functional lipase in soluble form whereas the main fraction was still inactive in the form of inclusion bodies. Another controversial finding was that the dual expression cassette plasmid systems E. coli BL21/pELipAB-LipB1a and E. coli/pELipAB-LipB3a secreted the active lipase into the culture medium of 51 and 29 times as high as the single expression cassette plasmid system E. coli pELipABa did, respectively, which has never been reported before. Another interesting finding was that the lipase form LipA6xHis (mature lipase fused with 6× histidine tag) expressed in the dual expression cassette plasmid systems (BL21/pELipA-LipB1a and BL21/pELipA-LipB3a) showed no lipase activity although the expression level of the lipase and two chaperone forms LipB1 and LipB3 in these systems remained as high as that in E. coli BL21/pELipABa + pELipB1k, BL21/pELipABa + pELipB3k, BL21/pELipAB-LipB1a, and BL21/pELipAB-LipB3a. The addition of Neptune oil or detergents into the LB medium increased the lipase production and secretion by up to 94%. Conclusions Our findings demonstrated that a dual expression cassette plasmid system E. coli could overproduce and secrete the active chaperone-dependent lipase (subfamilies I.1 and I.2) in vivo and an improved dual expression cassette plasmid system E. coli could be potentially applied for industrial-scale production of subfamily I.1 and I.2 lipases. PMID:22380513

  19. Lysine Specific Demethylase 1 has Dual Functions as a Major Regulator of Androgen Receptor Transcriptional Activity

    PubMed Central

    Cai, Changmeng; He, Housheng Hansen; Gao, Shuai; Chen, Sen; Yu, Ziyang; Gao, Yanfei; Chen, Shaoyong; Chen, Mei Wei; Zhang, Jesse; Ahmed, Musaddeque; Wang, Yang; Metzger, Eric; Schüle, Roland; Liu, X. Shirley; Brown, Myles; Balk, Steven P.

    2014-01-01

    SUMMARY Lysine Specific Demethylase 1 (LSD1, KDM1A) functions as a transcriptional corepressor through demethylation of histone 3 lysine 4 (H3K4), but has coactivator function on some genes through unclear mechanisms. We show that LSD1, interacting with CoREST, associates with and coactivates androgen receptor (AR) on a large fraction of androgen-stimulated genes. A subset of these AR/LSD1-associated enhancer sites have histone 3 threonine 6 phosphorylation (H3T6ph), and these sites are further enriched for androgen-stimulated genes. Significantly, despite its coactivator activity, LSD1 still mediates H3K4me2 demethylation at these androgen-stimulated enhancers. FOXA1 is also associated with LSD1 at AR regulated enhancer sites, and a FOXA1 interaction with LSD1 enhances binding of both proteins at these sites. These findings show LSD1 functions broadly as a regulator of AR function, that it maintains a transcriptional repression function at AR-regulated enhancers through H3K4 demethylation, and has a distinct AR-linked coactivator function mediated by demethylation of other substrates. PMID:25482560

  20. The narrow sheath duplicate genes: sectors of dual aneuploidy reveal ancestrally conserved gene functions during maize leaf development.

    PubMed Central

    Scanlon, M J; Chen, K D; McKnight CC, I V

    2000-01-01

    The narrow sheath mutant of maize displays a leaf and plant stature phenotype controlled by the duplicate factor mutations narrow sheath1 and narrow sheath2. Mutant leaves fail to develop a lateral domain that includes the leaf margins. Genetic data are presented to show that the narrow sheath mutations map to duplicated chromosomal regions, reflecting an ancestral duplication of the maize genome. Genetic and cytogenetic evidence indicates that the original mutation at narrow sheath2 is associated with a chromosomal inversion on the long arm of chromosome 4. Meristematic sectors of dual aneuploidy were generated, producing plants genetically mosaic for NARROW SHEATH function. These mosaic plants exhibited characteristic half-plant phenotypes, in which leaves from one side of the plant were of nonmutant morphology and leaves from the opposite side were of narrow sheath mutant phenotype. The data suggest that the narrow sheath duplicate genes may perform ancestrally conserved, redundant functions in the development of a lateral domain in the maize leaf. PMID:10880496

  1. Functional Assessment of Disease-Associated Regulatory Variants In Vivo Using a Versatile Dual Colour Transgenesis Strategy in Zebrafish

    PubMed Central

    Bhatia, Shipra; Gordon, Christopher T.; Foster, Robert G.; Melin, Lucie; Abadie, Véronique; Baujat, Geneviève; Vazquez, Marie-Paule; Amiel, Jeanne; Lyonnet, Stanislas; van Heyningen, Veronica; Kleinjan, Dirk A.

    2015-01-01

    Disruption of gene regulation by sequence variation in non-coding regions of the genome is now recognised as a significant cause of human disease and disease susceptibility. Sequence variants in cis-regulatory elements (CREs), the primary determinants of spatio-temporal gene regulation, can alter transcription factor binding sites. While technological advances have led to easy identification of disease-associated CRE variants, robust methods for discerning functional CRE variants from background variation are lacking. Here we describe an efficient dual-colour reporter transgenesis approach in zebrafish, simultaneously allowing detailed in vivo comparison of spatio-temporal differences in regulatory activity between putative CRE variants and assessment of altered transcription factor binding potential of the variant. We validate the method on known disease-associated elements regulating SHH, PAX6 and IRF6 and subsequently characterise novel, ultra-long-range SOX9 enhancers implicated in the craniofacial abnormality Pierre Robin Sequence. The method provides a highly cost-effective, fast and robust approach for simultaneously unravelling in a single assay whether, where and when in embryonic development a disease-associated CRE-variant is affecting its regulatory function. PMID:26030420

  2. Bridging Adhesion of a Protein onto an Inorganic Surface Using Self-Assembled Dual-Functionalized Spheres.

    PubMed

    Sato, Sota; Ikemi, Masatoshi; Kikuchi, Takashi; Matsumura, Sachiko; Shiba, Kiyotaka; Fujita, Makoto

    2015-10-14

    For the bridging adhesion of different classes of materials in their intact functional states, the adhesion of biomolecules onto inorganic surfaces is a necessity. A new molecular design strategy for bridging adhesion was demonstrated by the introduction of two independent recognition groups on the periphery of spherical complexes self-assembled from metal ions (M) and bidentate ligands (L). These dual-functionalized M12L24 spheres were quantitatively synthesized in one step from two ligands, bearing either a biotin for streptavidin recognition or a titania-binding aptamer, and Pd(II) ions. The selective recognition of titania surfaces was achieved by ligands with hexapeptide aptamers (Arg-Lys-Leu-Pro-Asp-Ala: minTBP-1), whose fixation ability was enhanced by the accumulation effect on the surface of the M12L24 spheres. These well-defined spherical structures can be specifically tailored to promote interactions with both titania and streptavidin simultaneously without detrimentally affecting either recognition motif. The irreversible immobilization of the spheres onto titania was revealed quantitatively by quartz crystal microbalance measurements, and the adhesion of streptavidin to the titania surface mediated by the biotin surrounding the spheres was visually demonstrated by lithographic patterning experiments.

  3. A single-point mutation enhances dual functionality of a scorpion toxin.

    PubMed

    Wang, Xueli; Gao, Bin; Zhu, Shunyi

    2016-01-01

    Scorpion venom represents a tremendous, hitherto partially explored peptide library that has been proven to be useful not only for understanding ion channels but also for drug design. MeuTXKα3 is a functionally unknown scorpion toxin-like peptide. Here we describe new transcripts of this gene arising from alternative polyadenylation and its biological function as well as a mutant with a single-point substitution at site 30. Native-like MeuTXKα3 and its mutant were produced in Escherichia coli and their toxic function against Drosophila Shaker K(+) channel and its mammalian counterparts (rKv1.1-rKv1.3) were assayed by two-electrode voltage clamp technique. The results show that MeuTXKα3 is a weak toxin with a wide-spectrum of activity on both Drosophila and mammalian K(+) channels. The substitution of a proline at site 30 by an asparagine, an evolutionarily conserved functional residue in the scorpion α-KTx family, led to an increased activity on rKv1.2 and rKv1.3 but a decreased activity on the Shaker channel without changing the potency on rKv1.1, suggesting a key role of this site in species selectivity of scorpion toxins. MeuTXKα3 was also active on a variety of bacteria with lethal concentrations ranging from 4.66 to 52.01μM and the mutant even had stronger activity on some of these bacterial species. To the best of our knowledge, this is the first report on a bi-functional short-chain peptide in the lesser Asian scorpion venom. Further extensive mutations of MeuTXKα3 at site 30 could help improve its K(+) channel-blocking and antibacterial functions.

  4. Semiclassical partition function for strings dual to Wilson loops with small cusps in ABJM

    NASA Astrophysics Data System (ADS)

    Aguilera-Damia, Jeremías; Correa, Diego H.; Silva, Guillermo A.

    2015-03-01

    We compute the 1-loop partition function for strings in , whose worldsheets end along a line with small cusp angles in the boundary of AdS. We obtain these 1-loop results in terms of the vacuum energy for on-shell modes. Our results verify the proposal by Lewkowycz and Maldacena in arXiv:1312.5682 for the exact Bremsstrahlung function up to the next to leading order in the strong coupling expansion. The agreement is observed for cusps distorting either the 1/2 BPS or the 1/6 BPS Wilson line.

  5. Synthesis and characterization of dual-functionalized core-shell fluorescent microspheres for bioconjugation and cellular delivery.

    PubMed

    Behrendt, Jonathan M; Nagel, David; Chundoo, Evita; Alexander, Lois M; Dupin, Damien; Hine, Anna V; Bradley, Mark; Sutherland, Andrew J

    2013-01-01

    The efficient transport of micron-sized beads into cells, via a non-endocytosis mediated mechanism, has only recently been described. As such there is considerable scope for optimization and exploitation of this procedure to enable imaging and sensing applications to be realized. Herein, we report the design, synthesis and characterization of fluorescent microsphere-based cellular delivery agents that can also carry biological cargoes. These core-shell polymer microspheres possess two distinct chemical environments; the core is hydrophobic and can be labeled with fluorescent dye, to permit visual tracking of the microsphere during and after cellular delivery, whilst the outer shell renders the external surfaces of the microspheres hydrophilic, thus facilitating both bioconjugation and cellular compatibility. Cross-linked core particles were prepared in a dispersion polymerization reaction employing styrene, divinylbenzene and a thiol-functionalized co-monomer. These core particles were then shelled in a seeded emulsion polymerization reaction, employing styrene, divinylbenzene and methacrylic acid, to generate orthogonally functionalized core-shell microspheres which were internally labeled via the core thiol moieties through reaction with a thiol reactive dye (DY630-maleimide). Following internal labeling, bioconjugation of green fluorescent protein (GFP) to their carboxyl-functionalized surfaces was successfully accomplished using standard coupling protocols. The resultant dual-labeled microspheres were visualized by both of the fully resolvable fluorescence emissions of their cores (DY630) and shells (GFP). In vitro cellular uptake of these microspheres by HeLa cells was demonstrated conventionally by fluorescence-based flow cytometry, whilst MTT assays demonstrated that 92% of HeLa cells remained viable after uptake. Due to their size and surface functionalities, these far-red-labeled microspheres are ideal candidates for in vitro, cellular delivery of proteins.

  6. Single and dual incision technique for acute distal biceps rupture: clinical and functional outcomes

    PubMed Central

    Guglielmino, Claudia; Massimino, Paolo; Ioppolo, Francesco; Castorina, Sergio; Musumeci, Giuseppe; Di Giunta, Angelo

    2016-01-01

    Summary Background Distal bicep tendon injuries are a traumatic event though rather rare. The pathogenesis is not entirely clear. The most common cause for injury is an unexpected load on the biceps when the elbow is in an extended position. Although several studies have provided insight into the pathogenetic processes of the lesion, the literature suggests to treat all injuries surgically (whether partial or total) if there is high functional demand. Methods Between January 2006 and March 2016 were studied 20 patients surgically treated for a disconnected distal bicep, 15 with a total lesion and 5 with a partial lesion. The patients were divided into 2 groups. Surgical access with single incision was performed on 13 patients while a double surgical access was performed on 7 patients. The clinical and functional results were studied using an Ewald System Score (ESS). Results In both groups, the most rapid improvement was achieved for the parameters of pain and deformity with excellent results, while those of function and movement were normalized as gradual and progressive over next 2 months. Conclusion The clinical and functional outcomes during the follow-up examination after surgery showed excellent results in patients treated with both types of surgical procedures. PMID:28217566

  7. The Dual Function of "usted:" Forms of Address in Bogota, Colombia.

    ERIC Educational Resources Information Center

    Uber, Diane Ringer

    1985-01-01

    Shows that "usted" has two functions: showing lack of solidarity and showing extreme solidarity, with "tu" falling somewhere in between on the continuum. Discusses the increasing use of "tu," especially among younger people, and presents some possible reasons for this. (SED)

  8. Dual bronchodilation in COPD: lung function and patient-reported outcomes - a review.

    PubMed

    Price, David; Østrem, Anders; Thomas, Mike; Welte, Tobias

    2017-01-01

    Several fixed-dose combinations (FDCs) of long-acting bronchodilators (a long-acting muscarinic antagonist [LAMA] plus a long-acting β2-agonist [LABA]) are available for the treatment of COPD. Studies of these FDCs have demonstrated substantial improvements in lung function (forced expiratory volume in 1 second) in comparison with their respective constituent monocomponents. Improvements in patient-reported outcomes (PROs), such as symptoms and health status, as well as exacerbation rates, have been reported compared with a LABA or LAMA alone, but results are less consistent. The inconsistencies may in part be owing to differences in study design, methods used to assess study end points, and patient populations. Nevertheless, these observations tend to support an association between improvements in forced expiratory volume in 1 second and improvements in symptom-based outcomes. In order to assess the effects of FDCs on PROs and evaluate relationships between PROs and changes in lung function, we performed a systematic literature search of publications reporting randomized controlled trials of FDCs. Results of this literature search were independently assessed by two reviewers, with a third reviewer resolving any conflicting results. In total, 22 Phase III randomized controlled trials of FDC bronchodilators in COPD were identified, with an additional study including a post-literature search (ten for indacaterol-glycopyrronium once daily, eight for umeclidinium-vilanterol once daily, three for tiotropium-olodaterol once daily, and two for aclidinium-formoterol twice daily). Results from these studies demonstrated that the LAMA-LABA FDCs significantly improved lung function compared with their component monotherapies or other single-agent treatments. Furthermore, LABA-LAMA combinations also generally improved symptoms and health status versus monotherapies, although some discrepancies between lung function and PROs were observed. Overall, the safety profiles of the

  9. Dual bronchodilation in COPD: lung function and patient-reported outcomes – a review

    PubMed Central

    Price, David; Østrem, Anders; Thomas, Mike; Welte, Tobias

    2017-01-01

    Several fixed-dose combinations (FDCs) of long-acting bronchodilators (a long-acting muscarinic antagonist [LAMA] plus a long-acting β2-agonist [LABA]) are available for the treatment of COPD. Studies of these FDCs have demonstrated substantial improvements in lung function (forced expiratory volume in 1 second) in comparison with their respective constituent monocomponents. Improvements in patient-reported outcomes (PROs), such as symptoms and health status, as well as exacerbation rates, have been reported compared with a LABA or LAMA alone, but results are less consistent. The inconsistencies may in part be owing to differences in study design, methods used to assess study end points, and patient populations. Nevertheless, these observations tend to support an association between improvements in forced expiratory volume in 1 second and improvements in symptom-based outcomes. In order to assess the effects of FDCs on PROs and evaluate relationships between PROs and changes in lung function, we performed a systematic literature search of publications reporting randomized controlled trials of FDCs. Results of this literature search were independently assessed by two reviewers, with a third reviewer resolving any conflicting results. In total, 22 Phase III randomized controlled trials of FDC bronchodilators in COPD were identified, with an additional study including a post-literature search (ten for indacaterol–glycopyrronium once daily, eight for umeclidinium–vilanterol once daily, three for tiotropium–olodaterol once daily, and two for aclidinium–formoterol twice daily). Results from these studies demonstrated that the LAMA–LABA FDCs significantly improved lung function compared with their component monotherapies or other single-agent treatments. Furthermore, LABA–LAMA combinations also generally improved symptoms and health status versus monotherapies, although some discrepancies between lung function and PROs were observed. Overall, the safety

  10. Use of internal scintillator radioactivity to calibrate DOI function of a PET detector with a dual-ended-scintillator readout

    SciTech Connect

    Bircher, Chad; Shao Yiping

    2012-02-15

    Purpose: Positron emission tomography (PET) detectors that use a dual-ended-scintillator readout to measure depth-of-interaction (DOI) must have an accurate DOI function to provide the relationship between DOI and signal ratios to be used for detector calibration and recalibration. In a previous study, the authors used a novel and simple method to accurately and quickly measure DOI function by irradiating the detector with an external uniform flood source; however, as a practical concern, implementing external uniform flood sources in an assembled PET system is technically challenging and expensive. In the current study, therefore, the authors investigated whether the same method could be used to acquire DOI function from scintillator-generated (i.e., internal) radiation. The authors also developed a method for calibrating the energy scale necessary to select the events within the desired energy window. Methods: The authors measured the DOI function of a PET detector with lutetium yttrium orthosilicate (LYSO) scintillators. Radiation events originating from the scintillators' internal Lu-176 beta decay were used to measure DOI functions which were then compared with those measured from both an external uniform flood source and an electronically collimated external point source. The authors conducted these studies with several scintillators of differing geometries (1.5 x 1.5 and 2.0 x 2.0 mm{sup 2} cross-section area and 20, 30, and 40 mm length) and various surface finishes (mirror-finishing, saw-cut rough, and other finishes in between), and in a prototype array. Results: All measured results using internal and external radiation sources showed excellent agreement in DOI function measurement. The mean difference among DOI values for all scintillators measured from internal and external radiation sources was less than 1.0 mm for different scintillator geometries and various surface finishes. Conclusions: The internal radioactivity of LYSO scintillators can be used

  11. Dual characterization of critical fluctuations: Density functional theory & nonlinear dynamics close to a tangent bifurcation

    NASA Astrophysics Data System (ADS)

    Riquelme-Galván, Mauricio; Robledo, Alberto

    2017-02-01

    We improve on the description of the relationship that exists between critical clusters in thermal systems and intermittency near the onset of chaos in low-dimensional systems. We make use of the statistical-mechanical language of inhomogeneous systems and of the renormalization group (RG) method in nonlinear dynamics to provide a more accurate, formal, approach to the subject. The description of this remarkable correspondence encompasses, on the one hand, the density functional formalism, where classical and quantum mechanical analogues match the procedure for one-dimensional clusters, and, on the other, the RG fixed-point map of functional compositions that captures the essential dynamical behavior. We provide details of how the above-referred theoretical approaches interrelate and discuss the implications of the correspondence between the high-dimensional (degrees of freedom) phenomenon and low-dimensional dynamics.

  12. Dual function of a nuclear factor I binding site in MMTV transcription regulation.

    PubMed Central

    Buetti, E; Kühnel, B; Diggelmann, H

    1989-01-01

    Using linker-scanning mutagenesis we had previously identified four elements within the MMTV LTR which are necessary for transcriptional stimulation by glucocorticoid hormones. Two of them overlapped with regions to which the glucocorticoid receptor binds in vitro. The third element contained a NF-I binding site, and the fourth the TATA box. Here we show that mutations that abolish in vitro binding of NF-I had a negative effect also on the basal activity of the MMTV promoter of LTR-containing plasmids stably integrated in Ltk- fibroblasts. The analysis of double mutants altered in the NF-I plus either one of the receptor binding elements further demonstrated that the NF-I site functionally cooperated with the proximal (-120) element, which alone was extremely inefficient in stimulation. The stronger distal (-181/-172) element was independent of NF-I and showed functional cooperativity with the proximal hormone-binding element. Images PMID:2542892

  13. A dual molecular analogue tuner for dissecting protein function in mammalian cells

    PubMed Central

    Brosh, Ran; Hrynyk, Iryna; Shen, Jessalyn; Waghray, Avinash; Zheng, Ning; Lemischka, Ihor R.

    2016-01-01

    Loss-of-function studies are fundamental for dissecting gene function. Yet, methods to rapidly and effectively perturb genes in mammalian cells, and particularly in stem cells, are scarce. Here we present a system for simultaneous conditional regulation of two different proteins in the same mammalian cell. This system harnesses the plant auxin and jasmonate hormone-induced degradation pathways, and is deliverable with only two lentiviral vectors. It combines RNAi-mediated silencing of two endogenous proteins with the expression of two exogenous proteins whose degradation is induced by external ligands in a rapid, reversible, titratable and independent manner. By engineering molecular tuners for NANOG, CHK1, p53 and NOTCH1 in mammalian stem cells, we have validated the applicability of the system and demonstrated its potential to unravel complex biological processes. PMID:27230261

  14. Dual-Function Air Cathode for Metal-Air Batteries with Pulse-Power Capability

    DTIC Science & Technology

    2013-01-28

    conformal nanoscale coatings of manganese oxide ( MnO x ) exhibit both energy storage and conversion function by providing electrocatalytic activity...at the nanoscale MnO x coating— oxygen reduction to sustain long-term energy delivery and faradaic electron/cation charge-storage reactions to...2 ) and z (60–540 μ m). [ 15 ] Ultrathin ( ∼ 10 nm), conformal coatings of Na + -birnessite-type MnO x are applied to the interior and exterior

  15. A twisted wire-shaped dual-function energy device for photoelectric conversion and electrochemical storage.

    PubMed

    Sun, Hao; You, Xiao; Deng, Jue; Chen, Xuli; Yang, Zhibin; Chen, Peining; Fang, Xin; Peng, Huisheng

    2014-06-23

    A wire-shaped energy device that can perform photoelectric conversion and electrochemical storage was developed through a simple but effective twisting process. The energy wire exhibited a high energy conversion efficiency of 6.58 % and specific capacitance of 85.03 μF cm(-1) or 2.13 mF cm(-2), and the two functions were alternately realized without sacrificing either performance.

  16. Dual surface-functionalized Janus nanocomposites for targeted stimulus responsive drug delivery.

    NASA Astrophysics Data System (ADS)

    Wang, Feng; Wang, Yilong; Pauletti, Giovanni; Shi, Donglu

    2014-03-01

    A novel superparamagnetic Janus nanocomposite (SJNC) of polystyrene/Fe3O4@SiO2 was designed and developed for the first time using a miniemulsion method. Both surfaces were readily functionalized for bio-medical application. Folic acid (FA) and doxorubicin (DOX) were conjugated stepwise to the surfaces. It was found that SJNCs achieved cell-targeted drug delivery in a pH-responsive manner.

  17. Dual Functional Roles of Molecular Beacon as a MicroRNA Detector and Inhibitor.

    PubMed

    Li, Wai Ming; Chan, Ching-Man; Miller, Andrew L; Lee, Chow H

    2017-03-03

    MicroRNAs are essential in many cellular processes. The ability to detect microRNAs is important for understanding its function and biogenesis. This study is aimed at using a molecular beacon to detect miR-430 in developing zebrafish embryos as a proof of principle. miR-430 is crucial for the clearance of maternal mRNA during maternal zygotic transition in embryonic development. Despite its known function, the temporal and spatial expression of miR-430 remains unclear. We used various imaging techniques, including laser scanning confocal microscopy, spinning disk, and lightsheet microscopy, to study the localization of miR-430 and any developmental defects possibly caused by the molecular beacon. Our results show that miR-430 is expressed early in development and is localized in distinct cytoplasmic granules where its target mRNA can be detected. We also show that the designed molecular beacon can inhibit the function of miR-430 and cause developmental defect in the brain, notochord, heart, and kidney, depending on the delivery site within the embryo, suggesting that miR-430 plays a diverse role in embryonic morphogenesis. When compared with morpholino, molecular beacon is 2 orders of magnitude more potent in inhibiting miR-430. Thus, our results reveal that in addition to being used as a valuable tool for the detection of microRNAs in vivo, molecular beacons can also be employed to inhibit microRNAs in a specific manner.

  18. An α-helical core encodes the dual functions of the chlamydial protein IncA.

    PubMed

    Ronzone, Erik; Wesolowski, Jordan; Bauler, Laura D; Bhardwaj, Anshul; Hackstadt, Ted; Paumet, Fabienne

    2014-11-28

    Chlamydia is an intracellular bacterium that establishes residence within parasitophorous compartments (inclusions) inside host cells. Chlamydial inclusions are uncoupled from the endolysosomal pathway and undergo fusion with cellular organelles and with each other. To do so, Chlamydia expresses proteins on the surface of the inclusion using a Type III secretion system. These proteins, termed Incs, are located at the interface between host and pathogen and carry out the functions necessary for Chlamydia survival. Among these Incs, IncA plays a critical role in both protecting the inclusion from lysosomal fusion and inducing the homotypic fusion of inclusions. Within IncA are two regions homologous to eukaryotic SNARE (soluble N-ethylmaleimide-sensitive factor attachment receptor) domains referred to as SNARE-like domain 1 (SLD1) and SNARE-like domain 2 (SLD2). Using a multidisciplinary approach, we have discovered the functional core of IncA that retains the ability to both inhibit SNARE-mediated fusion and promote the homotypic fusion of Chlamydia inclusions. Circular dichroism and analytical ultracentrifugation experiments show that this core region is composed almost entirely of α-helices and assembles into stable homodimers in solution. Altogether, we propose that both IncA functions are encoded in a structured core domain that encompasses SLD1 and part of SLD2.

  19. A dual function of the CRISPR-Cas system in bacterial antivirus immunity and DNA repair.

    PubMed

    Babu, Mohan; Beloglazova, Natalia; Flick, Robert; Graham, Chris; Skarina, Tatiana; Nocek, Boguslaw; Gagarinova, Alla; Pogoutse, Oxana; Brown, Greg; Binkowski, Andrew; Phanse, Sadhna; Joachimiak, Andrzej; Koonin, Eugene V; Savchenko, Alexei; Emili, Andrew; Greenblatt, Jack; Edwards, Aled M; Yakunin, Alexander F

    2011-01-01

    Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) and the associated proteins (Cas) comprise a system of adaptive immunity against viruses and plasmids in prokaryotes. Cas1 is a CRISPR-associated protein that is common to all CRISPR-containing prokaryotes but its function remains obscure. Here we show that the purified Cas1 protein of Escherichia coli (YgbT) exhibits nuclease activity against single-stranded and branched DNAs including Holliday junctions, replication forks and 5'-flaps. The crystal structure of YgbT and site-directed mutagenesis have revealed the potential active site. Genome-wide screens show that YgbT physically and genetically interacts with key components of DNA repair systems, including recB, recC and ruvB. Consistent with these findings, the ygbT deletion strain showed increased sensitivity to DNA damage and impaired chromosomal segregation. Similar phenotypes were observed in strains with deletion of CRISPR clusters, suggesting that the function of YgbT in repair involves interaction with the CRISPRs. These results show that YgbT belongs to a novel, structurally distinct family of nucleases acting on branched DNAs and suggest that, in addition to antiviral immunity, at least some components of the CRISPR-Cas system have a function in DNA repair.

  20. The use of a dual PEDOT and RGD-functionalized alginate hydrogel coating to provide sustained drug delivery and improved cochlear implant function

    PubMed Central

    Chikar, JA; Hendricks, JL; Richardson-Burns, SM; Raphael, Y; Pfingst, BE; Martin, DC

    2011-01-01

    Cochlear implants provide hearing by electrically stimulating the auditory nerve. Implant function can be hindered by device design variables, including electrode size and electrode-to-nerve distance, and cochlear environment variables, including the degeneration of the auditory nerve following hair cell loss. We have developed a dual component cochlear implant coating to improve both the electrical function of the implant and the biological stability of the inner ear, thereby facilitating the long-term perception of sound through a cochlear implant. This coating is a combination of an arginine-glycine-aspartic acid (RGD)-functionalized alginate hydrogel and the conducting polymer poly(3, 4-ethylenedioxythiophene) (PEDOT). Both in vitro and in vivo assays on the effects of these electrode coatings demonstrated improvements in device performance. We found that the coating reduced electrode impedance, improved charge delivery, and locally released significant levels of a trophic factor into cochlear fluids. This coating is non-cytotoxic, clinically relevant, and has the potential to significantly improve the cochlear implant user’s experience. PMID:22182748

  1. A Neuronal Activity-Dependent Dual Function Chromatin-Modifying Complex Regulates Arc Expression1,2,3

    PubMed Central

    Oey, Nicodemus E.; Leung, How Wing; Ezhilarasan, Rajaram; Zhou, Lei; Beuerman, Roger W.; VanDongen, Hendrika M.A.

    2015-01-01

    Abstract Chromatin modification is an important epigenetic mechanism underlying neuroplasticity. Histone methylation and acetylation have both been shown to modulate gene expression, but the machinery responsible for mediating these changes in neurons has remained elusive. Here we identify a chromatin-modifying complex containing the histone demethylase PHF8 and the acetyltransferase TIP60 as a key regulator of the activity-induced expression of Arc, an important mediator of synaptic plasticity. Clinically, mutations in PHF8 cause X-linked mental retardation while TIP60 has been implicated in the pathogenesis of Alzheimer’s disease. Within minutes of increased synaptic activity, this dual function complex is rapidly recruited to the Arc promoter, where it specifically counteracts the transcriptionally repressive histone mark H3K9me2 to facilitate the formation of the transcriptionally permissive H3K9acS10P, thereby favoring transcriptional activation. Consequently, gain-of-function of the PHF8−TIP60 complex in primary rat hippocampal neurons has a positive effect on early activity-induced Arc gene expression, whereas interfering with the function of this complex abrogates it. A global proteomics screen revealed that the majority of common interactors of PHF8 and TIP60 were involved in mRNA processing, including PSF, an important molecule involved in neuronal gene regulation. Finally, we proceeded to show, using super-resolution microscopy, that PHF8 and TIP60 interact at the single molecule level with PSF, thereby situating this chromatin modifying complex at the crossroads of transcriptional activation. These findings point toward a mechanism by which an epigenetic pathway can regulate neuronal activity-dependent gene transcription, which has implications in the development of novel therapeutics for disorders of learning and memory. PMID:26464965

  2. Structural basis of the mercury(II)-mediated conformational switching of the dual-function transcriptional regulator MerR

    PubMed Central

    Chang, Chih-Chiang; Lin, Li-Ying; Zou, Xiao-Wei; Huang, Chieh-Chen; Chan, Nei-Li

    2015-01-01

    The mer operon confers bacterial resistance to inorganic mercury (Hg2+) and organomercurials by encoding proteins involved in sensing, transport and detoxification of these cytotoxic agents. Expression of the mer operon is under tight control by the dual-function transcriptional regulator MerR. The metal-free, apo MerR binds to the mer operator/promoter region as a repressor to block transcription initiation, but is converted into an activator upon Hg2+-binding. To understand how MerR interacts with Hg2+ and how Hg2+-binding modulates MerR function, we report here the crystal structures of apo and Hg2+-bound MerR from Bacillus megaterium, corresponding respectively to the repressor and activator conformation of MerR. To our knowledge, the apo-MerR structure represents the first visualization of a MerR family member in its intact and inducer-free form. And the Hg2+-MerR structure offers the first view of a triligated Hg2+-thiolate center in a metalloprotein, confirming that MerR binds Hg2+ via trigonal planar coordination geometry. Structural comparison revealed the conformational transition of MerR is coupled to the assembly/disassembly of a buried Hg2+ binding site, thereby providing a structural basis for the Hg2+-mediated functional switching of MerR. The pronounced Hg2+-induced repositioning of the MerR DNA-binding domains suggests a plausible mechanism for the transcriptional regulation of the mer operon. PMID:26150423

  3. Identification of Transcriptional Targets of the Dual Function Transcription Factor/Phosphatase Eyes Absent

    PubMed Central

    Jemc, Jennifer; Rebay, Ilaria

    2007-01-01

    Drosophila eye specification and development relies on a collection of transcription factors termed the retinal determination gene network (RDGN). Two members of this network, Eyes absent (EYA) and Sine oculis (SO), form a transcriptional complex in which EYA provides the transactivation function while SO provides the DNA binding activity. EYA also functions as a protein tyrosine phosphatase, raising the question of whether transcriptional output is dependent or independent of phosphatase activity. To explore this, we used microarrays together with binding site analysis, quantitative real-time PCR, chromatin immunoprecipitation, genetics and in vivo expression analysis to identify new EYA-SO targets. In parallel, we examined the expression profiles of tissue expressing phosphatase mutant eya and found that reducing phosphatase activity did not globally impair transcriptional output. Among the targets identified by our analysis was the cell cycle regulatory gene, string (stg), suggesting that EYA and SO may influence cell proliferation through transcriptional regulation of stg. Future investigation into the regulation of stg and other EYA-SO targets identified in this study will help elucidate the transcriptional circuitries whereby output from the RDGN integrates with other signaling inputs to coordinate retinal development. PMID:17714699

  4. Molecular Basis for the Dual Function of Eps8 on Actin Dynamics: Bundling and Capping

    PubMed Central

    Hazelwood, Larnele; Disanza, Andrea; Liu, HongJun; Perlade, Emilie; Malabarba, Maria Grazia; Pasqualato, Sebastiano; Maiolica, Alessio; Confalonieri, Stefano; Le Clainche, Christophe; Offenhauser, Nina; Block, Jennifer; Rottner, Klemens; Di Fiore, Pier Paolo; Carlier, Marie-France; Volkmann, Niels; Hanein, Dorit; Scita, Giorgio

    2010-01-01

    Actin capping and cross-linking proteins regulate the dynamics and architectures of different cellular protrusions. Eps8 is the founding member of a unique family of capping proteins capable of side-binding and bundling actin filaments. However, the structural basis through which Eps8 exerts these functions remains elusive. Here, we combined biochemical, molecular, and genetic approaches with electron microscopy and image analysis to dissect the molecular mechanism responsible for the distinct activities of Eps8. We propose that bundling activity of Eps8 is mainly mediated by a compact four helix bundle, which is contacting three actin subunits along the filament. The capping activity is mainly mediated by a amphipathic helix that binds within the hydrophobic pocket at the barbed ends of actin blocking further addition of actin monomers. Single-point mutagenesis validated these modes of binding, permitting us to dissect Eps8 capping from bundling activity in vitro. We further showed that the capping and bundling activities of Eps8 can be fully dissected in vivo, demonstrating the physiological relevance of the identified Eps8 structural/functional modules. Eps8 controls actin-based motility through its capping activity, while, as a bundler, is essential for proper intestinal morphogenesis of developing Caenorhabditis elegans. PMID:20532239

  5. Dual function MITO-Porter, a nano carrier integrating both efficient cytoplasmic delivery and mitochondrial macromolecule delivery.

    PubMed

    Yamada, Yuma; Furukawa, Ryo; Yasuzaki, Yukari; Harashima, Hideyoshi

    2011-08-01

    Mitochondrial dysfunction is associated with a variety of human diseases including inherited mitochondrial diseases, neurodegenerative disorders, diabetes mellitus, and cancer. Effective medical therapies for mitochondrial diseases will ultimately require an optimal drug delivery system, which will likely be achieved through innovations in the nanotechnology of intracellular trafficking. To achieve efficient mitochondrial drug delivery, two independent processes, i.e., "cytoplasmic delivery through the cell membrane" and "mitochondrial delivery through the mitochondrial membrane" are required. In previous studies, we developed an octaarginine (R8) modified nano carrier for efficient cytoplasmic delivery, showing that R8-modified liposomes were internalized into cells efficiently. On the other hand, we also constructed MITO-Porter for the mitochondrial delivery of macromolecules, a liposome-based carrier that delivers cargos to mitochondria via membrane fusion. Here, we report the development of a dual function MITO-Porter (DF-MITO-Porter), based on the concept of integrating both R8-modified liposomes and MITO-Porter. We show that the DF-MITO-Porter effectively delivers exogenous macro-biomolecules into the mitochondrial matrix, and provide a demonstration of its potential use in therapies aimed at mitochondrial DNA.

  6. A dual-functional asymmetric squaraine-based low band gap hole transporting material for efficient perovskite solar cells.

    PubMed

    Paek, Sanghyun; Rub, Malik Abdul; Choi, Hyeju; Kosa, Samia A; Alamry, Khalid A; Cho, Jin Woo; Gao, Peng; Ko, Jaejung; Asiri, Abdullah M; Nazeeruddin, Mohammad Khaja

    2016-03-28

    We demonstrate for the first time an asymmetric squaraine-based low band-gap hole transporting material, which acted as both light harvesting and hole transporting layers in methylammonium lead triiodide perovskite solar cells. Opto-electrochemical characterization revealed extremely high molar extinction coefficients of the absorption bands in the low energy region and prominent space charge delocalization due to its electronically asymmetric nature. A suitable band alignment of the squaraine HOMO level with the valence band edge of the perovskite, and the conduction band of the TiO2 with LUMO of the perovskite allowed a cascade of hole extraction and electron injection, respectively. Red-shifted absorption was observed for both HTMs in thin films coated on the perovskite, and the optimized devices exhibited an impressive PCE of 14.7% under full sunlight illumination (100 mW cm(-2), AM1.5 G). The efficiency value is comparable to that of the devices using a state-of-the-art spiro-OMeTAD hole transport layer under similar conditions. Ambient stability after 300 h revealed that 88% of the initial efficiency remained for , and almost no change for , indicating that the devices had good long-term stability thus suggesting that the asymmetric squaraines have great potential as a dual-functional HTM for high performance perovskite solar cells.

  7. Fabrication and characterization of dual-functional ultrafine composite fibers with phase-change energy storage and luminescence properties

    NASA Astrophysics Data System (ADS)

    Xi, Peng; Zhao, Tianxiang; Xia, Lei; Shu, Dengkun; Ma, Menjiao; Cheng, Bowen

    2017-01-01

    Ultrafine composite fibers consisting of a thermoplastic polyurethane solid-solid phase-change material and organic lanthanide luminescent materials were prepared through a parallel electrospinning technique as an innovative type of ultrafine, dual-functional fibers containing phase-change and luminescent properties. The morphology and structure, thermal energy storage, and luminescent properties of parallel electrospun ultrafine fibers were investigated. Scanning electron microscopy (SEM) images showed that the parallel electrospun ultrafine fibers possessed the desired morphologies with smaller average fiber diameters than those of traditional mixed electrospun ultrafine fibers. Transmission electron microscopy (TEM) images revealed that the parallel electrospun ultrafine fibers were composed of two parts. Polymeric phase-change materials, which can be directly produced and spun, were used to provide temperature stability, while a mixture of polymethyl methacrylate and an organic lanthanide complex acted as the luminescent unit. Differential scanning calorimetry (DSC) and luminescence measurements indicated that the unique structure of the parallel electrospun ultrafine fibers provides the products with good thermal energy storage and luminescence properties. The fluorescence intensity and the phase-change enthalpy values of the ultrafine fibers prepared by parallel electrospinning were respectively 1.6 and 2.1 times those of ultrafine fibers prepared by mixed electrospinning.

  8. Silver nanoparticles-containing dual-function hydrogels based on a guar gum-sodium borohydride system

    PubMed Central

    Dai, Lei; Nadeau, Ben; An, Xingye; Cheng, Dong; Long, Zhu; Ni, Yonghao

    2016-01-01

    Dual-function hydrogels, possessing both stimuli-responsive and self-healing properties, have recently attracted attention of both chemists and materials scientists. Here we report a new paradigm using natural polymer (guar gum, GG) and sodium borohydride (NaBH4), for the preparation of silver nanoparticles (AgNPs)-containing smart hydrogels in a simple, fast and economical way. NaBH4 performs as a reducing agent for AgNPs synthesis using silver nitrate (AgNO3) as the precursor. Meanwhile, sodium metaborate (NaBO2) (from NaBH4) behaves as a cross-linking agent between GG molecular chains. The AgNPs/GG hydrogels with excellent viscoelastic properties can be obtained within 3 min at room temperature without the addition of other cross-linkers. The resultant AgNPs/GG hydrogels are flowable and injectable, and they possess excellent pH/thermal responsive properties. Additionally, they exhibit rapid self-healing capacity. This work introduces a facile and scale-up way to prepare a class of hydrogels that can have great potential to biomedical and other industrial applications. PMID:27819289

  9. Development of dual-function microbeads embedded with quantum dots and iron oxide nanocrystals for biomedical applications

    NASA Astrophysics Data System (ADS)

    Sathe, Tushar; Nie, Shuming

    2007-02-01

    Nanomaterials, such as semiconductor Quantum Dots (QD) and Iron Oxide nanocrystals possess unique properties that are not available in their bulk phase. Some of these properties include the narrow emission spectra, superior brightness and higher photostability of QDs, and the superparamagnetic properties of Iron Oxide nanocrystals. In the past decade, these two nanomaterials have separately seen widespread use in a variety of biomedical applications ranging from multiplexed biomolecular detection to isolation and magnetic manipulation of disease cells and molecules respectively. Here, we describe a method for combining QDs and Iron Oxide nanocrystals into a micron-sized host material in a rapid fashion. The resulting beads are dual functional, i.e. they are optically encoded, and can be manipulated with a permanent magnet. The beads have great potential in biomedical applications because of the combined ability to enrich and detect multiple target molecules from heterogeneous and diluted biological samples. The development of multifunctional composite materials by combining novel nanomaterials is bound to open avenues for ultrasensitive and quantitative bioassays.

  10. Fabrication and characterization of dual-functional ultrafine composite fibers with phase-change energy storage and luminescence properties.

    PubMed

    Xi, Peng; Zhao, Tianxiang; Xia, Lei; Shu, Dengkun; Ma, Menjiao; Cheng, Bowen

    2017-01-09

    Ultrafine composite fibers consisting of a thermoplastic polyurethane solid-solid phase-change material and organic lanthanide luminescent materials were prepared through a parallel electrospinning technique as an innovative type of ultrafine, dual-functional fibers containing phase-change and luminescent properties. The morphology and structure, thermal energy storage, and luminescent properties of parallel electrospun ultrafine fibers were investigated. Scanning electron microscopy (SEM) images showed that the parallel electrospun ultrafine fibers possessed the desired morphologies with smaller average fiber diameters than those of traditional mixed electrospun ultrafine fibers. Transmission electron microscopy (TEM) images revealed that the parallel electrospun ultrafine fibers were composed of two parts. Polymeric phase-change materials, which can be directly produced and spun, were used to provide temperature stability, while a mixture of polymethyl methacrylate and an organic lanthanide complex acted as the luminescent unit. Differential scanning calorimetry (DSC) and luminescence measurements indicated that the unique structure of the parallel electrospun ultrafine fibers provides the products with good thermal energy storage and luminescence properties. The fluorescence intensity and the phase-change enthalpy values of the ultrafine fibers prepared by parallel electrospinning were respectively 1.6 and 2.1 times those of ultrafine fibers prepared by mixed electrospinning.

  11. Graphene oxide as a dual-function conductive binder for PEEK-derived microporous carbons in high performance supercapacitors

    NASA Astrophysics Data System (ADS)

    Kim, Christine H. J.; Zhang, Hongbo; Liu, Jie

    2015-06-01

    Microporous carbons (MPCs) are promising electrode materials for supercapacitors because of their high surface area and accessible pores. However, their low electrical conductivity and mechanical instability result in limited power density and poor cycle life. This work proposes a unique two-layered film made of polyetheretherketone-derived MPCs and reduced graphene oxide (rGO) as an electrode for supercapacitors. Electrochemical characterizations of films show that such a layered structure is more effective in increasing the accessibility of ions to the hydrophilic MPCs and establishing conductive paths through the rGO network than a simple mixed composite film. The two-layered structure increases the capacitance by ˜124% (237 F g-1) with excellent cycling stability (˜93% after 6000 cycles). More importantly, we demonstrate that such performance improvements result from an optimal balance between electrical conductivity and ion accessibility, which maximizes the synergistic effects of MPC and rGO. The MPCs, which are exposed to the surface, provide a highly accessible surface area for ion adsorption. The rGO serves a dual function as a conductive filler to increase the electrical conductivity and as a binder to interconnect individual MPC particles into a robust and flexible film. These findings provide a rational basis for the design of MPC-based electrodes in high performance supercapacitors.

  12. Fabrication and characterization of dual-functional ultrafine composite fibers with phase-change energy storage and luminescence properties

    PubMed Central

    Xi, Peng; Zhao, Tianxiang; Xia, Lei; Shu, Dengkun; Ma, Menjiao; Cheng, Bowen

    2017-01-01

    Ultrafine composite fibers consisting of a thermoplastic polyurethane solid-solid phase-change material and organic lanthanide luminescent materials were prepared through a parallel electrospinning technique as an innovative type of ultrafine, dual-functional fibers containing phase-change and luminescent properties. The morphology and structure, thermal energy storage, and luminescent properties of parallel electrospun ultrafine fibers were investigated. Scanning electron microscopy (SEM) images showed that the parallel electrospun ultrafine fibers possessed the desired morphologies with smaller average fiber diameters than those of traditional mixed electrospun ultrafine fibers. Transmission electron microscopy (TEM) images revealed that the parallel electrospun ultrafine fibers were composed of two parts. Polymeric phase-change materials, which can be directly produced and spun, were used to provide temperature stability, while a mixture of polymethyl methacrylate and an organic lanthanide complex acted as the luminescent unit. Differential scanning calorimetry (DSC) and luminescence measurements indicated that the unique structure of the parallel electrospun ultrafine fibers provides the products with good thermal energy storage and luminescence properties. The fluorescence intensity and the phase-change enthalpy values of the ultrafine fibers prepared by parallel electrospinning were respectively 1.6 and 2.1 times those of ultrafine fibers prepared by mixed electrospinning. PMID:28067299

  13. Functional evaluation of hemodynamic response during neural activation using optical microangiography integrated with dual-wavelength laser speckle imaging

    PubMed Central

    Qin, Jia; Shi, Lei; Wang, Hequn; Reif, Roberto; Wang, Ruikang K.

    2014-01-01

    Abstract. Evaluation of spatiotemporal hemodynamic and metabolic responses during neural activation is crucial in studying brain function. We explore the use of a noninvasive multifunctional optical imaging system to measure these responses in a mouse brain upon electrically stimulated neural activation, with the cranium left intact. The system is developed by integrating an optical microangiography (OMAG) imaging system with a dual-wavelength laser speckle imaging (DW-LSI) system. The DW-LSI, running at an image acquisition speed of ∼100  Hz, is used to extract the large-scale two-dimensional map, revealing the localized response of blood flow, hemoglobin concentration, and metabolic rate of oxygen change. Guided by DW-LSI, the OMAG is, however, used to image the response of individual blood vessels with its unique depth-resolved capability. We show that the integrated system is capable of investigating neural activation, thus is potentially valuable in the preclinical study of the mechanism of neurovascular coupling. PMID:24549439

  14. Balancing polymer hydrophobicity for ligand presentation and siRNA delivery in dual function CXCR4 inhibiting polyplexes.

    PubMed

    Wang, Y; Li, J; Chen, Y; Oupický, D

    2015-07-01

    In the present study, a series of copolymers (PAMD-Ch) was synthesized by grafting polymeric Plerixafor/AMD3100 (PAMD) with different amounts of cholesterol and the effect of cholesterol modification on siRNA delivery was investigated. PAMD-Ch/siRNA polyplexes exhibited improved colloidal and enzymatic stability when compared with PAMD/siRNA polyplexes containing no cholesterol. PAMD-Ch with low (17 wt%) and medium (25 wt%) cholesterol content exhibited CXCR4 antagonism comparable to unmodified PAMD. Cholesterol modification increased cell uptake of siRNA polyplexes and significantly decreased sensitivity of siRNA transfection to the presence of serum. When used to deliver anticancer siRNA against polo-like kinase 1 (PLK1), polyplexes based on PAMD-Ch with 17 wt% cholesterol exhibited the highest cancer cell killing activity both in serum-free and serum-containing conditions. Overall, the results of this study validate cholesterol modified PAMD as dual-function delivery vectors suitable for efficient delivery of anticancer siRNA and simultaneous CXCR4 inhibition for combined anticancer therapies.

  15. The effect of tin and antimony addition on the performance of dual function cracking catalyst (DFCC) mixtures

    SciTech Connect

    Occelli, M.L. ); Naraghi, S.M.; Krishnan, V.; Suib, S.L. )

    1992-05-01

    In 1976, the Phillips Petroleum Company successfully demonstrated that the addition of certain organo-antimony compounds to a metal-contaminated heavy gas oil reduced the deleterious effects that metals such as Ni and V have on gasoline yields, coke, and hydrogen selectivities. Nickel has little effect on the activity of a fluidized cracking catalyst (FCC) but generates large amounts of gases, placing severe demands on capabilities of gas compressors. Marketed by Phillips Petroleum Company. Phil-Ad CA antimony organics have been shown to reduce by 50% gas formation due to metal contaminants, especially nickel. However, Sb, when introduced into a fluidized cracking unit, could reduce and form SbH[sub 3], stibine, that like arsine (AsH[sub 3]) is a highly toxic compound. Procedures for the safe usage of Sb in refining operations have been outlined; when used properly, Sb-containing passivating agents did not generate any detectable stibine. Recently, it has been reported that at microactivity test conditions, the additions of diluents (such as aluminas and layered magnesium silicates) capable of selectively sorbing metal contaminants from gas oils can form dual function cracking catalysts (DFCC) that retain most of their useful cracking activity even in the presence of as much as 1.0-1.5% V. It is the purpose of this paper to report the stability of Sb- and Sn-loaded alumina particles and the effects that the addition of metal passivation compounds such as Sb and Sn have on the performance of DFCC mixtures.

  16. Balancing polymer hydrophobicity for ligand presentation and siRNA delivery in dual function CXCR4 inhibiting polyplexes

    PubMed Central

    Wang, Y.; Li, J.; Chen, Y.; Oupický, D.

    2015-01-01

    In the present study, a series of copolymers (PAMD-Ch) was synthesized by grafting polymeric Plerixafor/AMD3100 (PAMD) with different amounts of cholesterol and the effect of cholesterol modification on siRNA delivery was investigated. PAMD-Ch/siRNA polyplexes exhibited improved colloidal and enzymatic stability when compared with PAMD/siRNA polyplexes containing no cholesterol. PAMD-Ch with low (17 wt%) and medium (25 wt%) cholesterol content exhibited CXCR4 antagonism comparable to unmodified PAMD. Cholesterol modification increased cell uptake of siRNA polyplexes and significantly decreased sensitivity of siRNA transfection to the presence of serum. When used to deliver anticancer siRNA against polo-like kinase 1 (PLK1), polyplexes based on PAMD-Ch with 17 wt% cholesterol exhibited the highest cancer cell killing activity both in serum-free and serum-containing conditions. Overall, the results of this study validate cholesterol modified PAMD as dual-function delivery vectors suitable for efficient delivery of anticancer siRNA and simultaneous CXCR4 inhibition for combined anticancer therapies. PMID:26146552

  17. Preparation of a novel weak cation exchange/hydrophobic interaction chromatography dual-function polymer-based stationary phase for protein separation using "thiol-ene click chemistry".

    PubMed

    Yang, Fan; Bai, Quan; Zhao, Kailou; Gao, Dong; Tian, Lei

    2015-02-01

    A novel dual-function mixed-mode stationary phase based on poly(glycidyl methacrylate-co-ethylene dimethacrylate) microspheres was synthesized by thiol-ene click chemistry and characterized by infrared spectroscopy and elemental analysis. The new system displays both hydrophobic interaction chromatography (HIC) character in a high salt concentration mobile phase, and weak cation exchange (WCX) chromatography character in a low salt concentration mobile phase. It can be used to separate proteins in both ion-exchange chromatography (IEC) mode and HIC mode. The resolution and selectivity of the stationary phase were evaluated in both HIC mode and IEC mode using protein standards. In comparison with the conventional WCX and HIC columns, the results were satisfactory and acceptable. Protein mass and bioactivity recoveries of more than 96% can be achieved in both HIC mode and IEC mode using this column. The results indicate that the novel dual-function mixed-mode column in many cases can replace the use of two individual WCX and HIC columns. In addition, the effects on protein separation of different ligand structures in the dual-function stationary phase and the pH of the mobile phase used were also investigated in detail. The results show that electrostatic interaction of the ligand with proteins must match the hydrophobicity of the ligand, which is an important factor to prepare the dual-function stationary phase. On the basis of this dual-function mixed-mode chromatography column, a new two-dimensional liquid chromatography technology with a single column system was also developed in this study, and was used to renature and purify recombinant human interferon-γ from inclusion bodies. The mass recovery, purity, and specific bioactivity obtained for the purified recombinant human interferon-γ were 87.2%, 92.4%, and 2.8 × 10(7) IU/mg, respectively, in IEC mode, and 83.4%, 95.2%, and 4.3 × 10(7) IU/mg, respectively, in HIC mode. The results indicate that the

  18. Structure of dual function iron regulatory protein 1 complexed with ferritin IRE-RNA

    SciTech Connect

    Walden, William E.; Selezneva, Anna I.; Dupuy, Jérôme; Volbeda, Anne; Fontecilla-Camps, Juan C.; Theil, Elizabeth C.; Volz1, Karl

    2011-07-27

    Iron regulatory protein 1 (IRP1) binds iron-responsive elements (IREs) in messenger RNAs (mRNAs), to repress translation or degradation, or binds an iron-sulfur cluster, to become a cytosolic aconitase enzyme. The 2.8 angstrom resolution crystal structure of the IRP1:ferritin H IRE complex shows an open protein conformation compared with that of cytosolic aconitase. The extended, L-shaped IRP1 molecule embraces the IRE stem-loop through interactions at two sites separated by {approx}30 angstroms, each involving about a dozen protein:RNA bonds. Extensive conformational changes related to binding the IRE or an iron-sulfur cluster explain the alternate functions of IRP1 as an mRNA regulator or enzyme.

  19. Dual functions of TiC nanoparticles on tribological performance of Al/graphite composites

    NASA Astrophysics Data System (ADS)

    Fallahdoost, Hamid; Nouri, Alireza; Azimi, Amin

    2016-06-01

    In this study, the effect of TiC nanoparticles as a reinforcement on the mechanical and tribological properties of Aluminum-based self lubricating composite was investigated. The microstructure, relative density, hardness, and tribological properties of Al/graphite and Al/TiC/graphite composites were examined as a function of graphite content. The tribo-surfaces of the samples were analyzed using SEM and EDS elemental mapping. The results indicated that the addition of TiC nanoparticles not only decreased the wear rate and coefficient of friction of the composites, but also facilitated the formation of a stable graphite layer at longer sliding distances and high sliding velocities by forming a durable graphite/TiC composite on the tribo-surface. Therefore, the stability of graphite layer can be considered as a possible cause for decrease in wear rate of the Al/TiC/graphite composite.

  20. Cation-Specific Conformations in a Dual-Function Ion-Pumping Microbial Rhodopsin.

    PubMed

    da Silva, Giordano F Z; Goblirsch, Brandon R; Tsai, Ah-Lim; Spudich, John L

    2015-06-30

    A recently discovered rhodopsin ion pump (DeNaR, also known as KR2) in the marine bacterium Dokdonia eikasta uses light to pump protons or sodium ions from the cell depending on the ionic composition of the medium. In cells suspended in a KCl solution, DeNaR functions as a light-driven proton pump, whereas in a NaCl solution, DeNaR conducts light-driven sodium ion pumping, a novel activity within the rhodopsin family. These two distinct functions raise the questions of whether the conformations of the protein differ in the presence of K(+) or Na(+) and whether the helical movements that result in the canonical E → C conformational change in other microbial rhodopsins are conserved in DeNaR. Visible absorption maxima of DeNaR in its unphotolyzed (dark) state show an 8 nm difference between Na(+) and K(+) in decyl maltopyranoside micelles, indicating an influence of the cations on the retinylidene photoactive site. In addition, electronic paramagnetic resonance (EPR) spectra of the dark states reveal repositioning of helices F and G when K(+) is replaced with Na(+). Furthermore, the conformational changes assessed by EPR spin-spin dipolar coupling show that the light-induced transmembrane helix movements are very similar to those found in bacteriorhodopsin but are altered by the presence of Na(+), resulting in a new feature, the clockwise rotation of helix F. The results establish the first observation of a cation switch controlling the conformations of a microbial rhodopsin and indicate specific interactions of Na(+) with the half-channels of DeNaR to open an appropriate path for ion translocation.

  1. Dual host-defence functions of SPLUNC2/PSP and synthetic peptides derived from the protein.

    PubMed

    Gorr, Sven-Ulrik; Abdolhosseini, Mahsa; Shelar, Anuradha; Sotsky, Julie

    2011-08-01

    PSP (parotid secretory protein)/SPLUNC2 (short palate, lung and nasal epithelium clone 2) is expressed in human salivary glands and saliva. The protein exists as an N-glycosylated and non-glycosylated form and both appear to induce agglutination of bacteria, a major antibacterial function for salivary proteins. Both forms of PSP/SPLUNC2 bind LPS (lipopolysaccharide), suggesting that the protein may also play an anti-inflammatory role. Based on the predicted structure of PSP/SPLUNC2 and the location of known antibacterial and anti-inflammatory peptides in BPI (bactericidal/permeability-increasing protein) and LBP (LPS-binding protein), we designed GL13NH2 and GL13K, synthetic peptides that capture these proposed functions of PSP/SPLUNC2. GL13NH3 agglutinates bacteria, leading to increased clearance by macrophages and reduced spread of infection in a plant model. GL13K kills bacteria with a minimal inhibitory concentration of 5-10 μg/ml, kills bacteria in biofilm and retains activity in 150 mM NaCl and 50% saliva. Both peptides block endotoxin action, but only GL13K appears to bind endotoxin. The peptides do not cause haemolysis, haemagglutination in serum, inhibit mammalian cell proliferation or induce an inflammatory response in macrophages. These results suggest that the GL13NH2 and the modified peptide GL13K capture the biological activity of PSP/SPLUNC2 and can serve as lead compounds for the development of novel antimicrobial and anti-inflammatory peptides.

  2. The dual PPARα/γ agonist aleglitazar increases the number and function of endothelial progenitor cells: implications for vascular function and atherogenesis

    PubMed Central

    Werner, C M; Schirmer, S H; Gensch, C; Pavlickova, V; Pöss, J; Wright, M B; Böhm, M; Laufs, U

    2014-01-01

    Background and Purpose Aleglitazar is a dual PPARα/γ agonist but little is known about its effects on vascular function and atherogenesis. Hence, we characterized its effects on circulating angiogenic cells (CAC), neoangiogenesis, endothelial function, arteriogenesis and atherosclerosis in mice. Experimental Approach C57Bl/6 wild-type (WT, normal chow), endothelial NOS (eNOS)−/− (normal chow) and ApoE−/− (Western-type diet) mice were treated with aleglitazar (10 mg·kg−1·day−1, i.p.) or vehicle. Key Results Aleglitazar enhanced expression of PPARα and PPARγ target genes, normalized glucose tolerance and potently reduced hepatic fat in ApoE−/− mice. In WT mice, but not in eNOS−/−, aleglitazar up-regulated Sca-1/VEGFR2-positive CAC in the blood and bone marrow and up-regulated diLDL/lectin-positive CAC. Aleglitazar augmented CAC migration and enhanced neoangiogenesis. In ApoE−/− mice, aleglitazar up-regulated CAC number and function, reduced markers of vascular inflammation and potently improved perfusion restoration after hindlimb ischaemia and aortic endothelium-dependent vasodilatation. This was associated with markedly reduced formation of atherosclerotic plaques. In human cultured CAC from healthy donors and patients with coronary artery disease with or without diabetes mellitus, aleglitazar increased migration and colony-forming units in a concentration-dependent manner. Furthermore, oxidative stress-induced CAC apoptosis and expression of p53 were reduced, while telomerase activity and expression of phospho-eNOS and phospho-Akt were elevated. Comparative agonist and inhibitor experiments revealed that aleglitazar's effects on CAC migration and colony-forming units were mediated by both PPARα and PPARγ signalling and required Akt. Conclusions and Implications Aleglitazar augments the number, function and survival of CAC, which correlates with improved vascular function, enhanced arteriogenesis and prevention of atherosclerosis

  3. A Novel Dual Expression Platform for High Throughput Functional Screening of Phage Libraries in Product like Format

    PubMed Central

    Mugabe, Sheila; Gao, Changshou; Tkaczyk, Christine; Mazor, Yariv; Pavlik, Peter; Wu, Herren; Dall’Acqua, William; Chowdhury, Partha Sarathi

    2015-01-01

    High throughput screenings of single chain Fv (scFv) antibody phage display libraries are currently done as soluble scFvs produced in E.coli. Due to endotoxin contaminations from bacterial cells these preparations cannot be reliably used in mammalian cell based assays. The monovalent nature and lack of Fc in soluble scFvs prevent functional assays that are dependent on target cross linking and/or Fc functions. A convenient approach is to convert scFvs into scFv.Fc fusion proteins and express them in mammalian cell lines for screening. This approach is low throughput and is only taken after primary screening of monovalent scFvs that are expressed in bacteria. There is no platform at present that combines the benefits of both bacterial and mammalian expression system for screening phage library output. We have, therefore, developed a novel dual expression vector, called pSplice, which can be used to express scFv.Fc fusion proteins both in E.coli and mammalian cell lines. The hallmark of the vector is an engineered intron which houses the bacterial promoter and signal peptide for expression and secretion of scFv.Fc in E.coli. When the vector is transfected into a mammalian cell line, the intron is efficiently spliced out resulting in a functional operon for expression and secretion of the scFv.Fc fusion protein into the culture medium. By applying basic knowledge of mammalian introns and splisosome, we designed this vector to enable screening of phage libraries in a product like format. Like IgG, the scFv.Fc fusion protein is bi-valent for the antigen and possesses Fc effector functions. Expression in E.coli maintains the speed of the bacterial expression platform and is used to triage clones based on binding and other assays that are not sensitive to endotoxin. Triaged clones are then expressed in a mammalian cell line without the need for any additional cloning steps. Conditioned media from the mammalian cell line containing the fusion proteins are then used for

  4. Monodisperse Dual-Functional Upconversion Nanoparticles Enabled Near-Infrared Organolead Halide Perovskite Solar Cells.

    PubMed

    He, Ming; Pang, Xinchang; Liu, Xueqin; Jiang, Beibei; He, Yanjie; Snaith, Henry; Lin, Zhiqun

    2016-03-18

    Extending the spectral absorption of organolead halide perovskite solar cells from visible into near-infrared (NIR) range renders the minimization of non-absorption loss of solar photons with improved energy alignment. Herein, we report on, for the first time, a viable strategy of capitalizing on judiciously synthesized monodisperse NaYF4 :Yb/Er upconversion nanoparticles (UCNPs) as the mesoporous electrode for CH3 NH3 PbI3 perovskite solar cells and more importantly confer perovskite solar cells to be operative under NIR light. Uniform NaYF4 :Yb/Er UCNPs are first crafted by employing rationally designed double hydrophilic star-like poly(acrylic acid)-block-poly(ethylene oxide) (PAA-b-PEO) diblock copolymer as nanoreactor, imparting the solubility of UCNPs and the tunability of film porosity during the manufacturing process. The subsequent incorporation of NaYF4 :Yb/Er UCNPs as the mesoporous electrode led to a high efficiency of 17.8 %, which was further increased to 18.1 % upon NIR irradiation. The in situ integration of upconversion materials as functional components of perovskite solar cells offers the expanded flexibility for engineering the device architecture and broadening the solar spectral use.

  5. Dual function of suppressor of fused in Hh pathway activation and mouse spinal cord patterning.

    PubMed

    Liu, Jinling; Heydeck, Westley; Zeng, Huiqing; Liu, Aimin

    2012-02-15

    The morphogen Sonic hedgehog, one of the Hedgehog (Hh) family of secreted proteins, plays a key role in patterning the mammalian spinal cord along its dorsoventral (D/V) axis through the activation of Glioma-associated oncogene (Gli) family of transcription factors. Suppressor of Fused (Sufu), a Gli-interacting protein, modulates the D/V patterning of the spinal cord by antagonizing Hh signaling. The molecular mechanisms underlying the function of Sufu in Hh pathway activation and spinal cord D/V patterning remain controversial, particularly in light of recent findings that Sufu protects Gli2 and Gli3 proteins from proteasomal degradation. In the current study, we show that Hh pathway activation and dorsal expansion of ventral spinal cord cell types in the absence of Sufu depend on the activator activities of all three Gli family proteins. We also show that Sufu plays a positive role in the maximal activation of Hh signaling that defines the ventral-most cell fate in the mammalian spinal cord, likely through protecting Gli2 and Gli3 proteins from degradation. Finally, by altering the level of Gli3 repressor on a background of reduced Gli activator activities, we reveal an important contribution of Gli3 repressor activity to the Hh pathway activation and the D/V patterning of the spinal cord.

  6. Dual epithelial and immune cell function of Dvl1 regulates gut microbiota composition and intestinal homeostasis

    PubMed Central

    Belinson, Haim; Savage, Adam K.; Fadrosh, Douglas; Kuo, Yien-Ming; Lin, Din; Valladares, Ricardo; Nusse, Ysbrand; Wynshaw-Boris, Anthony; Lynch, Susan V.; Locksley, Richard M.

    2016-01-01

    Homeostasis of the gastrointestinal (GI) tract is controlled by complex interactions between epithelial and immune cells and the resident microbiota. Here, we studied the role of Wnt signaling in GI homeostasis using Disheveled 1 knockout (Dvl1–/–) mice, which display an increase in whole gut transit time. This phenotype is associated with a reduction and mislocalization of Paneth cells and an increase in CD8+ T cells in the lamina propria. Bone marrow chimera experiments demonstrated that GI dysfunction requires abnormalities in both epithelial and immune cells. Dvl1–/– mice exhibit a significantly distinct GI microbiota, and manipulation of the gut microbiota in mutant mice rescued the GI transit abnormality without correcting the Paneth and CD8+ T cell abnormalities. Moreover, manipulation of the gut microbiota in wild-type mice induced a GI transit abnormality akin to that seen in Dvl1–/– mice. Together, these data indicate that microbiota manipulation can overcome host dysfunction to correct GI transit abnormalities. Our findings illustrate a mechanism by which the epithelium and immune system coregulate gut microbiota composition to promote normal GI function. PMID:27525310

  7. Fluorescence-Magnetism Functional EuS Nanocrystals with Controllable Morphologies for Dual Bioimaging.

    PubMed

    Sun, Yuanqing; Wang, Dandan; Zhao, Tianxin; Jiang, Yingnan; Zhao, Yueqi; Wang, Chuanxi; Sun, Hongchen; Yang, Bai; Lin, Quan

    2016-12-14

    Multiple functions incorporated in one single component material offer important applications in biosystems. Here we prepared a divalent state of rare earth EuS nanocrystals (NCs), which provides luminescent and magnetic properties, using both 1-Dodecanethiol (DT) and oleylamine (OLA) as reducing agents. The resultant EuS NCs exhibit controllable shapes, uniform size, and bright luminescence with a quantum yield as high as 3.5%. OLA as a surface ligand plays an important role in tunable morphologies, such as nanowires, nanorods, nanospheres et al. Another attractive nature of the EuS NCs is their paramagnetism at room temperature. In order to expand the biological applications, the resultant EuS NCs were modified with amphiphilic block copolymer F127 and transferred from oil to water phase. The excellent biocompatibility of EuS NCs is demonstrated as well as preservation of their luminescence and paramagnetic properties. The EuS NCs offer multifunction and great advantages of bright luminescence, paramagnetic, controllable morphologies, and good biocompatibility promising applications in the field of simultaneous magnetic resonance and fluorescence bioimaging.

  8. Dual functionality of O-GlcNAc transferase is required for Drosophila development.

    PubMed

    Mariappa, Daniel; Zheng, Xiaowei; Schimpl, Marianne; Raimi, Olawale; Ferenbach, Andrew T; Müller, H-Arno J; van Aalten, Daan M F

    2015-12-01

    Post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc) catalysed by O-GlcNAc transferase (OGT) has been linked to regulation of diverse cellular functions. OGT possesses a C-terminal glycosyltransferase catalytic domain and N-terminal tetratricopeptide repeats that are implicated in protein-protein interactions. Drosophila OGT (DmOGT) is encoded by super sex combs (sxc), mutants of which are pupal lethal. However, it is not clear if this phenotype is caused by reduction of O-GlcNAcylation. Here we use a genetic approach to demonstrate that post-pupal Drosophila development can proceed with negligible OGT catalysis, while early embryonic development is OGT activity-dependent. Structural and enzymatic comparison between human OGT (hOGT) and DmOGT informed the rational design of DmOGT point mutants with a range of reduced catalytic activities. Strikingly, a severely hypomorphic OGT mutant complements sxc pupal lethality. However, the hypomorphic OGT mutant-rescued progeny do not produce F2 adults, because a set of Hox genes is de-repressed in F2 embryos, resulting in homeotic phenotypes. Thus, OGT catalytic activity is required up to late pupal stages, while further development proceeds with severely reduced OGT activity.

  9. Dual functionality of O-GlcNAc transferase is required for Drosophila development

    PubMed Central

    Mariappa, Daniel; Zheng, Xiaowei; Schimpl, Marianne; Raimi, Olawale; Ferenbach, Andrew T.; Müller, H.-Arno J.; van Aalten, Daan M. F.

    2015-01-01

    Post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc) catalysed by O-GlcNAc transferase (OGT) has been linked to regulation of diverse cellular functions. OGT possesses a C-terminal glycosyltransferase catalytic domain and N-terminal tetratricopeptide repeats that are implicated in protein–protein interactions. Drosophila OGT (DmOGT) is encoded by super sex combs (sxc), mutants of which are pupal lethal. However, it is not clear if this phenotype is caused by reduction of O-GlcNAcylation. Here we use a genetic approach to demonstrate that post-pupal Drosophila development can proceed with negligible OGT catalysis, while early embryonic development is OGT activity-dependent. Structural and enzymatic comparison between human OGT (hOGT) and DmOGT informed the rational design of DmOGT point mutants with a range of reduced catalytic activities. Strikingly, a severely hypomorphic OGT mutant complements sxc pupal lethality. However, the hypomorphic OGT mutant-rescued progeny do not produce F2 adults, because a set of Hox genes is de-repressed in F2 embryos, resulting in homeotic phenotypes. Thus, OGT catalytic activity is required up to late pupal stages, while further development proceeds with severely reduced OGT activity. PMID:26674417

  10. Evaluation of benzaldehyde derivatives from Morinda officinalis as anti-mite agents with dual function as acaricide and mite indicator.

    PubMed

    Yang, Ji-Yeon; Kim, Min-Gi; Park, Jun-Hwan; Hong, Seong-Tshool; Lee, Hoi-Seon

    2014-12-01

    Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by SFTS virus with 12-30% fatality rate. Despite severity of the disease, any medication or treatment for SFTS has not developed yet. One approach to prevent SFTS spreading is to control the arthropod vector carrying SFTS virus. We report that 2-methylbenzaldehyde analogues from M. officinalis have a dual function as acaricide against Dermatophagoides spp. and Haemaphysalis longicornis and indicator (color change) against Dermatophagoides spp. Based on the LD50 values, 2,4,5-trimethylbenzaldehyde (0.21, 0.19, and 0.68 μg/cm(3)) had the highest fumigant activity against D. farinae, D. pteronyssinus, and H. longicornis, followed by 2,3-dimethylbenzaldehyde (0.46, 0.44, and 0.79 μg/cm(3)), 2,4-dimethylbenzaldehyde (0.66, 0.59, and 0.95 μg/cm(3)), 2,5-dimethylbenzaldehyde (0.65, 0.68, and 0.88 μg/cm(3)), 2-methylbenzaldehyde (0.95, 0.87, and 1.28 μg/cm(3)), 3-methylbenzaldehyde (0.99, 0.93, and 1.38 μg/cm(3)), 4-methylbenzaldehyde (1.17, 1.15, and 3.67 μg/cm(3)), and M. officinalis oil (7.05, 7.00, and 19.70 μg/cm(3)). Furthermore, color alteration of Dermatophagoides spp. was shown to be induced, from colorless to dark brown, by the treatment of 2,3-dihydroxybenzaldehyde. These finding indicated that 2-methylbenzaldehyde analogues could be developed as functional agent associated with the arthropod vector of SFTS virus and allergen.

  11. Evaluation of benzaldehyde derivatives from Morinda officinalis as anti-mite agents with dual function as acaricide and mite indicator

    PubMed Central

    Yang, Ji-Yeon; Kim, Min-Gi; Park, Jun-Hwan; Hong, Seong-Tshool; Lee, Hoi-Seon

    2014-01-01

    Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by SFTS virus with 12–30% fatality rate. Despite severity of the disease, any medication or treatment for SFTS has not developed yet. One approach to prevent SFTS spreading is to control the arthropod vector carrying SFTS virus. We report that 2–methylbenzaldehyde analogues from M. officinalis have a dual function as acaricide against Dermatophagoides spp. and Haemaphysalis longicornis and indicator (color change) against Dermatophagoides spp. Based on the LD50 values, 2,4,5–trimethylbenzaldehyde (0.21, 0.19, and 0.68 μg/cm3) had the highest fumigant activity against D. farinae, D. pteronyssinus, and H. longicornis, followed by 2,3–dimethylbenzaldehyde (0.46, 0.44, and 0.79 μg/cm3), 2,4–dimethylbenzaldehyde (0.66, 0.59, and 0.95 μg/cm3), 2,5–dimethylbenzaldehyde (0.65, 0.68, and 0.88 μg/cm3), 2–methylbenzaldehyde (0.95, 0.87, and 1.28 μg/cm3), 3–methylbenzaldehyde (0.99, 0.93, and 1.38 μg/cm3), 4–methylbenzaldehyde (1.17, 1.15, and 3.67 μg/cm3), and M. officinalis oil (7.05, 7.00, and 19.70 μg/cm3). Furthermore, color alteration of Dermatophagoides spp. was shown to be induced, from colorless to dark brown, by the treatment of 2,3–dihydroxybenzaldehyde. These finding indicated that 2–methylbenzaldehyde analogues could be developed as functional agent associated with the arthropod vector of SFTS virus and allergen. PMID:25434408

  12. Synthesis and biomedical applications of functionalized fluorescent and magnetic dual reporter nanoparticles as obtained in the miniemulsion process

    NASA Astrophysics Data System (ADS)

    Holzapfel, Verena; Lorenz, Myriam; Kilian Weiss, Clemens; Schrezenmeier, Hubert; Landfester, Katharina; Mailänder, Volker

    2006-09-01

    As superparamagnetic nanoparticles capture new applications and markets, the flexibility and modifications of these nanoparticles are increasingly important aspects. Therefore a series of magnetic polystyrene particles encapsulating magnetite nanoparticles (10-12 nm) in a hydrophobic poly(styrene-co-acrylic acid) shell was synthesized by a three-step miniemulsion process. A high amount of iron oxide was incorporated by this process (typically 30-40% (w/w)). As a second reporter, a fluorescent dye was also integrated in order to obtain 'dual reporter particles'. Finally, polymerization of the monomer styrene yielded nanoparticles in the range 45-70 nm. By copolymerization of styrene with the hydrophilic acrylic acid, the amount of carboxyl groups on the surface was varied. The characterization of the latexes included dynamic light scattering, transmission electron microscopy, surface charge and magnetic measurements. For biomedical evaluation, the nanoparticles were incubated with different cell types. The introduction of carboxyl groups on the particle surfaces enabled the uptake of nanoparticles as demonstrated by the detection of the fluorescent signal by fluorescent activated cell sorter (FACS) and laser scanning microscopy. The quantity of iron in the cells that is required for most biomedical applications (like detection by magnetic resonance imaging) has to be significantly higher, as can be achieved by the uptake of magnetite encapsulated nanoparticles functionalized only with carboxyl groups. A further increase of uptake can be accomplished by transfection agents like poly-L-lysine or other positively charged polymers. This functionality was also engrafted into the surface of the nanoparticles by covalently coupling lysine to the carboxyl groups. The amount of iron that can be transfected was even higher than with the nanoparticles with a transfection agent added and this only physically adsorbed. Furthermore, the subcellular localization of these

  13. Amino acid derivative-mediated detoxification and functionalization of dual cure dental restorative material for dental pulp cell mineralization.

    PubMed

    Minamikawa, Hajime; Yamada, Masahiro; Iwasa, Fuminori; Ueno, Takeshi; Deyama, Yoshiaki; Suzuki, Kuniaki; Yawaka, Yasutaka; Ogawa, Takahiro

    2010-10-01

    Current dental restorative materials are only used to fill the defect of hard tissues, such as dentin and enamel, because of their cytotoxicity. Therefore, exposed dental pulp tissues in deep cavities must be first covered by a pulp capping material like calcium hydroxide to form a layer of mineralized tissue. However, this tissue mineralization is based on pathological reaction and triggers long-lasting inflammation, often causing clinical problems. This study tested the ability of N-acetyl cysteine (NAC), amino acid derivative, to reduce cytotoxicity and induce mineralized tissue conductivity in resin-modified glass ionomer (RMGI), a widely used dental restorative material having dual cure mechanism. Rat dental pulp cells were cultured on untreated or NAC-supplemented RMGI. NAC supplementation substantially increased the percentage of viable cells from 46.7 to 73.3% after 24-h incubation. Cell attachment, spreading, proliferative activity, and odontoblast-related gene and protein expressions increased significantly on NAC-supplemented RMGI. The mineralization capability of cells, which was nearly suppressed on untreated RMGI, was induced on NAC-supplemented RMGI. These improved behaviors and functions of dental pulp cells on NAC-supplemented RMGI were associated with a considerable reduction in the production of intracellular reactive oxygen species and with the increased level of intracellular glutathione reserves. These results demonstrated that NAC could detoxify and functionalize RMGIs via two different mechanisms involving in situ material detoxification and antioxidant cell protection. We believe that this study provides a new approach for developing dental restorative materials that enables mineralized tissue regeneration.

  14. Executive function deficits in team sport athletes with a history of concussion revealed by a visual-auditory dual task paradigm.

    PubMed

    Tapper, Anthony; Gonzalez, Dave; Roy, Eric; Niechwiej-Szwedo, Ewa

    2017-02-01

    The purpose of this study was to examine executive functions in team sport athletes with and without a history of concussion. Executive functions comprise many cognitive processes including, working memory, attention and multi-tasking. Past research has shown that concussions cause difficulties in vestibular-visual and vestibular-auditory dual-tasking, however, visual-auditory tasks have been examined rarely. Twenty-nine intercollegiate varsity ice hockey athletes (age = 19.13, SD = 1.56; 15 females) performed an experimental dual-task paradigm that required simultaneously processing visual and auditory information. A brief interview, event description and self-report questionnaires were used to assign participants to each group (concussion, no-concussion). Eighteen athletes had a history of concussion and 11 had no concussion history. The two tests involved visuospatial working memory (i.e., Corsi block test) and auditory tone discrimination. Participants completed both tasks individually, then simultaneously. Two outcome variables were measured, Corsi block memory span and auditory tone discrimination accuracy. No differences were shown when each task was performed alone; however, athletes with a history of concussion had a significantly worse performance on the tone discrimination task in the dual-task condition. In conclusion, long-term deficits in executive functions were associated with a prior history of concussion when cognitive resources were stressed. Evaluations of executive functions and divided attention appear to be helpful in discriminating participants with and without a history concussion.

  15. Preparation of a weak anion exchange/hydrophobic interaction dual-function mixed-mode chromatography stationary phase for protein separation using click chemistry.

    PubMed

    Zhao, Kailou; Yang, Fan; Xia, Hongjun; Wang, Fei; Song, Qingguo; Bai, Quan

    2015-03-01

    In this study, 3-diethylamino-1-propyne was covalently bonded to the azide-silica by a click reaction to obtain a novel dual-function mixed-mode chromatography stationary phase for protein separation with a ligand containing tertiary amine and two ethyl groups capable of electrostatic and hydrophobic interaction functionalities, which can display hydrophobic interaction chromatography character in a high-salt-concentration mobile phase and weak anion exchange character in a low-salt-concentration mobile phase employed for protein separation. As a result, it can be employed to separate proteins with weak anion exchange and hydrophobic interaction modes, respectively. The resolution and selectivity of the stationary phase were evaluated in both hydrophobic interaction and ion exchange modes with standard proteins, respectively, which can be comparable to that of conventional weak anion exchange and hydrophobic interaction chromatography columns. Therefore, the synthesized weak anion exchange/hydrophobic interaction dual-function mixed-mode chromatography column can be used to replace two corresponding conventional weak anion exchange and hydrophobic interaction chromatography columns to separate proteins. Based on this mixed-mode chromatography stationary phase, a new off-line two-dimensional liquid chromatography technology using only a single dual-function mixed-mode chromatography column was developed. Nine kinds of tested proteins can be separated completely using the developed method within 2.0 h.

  16. The use of PIB-PET as a dual pathological and functional biomarker in AD.

    PubMed

    Forsberg, Anton; Engler, Henry; Blomquist, Gunnar; Långström, Bengt; Nordberg, Agneta

    2012-03-01

    Amyloid imaging with positron emission tomography (PET) is presently used in Alzheimer's disease (AD) research. In this study we investigated the possibility to use early frames (ePIB) of the PIB scans as a rough index of CBF by comparing normalised early PIB values with cerebral glucose metabolism (rCMRglc). PIB-PET and FDG-PET were performed in 37 AD patients, 21 subjects with mild cognitive impairment (MCI) and 6 healthy controls (HC). The patients were divided based on their PIB retention (amyloid load) as either PIB positive (PIB+) or PIB negative (PIB-). Data of the unidirectional influx K(1) from a subset of the subjects including 7 AD patients and 3 HC was used for correlative analysis. Data was analysed using regions of interest (ROI) analysis. A strong, positive correlation was observed across brain regions between K(1) and ePIB (r=0.70; p≤0.001). The ePIB values were significantly lower in the posterior cingulate (p≤0.001) and the parietal cortices (p=0.002) in PIB+ subjects compared to PIB-, although the group difference were stronger for rCMRglc in cortical areas (p≤0.001). Strong positive correlations between ePIB and rCMRglc were observed in all cortical regions analysed, especially in the posterior cingulate and parietal cortices (p≤0.001). A single dynamic PIB-PET scan may provide information about pathological and functional changes (amyloidosis and impaired blood flow). This might be important for diagnosis of AD, enrichment of patients in clinical trials and evaluation of treatment effects. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.

  17. Novel Dual-Functional Membrane for Controlling Carbon Dioxide Emissions from Fossil Fuel Power Plants

    SciTech Connect

    C. Brinker; George Xomeritakis; C.-Y. Tsai; Ying-Bing Jiang

    2009-04-30

    CO{sub 2} captured from coal-fired power plants represents three-quarters of the total cost of an entire carbon sequestration process. Conventional amine absorption or cryogenic separation requires high capital investment and is very energy intensive. Our novel membrane process is energy efficient with great potential for economical CO{sub 2} capture. Three classes of microporous sol-gel derived silica-based membranes were developed for selective CO{sub 2} removal under simulated flue gas conditions (SFG), e.g. feed of 10% vol. CO{sub 22} in N{sub 2}, 1 atm total pressure, T = 50-60 C, RH>50%, SO2>10 ppm. A novel class of amine-functional microporous silica membranes was prepared using an amine-derivatized alkoxysilane precursor, exhibiting enhanced (>70) CO{sub 2}:N{sub 2} selectivity in the presence of H{sub 2}O vapor, but its CO{sub 2} permeance was lagging (<1 MPU). Pure siliceous membranes showed higher CO{sub 2} permeance (1.5-2 MPU) but subsequent densification occurred under prolonged SFG conditions. We incorporated NiO in the microporous network up to a loading of Ni:Si = 0.2 to retard densification and achieved CO2 permeance of 0.5 MPU and CO{sub 2}:N{sub 2} selectivity of 50 after 163 h exposure to SFG conditions. However, CO{sub 2} permeance should reach greater than 2.0 MPU in order to achieve the cost of electricity (COE) goal set by DOE. We introduced the atomic layer deposition (ALD), a molecular deposition technique that substantially reduces membrane thickness with intent to improve permeance and selectivity. The deposition technique also allows the incorporation of Ni or Ag cations by proper selection of metallorganic precursors. In addition, preliminary economic analysis provides a sensitivity study on the performance and cost of the proposed membranes for CO{sub 2} capture. Significant progress has been made toward the practical applications for CO{sub 2} capture. (1 MPU = 1.0 cm{sup 3}(STP){center_dot}cm-2{center_dot}min-1{center_dot}atm-1)

  18. Impactful study of dual work function, underlap and hetero gate dielectric on TFET with different drain doping profile for high frequency performance estimation and optimization

    NASA Astrophysics Data System (ADS)

    Yadav, Dharmendra Singh; Sharma, Dheeraj; Raad, Bhagwan Ram; Bajaj, Varun

    2016-08-01

    This manuscript presents a comparative study of different combination for the dual workfunction gate material, underlap and hetero gate dielectric tunnel field-effect transistors (TFET's). Their performances have been analyzed in terms of ON-state current, ambipolar behaviour and RF response along with different drain doping profile. For this, the Dual work function of gate provides enhancement in ON-state current by reducing the tunnel barrier width at source/channel interface. Whereas, the underlap of gate is done near to the drain region, helps in reduction of ambipolar conduction by creating deficiency of hole for the conduction, which is major hurdle for TFET. Further, the combinations of the dual workfunction and underlap give combine advantages of both such as improve ON-state current and suppressed ambipolar current. Apart from this, the combination of hetero gate dielectric dual workfunction under lapping leads to superior device performance in terms of ON-state current and ambipolar behaviour. The use of hetero gate dielectric and Gaussian doping profile with gate underlap reduces the gate to drain capacitance that also improves the RF parameters of the device.

  19. Two New Native β-Glucosidases from Clavispora NRRL Y-50464 Confer Its Dual Function as Cellobiose Fermenting Ethanologenic Yeast

    PubMed Central

    Wang, Xu; Liu, Z. Lewis; Weber, Scott A.; Zhang, Xiaoping

    2016-01-01

    Yeast strain Clavispora NRRL Y-50464 is able to produce cellulosic ethanol from lignocellulosic materials without addition of external β-glucosidase by simultaneous saccharification and fermentation. A β-glucosidase BGL1 protein from this strain was recently reported supporting its cellobiose utilization capability. Here, we report two additional new β-glucosidase genes encoding enzymes designated as BGL2 and BGL3 from strain NRRL Y-50464. Quantitative gene expression was analyzed and the gene function of BGL2 and BGL3 was confirmed by heterologous expression using cellobiose as a sole carbon source. Each gene was cloned and partially purified protein obtained separately for direct enzyme assay using varied substrates. Both proteins showed the highest specific activity at pH 5 and relatively strong affinity with a Km of 0.08 and 0.18 mM for BGL2 and BGL3, respectively. The optimum temperature was found to be 50°C for BGL2 and 55°C for BGL3. Both proteins were able to hydrolyze 1,4 oligosaccharides evaluated in this study. They also showed a strong resistance to glucose product inhibition with a Ki of 61.97 and 38.33 mM for BGL2 and BGL3, respectively. While BGL3 was sensitive showing a significantly reduced activity to 4% ethanol, BGL2 demonstrated tolerance to ethanol. Its activity was enhanced in the presence of ethanol but reduced at concentrations greater than 16%. The presence of the fermentation inhibitors furfural and HMF did not affect the enzyme activity. Our results suggest that a β-glucosidase gene family exists in Clavispora NRRL Y-50464 with at least three members in this group that validate its cellobiose hydrolysis functions for lower-cost cellulosic ethanol production. Results of this study confirmed the cellobiose hydrolysis function of strain NRRL Y-50464, and further supported this dual functional yeast as a candidate for lower-cost cellulosic ethanol production and next-generation biocatalyst development in potential industrial

  20. Functional test of pedotransfer functions to predict water flow and solute transport with the dual-permeability model MACRO

    NASA Astrophysics Data System (ADS)

    Moeys, J.; Larsbo, M.; Bergström, L.; Brown, C. D.; Coquet, Y.; Jarvis, N. J.

    2012-02-01

    Estimating pesticide leaching risks at the regional scale requires the ability to completely parameterise a pesticide fate model using only survey data, such as soil and land-use maps. Such parameterisation usually rely on a set of lookup tables and (pedo)transfer functions, relating elementary soil and site properties to model parameters. The aim of this paper is to describe and test a complete set of parameter estimation algorithms developed for the pesticide fate model MACRO, which accounts for preferential flow in soil macropores. We used tracer monitoring data from 16 lysimeter studies, carried out in three European countries, to evaluate the ability of MACRO and this "blind parameterisation" scheme to reproduce measured solute leaching at the base of each lysimeter. We focused on the prediction of early tracer breakthrough due to preferential flow, because this is critical for pesticide leaching. We then calibrated a selected number of parameters in order to assess to what extent the prediction of water and solute leaching could be improved. Our results show that water flow was generally reasonably well predicted (median model efficiency, ME, of 0.42). Although the general pattern of solute leaching was reproduced well by the model, the overall model efficiency was low (median ME = -0.26) due to errors in the timing and magnitude of some peaks. Preferential solute leaching at early pore volumes was also systematically underestimated. Nonetheless, the ranking of soils according to solute loads at early pore volumes was reasonably well estimated (concordance correlation coefficient, CCC, between 0.54 and 0.72). Moreover, we also found that ignoring macropore flow leads to a significant deterioration in the ability of the model to reproduce the observed leaching pattern, and especially the early breakthrough in some soils. Finally, the calibration procedure showed that improving the estimation of solute transport parameters is probably more important than the

  1. Functional test of pedotransfer functions to predict water flow and solute transport with the dual-permeability model MACRO

    NASA Astrophysics Data System (ADS)

    Moeys, J.; Larsbo, M.; Bergström, L.; Brown, C. D.; Coquet, Y.; Jarvis, N. J.

    2012-07-01

    Estimating pesticide leaching risks at the regional scale requires the ability to completely parameterise a pesticide fate model using only survey data, such as soil and land-use maps. Such parameterisations usually rely on a set of lookup tables and (pedo)transfer functions, relating elementary soil and site properties to model parameters. The aim of this paper is to describe and test a complete set of parameter estimation algorithms developed for the pesticide fate model MACRO, which accounts for preferential flow in soil macropores. We used tracer monitoring data from 16 lysimeter studies, carried out in three European countries, to evaluate the ability of MACRO and this "blind parameterisation" scheme to reproduce measured solute leaching at the base of each lysimeter. We focused on the prediction of early tracer breakthrough due to preferential flow, because this is critical for pesticide leaching. We then calibrated a selected number of parameters in order to assess to what extent the prediction of water and solute leaching could be improved. Our results show that water flow was generally reasonably well predicted (median model efficiency, ME, of 0.42). Although the general pattern of solute leaching was reproduced well by the model, the overall model efficiency was low (median ME = -0.26) due to errors in the timing and magnitude of some peaks. Preferential solute leaching at early pore volumes was also systematically underestimated. Nonetheless, the ranking of soils according to solute loads at early pore volumes was reasonably well estimated (concordance correlation coefficient, CCC, between 0.54 and 0.72). Moreover, we also found that ignoring macropore flow leads to a significant deterioration in the ability of the model to reproduce the observed leaching pattern, and especially the early breakthrough in some soils. Finally, the calibration procedure showed that improving the estimation of solute transport parameters is probably more important than the

  2. Overcoming drug-resistant lung cancer by paclitaxel loaded dual-functional liposomes with mitochondria targeting and pH-response.

    PubMed

    Jiang, Lei; Li, Li; He, Xiaodan; Yi, Qiangying; He, Bin; Cao, Jun; Pan, Weisan; Gu, Zhongwei

    2015-06-01

    Mitochondrion-orientated transportation of smart liposomes has been developed as a promising strategy to deliver anticancer drugs directly to tumor sites, and these have a tremendous potential for killing cancer cells, especially those with multidrug resistance (MDR). Herein we report a novel dual-functional liposome system possessing both extracellular pH response and mitochondrial targeting properties to enhance drug accumulation in mitochondria and trigger apoptosis of drug-resistant cancer cells. Briefly, peptide D[KLAKLAK]2 (KLA) was modified with 2, 3-dimethylmaleic anhydride (DMA) and combined with 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) to yield a DSPE-KLA-DMA (DKD) lipid. This dual-functional DKD was then mixed with other commercially available lipids to fabricate liposomes. In vitro anticancer efficacy of this liposome system was evaluated in human lung cancer A549 cells and drug-resistant lung cancer A549/Taxol cells. At tumor extracellular pH (∼6.8), liposomes could reverse their surface charge (negative to positive), facilitating liposome internalization. After cellular uptake, KLA peptide directed delivery-enabled selective accumulation of these liposomes into mitochondria and favored release of their cargo paclitaxel (PTX) into desired sites. Specifically, enhanced apoptosis of MDR cancer cells through mitochondrial signaling pathways was evidenced by release of cytochrome c and increased activity of caspase-9 and -3. These dual-functional liposomes had the greatest efficacy for treating A549 cells and A549/Taxol cells in vitro, and in treating drug-resistant lung cancer A549/Taxol cells xenografted onto nude mice (tumor growth inhibition 86.7%). In conclusion, dual-functional liposomes provide a novel and versatile approach for overcoming MDR in cancer treatment.

  3. A dual enzyme functionalized nanostructured thulium oxide based interface for biomedical application

    NASA Astrophysics Data System (ADS)

    Singh, Jay; Roychoudhury, Appan; Srivastava, Manish; Solanki, Pratima R.; Lee, Dong Won; Lee, Seung Hee; Malhotra, B. D.

    2013-12-01

    nanorods has been electrophoretically deposited (EPD) onto an indium-tin-oxide (ITO) glass substrate. The n-Tm2O3 nanorods are found to provide improved sensing characteristics to the electrode interface in terms of electroactive surface area, diffusion coefficient, charge transfer rate constant and electron transfer kinetics. The structural and morphological studies of n-Tm2O3 nanorods have been carried out by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FTIR) spectroscopic techniques. This interfacial platform has been used for fabrication of a total cholesterol biosensor by immobilizing cholesterol esterase (ChEt) and cholesterol oxidase (ChOx) onto a Tm2O3 nanostructured surface. The results of response studies of the fabricated ChEt-ChOx/n-Tm2O3/ITO bioelectrode show a broad linear range of 8-400 mg dL-1, detection limit of 19.78 mg (dL cm-2)-1, and high sensitivity of 0.9245 μA (mg per dL cm-2)-1 with a response time of 40 s. Further, this bioelectrode has been utilized for estimation of total cholesterol with negligible interference (3%) from analytes present in human serum samples. The utilization of this n-Tm2O3 modified electrode for enzyme-based biosensor analysis offers an efficient strategy and a novel interface for application of the rare earth metal oxide materials in the field of electrochemical sensors and bioelectronic devices. Electronic supplementary information (ESI) available: XPS spectra of n-Tm2O3, differential pulse voltammograms, magnitude of potential difference as a function of scan rate (10-100 mV s-1), effect of working potential, amount of enzyme used for immobilization, amount of enzyme loading, effect of interferents, response time, effect of temperature, determination of cholesterol in serum samples and photometric enzyme activity studies. See DOI: 10.1039/c3nr05043b

  4. A dual-functional asymmetric squaraine-based low band gap hole transporting material for efficient perovskite solar cells

    NASA Astrophysics Data System (ADS)

    Paek, Sanghyun; Rub, Malik Abdul; Choi, Hyeju; Kosa, Samia A.; Alamry, Khalid A.; Cho, Jin Woo; Gao, Peng; Ko, Jaejung; Asiri, Abdullah M.; Nazeeruddin, Mohammad Khaja

    2016-03-01

    We demonstrate for the first time an asymmetric squaraine-based low band-gap hole transporting material, which acted as both light harvesting and hole transporting layers in methylammonium lead triiodide perovskite solar cells. Opto-electrochemical characterization revealed extremely high molar extinction coefficients of the absorption bands in the low energy region and prominent space charge delocalization due to its electronically asymmetric nature. A suitable band alignment of the squaraine HOMO level with the valence band edge of the perovskite, and the conduction band of the TiO2 with LUMO of the perovskite allowed a cascade of hole extraction and electron injection, respectively. Red-shifted absorption was observed for both HTMs in thin films coated on the perovskite, and the optimized devices exhibited an impressive PCE of 14.7% under full sunlight illumination (100 mW cm-2, AM1.5 G). The efficiency value is comparable to that of the devices using a state-of-the-art spiro-OMeTAD hole transport layer under similar conditions. Ambient stability after 300 h revealed that 88% of the initial efficiency remained for JK-216D, and almost no change for JK-217D, indicating that the devices had good long-term stability thus suggesting that the asymmetric squaraines have great potential as a dual-functional HTM for high performance perovskite solar cells.We demonstrate for the first time an asymmetric squaraine-based low band-gap hole transporting material, which acted as both light harvesting and hole transporting layers in methylammonium lead triiodide perovskite solar cells. Opto-electrochemical characterization revealed extremely high molar extinction coefficients of the absorption bands in the low energy region and prominent space charge delocalization due to its electronically asymmetric nature. A suitable band alignment of the squaraine HOMO level with the valence band edge of the perovskite, and the conduction band of the TiO2 with LUMO of the perovskite allowed

  5. The effect of dual-functional hyaluronic acid-vitamin E succinate micelles on targeting delivery of doxorubicin

    PubMed Central

    Wang, Jinling; Ma, Wenzhuan; Guo, Qiang; Li, Ying; Hu, Zhongdong; Zhu, Zhixiang; Wang, Xiaohui; Zhao, Yunfang; Chai, Xingyun; Tu, Pengfei

    2016-01-01

    Tumor-targeted delivery system has been developed as an attractive strategy for effective tumor therapy. In this study, in order to enhance the antitumor effects of doxorubicin (DOX), amphiphilic hyaluronic acid (HA)-conjugated vitamin E succinate (VES) copolymers (HA-VES) with different degrees of substitution (DS) were prepared with synergistic antitumor effects and active targeting activities, and utilized as nanocarriers for the efficient delivery of DOX. DOX-loaded HA-VES polymeric micelles (HA-VES/DOX) self-assembled from dual-functional HA-VES copolymer and exhibited excellent loading efficiency and superior colloidal stability. In vitro, HA-VES/DOX displayed enhanced cytotoxicity with synergistic anticancer effects of HA-VES copolymer, high apoptosis-inducing activities of tumor cells, and reversal effects of DOX on multidrug resistance, in comparison with DOX. Also, in vitro cellular uptake and subcellular localization studies revealed that HA-VES/DOX could more efficiently internalize into cancer cells and selectively release DOX within lysosomes, thereby enhancing the distribution of DOX in nuclei and facilitating its interactions with DNA. Specifically, HA-VES/DOX decreased the activity of CD44 mRNA and improved the targeting efficiency on MCF-7 cells, based on the active recognition between HA and CD44 receptor. More importantly, HA-VES/DOX displayed better tumor accumulation and targeting, and enhanced antitumor efficacy with reduced systemic toxicity in 4T1 tumor-bearing mice. In summary, the developed HA-VES–based drug delivery system, which increased drug targeting on the tumor site and exhibited preferable anticancer activity, could hold great potential as an effective and promising strategy for efficient tumor therapy. PMID:27853369

  6. A dual-channel fluorescent chemosensor for discriminative detection of glutathione based on functionalized carbon quantum dots.

    PubMed

    Huang, Yuanyuan; Zhou, Jin; Feng, Hui; Zheng, Jieyu; Ma, Hui-Min; Liu, Weidong; Tang, Cong; Ao, Hang; Zhao, Meizhi; Qian, Zhaosheng

    2016-12-15

    A convenient, fluorescent dual-channel chemosensor on the basis of bis(3-pyridylmethyl)amine-functionalized carbon quantum dots (BPMA-CQDs) nanoprobe was constructed, and it can discriminatively detect glutathione from its analogues cysteine and homocysteine based on two distinctive strategies. Two distinct fluorescence responses of BPMA-CQDs probe to Cu(II) and Ag(I) were identified and further employed to achieve selective detection of Cu(II) and Ag(I) respectively. Based on the BPMA-CQDs/Cu(II) conjugate, discriminative detection of GSH was achieved in terms of correlation between the amounts of GSH and fluorescence recovery. The addition of GSH into BPMA-CQDs/Cu(II) system induces the reduction of Cu(II) to Cu(I), which could efficiently block PET process resulting in the following fluorescence recovery. Based on the BPMA-CQDs/Ag(I) conjugate, GSH assay could also be established on the basis of fluorescence response to GSH. The introduction of GSH into the preceding system triggers the competitive coordination to Ag(I) between BPMA and GSH, and silver ions are finally taken away by GSH from the probe, where the fluorescence is restored to its original weak state. Both of the detection strategies can achieve discriminative detection of GSH from Cys and Hcy. The assays showed good stability and repeatability, and covered a broad linear range of up to 13.3μM with a lowest detection limit of 42.0nM. Moreover, both of them were utilized to monitor GSH level in live cells.

  7. A dual positional specific lipoxygenase functions in the generation of flavor compounds during climacteric ripening of apple

    PubMed Central

    Schiller, Doreen; Contreras, Carolina; Vogt, Jörg; Dunemann, Frank; Defilippi, Bruno G; Beaudry, Randolph; Schwab, Wilfried

    2015-01-01

    Lipoxygenase (LOX) is an important contributor to the formation of aroma-active C6 aldehydes in apple (Malus × domestica) fruit upon tissue disruption but little is known about its role in autonomously produced aroma volatiles from intact tissue. We explored the expression of 22 putative LOX genes in apple throughout ripening, but only six LOXs were expressed in a ripening-dependent manner. Recombinant LOX1:Md:1a, LOX1:Md:1c, LOX2:Md:2a and LOX2:Md:2b proteins showed 13/9-LOX, 9-LOX, 13/9-LOX and 13-LOX activity with linoleic acid, respectively. While products of LOX1:Md:1c and LOX2:Md:2b were S-configured, LOX1:Md:1a and LOX2:Md:2a formed 13(R)-hydroperoxides as major products. Site-directed mutagenesis of Gly567 to an alanine converted the dual positional specific LOX1:Md:1a to an enzyme with a high specificity for 9(S)-hydroperoxide formation. The high expression level of the corresponding MdLOX1a gene in stored apple fruit, the genetic association with a quantitative trait locus for fruit ester and the remarkable agreement in regio- and stereoselectivity of the LOX1:Md:1a reaction with the overall LOX activity found in mature apple fruits, suggest a major physiological function of LOX1:Md:1a during climacteric ripening of apples. While LOX1:Md:1c, LOX2:Md:2a and LOX2:Md:2b may contribute to aldehyde production in immature fruit upon cell disruption our results furnish additional evidence that LOX1:Md:1a probably regulates the availability of precursors for ester production in intact fruit tissue. PMID:26504564

  8. Characterization of U-97775 as a GABAA receptor ligand of dual functionality in cloned rat GABAA receptor subtypes.

    PubMed Central

    Im, H. K.; Im, W. B.; Pregenzer, J. F.; Carter, D. B.; Jacobsen, E. J.; Hamilton, B. J.

    1995-01-01

    1. U-97775 (tert-butyl 7-chloro-4,5-dihydro-5-[(1-(3,4,5-trimethyl)piperazino)carbonyl]- imidazo[1,5-a])quinoxaline-3-carboxylate) is a novel GABAA receptor ligand of dual functionality and was characterized for its interactions with cloned rat GABAA receptors expressed in human embryonic kidney cells. 2. The drug produced a bell-shaped dose-response profile in the alpha 1 beta 2 gamma 2 receptor subtype as monitored with GABA-induced Cl- currents in the whole cell patch-clamp technique. At low concentrations (< 0.5 microM), U-97775 enhanced the currents with a maximal increase of 120% as normalized to 5 microM GABA response (control). An agonist interaction of U-97775 with the benzodiazepine site is suggested, because Ro 15-1788 (an antagonist at the benzodiazepine site) abolished the current increase and [3H]-flunitrazepam binding was inhibited by U-97775 with a Ki of 1.2 nM. 3. The enhancement of GABA currents progressively disappeared as the U-97775 concentration was raised above 1 microM, and the current amplitude was reduced to 40% below the control at 10 microM U-97775. The current inhibition by U-97775 (10 microM) was not affected by Ro 15-1788. It appears that U-97775 interacts with a second site on GABA receptors, distinct from the benzodiazepine site, to reverse its agonistic activity on the benzodiazepine site and also to inhibit GABA currents. 4. U-97775 at low concentrations reduced and at high concentrations enhanced [35S]-TBPS binding. Ro 15-1788 selectively blocked the effect of U-97775 at low concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7647975

  9. Efficient, dual-stimuli responsive cytosolic gene delivery using a RGD modified disulfide-linked polyethylenimine functionalized gold nanorod.

    PubMed

    Wang, Feihu; Shen, Yuanyuan; Zhang, Wenjun; Li, Min; Wang, Yun; Zhou, Dejian; Guo, Shengrong

    2014-12-28

    Controlled-release systems capable of responding to external stimuli and/or unique internal environments have received great interests in site-specific gene and/or drug delivery. In this work, a functionalized gene nanocarrier for dual-stimuli triggered cytosolic gene delivery is developed and showing high gene delivery efficacy with low cytotoxicity. The nanocarrier is prepared by conjugating gold nanorod (GNR) with multiple disulfide cross-linked short PEIs to harness the advantageous properties of GNR based near infrared (NIR) laser induced photothermal heating and intracellular stimuli-triggered degradability of disulfide cross-linked short PEIs (DSPEI). The DSPEI is further grafted with a poly(ethylene glycol) (PEG) section to afford high carrier stability in cell cultures and a terminal RGD peptide for specific targeting of cancer cells. The nanocarrier is found to effectively condense plasmid DNA to form a highly stable GNR-DSPEI-PEG-RGD/DNA complex with tumor cell-targeting ability that can be efficiently uptaken by cancer cells. Moreover, the loaded genes can be effectively released from the complex triggered by the high intracellular glutathione content and/or by photothermal effect of NIR irradiation at 808 nm. Interestingly, the GNRs-based complex can easily escape from intracellular endo-/lyso-somal compartments and release the gene load into the cytosol upon exposure to NIR irradiation, resulting in significantly improved gene transfection efficiency. Our new gene carrier exhibits high gene transfection efficiency, comparable to or even better than that of high MW PEIs, but with a much lower cytotoxicity. Additionally, neither the GNR-based carrier nor the laser treatment shows any significant evidence of cytotoxicity. This work demonstrates a promising strategy for intracellular stimuli triggered, photothermal controllable gene delivery system, which can be further applied to many other nanomedicine fields.

  10. Dual-Functional Carbon Dots Pattern on Paper Chips for Fe(3+) and Ferritin Analysis in Whole Blood.

    PubMed

    Hu, Shan-Wen; Qiao, Shu; Xu, Bi-Yi; Peng, Xiang; Xu, Jing-Juan; Chen, Hong-Yuan

    2017-02-07

    Though microfluidic paper analytical devices (μPADs) have attracted paramounting attentions in recent years as promising devices for low cost point-of-care tests, their real applications for blood analysis are still challenged by integrating sample preparation with different detection modes on a same μPAD. Herein, we developed a novel μPAD, which well coupled automatic serum extraction with reliable dual mode iron health tests: fluorescent analysis for Fe(3+) and colorimetric ELISA for ferritin. All these functions are made available by in situ carbon dots (CDs) and AuNPs sequential patterning techniques. For CDs immobilization, hydrothermal reaction was taken on paper, to which a patterned through-hole polydimethylsiloxane (PDMS) mask was applied. None fluorescence CDs (nF-CDs) were generated on exposed regions, while the fluorescent CDs (F-CDs) were generated simultaneously on covered regions. Sensitive serum iron quantification was realized on the F-CDs modified regions, where Fe(3+) ion can selectively quench the fluorescence of F-CDs. For AuNPs immobilization, electroless plating was taken on nF-CDs modified regions. The resulting AuNPs on nF-CDs layer on one hand triggered the coagulation of blood cells and thus led to the longest ever wicking distance for serum separation, on the other hand facilitated colorimetric enzyme linked immunosorbent assay (ELISA) for detection of serum ferritin. Combining the two readings, the μPAD can provide reliable measurement for serum iron and serum ferritin in whole blood. Furthermore, as CDs and AuNPs modified μPAD has the features of easy handling, low-cost, lightweight, and disposability, it is accounting for a promising prototype for whole blood point-of-care analysis.

  11. Phosphorylation controls a dual-function polybasic nuclear localization sequence in the adapter protein SH2B1β to regulate its cellular function and distribution.

    PubMed

    Maures, Travis J; Su, Hsiao-Wen; Argetsinger, Lawrence S; Grinstein, Sergio; Carter-Su, Christin

    2011-05-01

    An intriguing question in cell biology is what targets proteins to, and regulates their translocation between, specific cellular locations. Here we report that the polybasic nuclear localization sequence (NLS) required for nuclear entry of the adapter protein and candidate human obesity gene product SH2B1β, also localizes SH2B1β to the plasma membrane (PM), most probably via electrostatic interactions. Binding of SH2B1β to the PM also requires its dimerization domain. Phosphorylation of serine residues near this polybasic region, potentially by protein kinase C, releases SH2B1β from the PM and enhances nuclear entry. Release of SH2B1β from the PM and/or nuclear entry appear to be required for SH2B1β enhancement of nerve growth factor (NGF)-induced expression of urokinase plasminogen activator receptor gene and neurite outgrowth of PC12 cells. Taken together, our results provide strong evidence that the polybasic NLS region of SH2B1 serves the dual function of localizing SH2B1 to both the nucleus and the PM, the latter most probably through electrostatic interactions that are enhanced by SH2B1β dimerization. Cycling between the different cellular compartments is a consequence of the phosphorylation and dephosphorylation of serine residues near the NLS and is important for physiological effects of SH2B1, including NGF-induced gene expression and neurite outgrowth.

  12. Dual NEP/ECE inhibition improves endothelial function in mesenteric resistance arteries of 32-week-old SHR.

    PubMed

    Lemkens, Pieter; Spijkers, Leon Ja; Meens, Merlijn J; Nelissen, Jelly; Janssen, Ben; Peters, Stephan Lm; Schiffers, Paul Mh; De Mey, Jo Gr

    2017-03-16

    Endothelin 1 (ET-1), a potent vasoconstrictor, pro-mitogenic and pro-inflammatory peptide, may promote development of endothelial dysfunction and arterial remodeling. ET-1 can be formed through cleavage of big-ET-1 by endothelin-converting enzyme (ECE) or neutral endopeptidase (NEP). We investigated whether chronic treatment with the novel dual NEP/ECE inhibitor SOL1 improves functional and structural properties of resistance-sized arteries of 32-week-old male spontaneously hypertensive rats (SHR). SHR received a chronic 4-week treatment with SOL1, losartan or hydralazine. We then compared effects of inhibition of NO synthase (NOS) (100 μM l-NAME), blockade of ETA- and ETB-receptors (10 μM bosentan) and stimulation of the endothelium with 0.001-10 μM acetylcholine (ACh) in isolated third-order mesenteric resistance arteries. Losartan and hydralazine significantly lowered blood pressure. Losartan decreased the media-to-lumen ratio of resistance arteries. l-NAME (1) increased arterial contractile responses to K(+) (5.9-40 mM) in the losartan, SOL1 and vehicle group and (2) increased the sensitivity to phenylephrine (PHE; 0.16-20 μM) in the SOL1 group but not in the losartan, hydralazine and vehicle group. Relaxing responses to ACh in the absence or presence of l-NAME during contractions induced by either 10 μM PHE or 40 mM K(+) were not altered by any in vivo treatment. Acute treatment with bosentan did, however, significantly improve maximal relaxing responses involving endothelium-derived nitric oxide and -hyperpolarizing factors in the SOL1 group but not in the losartan, hydralazine or vehicle group. Thus, chronic inhibition of NEP/ECE improved basal endothelial function but did not alter blood pressure, resistance artery structure and stimulated endothelium-dependent relaxing responses in 32-week-old SHR.Hypertension Research advance online publication, 16 March 2017; doi:10.1038/hr.2017.38.

  13. Effects of Physical-Cognitive Dual Task Training on Executive Function and Gait Performance in Older Adults: A Randomized Controlled Trial

    PubMed Central

    Falbo, S.; Condello, G.; Capranica, L.; Forte, R.

    2016-01-01

    Physical and cognitive training seem to counteract age-related decline in physical and mental function. Recently, the possibility of integrating cognitive demands into physical training has attracted attention. The purpose of this study was to evaluate the effects of twelve weeks of designed physical-cognitive training on executive cognitive function and gait performance in older adults. Thirty-six healthy, active individuals aged 72.30 ± 5.84 years were assigned to two types of physical training with major focus on physical single task (ST) training (n = 16) and physical-cognitive dual task (DT) training (n = 20), respectively. They were tested before and after the intervention for executive function (inhibition, working memory) through Random Number Generation and for gait (walking with/without negotiating hurdles) under both single and dual task (ST, DT) conditions. Gait performance improved in both groups, while inhibitory performance decreased after exercise training with ST focus but tended to increase after training with physical-cognitive DT focus. Changes in inhibition performance were correlated with changes in DT walking performance with group differences as a function of motor task complexity (with/without hurdling). The study supports the effectiveness of group exercise classes for older individuals to improve gait performance, with physical-cognitive DT training selectively counteracting the age-related decline in a core executive function essential for daily living. PMID:28053985

  14. Effects of Physical-Cognitive Dual Task Training on Executive Function and Gait Performance in Older Adults: A Randomized Controlled Trial.

    PubMed

    Falbo, S; Condello, G; Capranica, L; Forte, R; Pesce, C

    2016-01-01

    Physical and cognitive training seem to counteract age-related decline in physical and mental function. Recently, the possibility of integrating cognitive demands into physical training has attracted attention. The purpose of this study was to evaluate the effects of twelve weeks of designed physical-cognitive training on executive cognitive function and gait performance in older adults. Thirty-six healthy, active individuals aged 72.30 ± 5.84 years were assigned to two types of physical training with major focus on physical single task (ST) training (n = 16) and physical-cognitive dual task (DT) training (n = 20), respectively. They were tested before and after the intervention for executive function (inhibition, working memory) through Random Number Generation and for gait (walking with/without negotiating hurdles) under both single and dual task (ST, DT) conditions. Gait performance improved in both groups, while inhibitory performance decreased after exercise training with ST focus but tended to increase after training with physical-cognitive DT focus. Changes in inhibition performance were correlated with changes in DT walking performance with group differences as a function of motor task complexity (with/without hurdling). The study supports the effectiveness of group exercise classes for older individuals to improve gait performance, with physical-cognitive DT training selectively counteracting the age-related decline in a core executive function essential for daily living.

  15. Breeding goals for the Kenya dual purpose goat. II. Estimation of economic values for production and functional traits.

    PubMed

    Bett, R C; Kosgey, I S; Bebe, B O; Kahi, A K

    2007-10-01

    Economic values for production traits (milk yield, MY, kg; 12-month sale weight, LW, kg; consumable meat percentage, CMP) and functional traits (doe live weight, DoWT, kg; number of kids weaned, NKW; kidding frequency, KF; kidding rate, KR, %; doe weaning rate, DoWR, %; doe survival rate, DoSR, %; post-weaning survival rate, PoSR, %; pre-weaning survival rate, PrSR, % and; residual feed intake of yearlings, RFIgamma, kg and does RFId, kg) were estimated for the Kenya Dual Purpose goat (KDPG) for systems under two bases of evaluation. The production systems included smallholder low-potential (SLP), smallholder medium-potential (SMP) and smallholder high-potential (SHP), while the bases of evaluation considered were fixed flock-size and fixed feed resource. Under both bases of evaluation, economic values were highest in SMP apart from the economic values for feed intake-related traits (RFIy and RFId). In SMP, the economic values under fixed flock-size scenario were KSh 71.61 (LW), 20.90 (MY), 45.20 (CMP), 13.68 (NKW), 3.61 (KF), 6.52 (KR), 12.39 (DoWR), 22.96 (DoSR), 22.87 (PoSR), 13.18 (PrSR), -2.76 (RFIy) and -3.00 (RFId). The corresponding economic values under fixed feed resources scenario were KSh 73.28, 29.39, 45.20, 16.91, 4.76, 9.45, 13.84, 25.67, 25.15, 16.19, -2.76 and -3.00. Generally in all production systems, economic values for most traits were higher under fixed feed resource than under fixed flock-size scenario. In all systems, the economic values for most of the traits were sensitive to changes in prices of feed, milk and meat. The positive economic values for most traits under fixed flock-size scenario and fixed feed resource indicates that a unit increase in genetic merit for the traits would have a positive effect on the profitability of the systems.

  16. Dynamic behavior of hydrogen bonds from pure closed shell to shared shell interaction regions elucidated by AIM dual functional analysis.

    PubMed

    Hayashi, Satoko; Matsuiwa, Kohei; Kitamoto, Masayuki; Nakanishi, Waro

    2013-02-28

    The dynamic behavior of hydrogen bonds (HBs) was clarified for the wide range of interactions applying AIM dual functional analysis. Plots of H(b)(r(c)) versus H(b)(r(c)) - V(b)(r(c))/2 are analyzed in the polar (R, θ) representation, where H(b)(r(c)) and V(b)(r(c)) are total electron and potential energy densities at bond critical points, respectively, for the fully optimized structures. Data of the fully optimized structure and four perturbed ones around it are plotted for each interaction, which give a specific curve. The curve is analyzed by (θ(p), κ(p)): θ(p) corresponds to the tangent line from the y-direction and κ(p) is the curvature. Whereas (R, θ) correspond to the static nature, (θ(p), κ(p)) represent the dynamic nature of interactions. Indeed, HBs can be classified only by one parameter of θ, but θ(p) supplies more information necessary for better understanding of HBs. Although H(2)Se-*-HSeH and H(3)N-*-HNH(2) show the nature of pure CS (closed shell) of the vdW-type, H(2)S-*-HSH and H(2)O-*-HOH contain the nature of pure CS other than the vdW-type (HB-typical). The regular CS nature is observed for B-*-HF (B = HF, H(2)Se, H(2)S, H(2)O, and H(2)C═O). The HF-*-HF interaction is described as HB-typical, whereas others are by CT(MC)-type. The nature of H(3)N-*-HX (X = F, Cl, Br) is regular CS of the CT(TBP)-type. HBs in charged species, such as [HOH-*-OH](-) and [H(2)O-*-H-*-OH(2)], show the weak covalent nature of SS (shard shell). The dynamic behavior of HBs helps us to understand HBs in more detail, in addition to the static behavior.

  17. Gadolinium-functionalized aggregation-induced emission dots as dual-modality probes for cancer metastasis study.

    PubMed

    Li, Kai; Ding, Dan; Prashant, Chandrasekharan; Qin, Wei; Yang, Chang-Tong; Tang, Ben Zhong; Liu, Bin

    2013-12-01

    Understanding the localization and engraftment of tumor cells at postintravasation stage of metastasis is of high importance in cancer diagnosis and treatment. Advanced fluorescent probes and facile methodologies for cell tracing play a key role in metastasis studies. In this work, we design and synthesize a dual-modality imaging dots with both optical and magnetic contrast through integration of a magnetic resonance imaging reagent, gadolinium(III), into a novel long-term cell tracing probe with aggregation-induced emission (AIE) in far-red/near-infrared region. The obtained fluorescent-magnetic AIE dots have both high fluorescence quantum yield (25%) and T1 relaxivity (7.91 mM(-1) s(-1) ) in aqueous suspension. After further conjugation with a cell membrane penetrating peptide, the dual-modality dots can be efficiently internalized into living cells. The gadolinium(III) allows accurate quantification of biodistribution of cancer cells via intraveneous injection, while the high fluorescence provides engraftment information of cells at single cellular level. The dual-modality AIE dots show obvious synergistic advantages over either single imaging modality and hold great promises in advanced biomedical studies.

  18. Rapid asymmetric evolution of a dual-coding tumor suppressor INK4a/ARF locus contradicts its function

    PubMed Central

    Szklarczyk, Radek; Heringa, Jaap; Pond, Sergei Kosakovsky; Nekrutenko, Anton

    2007-01-01

    INK4a/ARF tumor suppressor locus encodes two protein products, INK4a and ARF, essential for controlling tumorigenesis and mutated in more than half of human cancers. There is no resemblance between the two proteins: their coding regions are assembled by alternative splicing of two mutually exclusive 5′ exons into a constitutive one containing overlapping out-of-phase reading frames. We show that the dual-coding arrangement conflicts with the high cost of mutations within INK4a/ARF. Unexpectedly, the locus evolves rapidly and asymmetrically, with ARF accumulating the majority of amino acid replacements. Rapid evolution drives both INK4a and ARF proteins out of sync with other members of the RB and p53 tumor suppressor pathways, both of which are controlled by the locus. Yet, the asymmetric behavior may be an intrinsic property of dual-coding exons: INK4a/ARF closely mimics the evolution of 90 newly identified genes with similar dual-coding structure. Thus, the strong link between mutations in INK4a/ARF and cancer may be a direct consequence of the architecture of the locus. PMID:17652172

  19. The dual role of oxygen functions in coal pretreatment and liquefaction: Crosslinking and cleavage reactions. First annual report, April 1, 1991--March 31, 1992

    SciTech Connect

    Serio, M.A.; Kroo, E.; Teng, H.; Charpenay, S.; Solomon, P.R.

    1992-08-01

    The overall objective of this project is elucidate and model the dual role of oxygen functions in thermal pretreatment and liquefaction of low rank coals through the application of analytical techniques and theoretical models. The project will be an integrated study of model polymers representative of coal structures, raw coals of primarily low rank, and selectivity modified coals in order to provide specific information relevant to the reactions of real coals. The investigations will include liquefaction experiments in microautoclave reactors along with extensive analysis of intermediate solid, liquid and gaseous products. Attempts will be made to incorporate the results of experiments on the different systems into a liquefaction model.

  20. Ultrasound-targeted microbubble destruction combined with dual targeting of HSP72 and HSC70 inhibits HSP90 function and induces extensive tumor-specific apoptosis.

    PubMed

    Wang, Hanghui; Song, Yixin; Hao, Dingjun; Bai, Min; Jin, Lifang; Gu, Jiying; Su, Yijin; Liu, Long; Jia, Chao; Du, Lianfang

    2014-07-01

    The specific and efficient delivery of small interfering RNA (siRNA) into cancer cells in vivo remains a major obstacle. In this study, we investigated whether ultrasound-targeted microbubble destruction (UTMD) combined with dual targeting of HSP72 and HSC70 in prostate cancer cell lines improve the specific and efficient cell uptake of siRNA, inhibit HSP90 function and induce extensive tumor-specific apoptosis. VCaP cells were transfected with siRNA oligonucleotides. Cell viability assays were used to evaluate the safety of UTMD. The expression of HSP70, HSP90, caspase-8, caspase-3, PARP-1 and cleaved caspase-3 were determined by quantitative PCR and western blotting. Apoptosis and transfection efficiency were detected by flow cytometry. We found that HSP72, HSC70 and HSP90 expression was absent or weak in normal prostate epithelial cells (RWPE-1), and became uniformly and strongly expressed in prostate cancer cells (VCaP). VCaP and RWPE-1 cells expressed very low levels of caspase-8, caspase-3, PARP-1 and cleaved caspase-3. UTMD combined with dual targeting of HSP72 and HSC70 siRNA impoved the efficiency of transfection, cell uptake of siRNA, downregulated HSP70 and HSP90 expression in VCaP cells on the mRNA and protein levels, and upregulated major apoptotic markers (PARP-1, caspase-8, caspase-3 and cleaved caspase-3), thus, inducing extensive tumor-specific apoptosis. The Cell Counting Kit-8 assay showed decreased cellular viability in the HSP72/HSC70-siRNA silenced group. These results suggest that the combination of UTMD with dual targeting of HSP72 and HSC70 may improve the specific and efficient cell uptake of siRNA, inhibit HSP90 function and induce extensive tumor-specific apoptosis, indicating a novel, potential means for targeting therapeutic strategy to prostate cancer cells.

  1. A Pivotal Role for Pro-335 in Balancing the Dual Functions of Munc18-1 Domain-3a in Regulated Exocytosis*

    PubMed Central

    Han, Gayoung Anna; Park, Seungmee; Bin, Na-Ryum; Jung, Chang Hun; Kim, Byungjin; Chandrasegaram, Prashanth; Matsuda, Maiko; Riadi, Indira; Han, Liping; Sugita, Shuzo

    2014-01-01

    Munc18-1 plays essential dual roles in exocytosis: (i) stabilizing and trafficking the central SNARE protein, syntaxin-1 (i.e. chaperoning function), by its domain-1; and (ii) priming/stimulating exocytosis by its domain-3a. Here, we examine whether or not domain-3a also plays a significant role in the chaperoning of syntaxin-1 and, if so, how these dual functions of domain-3a are regulated. We demonstrate that introduction of quintuple mutations (K332E/K333E/P335A/Q336A/Y337L) in domain-3a of Munc18-1 abolishes its ability to bind syntaxin-1 and fails to rescue the level and trafficking of syntaxin-1 as well as to restore exocytosis in Munc18-1/2 double knockdown cells. By contrast, a quadruple mutant (K332E/K333E/Q336A/Y337L) sparing the Pro-335 residue retains all of these capabilities. A single point mutant of P335A reduces the ability to bind syntaxin-1 and rescue syntaxin-1 levels. Nonetheless, it surprisingly outperforms the wild type in the rescue of exocytosis. However, when additional mutations in the neighboring residues are combined with P335A mutation (K332E/K333E/P335A, P335A/Q336A/Y337L), the ability of the Munc18-1 variants to chaperone syntaxin-1 and to rescue exocytosis is strongly impaired. Our results indicate that residues from Lys-332 to Tyr-337 of domain-3a are intimately tied to the chaperoning function of Munc18-1. We also propose that Pro-335 plays a pivotal role in regulating the balance between the dual functions of domain-3a. The hinged conformation of the α-helix containing Pro-335 promotes the syntaxin-1 chaperoning function, whereas the P335A mutation promotes its priming function by facilitating the α-helix to adopt an extended conformation. PMID:25326390

  2. Examining the role of endogenous orexins in hypothalamus-pituitary-adrenal axis endocrine function using transient dual orexin receptor antagonism in the rat.

    PubMed

    Steiner, Michel A; Sciarretta, Carla; Brisbare-Roch, Catherine; Strasser, Daniel S; Studer, Rolf; Jenck, Francois

    2013-04-01

    The orexin neuropeptide system regulates wakefulness and contributes to physiological and behavioral stress responses. Moreover, a role for orexins in modulating hypothalamus-pituitary-adrenal (HPA) axis activity has been proposed. Brain penetrating dual orexin receptor (OXR) antagonists such as almorexant decrease vigilance and have emerged as a novel therapeutic class for the treatment of insomnia. Almorexant was used here as a pharmacological tool to examine the role of endogenous orexin signaling in HPA axis endocrine function under natural conditions. After confirming the expression of prepro-orexin and OXR-1 and OXR-2 mRNA in hypothalamus, pituitary and adrenal glands, the effects of systemic almorexant were investigated on peripheral HPA axis hormone release in the rat under baseline, stress and pharmacological challenge conditions. Almorexant did not alter basal or stress-induced corticosterone release despite affecting wake and sleep stages (detected by radiotelemetric electroencephalography/electromyography) during the stress exposure. Moreover, almorexant did not affect the release of adrenocorticotropin (ACTH) and corticosterone at different time points along the diurnal rhythm, nor corticotrophin-releasing hormone (CRH)- and ACTH-stimulated neuroendocrine responses, measured in vivo under stress-free conditions. These results illustrate that dual OXR antagonists, despite modulating stress-induced wakefulness, do not interfere with endocrine HPA axis function in the rat. They converge to suggest that endogenous orexin signaling plays a minor role in stress hormone release under basal conditions and under challenge.

  3. Dual-beam ELF wave generation as a function of power, frequency, modulation waveform, and receiver location

    NASA Astrophysics Data System (ADS)

    Agrawal, D.; Moore, R. C.

    2012-12-01

    Dual-beam ELF wave generation experiments performed at the High-frequency Active Auroral Research Program (HAARP) HF transmitter are used to investigate the dependence of the generated ELF wave magnitude on HF power, HF frequency, modulation waveform, and receiver location. During the experiments, two HF beams transmit simultaneously: one amplitude modulated (AM) HF beam modulates the conductivity of the lower ionosphere at ELF frequencies while a second HF beam broadcasts a continuous waveform (CW) signal, modifying the efficiency of ELF conductivity modulation and thereby the efficiency of ELF wave generation. We report experimental results for different ambient ionospheric conditions, and we interpret the observations in the context of a newly developed dual-beam HF heating model. A comparison between model predictions and experimental observations indicates that the theoretical model includes the essential physics involved in multifrequency HF heating of the lower ionosphere. In addition to the HF transmission parameters mentioned above, the model is used to predict the dependence of ELF wave magnitude on the polarization of the CW beam and on the modulation frequency of the modulated beam. We consider how these effects vary with ambientD-region electron density and electron temperature.

  4. Sensitive Immunosensor for Cancer Biomarker Based on Dual Signal Amplification Strategy of Graphene Sheets and Multi-Enzyme Functionalized Carbon Nanospheres

    SciTech Connect

    Du, Dan; Zou, Zhexiang; Shin, Yongsoon; Wang, Jun; Wu, Hong; Engelhard, Mark H.; Liu, Jun; Aksay, Ilhan A.; Lin, Yuehe

    2010-03-30

    A novel electrochemical immunosensor for sensitive detection of cancer biomarker α fetoprotein (AFP) is described that uses a graphene sheet sensor platform and functionalized carbon nanospheres (CNSs) labeling with horseradish peroxidase-secondary antibodies (HRP-Ab2). Greatly enhanced sensitivity for the cancer biomarker is based on a dual signal amplification strategy: first, the synthesized CNSs yielded a homogeneous and narrow size distribution, which allowed several binding events of HRP-Ab2 on each nanosphere. Enhanced sensitivity was achieved by introducing the multi-bioconjugates of HRP-Ab2-CNSs onto the electrode surface through sandwich immunoreactions. Secondly, functionalized graphene sheets used for the biosensor platform increased the surface area to capture a large amount of primary antibodies (Ab1), thus amplifying the detection response. This amplification strategy is a promising platform for clinical screening of cancer biomarkers and point-of-care diagnostics.

  5. Biomolecular Interaction Assays Identified Dual Inhibitors of Glutaminase and Glutamate Dehydrogenase That Disrupt Mitochondrial Function and Prevent Growth of Cancer Cells.

    PubMed

    Zhu, Min; Fang, Jinzhang; Zhang, Jingjing; Zhang, Zheng; Xie, Jianhui; Yu, Yan; Ruan, Jennifer Jin; Chen, Zhao; Hou, Wei; Yang, Gensheng; Su, Weike; Ruan, Benfang Helen

    2017-02-07

    Glutaminase (KGA/isoenzyme GAC) is an emerging and important drug target for cancer. Traditional methods for assaying glutaminase activity are coupled with several other enzymes. Such coupled assays do not permit the direct and stringent characterization of specific glutaminase inhibitors. Ebselen was identified as a potent 9 nM KGA inhibitor in the KGA/glutamate oxidase (GO)/horse radish peroxidase (HRP) coupled assay but showed very weak activity in inhibiting the growth of glutamine-dependent cancer cells. For rigorous characterization, we developed a direct kinetic binding assay for KGA using bio-layer interferometry (BLI) as the detection method; Ebselen was identified as a GDH inhibitor but not a KGA inhibitor. Furthermore, we designed and synthesized several benzo[d][1,2]selenazol-3(2H)-one dimers which were subjected to SAR analysis by several glutaminolysis specific biochemical and cell based assays. Novel glutamate dehydrogenase (GDH) or dual KGA/GDH inhibitors were discovered from the synthetic compounds; the dual inhibitors completely disrupt mitochondrial function and demonstrate potent anticancer activity with a minimum level of toxicity.

  6. Inhibition of MDR1 gene expression and enhancing cellular uptake for effective colon cancer treatment using dual-surface–functionalized nanoparticles

    PubMed Central

    Xiao, Bo; Zhang, Mingzhen; Viennois, Emilie; Zhang, Yuchen; Wei, Na; Baker, Mark T.; Jung, Yunjin; Merlin, Didier

    2015-01-01

    Nanomedicine options for colon cancer therapy have been limited by the lack of suitable carriers capable of delivering sufficient drug into tumors to cause lethal toxicity. To circumvent this limitation, we fabricated a camptothecin (CPT)-loaded poly(lactic-co-glycolic acid) nanoparticle (NP) with dual-surface functionalization—Pluronic F127 and chitosan—for inhibiting multi-drug resistant gene 1 (MDR1) expression and enhancing tumor uptake. The resultant spherical NPs-P/C had a desirable particle size (~268 nm), slightly positive zeta-potential, and the ability to efficiently down-regulate the expression of MDR1. In vitro cytotoxicity tests revealed that the 24 and 48 h IC50 values of NPs-P/C1 were 2.03 and 0.67 µM, respectively, which were much lower than those for free CPT and other NPs. Interestingly, NPs-P/C1 showed the highest cellular uptake efficiency (approximately 85.5%) among the different drug formulations. Most importantly, treatment of colon tumor-bearing mice with various drug formulations confirmed that the introduction of Pluronic F127 and chitosan to the NP surface significantly enhanced the therapeutic efficacy of CPT, induced tumor cell apoptosis, and reduced systemic toxicity. Collectively, these findings suggest that our one-step–fabricated, dual-surface–functionalized NPs may hold promise as a readily scalable and effective drug carrier with clinical potential in colon cancer therapy. PMID:25701040

  7. OFF-ON-OFF Dual Emission at Visible and UV Wavelengths from Carbazole Functionalized β-Diketonate Europium(III) Complex.

    PubMed

    Imai, Yuki; Kawai, Tsuyoshi; Yuasa, Junpei

    2016-06-23

    This work demonstrates dual emission "OFF-ON-OFF" switching at visible and UV wavelengths of a carbazole functionalized β-diketone (LH) by a simple change of a europium(III) ion (Eu(3+)) concentration in the submicromolar concentration range. In the presence of 0.25 equiv of Eu(3+) (5 μM), LH forms a luminescent 4:1 complex ([Eu(3+)(L(-))4](-)) exhibiting dual emission at 357 and 613 nm resulting from the local excitation of the carbazole ring and ligand-sensitized luminescence from the Eu(3+)-β-diketonate unit, respectively. The 4:1 complex begins to convert into a 2:1 complex ([Eu(3+)(L(-))2](+)) via a 3:1 complex [Eu(3+)(L(-))3] above a molar ratio ([Eu(3+)]/[LH]) of 0.25, which provides the opportunity for binding of solvent methanol molecules to the vacant site of the Eu(3+) ion in the complex ([Eu(3+)(L(-))2(MeOH)n](+)). The OH oscillators of coordinated methanol molecules facilitate the nonradiative pathway of the Eu(3+) emission; hence the emission at 613 nm almost disappears above the 0.50 equivalent of Eu(3+) (11 μM), while the UV emission at 357 nm remains mostly constant over the whole concentration range.

  8. A novel strategy for dual-channel detection of metallothioneins and mercury based on the conformational switching of functional chimera aptamer.

    PubMed

    Tang, Xian; Wang, Yong-Sheng; Xue, Jin-Hua; Zhou, Bin; Cao, Jin-Xiu; Chen, Si-Han; Li, Ming-Hui; Wang, Xiao-Feng; Zhu, Yu-Feng; Huang, Yan-Qin

    2015-03-25

    A novel strategy for dual-channel detection of metallothioneins (MTs) and Hg(2+) has been proposed. In the absence of Hg(2+), the functional chimera aptamer (FCA) designed can form an intact G-quadruplex with flexibility, which was demonstrated to have peroxidase-like activities upon hemin binding. In the presence of Hg(2+), the formation of T-Hg(2+)-T complex results in the conformational switching of FCA, which lost the peroxidase-like activities and cannot catalyze the oxidation of ABTS by H2O2. Upon addition of MTs in this solution, MTs could interact with Hg(2+) to form a MTs-Hg(2+) complex, leading to the recovery of the G-quadruplex DNAzyme. The color and absorbance of the sensing system were also changed accordingly. In the optimizing condition, ΔA was directly proportional to the concentration ranging from 8.84 nM to 1.0 μM for Hg(2+), and 7.82 nM to 0.462 μM for MTs with the detection limits of 2.65 nM and 2.34 nM, respectively. The proposed dual-channel method avoids the label steps in common methods, and allows direct analysis of the samples without costly instruments, and is reliable, inexpensive and sensitive.

  9. 5-Hydroxymethylfurfural modified rhodamine B dual-function derivative: Highly sensitive and selective optical detection of pH and Cu2+

    NASA Astrophysics Data System (ADS)

    Wang, Enze; Zhou, Yanmei; Huang, Qi; Pang, Lanfang; Qiao, Han; Yu, Fang; Gao, Bin; Zhang, Junli; Min, Yinghao; Ma, Tongsen

    2016-01-01

    A dual-function optical chemosensor (RBF) was designed and easily synthesized by condensation reaction of 5-Hydroxymethylfurfural and rhodamine B hydrazide. RBF exhibited highly sensitive, highly selective and quick response to acidic pH. The fluorescence intensity of RBF exhibited a more than 41-fold increase within the pH range from 7.50 to 3.73 with a pKa value of 5.02, which could be successfully applied to monitor intracellular pH in living PC12 cells and HeLa cells. Additionally, the spectroscopy of UV-Vis and EDTA-adding experiments indicated that RBF was a highly selective and reversible colorimetric chemosensor for Cu2+ in Tris-HCl (10 mM, pH = 7.2) aqueous buffer solution as well as other metal ions had no obvious interference. Moreover, RBF has been successfully applied to detect Cu2+ in real water samples.

  10. Highly dispersed palladium nanoparticles anchored on UiO-66(NH2) metal-organic framework as a reusable and dual functional visible-light-driven photocatalyst

    NASA Astrophysics Data System (ADS)

    Shen, Lijuan; Wu, Weiming; Liang, Ruowen; Lin, Rui; Wu, Ling

    2013-09-01

    Proper design and preparation of high-performance and stable dual functional photocatalytic materials remains a significant objective of research. In this work, highly dispersed Pd nanoparticles of about 3-6 nm in diameter are immobilized in the metal-organic framework (MOF) UiO-66(NH2) via a facile one-pot hydrothermal method. The resulting Pd@UiO-66(NH2) nanocomposite exhibits an excellent reusable and higher visible light photocatalytic activity for reducing Cr(vi) compared with UiO-66(NH2) owing to the high dispersion of Pd nanoparticles and their close contact with the matrix, which lead to the enhanced light harvesting and more efficient separation of photogenerated electron-hole pairs. More significantly, the Pd@UiO-66(NH2) could be used for simultaneous photocatalytic degradation of organic pollutants, like methyl orange (MO) and methylene blue (MB), and reduction of Cr(vi) with even further enhanced activity in the binary system, which could be attributed to the synergetic effect between photocatalytic oxidation and reduction by individually consuming photogenerated holes and electrons. This work represents the first example of using the MOFs-based materials as dual functional photocatalyst to remove different categories of pollutants simultaneously. Our finding not only proves great potential for the design and application of MOFs-based materials but also might bring light to new opportunities in the development of new high-performance photocatalysts.Proper design and preparation of high-performance and stable dual functional photocatalytic materials remains a significant objective of research. In this work, highly dispersed Pd nanoparticles of about 3-6 nm in diameter are immobilized in the metal-organic framework (MOF) UiO-66(NH2) via a facile one-pot hydrothermal method. The resulting Pd@UiO-66(NH2) nanocomposite exhibits an excellent reusable and higher visible light photocatalytic activity for reducing Cr(vi) compared with UiO-66(NH2) owing to the

  11. An all-solid-state perovskite-sensitized solar cell based on the dual function polyaniline as the sensitizer and p-type hole-transporting material

    NASA Astrophysics Data System (ADS)

    Xiao, Yaoming; Han, Gaoyi; Chang, Yunzhen; Zhou, Haihan; Li, Miaoyu; Li, Yanping

    2014-12-01

    High performance dual function of polyaniline (PANI) with brachyplast structure is synthesized by using a two-step cyclic voltammetry (CV) approach onto the fluorinated tin oxide (FTO) glass substrate, which acts as the sensitizer and p-type hole-transporting material (p-HTM) for the all-solid-state perovskite-sensitized solar cell (ass-PSSC) due to its π-π* transition and the localized polaron. The ass-PSSC based on the PANI delivers a photovoltaic conversion efficiency of 7.34%, and reduces from 7.34% to 6.71% after 1000 h, thereby 91.42% of the energy conversion efficiency is kept, indicating the device has a good long-term stability.

  12. Estimating Age Distributions of Base Flow in Watersheds Underlain by Single and Dual Porosity Formations Using Groundwater Transport Simulation and Weighted Weibull Functions

    NASA Astrophysics Data System (ADS)

    Sanford, W. E.

    2015-12-01

    Age distributions of base flow to streams are important to estimate for predicting the timing of water-quality responses to changes in distributed inputs of nutrients or pollutants at the land surface. Simple models of shallow aquifers will predict exponential age distributions, but more realistic 3-D stream-aquifer geometries will cause deviations from an exponential curve. In addition, in fractured rock terrains the dual nature of the effective and total porosity of the system complicates the age distribution further. In this study shallow groundwater flow and advective transport were simulated in two regions in the Eastern United States—the Delmarva Peninsula and the upper Potomac River basin. The former is underlain by layers of unconsolidated sediment, while the latter consists of folded and fractured sedimentary rocks. Transport of groundwater to streams was simulated using the USGS code MODPATH within 175 and 275 watersheds, respectively. For the fractured rock terrain, calculations were also performed along flow pathlines to account for exchange between mobile and immobile flow zones. Porosities at both sites were calibrated using environmental tracer data (3H, 3He, CFCs and SF6) in wells and springs, and with a 30-year tritium record from the Potomac River. Carbonate and siliciclastic rocks were calibrated to have mobile porosity values of one and six percent, and immobile porosity values of 18 and 12 percent, respectively. The age distributions were fitted to Weibull functions. Whereas an exponential function has one parameter that controls the median age of the distribution, a Weibull function has an extra parameter that controls the slope of the curve. A weighted Weibull function was also developed that potentially allows for four parameters, two that control the median age and two that control the slope, one of each weighted toward early or late arrival times. For both systems the two-parameter Weibull function nearly always produced a substantially

  13. An integrated dual functional recognition/amplification bio-label for the one-step impedimetric detection of Micro-RNA-21.

    PubMed

    Azzouzi, Sawsen; Mak, Wing Cheung; Kor, Kamalodin; Turner, Anthony P F; Ali, Mounir Ben; Beni, Valerio

    2017-06-15

    Alteration in expression of miRNAs has been correlated with different cancer types, tumour stage and response to treatments. In this context, a structurally responsive oligonucleotide-based electrochemical impedimetric biosensor has been developed for the simple and sensitive detection of miRNA-21. A highly specific biotinylated DNA/LNA molecular beacon (MB) probe was conjugated with gold nanoparticles (AuNPs) to create an integrated, dual function bio-label (biotin-MB-AuNPs) for both biorecognition and signal generation. In the presence of target miRNA-21, hybridisation takes place resulting in the "activation" of the biotin-MB; this event makes the biotin group, which was previously "protected" by the steric hindrance of the MB stem-loop structure, accessible. The activated biotin-MB-AuNPs/miRNA complexes become available for capture, via supramolecular interaction, onto a nentravidin-modified electrode for electrochemical transduction. The binding event results in a decrease of the charge transfer resistance at the working electrode/electrolyte interface. The biosensor responded linearly in the range 1-1000 pM of miRNA-21, with a limit of detection of 0.3 pM, good reproducibility (Relative Standard deviation (RSD) =3.3%) and high selectivity over other miRNAs (i.e. miRNA-221 and miRNA-205) sequences. Detection of miRNA-21 in spiked serum samples at clinically relevant levels (low pM range) was also demonstrated, thus illustrating the potential of the biosensor for point-of-care clinical applications. The proposed biosensor design, based on the combination of a neutravidin transducing surface and the dual-function biotin-MB-AuNPs bio-label, provides a simple and robust approach for detection of short-length nucleic acid targets, such as miRNAs.

  14. A Pterin-Dependent Signaling Pathway Regulates a Dual-Function Diguanylate Cyclase-Phosphodiesterase Controlling Surface Attachment in Agrobacterium tumefaciens

    PubMed Central

    Feirer, Nathan; Xu, Jing; Allen, Kylie D.; Koestler, Benjamin J.; Bruger, Eric L.; Waters, Christopher M.; White, Robert H.

    2015-01-01

    ABSTRACT The motile-to-sessile transition is an important lifestyle switch in diverse bacteria and is often regulated by the intracellular second messenger cyclic diguanylate monophosphate (c-di-GMP). In general, high c-di-GMP concentrations promote attachment to surfaces, whereas cells with low levels of signal remain motile. In the plant pathogen Agrobacterium tumefaciens, c-di-GMP controls attachment and biofilm formation via regulation of a unipolar polysaccharide (UPP) adhesin. The levels of c-di-GMP in A. tumefaciens are controlled in part by the dual-function diguanylate cyclase-phosphodiesterase (DGC-PDE) protein DcpA. In this study, we report that DcpA possesses both c-di-GMP synthesizing and degrading activities in heterologous and native genetic backgrounds, a binary capability that is unusual among GGDEF-EAL domain-containing proteins. DcpA activity is modulated by a pteridine reductase called PruA, with DcpA acting as a PDE in the presence of PruA and a DGC in its absence. PruA enzymatic activity is required for the control of DcpA and through this control, attachment and biofilm formation. Intracellular pterin analysis demonstrates that PruA is responsible for the production of a novel pterin species. In addition, the control of DcpA activity also requires PruR, a protein encoded directly upstream of DcpA with a predicted molybdopterin-binding domain. PruR is hypothesized to be a potential signaling intermediate between PruA and DcpA through an as-yet-unidentified mechanism. This study provides the first prokaryotic example of a pterin-mediated signaling pathway and a new model for the regulation of dual-function DGC-PDE proteins. PMID:26126849

  15. A Dual Functional Electroactive and Fluorescent Probe for Coupled Measurements of Vesicular Exocytosis with High Spatial and Temporal Resolution.

    PubMed

    Liu, Xiaoqing; Savy, Alexandra; Maurin, Sylvie; Grimaud, Laurence; Darchen, François; Quinton, Damien; Labbé, Eric; Buriez, Olivier; Delacotte, Jérôme; Lemaître, Frédéric; Guille-Collignon, Manon

    2017-02-20

    In this work, Fluorescent False Neurotransmitter 102 (FFN102), a synthesized analogue of biogenic neurotransmitters, was demonstrated to show both pH-dependent fluorescence and electroactivity. To study secretory behaviors at the single-vesicle level, FFN102 was employed as a new fluorescent/electroactive dual probe in a coupled technique (amperometry and total internal reflection fluorescence microscopy (TIRFM)). We used N13 cells, a stable clone of BON cells, to specifically accumulate FFN102 into their secretory vesicles, and then optical and electrochemical measurements of vesicular exocytosis were experimentally achieved by using indium tin oxide (ITO) transparent electrodes. Upon stimulation, FFN102 started to diffuse out from the acidic intravesicular microenvironment to the neutral extracellular space, leading to fluorescent emissions and to the electrochemical oxidation signals that were simultaneously collected from the ITO electrode surface. The correlation of fluorescence and amperometric signals resulting from the FFN102 probe allows real-time monitoring of single exocytotic events with both high spatial and temporal resolution. This work opens new possibilities in the investigation of exocytotic mechanisms.

  16. The Streptococcus pyogenes orphan protein tyrosine phosphatase, SP-PTP, possesses dual specificity and essential virulence regulatory functions.

    PubMed

    Kant, Sashi; Agarwal, Shivani; Pancholi, Preeti; Pancholi, Vijay

    2015-08-01

    Group A Streptococcus (GAS) is a human pathogen that causes high morbidity and mortality. GAS lacks a gene encoding tyrosine kinase but contains one encoding tyrosine phosphatase (SP-PTP). Thus, GAS is thought to lack tyrosine phosphorylation, and the physiological significance of SP-PTP is, therefore, questionable. Here, we demonstrate that SP-PTP possesses dual phosphatase specificity for Tyr- and Ser/Thr-phosphorylated GAS proteins, such as Ser/Thr kinase (SP-STK) and the SP-STK-phosphorylated CovR and WalR proteins. Phenotypic analysis of GAS mutants lacking SP-PTP revealed that the phosphatase activity per se positively regulates growth, cell division and the ability to adhere to and invade host cells. Furthermore, A549 human lung cells infected with GAS mutants lacking SP-PTP displayed increased Ser-/Thr-/Tyr-phosphorylation. SP-PTP also differentially regulates the expression of ∼50% of the total GAS genes, including several virulence genes potentially through the two-component regulators, CovR, WalR and PTS/HPr regulation of Mga. Although these mutants exhibit attenuated virulence, a GAS mutant overexpressing SP-PTP is hypervirulent. Our study provides the first definitive evidence for the presence and importance of Tyr-phosphorylation in GAS and the relevance of SP-PTP as an important therapeutic target.

  17. Dual functions of gold nanorods as photothermal agent and autofluorescence enhancer to track cell death during plasmonic photothermal therapy.

    PubMed

    Kannadorai, Ravi Kumar; Chiew, Geraldine Giap Ying; Luo, Kathy Qian; Liu, Quan

    2015-02-01

    Gold nanorods have the potential to localize the treatment procedure by hyperthermia and influence the fluorescence. The longitudinal plasmon peak contributes to the photothermal effect by converting light to heat. When these nanorods are PEGylated, it not only makes it biocompatible but also acts as a spacer layer during fluorescence enhancement. When the PEGylated nanorods are internalized inside the cells through endocytosis, the transverse plasmonic peak combined with the enhanced absorption and scattering properties of the nanorods can enhance the autofluorescence emission intensity from the cell. The autofluorescence from the mitochondria inside cells which reflects the respiratory status of the cell was enhanced two times by the presence of nanorods within the cell. At four minutes, the nanorods incubated cells reached the hyperthermic temperature when illuminated continuously with near infrared laser. The cell viability test and autofluorescence intensity curve showed a similar trend indicating the progress of cell death over time. This is the first report to the best of our knowledge to suggest the potential of exploiting the dual capabilities of gold nanorods as photothermal agents and autofluorescence enhancer to track cell death.

  18. Functional genomic screening identifies dual leucine zipper kinase as a key mediator of retinal ganglion cell death

    PubMed Central

    Welsbie, Derek S.; Yang, Zhiyong; Ge, Yan; Mitchell, Katherine L.; Zhou, Xinrong; Martin, Scott E.; Berlinicke, Cynthia A.; Hackler, Laszlo; Fuller, John; Fu, Jie; Cao, Li-hui; Han, Bing; Auld, Douglas; Xue, Tian; Hirai, Syu-ichi; Germain, Lucie; Simard-Bisson, Caroline; Blouin, Richard; Nguyen, Judy V.; Davis, Chung-ha O.; Enke, Raymond A.; Boye, Sanford L.; Merbs, Shannath L.; Marsh-Armstrong, Nicholas; Hauswirth, William W.; DiAntonio, Aaron; Nickells, Robert W.; Inglese, James; Hanes, Justin; Yau, King-Wai; Quigley, Harry A.; Zack, Donald J.

    2013-01-01

    Glaucoma, a major cause of blindness worldwide, is a neurodegenerative optic neuropathy in which vision loss is caused by loss of retinal ganglion cells (RGCs). To better define the pathways mediating RGC death and identify targets for the development of neuroprotective drugs, we developed a high-throughput RNA interference screen with primary RGCs and used it to screen the full mouse kinome. The screen identified dual leucine zipper kinase (DLK) as a key neuroprotective target in RGCs. In cultured RGCs, DLK signaling is both necessary and sufficient for cell death. DLK undergoes robust posttranscriptional up-regulation in response to axonal injury in vitro and in vivo. Using a conditional knockout approach, we confirmed that DLK is required for RGC JNK activation and cell death in a rodent model of optic neuropathy. In addition, tozasertib, a small molecule protein kinase inhibitor with activity against DLK, protects RGCs from cell death in rodent glaucoma and traumatic optic neuropathy models. Together, our results establish a previously undescribed drug/drug target combination in glaucoma, identify an early marker of RGC injury, and provide a starting point for the development of more specific neuroprotective DLK inhibitors for the treatment of glaucoma, nonglaucomatous forms of optic neuropathy, and perhaps other CNS neurodegenerations. PMID:23431148

  19. Soluble alpha-enolase activates monocytes by CD14-dependent TLR4 signalling pathway and exhibits a dual function

    PubMed Central

    Guillou, Clément; Fréret, Manuel; Fondard, Emeline; Derambure, Céline; Avenel, Gilles; Golinski, Marie-Laure; Verdet, Mathieu; Boyer, Olivier; Caillot, Frédérique; Musette, Philippe; Lequerré, Thierry; Vittecoq, Olivier

    2016-01-01

    Rheumatoid arthritis (RA) is the most common form of chronic inflammatory rheumatism. Identifying auto-antigens targeted by RA auto-antibodies is of major interest. Alpha-enolase (ENO1) is considered to be a pivotal auto-antigen in early RA but its pathophysiologic role remains unknown. The main objective of this study was to investigate the in vitro effects of soluble ENO1 on peripheral blood mononuclear cells (PBMC) from healthy donors and RA patients in order to determine the potential pathogenic role of ENO1. ELISA, transcriptomic analysis, experiments of receptor inhibition and flow cytometry analysis were performed to determine the effect, the target cell population and the receptor of ENO1. We showed that ENO1 has the ability to induce early production of pro-inflammatory cytokines and chemokines with delayed production of IL-10 and to activate the innate immune system. We demonstrated that ENO1 binds mainly to monocytes and activates the CD14-dependent TLR4 pathway both in healthy subjects and in RA patients. Our results establish for the first time that ENO1 is able to activate in vitro the CD14-dependent TLR4 pathway on monocytes involving a dual mechanism firstly pro-inflammatory and secondly anti-inflammatory. These results contribute to elucidating the role of this auto-antigen in the pathophysiologic mechanisms of RA. PMID:27025255

  20. Functional Magnetic Resonance Imaging Clinical Trial of a Dual-Processing Treatment Protocol for Substance-Dependent Adults

    ERIC Educational Resources Information Center

    Matto, Holly C.; Hadjiyane, Maria C.; Kost, Michelle; Marshall, Jennifer; Wiley, Joseph; Strolin-Goltzman, Jessica; Khatiwada, Manish; VanMeter, John W.

    2014-01-01

    Objectives: Empirical evidence suggests substance dependence creates stress system dysregulation which, in turn, may limit the efficacy of verbal-based treatment interventions, as the recovering brain may not be functionally capable of executive level processing. Treatment models that target implicit functioning are necessary. Methods: An RCT was…

  1. Auditory and visual impairments in patients with blast-related traumatic brain injury: Effect of dual sensory impairment on Functional Independence Measure.

    PubMed

    Lew, Henry L; Garvert, Donn W; Pogoda, Terri K; Hsu, Pei-Te; Devine, Jennifer M; White, Daniel K; Myers, Paula J; Goodrich, Gregory L

    2009-01-01

    The frequencies of hearing impairment (HI), vision impairment (VI), or dual (hearing and vision) sensory impairment (DSI) in patients with blast-related traumatic brain injury (TBI) and their effects on functional recovery are not well documented. In this preliminary study of 175 patients admitted to a Polytrauma Rehabilitation Center, we completed hearing and vision examinations and obtained Functional Independence Measure (FIM) scores at admission and discharge for 62 patients with blast-related TBI. We diagnosed HI only, VI only, and DSI in 19%, 34%, and 32% of patients, respectively. Only 15% of the patients had no sensory impairment in either auditory or visual modality. An analysis of variance showed a group difference for the total and motor FIM scores at discharge (p < 0.04). Regression model analyses demonstrated that DSI significantly contributed to reduced gain in total ( t = -2.25) and motor ( t = -2.50) FIM scores ( p < 0.05). Understanding the long-term consequences of sensory impairments in the functional recovery of patients with blast-related TBI requires further research.

  2. Evaluation of pulmonary function using single-breath-hold dual-energy computed tomography with xenon: Results of a preliminary study.

    PubMed

    Kyoyama, Hiroyuki; Hirata, Yusuke; Kikuchi, Satoshi; Sakai, Kosuke; Saito, Yuriko; Mikami, Shintaro; Moriyama, Gaku; Yanagita, Hisami; Watanabe, Wataru; Otani, Katharina; Honda, Norinari; Uematsu, Kazutsugu

    2017-01-01

    Xenon-enhanced dual-energy computed tomography (xenon-enhanced CT) can provide lung ventilation maps that may be useful for assessing structural and functional abnormalities of the lung. Xenon-enhanced CT has been performed using a multiple-breath-hold technique during xenon washout. We recently developed xenon-enhanced CT using a single-breath-hold technique to assess ventilation. We sought to evaluate whether xenon-enhanced CT using a single-breath-hold technique correlates with pulmonary function testing (PFT) results.Twenty-six patients, including 11 chronic obstructive pulmonary disease (COPD) patients, underwent xenon-enhanced CT and PFT. Three of the COPD patients underwent xenon-enhanced CT before and after bronchodilator treatment. Images from xenon-CT were obtained by dual-source CT during a breath-hold after a single vital-capacity inspiration of a xenon-oxygen gas mixture. Image postprocessing by 3-material decomposition generated conventional CT and xenon-enhanced images.Low-attenuation areas on xenon images matched low-attenuation areas on conventional CT in 21 cases but matched normal-attenuation areas in 5 cases. Volumes of Hounsfield unit (HU) histograms of xenon images correlated moderately and highly with vital capacity (VC) and total lung capacity (TLC), respectively (r = 0.68 and 0.85). Means and modes of histograms weakly correlated with VC (r = 0.39 and 0.38), moderately with forced expiratory volume in 1 second (FEV1) (r = 0.59 and 0.56), weakly with the ratio of FEV1 to FVC (r = 0.46 and 0.42), and moderately with the ratio of FEV1 to its predicted value (r = 0.64 and 0.60). Mode and volume of histograms increased in 2 COPD patients after the improvement of FEV1 with bronchodilators. Inhalation of xenon gas caused no adverse effects.Xenon-enhanced CT using a single-breath-hold technique depicted functional abnormalities not detectable on thin-slice CT. Mode, mean, and volume of HU histograms of xenon images reflected

  3. lcrR, a low-Ca2(+)-response locus with dual Ca2(+)-dependent functions in Yersinia pestis.

    PubMed Central

    Barve, S S; Straley, S C

    1990-01-01

    The low-Ca2+ response (Lcr) of Yersinia includes a regulatory cascade and a set of virulence-related proteins, one of which is the V antigen. The regulatory genes modulate both bacterial growth and expression of the virulence-related proteins in response to temperature and the presence of Ca2+ and nucleotides. In this study we defined a new Lcr locus, lcrR, in Yersinia pestis KIM. An lcrR mutant, obtained by insertion mutagenesis, failed to grow at 37 degrees C whether Ca2+ was present or not. However, it grew normally in the presence of ATP, showing that the Ca2(+)- and nucleotide-responsive mechanisms are separate in Y. pestis. The lcrR mutant was avirulent in mice, probably due to its compromised growth at 37 degrees C. beta-Galactosidase measurements and Northern (RNA blot) analysis revealed that lcrR transcription was regulated primarily by temperature. The DNA sequence of the lcrR locus contained a single open reading frame of 441 bases that could encode a protein with a molecular weight of 16,470 and a pI of 10.73. Expression of an lcrR-containing clone in Escherichia coli yielded a 16,000-molecular-weight protein. At 37 degrees C, the lcrR mutant strongly expressed V antigen and initiated lcrGVH transcription whether Ca2+ was present or not, indicating that this mutant had lost the transcriptional downregulation of lcrGVH shown by the parent in the presence of Ca2+. In the absence of Ca2+, the mutant failed to express LcrG, even though lcrGVH mRNA initiated upstream of lcrG at the normal sites. These data suggest that the lcrR locus is necessary for the regulation of LcrG expression in the absence of Ca2+. Therefore, this locus has a dual regulatory role in the low-Ca2+ response. Images PMID:1695896

  4. Mesoporous silica beads embedded with semiconductor quantum dots and iron oxide nanocrystals: dual-function microcarriers for optical encoding and magnetic separation.

    PubMed

    Sathe, Tushar R; Agrawal, Amit; Nie, Shuming

    2006-08-15

    Mesoporous beads are promising materials for embedding functional nanoparticles because of their nanometer-sized pores and large surface areas. Here we report the development of silica microbeads embedded with both semiconductor quantum dots (QD) and iron oxide (Fe3O4) nanocrystals as a new class of dual-function carriers for optical encoding and magnetic separation. The embedding (doping) process is carried out by either simultaneous or sequential addition of quantum dots and iron oxide (Fe3O4) nanocrystals in solution. The doping process is fast and quantitative, but the incorporated iron oxide strongly attenuates the signal intensity of QD fluorescence. We find that this attenuation is not due to conventional fluorescence quenching but is caused by the broad optical absorption spectrum of mixed-valence Fe3O4. For improved biocompatibility and reduced nonspecific binding, the encoded beads are further coated with amphiphilic polymers such as octylamine poly(acrylic acid). The results indicate that the polymer-coated beads are well suited for target capturing and enrichment, yielding magnetic separation efficiencies higher than 99%. By combining the multiplexing capability of QDs with the superparamagnetic properties of iron oxide nanocrystals, this class of encoded beads is expected to find broad applications in high-throughput and multiplexed biomolecular assays.

  5. Dual functions of 2D WS2 and MoS2-WS2 monolayers coupled with a Ag3PO4 photocatalyst

    NASA Astrophysics Data System (ADS)

    Wei, Zeng-Xi; Huang, Wei-Qing; Xu, Liang; Hu, Wangyu; Peng, P.; Huang, Gui-Fang

    2016-09-01

    The photocatalytic performance of semiconductors can be improved by coupling two-dimensional (2D) layered materials. Understanding the underlying mechanism of this phenomenon at the electronic level is important for the development of photocatalysts with a high efficiency. Here, we first present a theoretical elucidation of the dual functions of 2D layered material as a sensitizer and a co-catalyst by performing density functional theory calculations, taking WS2 and a lateral heterogeneous WS2-MoS2 monolayer as examples to couple with a promising photocatalyst Ag3PO4. The band alignment of a staggered type-II is formed between Ag3PO4 and the 2D monolayer with the latter possessing the higher electron affinity, resulting in the robust separation of photoexcited charge carriers between them, and indicating that the 2D monolayer is an effective sensitizer. Interestingly, the W (Mo) atoms, which are catalytically inert in the isolated 2D monolayer, turn into catalytic active sites, making the 2D monolayer a highly active co-catalyst in hybrids. A better photocatalytic performance in the coupled lateral heterogeneous WS2-MoS2 monolayer and Ag3PO4 can be expected. The calculated results can be rationalized by available experiments. These findings provide theoretical evidence supporting the experimental reports and may be used as a foundation for developing highly efficient 2D layered materials-based photocatalysts.

  6. Robust specification of sensory neurons by dual functions of charlatan, a Drosophila NRSF/REST-like repressor of extramacrochaetae and hairy.

    PubMed

    Yamasaki, Yasutoyo; Lim, Young-Mi; Niwa, Nao; Hayashi, Shigeo; Tsuda, Leo

    2011-08-01

    Sensory bristle formation in Drosophila is a well-characterized system for studying sensory organ development at the molecular level. The master proneural genes of the achaete-scute (ac-sc) complex, which encode basic-helix-loop-helix (bHLH) transcription factors, are necessary and sufficient for sensory bristle formation. charlatan (chn) was originally identified as a transcriptional activator of ac-sc gene expression through interaction with its enhancer, an activity that promotes sensory bristle development. In contrast, Chn was also identified as a functional homologue of mammalian neuron-restrictive silencing factor or RE1 silencing transcription factor (NRSF/REST), an important transcriptional repressor during vertebrate neurogenesis and stem cell development that acts through epigenetic gene silencing. Here, we report that Chn acts as a repressor of extramacrochaetae (emc) and hairy, molecules that inhibit ac-sc expression. This double-negative mechanism, together with direct activation via the achaete enhancer, increases expression of achaete and ensures robust development of sensory neurons. A mutation in the C-terminal repressor motif of Chn, which causes Chn to lose its repression activity, converted Chn to an activator of emc and hairy, suggesting that Chn is a dual functional regulator of transcription. Because chn-like sequences are found among arthropods, regulation of neuronal development by Chn-like molecules may be widely conserved.

  7. Dual function of Ixr1 in transcriptional regulation and recognition of cisplatin-DNA adducts is caused by differential binding through its two HMG-boxes.

    PubMed

    Vizoso-Vázquez, A; Lamas-Maceiras, M; Fernández-Leiro, R; Rico-Díaz, A; Becerra, M; Cerdán, M E

    2017-02-01

    Ixr1 is a transcriptional factor involved in the response to hypoxia, which is also related to DNA repair. It binds to DNA through its two in-tandem high mobility group box (HMG-box) domains. Each function depends on recognition of different DNA structures, B-form DNA at specific consensus sequences for transcriptional regulation, or distorted DNA, like cisplatin-DNA adducts, for DNA repair. However, the contribution of the HMG-box domains in the Ixr1 protein to the formation of different protein-DNA complexes is poorly understood. We have biophysically and biochemically characterized these interactions with specific DNA sequences from the promoters regulated by Ixr1, or with cisplatin-DNA adducts. Both HMG-boxes are necessary for transcriptional regulation, and they are not functionally interchangeable. The in-tandem arrangement of their HMG-boxes is necessary for functional folding and causes sequential cooperative binding to specific DNA sequences, with HMG-box A showing a higher contribution to DNA binding and bending than the HMG-box B. Binding of Ixr1 HMG boxes to specific DNA sequences is entropy driven, whereas binding to platinated DNA is enthalpy driven for HMG-box A and entropy driven for HMG-box B. This is the first proof that HMG-box binding to different DNA structures is associated with predictable thermodynamic differences. Based on our study, we present a model to explain the dual function of Ixr1 in the regulation of gene expression and recognition of distorted DNA structures caused by cisplatin treatment.

  8. PspB and PspC of Yersinia enterocolitica are dual function proteins: regulators and effectors of the phage-shock-protein response.

    PubMed

    Maxson, Michelle E; Darwin, Andrew J

    2006-03-01

    The phage-shock-protein (Psp) stress-response system is conserved in many bacteria and has been linked to important phenotypes in Escherichia coli, Salmonella enterica and also Yersinia enterocolitica, where it is essential for virulence. It is activated by specific extracytoplasmic stress events such as the mislocalization of secretin proteins. From studies of the Psp system in E. coli, the cytoplasmic membrane proteins PspB and PspC have only been proposed to act as positive regulators of psp gene expression. However, in this study we show that PspB and PspC of Y. enterocolitica are dual function proteins, acting both as regulators and effectors of the Psp system. Consistent with the current model, they positively control psp gene expression in response to diverse inducing cues. PspB and PspC must work together to achieve this regulatory function, and bacterial two-hybrid (BACTH) analysis demonstrated a specific interaction between them, which was confirmed by in vivo cross-linking. We also show that PspB and PspC play a second role in supporting growth when a secretin protein is overexpressed. This function is independent from their role as regulators of psp gene expression. Furthermore, whereas PspB and PspC must work together for their regulatory function, they can apparently act independently to support growth during secretin production. This study expands the current understanding of the roles played by PspB and PspC, and demonstrates that they cannot be considered only as positive regulators of psp gene expression in Y. enterocolitica.

  9. Core-Corona Functionalization of Diblock Copolymer Micelles by Heterogeneous Metal Nanoparticles for Dual Modality in Chemical Reactions.

    PubMed

    Jo, Seong Ho; Kim, Hyun Woo; Song, Minkyung; Je, Nam Jin; Oh, Sung-Hoon; Chang, Byoung-Yong; Yoon, Jinhwan; Kim, Joo Hyun; Chung, Bonghoon; Yoo, Seong Il

    2015-08-26

    Nanoscale assemblies composed of different types of nanoparticles (NPs) can reveal interesting aspects about material properties beyond the functions of individual constituent NPs. This research direction may also represent current challenges in nanoscience toward practical applications. With respect to the assembling method, synthetic or biological nanostructures can be utilized to organize heterogeneous NPs in specific sites via chemical or physical interactions. However, those assembling methods often encounter uncontrollable particle aggregation or phase separation. In this study, we anticipated that the self-segregating properties of block copolymer micelles could be particularly useful for organizing heterogeneous NPs, because the presence of chemically distinct domains such as the core and the corona can facilitate the selective placement of constituent NPs in separate domains. Here, we simultaneously functionalized the core and the corona of micelles by Au NPs and Ag NPs, which exhibited plasmonic and catalytic functions, respectively. Our primary question is whether these plasmonic and catalytic functions can be combined in the assembled structures to engineer the kinetics of a model chemical reaction. To test this hypothesis, the catalytic reduction of 4-nitrophenol was selected to evaluate the collective properties of the micellar assemblies in a chemical reaction.

  10. Heteroatom-Guided, Palladium-Catalyzed, Site-Selective C-H Arylation of 4H-Chromenes: Diastereoselective Assembly of the Core Structure of Myristinin B through Dual C-H Functionalization.

    PubMed

    Pawar, Govind Goroba; Tiwari, Virendra Kumar; Jena, Himanshu Sekhar; Kapur, Manmohan

    2015-06-26

    A highly site-selective, heteroatom-guided, palladium-catalyzed direct arylation of 4H-chromenes is reported. The C-H functionalization is driven not only by the substituents and structure of the substrate but also by the coupling partner being used. The diastereoselective assembly of the core structure of Myristinin B has been achieved by using a dual C-H functionalization strategy for regioselective direct arylation.

  11. Dual Functional Nanocarrier for Cellular Imaging and Drug Delivery in Cancer Cells Based on π-Conjugated Core and Biodegradable Polymer Arms.

    PubMed

    Kulkarni, Bhagyashree; Surnar, Bapurao; Jayakannan, Manickam

    2016-03-14

    Multipurpose polymer nanoscaffolds for cellular imaging and delivery of anticancer drug are urgently required for the cancer therapy. The present investigation reports a new polymer drug delivery concept based on biodegradable polycaprolactone (PCL) and highly luminescent π-conjugated fluorophore as dual functional nanocarrier for cellular imaging and delivery vehicles for anticancer drug to cancer cells. To accomplish this goal, a new substituted caprolactone monomer was designed, and it was subjected to ring opening polymerization using a blue luminescent bishydroxyloligo-phenylenevinylene (OPV) fluorophore as an initiator. A series of A-B-A triblock copolymer building blocks with a fixed OPV π-core and variable chain biodegradable PCL arm length were tailor-made. These triblocks self-assembled in organic solvents to produce well-defined helical nanofibers, whereas in water they produced spherical nanoparticles (size ∼150 nm) with blue luminescence. The hydrophobic pocket of the polymer nanoparticle was found to be an efficient host for loading water insoluble anticancer drug such as doxorubicin (DOX). The photophysical studies revealed that there was no cross-talking between the OPV and DOX chromophores, and their optical purity was retained in the nanoparticle assembly for cellular imaging. In vitro studies revealed that the biodegradable PCL arm was susceptible to enzymatic cleavage at the intracellular lysosomal esterase under physiological conditions to release the loaded drugs. The nascent nanoparticles were found to be nontoxic to cancer cells, whereas the DOX-loaded nanoparticles accomplished more than 80% killing in HeLa cells. Confocal microscopic analysis confirmed the cell penetrating ability of the blue luminescent polymer nanoparticles and their accumulation preferably in the cytoplasm. The DOX loaded red luminescent polymer nanoparticles were also taken up by the cells, and the drug was found to be accumulated at the perinuclear environment

  12. Core-shell structured carbonyl iron microspheres prepared via dual-step functionality coatings and their magnetorheological response.

    PubMed

    Fang, Fei Fei; Liu, Ying Dan; Choi, Hyoung Jin; Seo, Yongsok

    2011-09-01

    The dispersion stability of soft magnetic carbonyl iron (CI)-based magnetorheological (MR) fluids was improved by applying a unique functional coating composed of a conducting polyaniline layer and a multiwalled carbon nanotube nest to the surfaces of the CI particles via conventional dispersion polymerization, followed by facile solvent casting. The coating morphology and thickness were analyzed by SEM and TEM imaging. Chemical composition of the polyaniline layer was detected by Raman spectroscope, which also confirmed the coating performance successfully. The influence of the functional coating on the magnetic properties was investigated by measuring the MR performance and sedimentation properties using a vibrating sample magnetometer, rotational rheometer, and Turbiscan apparatus. Improved dispersion characteristics of the MR fluid were observed.

  13. A facile approach to prepare a dual functionalized DNA based material in a bio-deep eutectic solvent.

    PubMed

    Mondal, Dibyendu; Bhatt, Jitkumar; Sharma, Mukesh; Chatterjee, Shruti; Prasad, Kamalesh

    2014-04-18

    DNA (Salmon testes) was functionalized by Fe3O4 nanoparticles and protonated layered dititanate sheets (H2·Ti2O5·H2O) in a mixture of choline chloride and ethylene glycol (a deep eutectic solvent) to yield a hybrid material having magnetic and antibacterial properties. Ti sheets were found to interact with the phosphate moieties, while Fe interacted with the base pair of DNA in the hybrid material.

  14. Tumor suppression in basal keratinocytes via dual non-cell-autonomous functions of a Na,K-ATPase beta subunit

    PubMed Central

    Hatzold, Julia; Beleggia, Filippo; Herzig, Hannah; Altmüller, Janine; Nürnberg, Peter; Bloch, Wilhelm; Wollnik, Bernd; Hammerschmidt, Matthias

    2016-01-01

    The molecular pathways underlying tumor suppression are incompletely understood. Here, we identify cooperative non-cell-autonomous functions of a single gene that together provide a novel mechanism of tumor suppression in basal keratinocytes of zebrafish embryos. A loss-of-function mutation in atp1b1a, encoding the beta subunit of a Na,K-ATPase pump, causes edema and epidermal malignancy. Strikingly, basal cell carcinogenesis only occurs when Atp1b1a function is compromised in both the overlying periderm (resulting in compromised epithelial polarity and adhesiveness) and in kidney and heart (resulting in hypotonic stress). Blockade of the ensuing PI3K-AKT-mTORC1-NFκB-MMP9 pathway activation in basal cells, as well as systemic isotonicity, prevents malignant transformation. Our results identify hypotonic stress as a (previously unrecognized) contributor to tumor development and establish a novel paradigm of tumor suppression. DOI: http://dx.doi.org/10.7554/eLife.14277.001 PMID:27240166

  15. Genetic variability of drug-metabolizing enzymes: the dual impact on psychiatric therapy and regulation of brain function.

    PubMed

    Stingl, J C; Brockmöller, J; Viviani, R

    2013-03-01

    Polymorphic drug-metabolizing enzymes (DMEs) are responsible for the metabolism of the majority of psychotropic drugs. By explaining a large portion of variability in individual drug metabolism, pharmacogenetics offers a diagnostic tool in the burgeoning era of personalized medicine. This review updates existing evidence on the influence of pharmacogenetic variants on drug exposure and discusses the rationale for genetic testing in the clinical context. Dose adjustments based on pharmacogenetic knowledge are the first step to translate pharmacogenetics into clinical practice. However, also clinical factors, such as the consequences on toxicity and therapeutic failure, must be considered to provide clinical recommendations and assess the cost-effectiveness of pharmacogenetic treatment strategies. DME polymorphisms are relevant not only for clinical pharmacology and practice but also for research in psychiatry and neuroscience. Several DMEs, above all the cytochrome P (CYP) enzymes, are expressed in the brain, where they may contribute to the local biochemical homeostasis. Of particular interest is the possibility of DMEs playing a physiological role through their action on endogenous substrates, which may underlie the reported associations between genetic polymorphisms and cognitive function, personality and vulnerability to mental disorders. Neuroimaging studies have recently presented evidence of an effect of the CYP2D6 polymorphism on basic brain function. This review summarizes evidence on the effect of DME polymorphisms on brain function that adds to the well-known effects of DME polymorphisms on pharmacokinetics in explaining the range of phenotypes that are relevant to psychiatric practice.

  16. Dual redundant core memory systems

    NASA Technical Reports Server (NTRS)

    Hull, F. E.

    1972-01-01

    Electronic memory system consisting of series redundant drive switch circuits, triple redundant majority voted memory timing functions, and two data registers to provide functional dual redundancy is described. Signal flow through the circuits is illustrated and equence of events which occur within the memory system is explained.

  17. A dual extremum principle for a population equation

    NASA Technical Reports Server (NTRS)

    Chan, W. L.; Leininger, G. G.

    1974-01-01

    A dual extremum principle for the Verhulst-Pearl population equation is constructed using a complementary variational technique. The dual formulation utilizes a minimum principle recently developed by Leitmann to convert the functional optimization problem into a parameter optimization problem.

  18. Incorporation of the purified epstein barr virus/C3d receptor (CR2) into liposomes and demonstration of its dual ligand binding functions

    SciTech Connect

    Mold, C.; Cooper, N.R.; Nemerow, G.R.

    1986-06-01

    The 145-kDA molecule that has been identified as the C3d receptor CR2 was isolated from lysates of Raji cells by affinity chromatography by using the monoclonal antibody (MoAb)HB-5. The purified protein was incorporated into /sup 14/C-phosphatidylcholine liposomes by deoxycholate dialysis followed by flotation on discontinuous sucrose gradients. Incorporation of the receptor was verified by testing the gradient fractions for CR2 by an enzyme-linked immunosorbent assay. Liposomes were shown to be unilamellar vesicles ranging in diameter from 25 to 100 nm by electron microscopy. The external orientation of CR2 in the membranes was demonstrated by immunoelectron microscopy. The functional activities of liposomes containing CR2 and liposomes without protein were compared. CR2 liposomes bound to EC3d, but not to E, and this binding was inhibited by the anti-CR2 MoAb OKB7 and by a MoAb specific for C3d. Control liposomes failed to bind to either E or EC3D. The ability of CR2 to function as a receptor for Epstein Barr virus (EBV) was tested in two ways. First, CR2 liposomes bound to B95-8, a cell line expressing EBV membrane antigens, but not to B95-8 cells treated with the viral DNA polymerase inhibitor phosphonoformic acid. Second, liposomes containing CR2 were shown by ultracentrifugal analyses to bind directly to purified EBV, and this binding was also inhibited by OKB7. Control liposomes did not bind to B95-8 cells or to EBV. These findings show that CR2 purified from detergent extracts of Raji cells can be reconstituted into lipid membranes with maintenance of its dual functions as a receptor for C3d and EBV.

  19. MS_RHII-RSD, a Dual-Function RNase HII-(p)ppGpp Synthetase from Mycobacterium smegmatis

    PubMed Central

    Murdeshwar, Maya S.

    2012-01-01

    In the noninfectious soil saprophyte Mycobacterium smegmatis, intracellular levels of the stress alarmones guanosine tetraphosphate and guanosine pentaphosphate, together termed (p)ppGpp, are regulated by the enzyme RelMsm. This enzyme consists of a single, bifunctional polypeptide chain that is capable of both synthesizing and hydrolyzing (p)ppGpp. The relMsm knockout strain of M. smegmatis (ΔrelMsm) is expected to show a (p)ppGpp null [(p)ppGpp0] phenotype. Contrary to this expectation, the strain is capable of synthesizing (p)ppGpp in vivo. In this study, we identify and functionally characterize the open reading frame (ORF), MSMEG_5849, that encodes a second functional (p)ppGpp synthetase in M. smegmatis. In addition to (p)ppGpp synthesis, the 567-amino-acid-long protein encoded by this gene is capable of hydrolyzing RNA·DNA hybrids and bears similarity to the conventional RNase HII enzymes. We have classified this protein as actRelMsm in accordance with the recent nomenclature proposed and have named it MS_RHII-RSD, indicating the two enzymatic activities present [RHII, RNase HII domain, originally identified as domain of unknown function 429 (DUF429), and RSD, RelA_SpoT nucleotidyl transferase domain, the SYNTH domain responsible for (p)ppGpp synthesis activity]. MS_RHII-RSD is expressed and is constitutively active in vivo and behaves like a monofunctional (p)ppGpp synthetase in vitro. The occurrence of the RNase HII and (p)ppGpp synthetase domains together on the same polypeptide chain is suggestive of an in vivo role for this novel protein as a link connecting the essential life processes of DNA replication, repair, and transcription to the highly conserved stress survival pathway, the stringent response. PMID:22636779

  20. The structure of bradyzoite-specific enolase from Toxoplasma gondii reveals insights into its dual cytoplasmic and nuclear functions

    SciTech Connect

    Ruan, Jiapeng; Mouveaux, Thomas; Light, Samuel H.; Minasov, George; Anderson, Wayne F.; Tomavo, Stanislas; Ngô, Huân M.

    2015-03-01

    The second crystal structure of a parasite protein preferentially enriched in the brain cyst of T. gondii has been solved at 2.75 Å resolution. Bradyzoite enolase 1 is reported to have differential functions as a glycolytic enzyme and a transcriptional regulator in bradyzoites. In addition to catalyzing a central step in glycolysis, enolase assumes a remarkably diverse set of secondary functions in different organisms, including transcription regulation as documented for the oncogene c-Myc promoter-binding protein 1. The apicomplexan parasite Toxoplasma gondii differentially expresses two nuclear-localized, plant-like enolases: enolase 1 (TgENO1) in the latent bradyzoite cyst stage and enolase 2 (TgENO2) in the rapidly replicative tachyzoite stage. A 2.75 Å resolution crystal structure of bradyzoite enolase 1, the second structure to be reported of a bradyzoite-specific protein in Toxoplasma, captures an open conformational state and reveals that distinctive plant-like insertions are located on surface loops. The enolase 1 structure reveals that a unique residue, Glu164, in catalytic loop 2 may account for the lower activity of this cyst-stage isozyme. Recombinant TgENO1 specifically binds to a TTTTCT DNA motif present in the cyst matrix antigen 1 (TgMAG1) gene promoter as demonstrated by gel retardation. Furthermore, direct physical interactions of both nuclear TgENO1 and TgENO2 with the TgMAG1 gene promoter are demonstrated in vivo using chromatin immunoprecipitation (ChIP) assays. Structural and biochemical studies reveal that T. gondii enolase functions are multifaceted, including the coordination of gene regulation in parasitic stage development. Enolase 1 provides a potential lead in the design of drugs against Toxoplasma brain cysts.

  1. Dual functions of α-ketoglutarate dehydrogenase E2 in the Krebs cycle and mitochondrial DNA inheritance in Trypanosoma brucei.

    PubMed

    Sykes, Steven E; Hajduk, Stephen L

    2013-01-01

    The dihydrolipoyl succinyltransferase (E2) of the multisubunit α-ketoglutarate dehydrogenase complex (α-KD) is an essential Krebs cycle enzyme commonly found in the matrices of mitochondria. African trypanosomes developmentally regulate mitochondrial carbohydrate metabolism and lack a functional Krebs cycle in the bloodstream of mammals. We found that despite the absence of a functional α-KD, bloodstream form (BF) trypanosomes express α-KDE2, which localized to the mitochondrial matrix and inner membrane. Furthermore, α-KDE2 fractionated with the mitochondrial genome, the kinetoplast DNA (kDNA), in a complex with the flagellum. A role for α-KDE2 in kDNA maintenance was revealed in α-KDE2 RNA interference (RNAi) knockdowns. Following RNAi induction, bloodstream trypanosomes showed pronounced growth reduction and often failed to equally distribute kDNA to daughter cells, resulting in accumulation of cells devoid of kDNA (dyskinetoplastic) or containing two kinetoplasts. Dyskinetoplastic trypanosomes lacked mitochondrial membrane potential and contained mitochondria of substantially reduced volume. These results indicate that α-KDE2 is bifunctional, both as a metabolic enzyme and as a mitochondrial inheritance factor necessary for the distribution of kDNA networks to daughter cells at cytokinesis.

  2. Dual functions of Macpiwi1 in transposon silencing and stem cell maintenance in the flatworm Macrostomum lignano

    PubMed Central

    Zhou, Xin; Battistoni, Giorgia; El Demerdash, Osama; Gurtowski, James; Wunderer, Julia; Falciatori, Ilaria; Ladurner, Peter; Schatz, Michael C.; Hannon, Gregory J.; Wasik, Kaja A.

    2015-01-01

    PIWI proteins and piRNA pathways are essential for transposon silencing and some aspects of gene regulation during animal germline development. In contrast to most animal species, some flatworms also express PIWIs and piRNAs in somatic stem cells, where they are required for tissue renewal and regeneration. Here, we have identified and characterized piRNAs and PIWI proteins in the emerging model flatworm Macrostomum lignano. We found that M. lignano encodes at least three PIWI proteins. One of these, Macpiwi1, acts as a key component of the canonical piRNA pathway in the germline and in somatic stem cells. Knockdown of Macpiwi1 dramatically reduces piRNA levels, derepresses transposons, and severely impacts stem cell maintenance. Knockdown of the piRNA biogenesis factor Macvasa caused an even greater reduction in piRNA levels with a corresponding increase in transposons. Yet, in Macvasa knockdown animals, we detected no major impact on stem cell self-renewal. These results may suggest stem cell maintenance functions of PIWI proteins in flatworms that are distinguishable from their impact on transposons and that might function independently of what are considered canonical piRNA populations. PMID:26323280

  3. Dual-functional Memory and Threshold Resistive Switching Based on the Push-Pull Mechanism of Oxygen Ions

    PubMed Central

    Huang, Yi-Jen; Chao, Shih-Chun; Lien, Der-Hsien; Wen, Cheng-Yen; He, Jr-Hau; Lee, Si-Chen

    2016-01-01

    The combination of nonvolatile memory switching and volatile threshold switching functions of transition metal oxides in crossbar memory arrays is of great potential for replacing charge-based flash memory in very-large-scale integration. Here, we show that the resistive switching material structure, (amorphous TiOx)/(Ag nanoparticles)/(polycrystalline TiOx), fabricated on the textured-FTO substrate with ITO as the top electrode exhibits both the memory switching and threshold switching functions. When the device is used for resistive switching, it is forming-free for resistive memory applications with low operation voltage (<±1 V) and self-compliance to current up to 50 μA. When it is used for threshold switching, the low threshold current is beneficial for improving the device selectivity. The variation of oxygen distribution measured by energy dispersive X-ray spectroscopy and scanning transmission electron microscopy indicates the formation or rupture of conducting filaments in the device at different resistance states. It is therefore suggested that the push and pull actions of oxygen ions in the amorphous TiOx and polycrystalline TiOx films during the voltage sweep account for the memory switching and threshold switching properties in the device. PMID:27052322

  4. How does a protein with dual mitotic spindle and extracellular matrix receptor functions affect tumor susceptibility and progression?

    PubMed Central

    Tolg, Cornelia; McCarthy, James B

    2011-01-01

    The mechanisms responsible for the oncogenic effects of the hyaluronan (HA) receptor and mitotic spindle binding protein, RHAMM, are poorly understood. On one hand, extracellular RHAMM interacts with HA and cellsurface receptors such as CD44 to coordinately activate the MAPK/ERK1,2 pathway, thus contributing to the spread and proliferation of tumor cells. On the other hand, intracellular RHAMM decorates mitotic spindles and is necessary for spindle formation and progression through G2/M and overexpression or loss of RHAMM can result in multipole spindles and chromosome missegregation. The deregulation of these intracellular functions could lead to genomic instability and fuel tumor progression. This suggests that both extracellular and intracellular RHAMM can promote tumor progression. Intracellular RHAMM can bind directly to ERK1 to form complexes with ERK2, MEK1 and ERK1,2 substrates, and we present a model whereby RHAMM's function is as a scaffold protein, controlling activation and targeting of ERK1,2 to specific substrates. PMID:21655434

  5. The structure of bradyzoite-specific enolase from Toxoplasma gondii reveals insights into its dual cytoplasmic and nuclear functions.

    PubMed

    Ruan, Jiapeng; Mouveaux, Thomas; Light, Samuel H; Minasov, George; Anderson, Wayne F; Tomavo, Stanislas; Ngô, Huân M

    2015-03-01

    In addition to catalyzing a central step in glycolysis, enolase assumes a remarkably diverse set of secondary functions in different organisms, including transcription regulation as documented for the oncogene c-Myc promoter-binding protein 1. The apicomplexan parasite Toxoplasma gondii differentially expresses two nuclear-localized, plant-like enolases: enolase 1 (TgENO1) in the latent bradyzoite cyst stage and enolase 2 (TgENO2) in the rapidly replicative tachyzoite stage. A 2.75 Å resolution crystal structure of bradyzoite enolase 1, the second structure to be reported of a bradyzoite-specific protein in Toxoplasma, captures an open conformational state and reveals that distinctive plant-like insertions are located on surface loops. The enolase 1 structure reveals that a unique residue, Glu164, in catalytic loop 2 may account for the lower activity of this cyst-stage isozyme. Recombinant TgENO1 specifically binds to a TTTTCT DNA motif present in the cyst matrix antigen 1 (TgMAG1) gene promoter as demonstrated by gel retardation. Furthermore, direct physical interactions of both nuclear TgENO1 and TgENO2 with the TgMAG1 gene promoter are demonstrated in vivo using chromatin immunoprecipitation (ChIP) assays. Structural and biochemical studies reveal that T. gondii enolase functions are multifaceted, including the coordination of gene regulation in parasitic stage development. Enolase 1 provides a potential lead in the design of drugs against Toxoplasma brain cysts.

  6. A dual function for chaperones SSB–RAC and the NAC nascent polypeptide–associated complex on ribosomes

    PubMed Central

    Koplin, Ansgar; Preissler, Steffen; Ilina, Yulia; Koch, Miriam; Scior, Annika; Erhardt, Marc

    2010-01-01

    The yeast Hsp70/40 system SSB–RAC (stress 70 B–ribosome-associated complex) binds to ribosomes and contacts nascent polypeptides to assist cotranslational folding. In this study, we demonstrate that nascent polypeptide–associated complex (NAC), another ribosome-tethered system, is functionally connected to SSB–RAC and the cytosolic Hsp70 network. Simultaneous deletions of genes encoding NAC and SSB caused conditional loss of cell viability under protein-folding stress conditions. Furthermore, NAC mutations revealed genetic interaction with a deletion of Sse1, a nucleotide exchange factor regulating the cytosolic Hsp70 network. Cells lacking SSB or Sse1 showed protein aggregation, which is enhanced by additional loss of NAC; however, these mutants differ in their potential client repertoire. Aggregation of ribosomal proteins and biogenesis factors accompanied by a pronounced deficiency in ribosomal particles and translating ribosomes only occurs in ssbΔ and nacΔssbΔ cells, suggesting that SSB and NAC control ribosome biogenesis. Thus, SSB–RAC and NAC assist protein folding and likewise have important functions for regulation of ribosome levels. These findings emphasize the concept that ribosome production is coordinated with the protein-folding capacity of ribosome-associated chaperones. PMID:20368618

  7. Dual-functional Memory and Threshold Resistive Switching Based on the Push-Pull Mechanism of Oxygen Ions.

    PubMed

    Huang, Yi-Jen; Chao, Shih-Chun; Lien, Der-Hsien; Wen, Cheng-Yen; He, Jr-Hau; Lee, Si-Chen

    2016-04-07

    The combination of nonvolatile memory switching and volatile threshold switching functions of transition metal oxides in crossbar memory arrays is of great potential for replacing charge-based flash memory in very-large-scale integration. Here, we show that the resistive switching material structure, (amorphous TiOx)/(Ag nanoparticles)/(polycrystalline TiOx), fabricated on the textured-FTO substrate with ITO as the top electrode exhibits both the memory switching and threshold switching functions. When the device is used for resistive switching, it is forming-free for resistive memory applications with low operation voltage (<± 1 V) and self-compliance to current up to 50 μA. When it is used for threshold switching, the low threshold current is beneficial for improving the device selectivity. The variation of oxygen distribution measured by energy dispersive X-ray spectroscopy and scanning transmission electron microscopy indicates the formation or rupture of conducting filaments in the device at different resistance states. It is therefore suggested that the push and pull actions of oxygen ions in the amorphous TiOx and polycrystalline TiOx films during the voltage sweep account for the memory switching and threshold switching properties in the device.

  8. The structure of bradyzoite-specific enolase from Toxoplasma gondii reveals insights into its dual cytoplasmic and nuclear functions

    PubMed Central

    Ruan, Jiapeng; Mouveaux, Thomas; Light, Samuel H.; Minasov, George; Anderson, Wayne F.; Tomavo, Stanislas; Ngô, Huân M.

    2015-01-01

    In addition to catalyzing a central step in glycolysis, enolase assumes a remarkably diverse set of secondary functions in different organisms, including transcription regulation as documented for the oncogene c-Myc promoter-binding protein 1. The apicomplexan parasite Toxoplasma gondii differentially expresses two nuclear-localized, plant-like enolases: enolase 1 (TgENO1) in the latent bradyzoite cyst stage and enolase 2 (TgENO2) in the rapidly replicative tachyzoite stage. A 2.75 Å resolution crystal structure of bradyzoite enolase 1, the second structure to be reported of a bradyzoite-specific protein in Toxoplasma, captures an open conformational state and reveals that distinctive plant-like insertions are located on surface loops. The enolase 1 structure reveals that a unique residue, Glu164, in catalytic loop 2 may account for the lower activity of this cyst-stage isozyme. Recombinant TgENO1 specifically binds to a TTTTCT DNA motif present in the cyst matrix antigen 1 (TgMAG1) gene promoter as demonstrated by gel retardation. Furthermore, direct physical interactions of both nuclear TgENO1 and TgENO2 with the TgMAG1 gene promoter are demonstrated in vivo using chromatin immunoprecipitation (ChIP) assays. Structural and biochemical studies reveal that T. gondii enolase functions are multifaceted, including the coordination of gene regulation in parasitic stage development. Enolase 1 provides a potential lead in the design of drugs against Toxoplasma brain cysts. PMID:25760592

  9. Mastocarcinoma therapy synergistically promoted by lysosome dependent apoptosis specifically evoked by 5-Fu@nanogel system with passive targeting and pH activatable dual function.

    PubMed

    Zhu, Xiandi; Sun, Yn; Chen, Di; Li, Jingfeng; Dong, Xia; Wang, Jie; Chen, Huaiwen; Wang, Ying; Zhang, Fulei; Dai, Jinaxin; Pirraco, Rogério P; Guo, Shangjing; Marques, Alexandra P; Reis, Rui L; Li, Wei

    2017-03-22

    This manuscript describes a synergistic therapy for mastocarcinoma by pH and temperature dual-sensitive nanogel, and effects of microstructure, composition and properties of nanogel on the cellular response mechanism. The extracellular internalization of nanogels was obviously enhanced, due to the passive targeting function at T>VPTT. Interestingly, the increased cytotoxicity was further synergistically enhanced by an unexpected apoptosis as evoked by the 5-fluorouracil loaded nanogel (FLNG). The systemically evaluation of the effectors generated from different sub-cellular organelles including endosome, lysosome, autophagosome confirmed that it was a lysomal dependent apoptosis. Such specific apoptosis was mainly attributed to its activatable protonated PEI at low pH, which caused lysosomal membrane destruction and lysosomal enzyme cathepsin B (Cat B) leakage. This Cat B was then translocated to the mitochondria resulting in mitochondrial membrane permeability increase and mitochondrial membrane potential (MMP) decrease, followed by cytochrome c (Cyt C) release. Cyt C was the main molecule that evoked apoptosis as reflected by overexpression of caspase 9. Additionally, such lysosome dependent, apoptosis was further enhanced by the passive cellular targeting at T>VPTT. Thus, the tumor growth inhibition was synergistically enhanced by the extracellular temperature dependent passive targeting and intracellular pH activatable lysosomal dependent apoptosis.

  10. From the dual function lead AP2238 to AP2469, a multi-target-directed ligand for the treatment of Alzheimer's disease

    PubMed Central

    Tarozzi, Andrea; Bartolini, Manuela; Piazzi, Lorna; Valgimigli, Luca; Amorati, Riccardo; Bolondi, Cecilia; Djemil, Alice; Mancini, Francesca; Andrisano, Vincenza; Rampa, Angela

    2014-01-01

    The development of drugs with different pharmacological properties appears to be an innovative therapeutic approach for Alzheimer's disease. In this article, we describe a simple structural modification of AP2238, a first dual function lead, in particular the introduction of the catechol moiety performed in order to search for multi-target ligands. The new compound AP2469 retains anti-acetylcholinesterase (AChE) and beta-site amyloid precursor protein cleaving enzyme (BACE)1 activities compared to the reference, and is also able to inhibit Aβ42 self-aggregation, Aβ42 oligomer-binding to cell membrane and subsequently reactive oxygen species formation in both neuronal and microglial cells. The ability of AP2469 to interfere with Aβ42 oligomer-binding to neuron and microglial cell membrane gives this molecule both neuroprotective and anti-inflammatory properties. These findings, together with its strong chain-breaking antioxidant performance, make AP2469 a potential drug able to modify the course of the disease. PMID:25505579

  11. New ruthenium sensitizers featuring bulky ancillary ligands combined with a dual functioned coadsorbent for high efficiency dye-sensitized solar cells.

    PubMed

    Shi, Yongbo; Liang, Mao; Wang, Lina; Han, Hongyu; You, Lingshan; Sun, Zhe; Xue, Song

    2013-01-01

    Two ruthenium complexes featuring bulky ancillary ligands, XS48 and XS49, were synthesized and studied as dyes in dye-sensitized solar cells (DSCs). Both dyes exhibit higher solar-to-electrical energy conversion efficiency when compared to a commonly used N3 sensitizer under the same conditions. To examine the influence of the bulky ancillary ligands and alleviate the electron recombination in cells, we have developed a dual functioned truxene-based coadsorbent (MXD1) as an alternative candidate to chenodeoxycholic acid (CDCA). This coadsorbent not only effectively shields the back electron transfer from the TiO(2) to I(3)(-) ions but also enhances the light harvesting ability in the short wavelength regions. The photovoltaic performance of XS48-sensitized DSC was independent of the coadsorbents, while XS49 with large bulky ancillary ligand presented better performance when coadsorbent was employed. Interestingly, the simultaneous adsorption-to-sequential adsorption of XS48/49 and MXD1 has caused a notably improved photovoltage, which can be primarily ascribed to the enhanced dye adsorption and retardation of charge recombination. These results not only provide a new vision on how ancillary ligands affect the performance of ruthenium complexes but also open up a new way to achieve further efficiency enhancement of ruthenium complexes.

  12. Electrochemical aptasensor for mucin 1 based on dual signal amplification of poly(o-phenylenediamine) carrier and functionalized carbon nanotubes tracing tag.

    PubMed

    Chen, Xiaojun; Zhang, Qi; Qian, Chunhua; Hao, Ning; Xu, Lin; Yao, Cheng

    2015-02-15

    Mucin 1 (MUC 1), as a most studied mucin, has become a useful marker for identifying breast cancer in the early stages. In this work, a novel method for the determination of MUC 1 in serum was developed based on a sandwich-type electrochemical aptasensor, which combined a dual signal amplification strategy of poly(o-phenylenediamine)-Au nanoparticles (PoPD-AuNPs) hybrid film as carrier and AuNPs functionalized silica/multiwalled carbon nanotubes core-shell nanocomposites (AuNPs/SiO2@MWCNTs) as tracing tag. The PoPD-AuNPs film provides a suitable microenvironment for stabilizing the primary aptamer (Apt) assembly, and the AuNPs/SiO2@MWCNTs enhances the surface area for immobilizing abundant secondary Apts as well as load large amounts of electrochemical probe thionine (Thi). In the presence of MUC 1, the sandwich-type recognition reacted on the aptasensor surface, and the Thi-AuNPs/SiO2@MWCNTs nanoprobes were captured onto the electrode surface to form biocomplex. AuNPs and MWCNTs could facilitate the electron transfer from Thi to the electrode, thus amplifying the detection response. Under the optimized experimental conditions, the proposed sensing strategy provided a wider linear dynamic range over three orders of magnitude with the detection limit down to 1 pM. Moreover, the aptasensor demonstrated good precision, acceptable stability and reproducibility.

  13. From the dual function lead AP2238 to AP2469, a multi-target-directed ligand for the treatment of Alzheimer's disease.

    PubMed

    Tarozzi, Andrea; Bartolini, Manuela; Piazzi, Lorna; Valgimigli, Luca; Amorati, Riccardo; Bolondi, Cecilia; Djemil, Alice; Mancini, Francesca; Andrisano, Vincenza; Rampa, Angela

    2014-04-01

    The development of drugs with different pharmacological properties appears to be an innovative therapeutic approach for Alzheimer's disease. In this article, we describe a simple structural modification of AP2238, a first dual function lead, in particular the introduction of the catechol moiety performed in order to search for multi-target ligands. The new compound AP2469 retains anti-acetylcholinesterase (AChE) and beta-site amyloid precursor protein cleaving enzyme (BACE)1 activities compared to the reference, and is also able to inhibit Aβ 42 self-aggregation, Aβ 42 oligomer-binding to cell membrane and subsequently reactive oxygen species formation in both neuronal and microglial cells. The ability of AP2469 to interfere with Aβ 42 oligomer-binding to neuron and microglial cell membrane gives this molecule both neuroprotective and anti-inflammatory properties. These findings, together with its strong chain-breaking antioxidant performance, make AP2469 a potential drug able to modify the course of the disease.

  14. Sensitive immunosensor for tumor necrosis factor α based on dual signal amplification of ferrocene modified self-assembled peptide nanowire and glucose oxidase functionalized gold nanorod.

    PubMed

    Sun, Zhifang; Deng, Liu; Gan, Hao; Shen, Rujuan; Yang, Minghui; Zhang, Yi

    2013-01-15

    Sensitive electrochemical immunosensor for the detection of protein biomarker tumor necrosis factor α (TNF-α) was reported that uses ferrocene carboxylic acid (Fc) functionalized self-assembled peptide nanowire (Fc-PNW) as sensor platform and glucose oxidase (GOx) modified gold nanorod (GNR) as label. Greatly enhanced sensitivity is achieved based on a dual signal amplification strategy: first, the synthesized Fc-PNW used as the sensor platform increased the loading of primary anti-TNF-α antibody (Ab(1)) onto electrode surface due to its large surface area. At the same time, the Fc moiety on the nanowire is used as a mediator for GOx to catalyze the glucose reaction. Second, multiple GOx and secondary anti-TNF-α antibody (Ab(2)) molecules are bounded onto each GNR to increase the sensitivity of the immunosensor. After the preparation of the immunosensor based on the traditional sandwich protocol, the response of the immunosensor towards glucose was used as a signal to differentiate various concentrations of TNF-α. The resulting immunosensor has high sensitivity, wide linear range (0.005-10ng/mL) and good selectivity. This immunosensor preparation strategy is a promising platform for clinical screening of protein biomarkers.

  15. A functional near-infrared spectroscopy study of lexical decision task supports the dual route model and the phonological deficit theory of dyslexia.

    PubMed

    Sela, Itamar; Izzetoglu, Meltem; Izzetoglu, Kurtulus; Onaral, Banu

    2014-01-01

    The dual route model (DRM) of reading suggests two routes of reading development: the phonological and the orthographic routes. It was proposed that although the two routes are active in the process of reading; the first is more involved at the initial stages of reading acquisition, whereas the latter needs more reading training to mature. A number of studies have shown that deficient phonological processing is a core deficit in developmental dyslexia. According to the DRM, when the Lexical Decision Task (LDT) is performed, the orthographic route should also be involved when decoding words, whereas it is clear that when decoding pseudowords the phonological route should be activated. Previous functional near-infrared spectroscopy (fNIR) studies have suggested that the upper left frontal lobe is involved in decision making in the LDT. The current study used fNIR to compare left frontal lobe activity during LDT performance among three reading-level groups: 12-year-old children, young adult dyslexic readers, and young adult typical readers. Compared to typical readers, the children demonstrated lower activity under the word condition only, whereas the dyslexic readers showed lower activity under the pseudoword condition only. The results provide evidence for upper left frontal lobe involvement in LDT and support the DRM and the phonological deficit theory of dyslexia.

  16. Optimization of air-borne butyl acetate adsorption on dual-function Ag-Y adsorbent-catalyst using response surface methodology.

    PubMed

    Bhatia, Subhash; Wong, Cheng Teng; Abdullah, Ahmad Zuhairi

    2009-05-30

    The low concentration and high flow rate of air-borne butyl acetate (BA) could be effectively removed using combined adsorption-catalytic oxidation system. Ag-Y (Si/Al=80) dual-function adsorbent was investigated for the adsorption step of 1000 ppm of butyl acetate at gas hourly space velocity of 13,000 h(-1) at ambient temperature under dry and humid feeds. A central composite design (CCD) coupled with response surface methodology (RSM) was employed to obtain the optimum process conditions and the interactions between process variables were demonstrated and elucidated. Humidity and increasing organic concentration shortened the adsorption service time. The effect of moisture was more pronounced at low BA concentration. The interactions between the BA concentration and humidity were statistically significant at 95% confidence level. The optimum conditions were found to be at 4500 ppm of BA with 37 min saturation time to give 58 mg BA/g as adsorption capacity. The simulated data fitted the experimental data satisfactorily. The simulated data also correctly demonstrated the overall behaviors of the adsorption process.

  17. Simple fabrication of carbon/TiO2 composite nanotubes showing dual functions with adsorption and photocatalytic decomposition of Rhodamine B.

    PubMed

    Im, Ji Hyuk; Yang, Seung Jae; Yun, Chang Hun; Park, Chong Rae

    2012-01-27

    Carbon/TiO2 composite nanotubes were fabricated via a very simple electrospinning process and their dual functionalities of adsorptivity and photocatalytic activity were evaluated using Rhodamine B (RhB) as a model organic pollutant. A poly(vinyl alcohol) (PVA) aqueous solution was directly electrospun into a coagulation bath containing titanium (IV) tetraisopropoxide (TTIP) solution so that PVA-core/TiO2-shell composite nanofibers were formed through the in situ sol-gel reaction of TTIP. The carbon/TiO2 composite nanotubes were then fabricated by heat treatment of composite nanofibers under nitrogen atmosphere. By using several characterization methods, we confirmed that the resultant nanotubes consisted of anatase TiO2 nanocrystallites embedded in a carbonaceous matrix. The prepared nanotubes exhibited fast adsorption of RhB with high capacity compared with a commercial porous carbon, and they also showed the photocatalytic decomposition activity for the dye molecules under UV irradiation comparable to the degradation by P-25 and ST-01 (commercial TiO2). Finally, the carbon/TiO2 composite nanotubes exhibited several cycle performances of adsorption-photodegradation for RhB. This indicates that the composite nanotubes can adsorb and photodecompose organic pollutants repeatedly without additional activating processes.

  18. Simple fabrication of carbon/TiO2 composite nanotubes showing dual functions with adsorption and photocatalytic decomposition of Rhodamine B

    NASA Astrophysics Data System (ADS)

    Im, Ji Hyuk; Yang, Seung Jae; Yun, Chang Hun; Park, Chong Rae

    2012-01-01

    Carbon/TiO2 composite nanotubes were fabricated via a very simple electrospinning process and their dual functionalities of adsorptivity and photocatalytic activity were evaluated using Rhodamine B (RhB) as a model organic pollutant. A poly(vinyl alcohol) (PVA) aqueous solution was directly electrospun into a coagulation bath containing titanium (IV) tetraisopropoxide (TTIP) solution so that PVA-core/TiO2-shell composite nanofibers were formed through the in situ sol-gel reaction of TTIP. The carbon/TiO2 composite nanotubes were then fabricated by heat treatment of composite nanofibers under nitrogen atmosphere. By using several characterization methods, we confirmed that the resultant nanotubes consisted of anatase TiO2 nanocrystallites embedded in a carbonaceous matrix. The prepared nanotubes exhibited fast adsorption of RhB with high capacity compared with a commercial porous carbon, and they also showed the photocatalytic decomposition activity for the dye molecules under UV irradiation comparable to the degradation by P-25 and ST-01 (commercial TiO2). Finally, the carbon/TiO2 composite nanotubes exhibited several cycle performances of adsorption-photodegradation for RhB. This indicates that the composite nanotubes can adsorb and photodecompose organic pollutants repeatedly without additional activating processes.

  19. Optimization and extraction of functional information from in vitro flow models using dual-beam spectral-domain optical coherence tomography cross-correlation analysis.

    PubMed

    Daly, Susan M; Silien, Christophe; Leahy, Martin J

    2013-10-01

    As in vivo flow behavior can be pulsatile, intermittent, and/or otherwise changeable with time, the ability to provide clinicians with a means of real-time visualization and functional assessment of structures is of particular importance. The discernment of pulsatile flow behavior using a dual-beam spectral domain optical coherence tomography system (db-SdOCT) by quasi-simultaneous measurement by two planes of illumination is demonstrated. By cross-correlation analysis, it is possible to compute velocity metrics pertaining to flowing particle motion, without a priori angular knowledge. This is the first application of cross-correlation-based dynamic assessment for the extraction of pulsatile behavior in an in vitro environment using an optimized db-SdOCT system. The experimental results outlined have shown the db-SdOCT system and its associated algorithms to be successful in the discernment of intermittent pulsatile flow behavior in in vitro models, concurrent to yielding velocity values in good agreement with that of the applied flow rate.

  20. Preparation of dual-function starch-based flocculants for the simultaneous removal of turbidity and inhibition of Escherichia coli in water.

    PubMed

    Huang, Mu; Wang, Yawen; Cai, Jun; Bai, Junfeng; Yang, Hu; Li, Aimin

    2016-07-01

    A dual-function starch-based flocculant, carboxymethyl-starch-graft-aminomethylated-polyacrylamide (CMS-g-APAM), was designed and prepared by a simple method. The structure and solution properties of CMS-g-APAM were characterized by fourier transform infrared spectroscopy, (1)H nuclear magnetic resonance, and zeta-potential measurements. CMS-g-APAM was then applied to flocculate a kaolin suspension and an Escherichia coli suspension as well as a combination thereof. At suitable pH conditions, the starch-based flocculant not only effectively removed turbidity but it also disrupted bacterial cells. Interpretation of the zeta potential and floc properties (floc size and two-dimensional fractal structure) showed that, for the aforementioned three effluents, simple charge neutralization was the dominant mechanism of flocculation in acidic medium whereas an additional contribution from a patching effect was determined under neutral conditions. Three-dimensional excitation-emission matrix spectra and direct surface morphology observation under a scanning electron microscope both illuminated that the antibacterial activity of CMS-g-APAM involved the partial destruction of the cell wall of Escherichia coli. The mechanism can be attributed to the effective interaction between the tertiary amine group of the flocculant and the negatively charged surface of the bacterium.

  1. Upconversion-luminescent/magnetic dual-functional sub-20 nm core-shell SrF2:Yb,Tm@CaF2:Gd heteronanoparticles.

    PubMed

    Li, Ai-Hua; Lü, Mengyun; Yang, Jun; Chen, Lin; Cui, Xiaohong; Sun, Zhijun

    2016-04-07

    Sub-20 nm core-shell and water-soluble SrF2:Yb,Tm@CaF2:Gd heteronanoparticles with both upconversion luminescence (UCL) and magnetic resonance imaging (MRI) capabilities were designed and synthesized via a two-step hydrothermal method. In the design of the heteronanoparticles, SrF2:Yb,Tm nanoparticles with high UCL efficiency are chosen as the core material for strong UCL output; and by epitaxially coating the SrF2:Yb,Tm core particles with inert and biocompatible shells of CaF2:Gd, the core-shell heteronanoparticles are endowed with a magnetic capability (longitudinal relaxivity of 2.4 mM(-1) s(-1)) for MRI, as well as an enhancement of the near infrared (NIR) UCL by 9.2 times. The aqueous dispersion of SrF2:Yb,Tm@CaF2:Gd heteronanoparticles with a concentration of 2.6 wt% can emit NIR UCL so as to be easily detected with a fiber optical spectrometer under illumination of a 975 nm laser diode with a power density of 8.8 W cm(-2). Such a dispersion with a Gd(3+) concentration of 0.0143 mM in the shell region of the heteronanoparticles can also generate the detectable quickening of longitudinal relaxation. The results promise the strong potential of this nanomaterial for applications in bioimaging as a dual-functional probe.

  2. Copper-Nitride Nanowires Array: An Efficient Dual-Functional Catalyst Electrode for Sensitive and Selective Non-Enzymatic Glucose and Hydrogen Peroxide Sensing.

    PubMed

    Wang, Zao; Cao, Xiaoqin; Liu, Danni; Hao, Shuai; Kong, Rongmei; Du, Gu; Asiri, Abdullah M; Sun, Xuping

    2017-04-11

    It is highly attractive to develop non-noble-metal nanoarray architecture as a 3D-catalyst electrode for molecular detection due to its large specific surface area and easy accessibility to target molecules. Here, we report the development of a copper-nitride nanowires array on copper foam (Cu3 N NA/CF) as a dual-functional catalyst electrode for efficient glucose oxidation in alkaline solutions and hydrogen peroxide (H2 O2 ) reduction in neutral solutions. Electrochemical tests indicate that such Cu3 N NA/CF possesses superior non-enzymatic sensing ability toward rapid glucose and H2 O2 detection with high selectivity. At 0.40 V, this sensor offers a high sensitivity of 14 180 μA mm cm(-2) for glucose detection, with a wide linear range from 1 μm to 2 mm, a low detection limit of 13 nm (S/N=3), and satisfactory stability and reproducibility. Its application in determining glucose in human blood serum is also demonstrated. Amperometric H2 O2 sensing can also been realized with a sensitivity of 7600 μA mm cm(-2) , a linear range from 0.1 μm to 10 mm, and a detection limit of 8.9 nm (S/N=3). This 3D-nanoarray architecture holds great promise as an attractive sensing platform toward electrochemical small molecules detection.

  3. An integrative technique based on synergistic coremoval and sequential recovery of copper and tetracycline with dual-functional chelating resin: roles of amine and carboxyl groups.

    PubMed

    Ling, Chen; Liu, Fu-Qiang; Xu, Chao; Chen, Tai-Peng; Li, Ai-Min

    2013-11-27

    A novel chelating resin (R-AC) bearing dual-functional groups (amino and carboxyl groups) was self-synthesized and it showed superior properties on synergistic coremoval of Cu(II) and tetracycline (TC) to commercial resins (amine, carboxyl, and hydrophobic types), which was deeply investigated by equilibrium and kinetic tests in binary, preloading, and saline systems. The adsorption of TC on R-AC was markedly enhanced when coexisted with Cu(II), up to 13 times of that in sole system, whereas Cu(II) uptake seldom decreased in the copresence of TC. Decomplexing-bridging, which included [Cu-TC] decomplexing and [R-Cu] bridging for TC, was demonstrated as the leading mechanism for the synergistic coremoval of Cu(II) and TC. Carboxyl groups of R-AC played a dominant role in decomplexing of [Cu-TC] complex and releasing free TC. Cu(II) coordinated with amine groups of R-AC was further proved to participate in bridging interaction with free TC, and the bridging stoichiometric ratio ([NH-Cu]: TC) possibly was 2:1. About 96.9% of TC and 99.3% of Cu could be sequentially recovered with dilute NaOH followed by HCl. Considering stable application for five cycles in simulated and practical wastewater, R-AC shows great potential in green and simple coremoval of antibiotic and heavy metal ions.

  4. Dual functions for the endoplasmic reticulum calcium sensors STIM1 and STIM2 in T cell activation and tolerance

    PubMed Central

    Oh-hora, Masatsugu; Yamashita, Megumi; Hogan, Patrick G; Sharma, Sonia; Lamperti, Ed; Chung, Woo; Prakriya, Murali; Feske, Stefan; Rao, Anjana

    2009-01-01

    Store-operated Ca2+ entry through calcium release–activated calcium channels is the chief mechanism for increasing intracellular Ca2+ in immune cells. Here we show that mouse T cells and fibroblasts lacking the calcium sensor STIM1 had severely impaired store-operated Ca2+ influx, whereas deficiency in the calcium sensor STIM2 had a smaller effect. However, T cells lacking either STIM1 or STIM2 had much less cytokine production and nuclear translocation of the transcription factor NFAT. T cell–specific ablation of both STIM1 and STIM2 resulted in a notable lymphoproliferative phenotype and a selective decrease in regulatory T cell numbers. We conclude that both STIM1 and STIM2 promote store-operated Ca2+ entry into T cells and fibroblasts and that STIM proteins are required for the development and function of regulatory T cells. PMID:18327260

  5. Dual responsive dysprosium-doped hydroxyapatite particles and toxicity reduction after functionalization with folic and glucuronic acids.

    PubMed

    Sánchez Lafarga, Ana Karen; Pacheco Moisés, Fermín P; Gurinov, Andrey; Ortiz, Genaro Gabriel; Carbajal Arízaga, Gregorio Guadalupe

    2015-03-01

    The development of probes for biomedical applications demands materials with low toxicity levels besides fluorescence or magnetic properties to be detected by confocal microscopes or MRI resonators. Several drug delivery systems or other biomedical materials prepared with hydroxyapatite have been proposed, however, toxicity effects might arise when the size of particles is nanometric. In this study, hydroxyapatite functionalized with glucuronic or folic acids presented lower oxidative stress, measured from lipoperoxides and nitric oxide indicators in rats than pure hydroxyapatite. In separated experiments, hydroxyapatite was doped with dysprosium cations by coprecipitation producing a single crystal phase with fluorescent properties easily visualized by confocal microscopy when excited at 488nm. These particles also presented the ability to modify the proton relaxation time in T1 maps collected by magnetic resonance imaging. These modified hydroxyapatite nanoparticles could be candidates to design bimodal probes with low toxicity.

  6. Microporous metal-organic framework with dual functionalities for highly efficient removal of acetylene from ethylene/acetylene mixtures

    NASA Astrophysics Data System (ADS)

    Hu, Tong-Liang; Wang, Hailong; Li, Bin; Krishna, Rajamani; Wu, Hui; Zhou, Wei; Zhao, Yunfeng; Han, Yu; Wang, Xue; Zhu, Weidong; Yao, Zizhu; Xiang, Shengchang; Chen, Banglin

    2015-06-01

    The removal of acetylene from ethylene/acetylene mixtures containing 1% acetylene is a technologically very important, but highly challenging task. Current removal approaches include the partial hydrogenation over a noble metal catalyst and the solvent extraction of cracked olefins, both of which are cost and energy consumptive. Here we report a microporous metal-organic framework in which the suitable pore/cage spaces preferentially take up much more acetylene than ethylene while the functional amine groups on the pore/cage surfaces further enforce their interactions with acetylene molecules, leading to its superior performance for this separation. The single X-ray diffraction studies, temperature dependent gas sorption isotherms, simulated and experimental column breakthrough curves and molecular simulation studies collaboratively support the claim, underlying the potential of this material for the industrial usage of the removal of acetylene from ethylene/acetylene mixtures containing 1% acetylene at room temperature through the cost- and energy-efficient adsorption separation process.

  7. Microporous metal–organic framework with dual functionalities for highly efficient removal of acetylene from ethylene/acetylene mixtures

    PubMed Central

    Hu, Tong-Liang; Wang, Hailong; Li, Bin; Krishna, Rajamani; Wu, Hui; Zhou, Wei; Zhao, Yunfeng; Han, Yu; Wang, Xue; Zhu, Weidong; Yao, Zizhu; Xiang, Shengchang; Chen, Banglin

    2015-01-01

    The removal of acetylene from ethylene/acetylene mixtures containing 1% acetylene is a technologically very important, but highly challenging task. Current removal approaches include the partial hydrogenation over a noble metal catalyst and the solvent extraction of cracked olefins, both of which are cost and energy consumptive. Here we report a microporous metal–organic framework in which the suitable pore/cage spaces preferentially take up much more acetylene than ethylene while the functional amine groups on the pore/cage surfaces further enforce their interactions with acetylene molecules, leading to its superior performance for this separation. The single X-ray diffraction studies, temperature dependent gas sorption isotherms, simulated and experimental column breakthrough curves and molecular simulation studies collaboratively support the claim, underlying the potential of this material for the industrial usage of the removal of acetylene from ethylene/acetylene mixtures containing 1% acetylene at room temperature through the cost- and energy-efficient adsorption separation process. PMID:26041691

  8. A chimeric protein that functions as both an anthrax dual-target antitoxin and a trivalent vaccine.

    PubMed

    Wu, Gaobing; Hong, Yuzhi; Guo, Aizhen; Feng, Chunfang; Cao, Sha; Zhang, Cheng-Cai; Shi, Ruiping; Tan, Yadi; Liu, Ziduo

    2010-11-01

    Effective measures for the prophylaxis and treatment of anthrax are still required for counteracting the threat posed by inhalation anthrax. In this study, we first demonstrated that the chimeric protein LFn-PA, created by fusing the protective antigen (PA)-binding domain of lethal factor (LFn) to PA, retained the functions of the respective molecules. On the basis of this observation, we attempted to develop an antitoxin that targets the binding of lethal factor (LF) and/or edema factor (EF) to PA and the transportation of LF/EF. Therefore, we replaced PA in LFn-PA with a dominant-negative inhibitory PA (DPA), i.e., PA(F427D). In in vitro models of anthrax intoxication, the LFn-DPA chimera showed 3-fold and 2-fold higher potencies than DPA in protecting sensitive cells against anthrax lethal toxin (LeTx) and edema toxin (EdTx), respectively. In animal models, LFn-DPA exhibited strong potency in rescuing mice from lethal challenge with LeTx. We also evaluated the immunogenicity and immunoprotective efficacy of LFn-DPA as an anthrax vaccine candidate. In comparison with recombinant PA, LFn-DPA induced significantly higher levels of the anti-PA immune response. Moreover, LFn-DPA elicited an anti-LF antibody response that could cross-react with EF. Mice immunized with LFn-DPA tolerated a LeTx challenge that was 5 times its 50% lethal dose. Thus, LFn-DPA represents a highly effective trivalent vaccine candidate for both preexposure and postexposure vaccination. Overall, we have developed a novel and dually functional reagent for the prophylaxis and treatment of anthrax.

  9. Kinesins Have a Dual Function in Organizing Microtubules during Both Tip Growth and Cytokinesis in Physcomitrella patens[W][OPEN

    PubMed Central

    Hiwatashi, Yuji; Sato, Yoshikatsu; Doonan, John H.

    2014-01-01

    Microtubules (MTs) play a crucial role in the anisotropic deposition of cell wall material, thereby affecting the direction of growth. A wide range of tip-growing cells display highly polarized cell growth, and MTs have been implicated in regulating directionality and expansion. However, the molecular machinery underlying MT dynamics in tip-growing plant cells remains unclear. Here, we show that highly dynamic MT bundles form cyclically in the polarized expansion zone of the moss Physcomitrella patens caulonemal cells through the coalescence of growing MT plus ends. Furthermore, the plant-specific kinesins (KINID1) that are is essential for the proper MT organization at cytokinesis also regulate the turnover of the tip MT bundles as well as the directionality and rate of cell growth. The plus ends of MTs grow toward the expansion zone, and KINID1 is necessary for the stability of a single coherent focus of MTs in the center of the zone, whose formation coincides with the accumulation of KINID1. We propose that KINID-dependent MT bundling is essential for the correct directionality of growth as well as for promoting growth per se. Our findings indicate that two localized cell wall deposition processes, tip growth and cytokinesis, previously believed to be functionally and evolutionarily distinct, share common and plant-specific MT regulatory components. PMID:24642939

  10. An essential dual-function complex mediates erythrocyte invasion and channel-mediated nutrient uptake in malaria parasites

    PubMed Central

    Ito, Daisuke; Schureck, Marc A; Desai, Sanjay A

    2017-01-01

    Malaria parasites evade immune detection by growth and replication within erythrocytes. After erythrocyte invasion, the intracellular pathogen must increase host cell uptake of nutrients from plasma. Here, we report that the parasite-encoded RhopH complex contributes to both invasion and channel-mediated nutrient uptake. As rhoph2 and rhoph3 gene knockouts were not viable in the human P. falciparum pathogen, we used conditional knockdowns to determine that the encoded proteins are essential and to identify their stage-specific functions. We exclude presumed roles for RhopH2 and CLAG3 in erythrocyte invasion but implicate a RhopH3 contribution either through ligand-receptor interactions or subsequent parasite internalization. These proteins then traffic via an export translocon to the host membrane, where they form a nutrient channel. Knockdown of either RhopH2 or RhopH3 disrupts the entire complex, interfering with organellar targeting and subsequent trafficking. Therapies targeting this complex should attack the pathogen at two critical points in its cycle. DOI: http://dx.doi.org/10.7554/eLife.23485.001 PMID:28221136

  11. Tissue dual RNA-seq allows fast discovery of infection-specific functions and riboregulators shaping host-pathogen transcriptomes.

    PubMed

    Nuss, Aaron M; Beckstette, Michael; Pimenova, Maria; Schmühl, Carina; Opitz, Wiebke; Pisano, Fabio; Heroven, Ann Kathrin; Dersch, Petra

    2017-01-31

    Pathogenic bacteria need to rapidly adjust their virulence and fitness program to prevent eradication by the host. So far, underlying adaptation processes that drive pathogenesis have mostly been studied in vitro, neglecting the true complexity of host-induced stimuli acting on the invading pathogen. In this study, we developed an unbiased experimental approach that allows simultaneous monitoring of genome-wide infection-linked transcriptional alterations of the host and colonizing extracellular pathogens. Using this tool for Yersinia pseudotuberculosis-infected lymphatic tissues, we revealed numerous alterations of host transcripts associated with inflammatory and acute-phase responses, coagulative activities, and transition metal ion sequestration, highlighting that the immune response is dominated by infiltrating neutrophils and elicits a mixed TH17/TH1 response. In consequence, the pathogen's response is mainly directed to prevent phagocytic attacks. Yersinia up-regulates the gene and expression dose of the antiphagocytic type III secretion system (T3SS) and induces functions counteracting neutrophil-induced ion deprivation, radical stress, and nutritional restraints. Several conserved bacterial riboregulators were identified that impacted this response. The strongest influence on virulence was found for the loss of the carbon storage regulator (Csr) system, which is shown to be essential for the up-regulation of the T3SS on host cell contact. In summary, our established approach provides a powerful tool for the discovery of infection-specific stimuli, induced host and pathogen responses, and underlying regulatory processes.

  12. Dual functions of Mss51 couple synthesis of Cox1 to assembly of cytochrome c oxidase in Saccharomyces cerevisiae mitochondria.

    PubMed

    Perez-Martinez, Xochitl; Butler, Christine A; Shingu-Vazquez, Miguel; Fox, Thomas D

    2009-10-01

    Functional interactions of the translational activator Mss51 with both the mitochondrially encoded COX1 mRNA 5'-untranslated region and with newly synthesized unassembled Cox1 protein suggest that it has a key role in coupling Cox1 synthesis with assembly of cytochrome c oxidase. Mss51 is present at levels that are near rate limiting for expression of a reporter gene inserted at COX1 in mitochondrial DNA, and a substantial fraction of Mss51 is associated with Cox1 protein in assembly intermediates. Thus, sequestration of Mss51 in assembly intermediates could limit Cox1 synthesis in wild type, and account for the reduced Cox1 synthesis caused by most yeast mutations that block assembly. Mss51 does not stably interact with newly synthesized Cox1 in a mutant lacking Cox14, suggesting that the failure of nuclear cox14 mutants to decrease Cox1 synthesis, despite their inability to assemble cytochrome c oxidase, is due to a failure to sequester Mss51. The physical interaction between Mss51 and Cox14 is dependent upon Cox1 synthesis, indicating dynamic assembly of early cytochrome c oxidase intermediates nucleated by Cox1. Regulation of COX1 mRNA translation by Mss51 seems to be an example of a homeostatic mechanism in which a positive effector of gene expression interacts with the product it regulates in a posttranslational assembly process.

  13. Kinesins have a dual function in organizing microtubules during both tip growth and cytokinesis in Physcomitrella patens.

    PubMed

    Hiwatashi, Yuji; Sato, Yoshikatsu; Doonan, John H

    2014-03-01

    Microtubules (MTs) play a crucial role in the anisotropic deposition of cell wall material, thereby affecting the direction of growth. A wide range of tip-growing cells display highly polarized cell growth, and MTs have been implicated in regulating directionality and expansion. However, the molecular machinery underlying MT dynamics in tip-growing plant cells remains unclear. Here, we show that highly dynamic MT bundles form cyclically in the polarized expansion zone of the moss Physcomitrella patens caulonemal cells through the coalescence of growing MT plus ends. Furthermore, the plant-specific kinesins (KINID1) that are is essential for the proper MT organization at cytokinesis also regulate the turnover of the tip MT bundles as well as the directionality and rate of cell growth. The plus ends of MTs grow toward the expansion zone, and KINID1 is necessary for the stability of a single coherent focus of MTs in the center of the zone, whose formation coincides with the accumulation of KINID1. We propose that KINID-dependent MT bundling is essential for the correct directionality of growth as well as for promoting growth per se. Our findings indicate that two localized cell wall deposition processes, tip growth and cytokinesis, previously believed to be functionally and evolutionarily distinct, share common and plant-specific MT regulatory components.

  14. Dual-functional transdermal drug delivery system with controllable drug loading based on thermosensitive poloxamer hydrogel for atopic dermatitis treatment

    NASA Astrophysics Data System (ADS)

    Wang, Wenyi; Wat, Elaine; Hui, Patrick C. L.; Chan, Ben; Ng, Frency S. F.; Kan, Chi-Wai; Wang, Xiaowen; Hu, Huawen; Wong, Eric C. W.; Lau, Clara B. S.; Leung, Ping-Chung

    2016-04-01

    The treatment of atopic dermatitis (AD) has long been viewed as a problematic issue by the medical profession. Although a wide variety of complementary therapies have been introduced, they fail to combine the skin moisturizing and drug supply for AD patients. This study reports the development of a thermo-sensitive Poloxamer 407/Carboxymethyl cellulose sodium (P407/CMCs) composite hydrogel formulation with twin functions of moisture and drug supply for AD treatment. It was found that the presence of CMCs can appreciably improve the physical properties of P407 hydrogel, which makes it more suitable for tailored drug loading. The fabricated P407/CMCs composite hydrogel was also characterized in terms of surface morphology by field emission scanning electron microscopy (FE-SEM), rheological properties by a rheometer, release profile in vitro by dialysis method and cytotoxicity test. More importantly, the findings from transdermal drug delivery behavior revealed that P407/CMCs showed desirable percutaneous performance. Additionally, analysis of cytotoxicity test suggested that P407/CMCs composite hydrogel is a high-security therapy for clinical trials and thus exhibits a promising way to treat AD with skin moisturizing and medication.

  15. Dual functionality of triticale as a novel dietary source of prebiotics with antioxidant activity in fermented dairy products.

    PubMed

    Agil, Rania; Hosseinian, Farah

    2012-03-01

    The objectives of this study were to: (i) define the optimum concentration of triticale bran (TB) that can be incorporated in yogurt, (ii) evaluate the prebiotic effects of TB on microbial viability, pH and total titratable acidity (TTA) in yogurt across 28 days of cold storage, and (iii) measure the oxygen radical absorbance capacity (ORAC) of water-extractable polysaccharides (WEP) in TB. Lactobacillus bulgaricus and Streptococcus thermophilus were used as starter cultures. Lactobacillus acidophilus and Bifidobacterium lactis were used as probiotics. A concentration of 4% TB in yogurt was determined to be the maximum amount that could be added without causing synersis. By day 7, the number of bacteria greatly increased in yogurt samples containing TB and maintained higher viable bacteria counts at the end of the cold storage period, in comparison to controls (P ≤ 0.05). Confirming this data was the lower pH levels and higher TTA values of TB yogurt samples exhibited throughout 28 days (P ≤ 0.05). Polysaccharide extracts of TB exhibited strong antioxidant activity with an ORAC value of 33.86 ± 2.30 μmol trolox equivalents (TE)/g of bran. Results of this study suggest that TB may serve as a new prebiotic and antioxidant source for functional foods and nutraceutical applications.

  16. Dual functions of Rap1 are crucial for T-cell homeostasis and prevention of spontaneous colitis

    PubMed Central

    Ishihara, Sayaka; Nishikimi, Akihiko; Umemoto, Eiji; Miyasaka, Masayuki; Saegusa, Makoto; Katagiri, Koko

    2015-01-01

    Rap1-GTP activates leukocyte function-associated antigen-1 (LFA-1) to induce arrest on the high endothelial venule (HEV). Here we show that Rap1-GDP restrains rolling behaviours of T cells on the peripheral lymph node addressin (PNAd), P-selectin and mucosal addressin cell adhesion molecule-1 (MadCAM-1) by inhibiting tether formation. Consequently, Rap1 deficiency impairs homing of naive T cells to peripheral lymph nodes, but accelerates homing of TH17 and TH1 cells to the colon, resulting in spontaneous colitis with tumours. Rap1-GDP associates with and activates lymphocyte-oriented kinase, which phosphorylates ERM (ezrin, radixin and moesin) in resting T cells. Phosphomimetic ezrin reduces the rolling of Rap1-deficient cells, and thereby decreases their homing into the colon. On the other hand, chemokines activate Rap1 at the plasma membrane within seconds, and Rap1-GTP binds to filamins, which diminishes its association with the β2 chain of LFA-1 and results in LFA-1 activation. This Rap1-dependent regulation of T-cell circulation prevents the onset of colitis. PMID:26634692

  17. Dual-functional transdermal drug delivery system with controllable drug loading based on thermosensitive poloxamer hydrogel for atopic dermatitis treatment

    PubMed Central

    Wang, Wenyi; Wat, Elaine; Hui, Patrick C. L.; Chan, Ben; Ng, Frency S. F.; Kan, Chi-Wai; Wang, Xiaowen; Hu, Huawen; Wong, Eric C. W.; Lau, Clara B. S.; Leung, Ping-Chung

    2016-01-01

    The treatment of atopic dermatitis (AD) has long been viewed as a problematic issue by the medical profession. Although a wide variety of complementary therapies have been introduced, they fail to combine the skin moisturizing and drug supply for AD patients. This study reports the development of a thermo-sensitive Poloxamer 407/Carboxymethyl cellulose sodium (P407/CMCs) composite hydrogel formulation with twin functions of moisture and drug supply for AD treatment. It was found that the presence of CMCs can appreciably improve the physical properties of P407 hydrogel, which makes it more suitable for tailored drug loading. The fabricated P407/CMCs composite hydrogel was also characterized in terms of surface morphology by field emission scanning electron microscopy (FE-SEM), rheological properties by a rheometer, release profile in vitro by dialysis method and cytotoxicity test. More importantly, the findings from transdermal drug delivery behavior revealed that P407/CMCs showed desirable percutaneous performance. Additionally, analysis of cytotoxicity test suggested that P407/CMCs composite hydrogel is a high-security therapy for clinical trials and thus exhibits a promising way to treat AD with skin moisturizing and medication. PMID:27090158

  18. Dual functions of YF3:Eu3+ for improving photovoltaic performance of dye-sensitized solar cells

    PubMed Central

    Wu, Jihuai; Wang, Jiangli; Lin, Jianming; Xiao, Yaoming; Yue, Gentian; Huang, Miaoliang; Lan, Zhang; Huang, Yunfang; Fan, Leqing; Yin, Shu; Sato, Tsugio

    2013-01-01

    In order to enhance the photovoltaic performance of dye-sensitized solar cell (DSSC), a novel design is demonstrated by introducing rare-earth compound europium ion doped yttrium fluoride (YF3:Eu3+) in TiO2 film in the DSSC. As a conversion luminescence medium, YF3:Eu3+ transfers ultraviolet light to visible light via down-conversion, and increases incident harvest and photocurrent of DSSC. As a p-type dopant, Eu3+ elevates the Fermi level of TiO2 film and thus heightens photovoltage of the DSSC. The conversion luminescence and p-type doping effect are demonstrated by photoluminescence spectra and Mott-Schottky plots. When the ratio of YF3:Eu3+/TiO2 in the doping layer is optimized as 5 wt.%, the light-to-electric energy conversion efficiency of the DSSC reaches 7.74%, which is increased by 32% compared to that of the DSSC without YF3:Eu3+ doping. Double functions of doped rare-earth compound provide a new route for enhancing the photovoltaic performance of solar cells. PMID:23792787

  19. Dual functions of YF3:Eu3+ for improving photovoltaic performance of dye-sensitized solar cells

    NASA Astrophysics Data System (ADS)

    Wu, Jihuai; Wang, Jiangli; Lin, Jianming; Xiao, Yaoming; Yue, Gentian; Huang, Miaoliang; Lan, Zhang; Huang, Yunfang; Fan, Leqing; Yin, Shu; Sato, Tsugio

    2013-06-01

    In order to enhance the photovoltaic performance of dye-sensitized solar cell (DSSC), a novel design is demonstrated by introducing rare-earth compound europium ion doped yttrium fluoride (YF3:Eu3+) in TiO2 film in the DSSC. As a conversion luminescence medium, YF3:Eu3+ transfers ultraviolet light to visible light via down-conversion, and increases incident harvest and photocurrent of DSSC. As a p-type dopant, Eu3+ elevates the Fermi level of TiO2 film and thus heightens photovoltage of the DSSC. The conversion luminescence and p-type doping effect are demonstrated by photoluminescence spectra and Mott-Schottky plots. When the ratio of YF3:Eu3+/TiO2 in the doping layer is optimized as 5 wt.%, the light-to-electric energy conversion efficiency of the DSSC reaches 7.74%, which is increased by 32% compared to that of the DSSC without YF3:Eu3+ doping. Double functions of doped rare-earth compound provide a new route for enhancing the photovoltaic performance of solar cells.

  20. Dual functions of YF₃:Eu³⁺ for improving photovoltaic performance of dye-sensitized solar cells.

    PubMed

    Wu, Jihuai; Wang, Jiangli; Lin, Jianming; Xiao, Yaoming; Yue, Gentian; Huang, Miaoliang; Lan, Zhang; Huang, Yunfang; Fan, Leqing; Yin, Shu; Sato, Tsugio

    2013-01-01

    In order to enhance the photovoltaic performance of dye-sensitized solar cell (DSSC), a novel design is demonstrated by introducing rare-earth compound europium ion doped yttrium fluoride (YF₃:Eu³⁺) in TiO₂ film in the DSSC. As a conversion luminescence medium, YF₃:Eu³⁺ transfers ultraviolet light to visible light via down-conversion, and increases incident harvest and photocurrent of DSSC. As a p-type dopant, Eu³⁺ elevates the Fermi level of TiO₂ film and thus heightens photovoltage of the DSSC. The conversion luminescence and p-type doping effect are demonstrated by photoluminescence spectra and Mott-Schottky plots. When the ratio of YF₃:Eu³⁺/TiO₂ in the doping layer is optimized as 5 wt.%, the light-to-electric energy conversion efficiency of the DSSC reaches 7.74%, which is increased by 32% compared to that of the DSSC without YF₃:Eu³⁺ doping. Double functions of doped rare-earth compound provide a new route for enhancing the photovoltaic performance of solar cells.

  1. Edg8/S1P5: an oligodendroglial receptor with dual function on process retraction and cell survival.

    PubMed

    Jaillard, C; Harrison, S; Stankoff, B; Aigrot, M S; Calver, A R; Duddy, G; Walsh, F S; Pangalos, M N; Arimura, N; Kaibuchi, K; Zalc, B; Lubetzki, C

    2005-02-09

    Endothelial differentiation gene (Edg) proteins are G-protein-coupled receptors activated by lysophospholipid mediators: sphingosine-1-phosphate (S1P) or lysophosphatidic acid. We show that in the CNS, expression of Edg8/S1P5, a high-affinity S1P receptor, is restricted to oligodendrocytes and expressed throughout development from the immature stages to the mature myelin-forming cell. S1P activation of Edg8/S1P5 on O4-positive pre-oligodendrocytes induced process retraction via a Rho kinase/collapsin response-mediated protein signaling pathway, whereas no retraction was elicited by S1P on these cells derived from Edg8/S1P5-deficient mice. Edg8/S1P5-mediated process retraction was restricted to immature cells and was no longer observed at later developmental stages. In contrast, S1P activation promoted the survival of mature oligodendrocytes but not of pre-oligodendrocytes. The S1P-induced survival of mature oligodendrocytes was mediated through a pertussis toxin-sensitive, Akt-dependent pathway. Our data demonstrate that Edg8/S1P5 activation on oligodendroglial cells modulates two distinct functional pathways mediating either process retraction or cell survival and that these effects depend on the developmental stage of the cell.

  2. One-step post-imprint modification achieve dual-function of glycoprotein fluorescent sensor by "Click Chemistry".

    PubMed

    Zhao, Tao; Wang, Junping; He, Jianli; Deng, Qiliang; Wang, Shuo

    2017-05-15

    A novel molecular imprinting fluorescent sensor synthesized avoiding complicated design and synthesis of a fluorescent functional monomer, and without the extra cost of additional fluorescence materials (quantum dots, carbon dots and fluorescein), only by a click reaction making the common protein imprinting polymers upgraded to a fluorescent sensing material which can be applied to the fast detection of glycoproteins. In this study, a common protein imprinted polymer (protein-IP) which containing a disulfide bond in the imprinted cavities was first synthesized, then the disulfide linkage was cleaved by reduction, the exposed thiol groups were used for the click reaction to introduce 4-vinyl phenylboronic acid to improve the imprinted recognition for glycoproteins and convert recognition behavior into fluorescent signal simultaneously in one-step site-specific post-imprinting modifications (PIMs). Good linear relationship was obtained in the range of 0.1-10mgmL(-1) by fluorescence assay, comparison of the adsorption capacity of the MIPs before and after modification proved that the method has no negative impact on the imprinting effect and exhibit good imprinting effect for glycoproteins of different molecular size and weight.

  3. 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

  4. Gifsy-1 Prophage IsrK with Dual Function as Small and Messenger RNA Modulates Vital Bacterial Machineries

    PubMed Central

    Hershko-Shalev, Tal; Odenheimer-Bergman, Ahuva; Elgrably-Weiss, Maya; Ben-Zvi, Tamar; Govindarajan, Sutharsan; Seri, Hemda; Papenfort, Kai; Vogel, Jörg; Altuvia, Shoshy

    2016-01-01

    While an increasing number of conserved small regulatory RNAs (sRNAs) are known to function in general bacterial physiology, the roles and modes of action of sRNAs from horizontally acquired genomic regions remain little understood. The IsrK sRNA of Gifsy-1 prophage of Salmonella belongs to the latter class. This regulatory RNA exists in two isoforms. The first forms, when a portion of transcripts originating from isrK promoter reads-through the IsrK transcription-terminator producing a translationally inactive mRNA target. Acting in trans, the second isoform, short IsrK RNA, binds the inactive transcript rendering it translationally active. By switching on translation of the first isoform, short IsrK indirectly activates the production of AntQ, an antiterminator protein located upstream of isrK. Expression of antQ globally interferes with transcription termination resulting in bacterial growth arrest and ultimately cell death. Escherichia coli and Salmonella cells expressing AntQ display condensed chromatin morphology and localization of UvrD to the nucleoid. The toxic phenotype of AntQ can be rescued by co-expression of the transcription termination factor, Rho, or RNase H, which protects genomic DNA from breaks by resolving R-loops. We propose that AntQ causes conflicts between transcription and replication machineries and thus promotes DNA damage. The isrK locus represents a unique example of an island-encoded sRNA that exerts a highly complex regulatory mechanism to tune the expression of a toxic protein. PMID:27057757

  5. 7 CFR 7.17 - Dual office.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Dual office. 7.17 Section 7.17 Agriculture Office of the Secretary of Agriculture SELECTION AND FUNCTIONS OF AGRICULTURAL STABILIZATION AND CONSERVATION STATE, COUNTY AND COMMUNITY COMMITTEES § 7.17 Dual office. (a) County committee membership. A member...

  6. Au Nanocage Functionalized with Ultra-small Fe3O4 Nanoparticles for Targeting T1–T2Dual MRI and CT Imaging of Tumor

    NASA Astrophysics Data System (ADS)

    Wang, Guannan; Gao, Wei; Zhang, Xuanjun; Mei, Xifan

    2016-06-01

    Diagnostic approaches based on multimodal imaging of clinical noninvasive imaging (eg. MRI/CT scanner) are highly developed in recent years for accurate selection of the therapeutic regimens in critical diseases. Therefore, it is highly demanded in the development of appropriate all-in-one multimodal contrast agents (MCAs) for the MRI/CT multimodal imaging. Here a novel ideal MCAs (F-AuNC@Fe3O4) were engineered by assemble Au nanocages (Au NC) and ultra-small iron oxide nanoparticles (Fe3O4) for simultaneous T1–T2dual MRI and CT contrast imaging. In this system, the Au nanocages offer facile thiol modification and strong X-ray attenuation property for CT imaging. The ultra-small Fe3O4 nanoparticles, as excellent contrast agent, is able to provide great enhanced signal of T1- and T2-weighted MRI (r1 = 6.263 mM‑1 s‑1, r2 = 28.117 mM‑1 s‑1) due to their ultra-refined size. After functionalization, the present MCAs nanoparticles exhibited small average size, low aggregation and excellent biocompatible. In vitro and In vivo studies revealed that the MCAs show long-term circulation time, renal clearance properties and outstanding capability of selective accumulation in tumor tissues for simultaneous CT imaging and T1- and T2-weighted MRI. Taken together, these results show that as-prepared MCAs are excellent candidates as MRI/CT multimodal imaging contrast agents.

  7. Dual-colored graphene quantum dots-labeled nanoprobes/graphene oxide: functional carbon materials for respective and simultaneous detection of DNA and thrombin

    NASA Astrophysics Data System (ADS)

    Qian, Zhao Sheng; Shan, Xiao Yue; Chai, Lu Jing; Chen, Jian Rong; Feng, Hui

    2014-10-01

    Convenient and simultaneous detection of multiple biomarkers such as DNA and proteins with biocompatible materials and good analytical performance still remains a challenge. Herein, we report the respective and simultaneous detection of DNA and bovine α-thrombin (thrombin) entirely based on biocompatible carbon materials through a specially designed fluorescence on-off-on process. Colorful fluorescence, high emission efficiency, good photostability and excellent compatibility enables graphene quantum dots (GQDs) as the best choice for fluorophores in bioprobes, and thus two-colored GQDs as labeling fluorophores were chemically bonded with specific oligonucleotide sequence and aptamer to prepare two probes targeting the DNA and thrombin, respectively. Each probe can be assembled on the graphene oxide (GO) platform spontaneously by π-π stacking and electrostatic attraction; as a result, fast electron transfer in the assembly efficiently quenches the fluorescence of probe. The presence of DNA or thrombin can trigger the self-recognition between capturing a nucleotide sequence and its target DNA or between thrombin and its aptamer due to their specific hybridization and duplex DNA structures or the formation of apatamer-substrate complex, which is taken advantage of in order to achieve a separate quantitative analysis of DNA and thrombin. A dual-functional biosensor for simultaneous detection of DNA and thrombin was also constructed by self-assembly of two probes with distinct colors and GO platform, and was further evaluated with the presence of various concentrations of DNA and thrombin. Both biosensors serving as a general detection model for multiple species exhibit outstanding analytical performance, and are expected to be applied in vivo because of the excellent biocompatibility of their used materials.

  8. Au Nanocage Functionalized with Ultra-small Fe3O4 Nanoparticles for Targeting T1–T2Dual MRI and CT Imaging of Tumor

    PubMed Central

    Wang, Guannan; Gao, Wei; Zhang, Xuanjun; Mei, Xifan

    2016-01-01

    Diagnostic approaches based on multimodal imaging of clinical noninvasive imaging (eg. MRI/CT scanner) are highly developed in recent years for accurate selection of the therapeutic regimens in critical diseases. Therefore, it is highly demanded in the development of appropriate all-in-one multimodal contrast agents (MCAs) for the MRI/CT multimodal imaging. Here a novel ideal MCAs (F-AuNC@Fe3O4) were engineered by assemble Au nanocages (Au NC) and ultra-small iron oxide nanoparticles (Fe3O4) for simultaneous T1–T2dual MRI and CT contrast imaging. In this system, the Au nanocages offer facile thiol modification and strong X-ray attenuation property for CT imaging. The ultra-small Fe3O4 nanoparticles, as excellent contrast agent, is able to provide great enhanced signal of T1- and T2-weighted MRI (r1 = 6.263 mM−1 s−1, r2 = 28.117 mM−1 s−1) due to their ultra-refined size. After functionalization, the present MCAs nanoparticles exhibited small average size, low aggregation and excellent biocompatible. In vitro and In vivo studies revealed that the MCAs show long-term circulation time, renal clearance properties and outstanding capability of selective accumulation in tumor tissues for simultaneous CT imaging and T1- and T2-weighted MRI. Taken together, these results show that as-prepared MCAs are excellent candidates as MRI/CT multimodal imaging contrast agents. PMID:27312564

  9. Dual functional reduced graphene oxide as photoanode and counter electrode in dye-sensitized solar cells and its exceptional efficiency enhancement

    NASA Astrophysics Data System (ADS)

    Jumeri, F. A.; Lim, H. N.; Zainal, Z.; Huang, N. M.; Pandikumar, A.; Lim, S. P.

    2015-10-01

    The dual functionalities of reduced graphene oxide (rGO) as photoanode and counter electrode in dye-sensitized solar cells (DSSCs) is explored. A titanium dioxide (TiO2) film is deposited on an indium tin oxide (ITO) glass using an in-house aerosol-assisted chemical vapor deposition method. Graphene oxide (GO) is then introduced onto the TiO2-ITO substrate, and the GO layer is successively thermally treated to rGO. The TiO2-rGO film is used as a compact layer for the photoanode of the DSSC. A layer of zinc oxide-silver (ZnO-Ag) is introduced on top of the compact layer as an active material. Its highly porous flower-shaped morphology is advantageous for the adsorption of dye. The in-situ electrochemical polymerization method used for the fabrication of polypyrrole incorporated with rGO and p-toluenesulfonate (pTS) (Ppy-rGO-pTS) on an ITO glass is used as a counter electrode for the DSSC. The DSSC assembled with the Ppy-rGO-1.0pTS counter electrode exhibites an enhanced conversion efficiency of 1.99% under solar illumination, which is better than that using conventional Pt as a counter electrode (0.08%). This is attributed to the increased contact area between the Ppy-rGO-pTS counter electrode and electrolyte, which subsequently improves the conductivity and high electrocatalytic activities of the Ppy-rGO-pTS counter electrode.

  10. Theoretical investigation of the hydrogen abstraction reaction of the OH radical with CH3CHF2 (HFC152-a): a dual level direct density functional theory dynamics study.

    PubMed

    Taghikhani, Mahdi; Parsafar, G A; Sabzyan, Hassan

    2005-09-15

    The hydrogen abstraction reaction of the OH radical with CH(3)CHF(2) (HFC152-a) has been studied theoretically over a wide temperature range, 200-3000 K. Two different reactive sites of the molecule, CH(3) and CHF(2) groups have been investigated precisely, and results confirm that CHF(2) position of the molecule is a highly reactive site. In this study, three recently developed hybrid density functional theories, namely, MPWB1K, MPW1B95, and MPW1K, are used. The MPWB1K/6-31+G(d,p) method gives the best result for kinetic calculations, including barrier heights, reaction path information and geometry of transition state structures and other stationary points. To refine the barrier height of each channel, a single point energy calculation was performed in MPWB1K/MG3S method. The obtained rate constants by dual level direct dynamics with the interpolated single point energy method (VTST-ISPE) using DFT quantum computational methods, are consistent with available experimental data. The canonical variational transition state theory (CVT) with the zero-curvature and also the small-curvature tunneling correction methods is used to calculate the rate constants. Over the temperature range 200-3000 K, the variation effect, tunneling contribution, branching ratio of each channel are calculated. The rate constants and their temperature dependency in the form of a fitted three-parameter Arrhenius expression are k(1)(T) = 2.00 x 10(-19)(T)(2.24) exp(-1273/T), k(2)(T) = 1.95 x 10(-19)(T)(2.46) exp(-2374/T), and k(T) = 3.13 x 10(-19)(T)(2.47) exp(- 1694/T) cm(3) molecule(-1) s(-1). For the H abstraction from the CHF(2) group, a nonclassical reflection effect is detected as a dominant quantum effect.

  11. Dual functions of Lactobacillus acidophilus NCFM™ at the intermediate dose in protection against rotavirus diarrhea in gnotobiotic pigs vaccinated with a human rotavirus vaccine

    PubMed Central

    Liu, Fangning; Wen, Ke; Li, Guohua; Yang, Xingdong; Kocher, Jacob; Bui, Tammy; Jones, Dorothy; Pelzer, Kevin; Clark-Deener, Sherrie; Yuan, Lijuan

    2014-01-01

    Objectives To examine dose effects of Lactobacillus acidophilus NCFM (LA) ™ strain on rotavirus-specific antibody and B cell responses in gnotobiotic pigs vaccinated with an oral attenuated human rotavirus (AttHRV). Methods Pigs were inoculated with AttHRV vaccine in conjunction with high dose LA (14 doses, total 2.2×109 colony forming units [CFU]), intermediate dose LA (9 doses, total 3.2×106 CFU), low dose LA (5 doses, total 2.1×106 CFU) or without LA feeding. Protection against rotavirus shedding and diarrhea was assessed upon challenge with a virulent HRV. Rotavirus-specific IgA and IgG antibodies in serum and rotavirus-specific IgA and IgG antibody-secreting cells (ASC) and memory B cells in ileum, spleen and blood of the pigs were measured and compared among treatment groups. Results The intermediate dose LA (MidLA), but not high or low dose LA, significantly reduced rotavirus diarrhea (MidLA only group) and significantly improved the protection conferred by AttHRV vaccine (MidLA+AttHRV group). Associated with the increased protection, MidLA significantly enhanced rotavirus-specific antibody, ASC and memory B cell responses to AttHRV vaccine. High or low dose LA did not enhance virus-specific antibody and ASC responses, hence did not improve the vaccine efficacy. Conclusions These findings highlight the importance of dose selection and indicate that certain specific lactobacilli strains at the appropriate dose have the dual function of reducing rotavirus diarrhea and enhancing the immunogenicity and protective efficacy of rotavirus vaccines. PMID:24126832

  12. Probing the Structures and Electronic Properties of Dual-Phosphorus-Doped Gold Cluster Anions (AunP-2, n = 1–8): A Density functional Theory Investigation

    SciTech Connect

    Xu, Kang-Ming; Huang, Teng; Liu, Yi-Rong; Jiang, Shuai; Zhang, Yang; Lv, Yu-Zhou; Gai, Yan-Bo; Huang, Wei

    2015-07-29

    The geometries of gold clusters doped with two phosphorus atoms, (AunP-2, n = 1–8) were investigated using density functional theory (DFT) methods. Various two-dimensional (2D) and three-dimensional (3D) structures of the doped clusters were studied. The results indicate that the structures of dual-phosphorus-doped gold clusters exhibit large differences from those of pure gold clusters with small cluster sizes. In our study, as for Au6P-2, two cis–trans isomers were found. The global minimum of Au8P-2 presents a similar configuration to that of Au-20, a pyramid-shaped unit, and the potential novel optical and catalytic properties of this structure warrant further attention. The higher stability of AunP-2 clusters relative to Au-n+2 (n = 1–8) clusters was verified based on various energy parameters, and the results indicate that the phosphorus atom can improve the stabilities of the gold clusters. We then explored the evolutionary path of (n = 1–8) clusters. We found that AunP-2 clusters exhibit the 2D–3D structural transition at n = 6, which is much clearer and faster than that of pure gold clusters and single-phosphorus-doped clusters. The electronic properties of AunP-2 (n = 1–8) were then investigated. The photoelectron spectra provide additional fundamental information on the structures and molecular orbitals shed light on the evolution of AunP-2 (n = 1–8). Natural bond orbital (NBO) described the charge distribution in stabilizing structures and revealed the strong relativistic effects of the gold atoms.

  13. Influence of heme environment structure on dioxygen affinity for the dual function Amphitrite ornata hemoglobin/dehaloperoxidase. Insights into the evolutional structure-function adaptations

    SciTech Connect

    Sun, Shengfang; Sono, Masanori; Wang, Chunxue; Du, Jing; Lebioda, Lukasz; Dawson, John H.

    2014-05-15

    Sea worm, Amphitrite ornata, has evolved its globin (an O2 carrier) also to serves as a dehaloperoxidase (DHP) to detoxify haloaromatic pollutants generated by competing species. A previous mutagenesis study by our groups on both DHP and sperm whale myoglobin (SW Mb) revealed some structural factors that influence the dehaloperoxidase activities (significantly lower for Mb) of both proteins. Using an isocyanide/O2 partition constant measurement method in this study, we have examined the effects of these structural factors on the O2 equilibrium constants (KO2) of DHP, SW Mb, and their mutants. A clear trend of decreasing O2 affinity and increasing catalytic activity along with the increase in the distal His Nε–heme iron distance is observed. An H93K/T95H Mb double mutant mimicking the DHP proximal His positioning exhibited markedly enhanced O2 affinity, confirming the essential effect of proximal His rotation on the globin function of DHP. For DHP, the L100F, T56G and M86E variants showed the effects of distal volume, distal His flexibility and proximal electronic push, respectively, on the O2 affinity. This study provides insights into how DHP has evolved its heme environment to gain significantly enhanced peroxidase capability without compromising its primary function as an O2 carrier.

  14. Turbocharger with dual function actuator

    SciTech Connect

    Miller, C.D.; Janik, M.; Tomoyasu, R.S.

    1990-01-16

    This patent describes an exhaust gas driven turbocharger. It comprises: a housing, a shaft rotatably mounted in the housing, a turbine wheel and a compressor wheel mounted in the housing on the shaft for rotation therewith. The housing defining a turbine inlet passage and a compressor inlet passage for communicating exhaust gas to the turbine wheel and ambient air to the compressor wheel respectively and further defining a turbine outlet passage and a compressor outlet passage for communicating exhaust gas and compressed air respectively from the housing a wastegate valve for venting the turbine inlet passage.

  15. Iterative approach of dual regression with a sparse prior enhances the performance of independent component analysis for group functional magnetic resonance imaging (fMRI) data.

    PubMed

    Kim, Yong-Hwan; Kim, Junghoe; Lee, Jong-Hwan

    2012-12-01

    This study proposes an iterative dual-regression (DR) approach with sparse prior regularization to better estimate an individual's neuronal activation using the results of an independent component analysis (ICA) method applied to a temporally concatenated group of functional magnetic resonance imaging (fMRI) data (i.e., Tc-GICA method). An ordinary DR approach estimates the spatial patterns (SPs) of neuronal activation and corresponding time courses (TCs) specific to each individual's fMRI data with two steps involving least-squares (LS) solutions. Our proposed approach employs iterative LS solutions to refine both the individual SPs and TCs with an additional a priori assumption of sparseness in the SPs (i.e., minimally overlapping SPs) based on L(1)-norm minimization. To quantitatively evaluate the performance of this approach, semi-artificial fMRI data were created from resting-state fMRI data with the following considerations: (1) an artificially designed spatial layout of neuronal activation patterns with varying overlap sizes across subjects and (2) a BOLD time series (TS) with variable parameters such as onset time, duration, and maximum BOLD levels. To systematically control the spatial layout variability of neuronal activation patterns across the "subjects" (n=12), the degree of spatial overlap across all subjects was varied from a minimum of 1 voxel (i.e., 0.5-voxel cubic radius) to a maximum of 81 voxels (i.e., 2.5-voxel radius) across the task-related SPs with a size of 100 voxels for both the block-based and event-related task paradigms. In addition, several levels of maximum percentage BOLD intensity (i.e., 0.5, 1.0, 2.0, and 3.0%) were used for each degree of spatial overlap size. From the results, the estimated individual SPs of neuronal activation obtained from the proposed iterative DR approach with a sparse prior showed an enhanced true positive rate and reduced false positive rate compared to the ordinary DR approach. The estimated TCs of the

  16. Phylogeny of Cas9 determines functional exchangeability of dual-RNA and Cas9 among orthologous type II CRISPR-Cas systems

    PubMed Central

    Fonfara, Ines; Le Rhun, Anaïs; Chylinski, Krzysztof; Makarova, Kira S.; Lécrivain, Anne-Laure; Bzdrenga, Janek; Koonin, Eugene V.; Charpentier, Emmanuelle

    2014-01-01

    The CRISPR-Cas-derived RNA-guided Cas9 endonuclease is the key element of an emerging promising technology for genome engineering in a broad range of cells and organisms. The DNA-targeting mechanism of the type II CRISPR-Cas system involves maturation of tracrRNA:crRNA duplex (dual-RNA), which directs Cas9 to cleave invading DNA in a sequence-specific manner, dependent on the presence of a Protospacer Adjacent Motif (PAM) on the target. We show that evolution of dual-RNA and Cas9 in bacteria produced remarkable sequence diversity. We selected eight representatives of phylogenetically defined type II CRISPR-Cas groups to analyze possible coevolution of Cas9 and dual-RNA. We demonstrate that these two components are interchangeable only between closely related type II systems when the PAM sequence is adjusted to the investigated Cas9 protein. Comparison of the taxonomy of bacterial species that harbor type II CRISPR-Cas systems with the Cas9 phylogeny corroborates horizontal transfer of the CRISPR-Cas loci. The reported collection of dual-RNA:Cas9 with associated PAMs expands the possibilities for multiplex genome editing and could provide means to improve the specificity of the RNA-programmable Cas9 tool. PMID:24270795

  17. 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…

  18. A Functional Near-Infrared Spectroscopy Study of Lexical Decision Task Supports the Dual Route Model and the Phonological Deficit Theory of Dyslexia

    ERIC Educational Resources Information Center

    Sela, Itamar; Izzetoglu, Meltem; Izzetoglu, Kurtulus; Onaral, Banu

    2014-01-01

    The dual route model (DRM) of reading suggests two routes of reading development: the phonological and the orthographic routes. It was proposed that although the two routes are active in the process of reading; the first is more involved at the initial stages of reading acquisition, whereas the latter needs more reading training to mature. A…

  19. Simultaneous synthesis and amine-functionalization of single-phase BaYF5:Yb/Er nanoprobe for dual-modal in vivo upconversion fluorescence and long-lasting X-ray computed tomography imaging

    NASA Astrophysics Data System (ADS)

    Liu, Hongrong; Lu, Wei; Wang, Haibo; Rao, Ling; Yi, Zhigao; Zeng, Songjun; Hao, Jianhua

    2013-06-01

    In this work, we developed a novel and biocompatible dual-modal nanoprobe based on single-phase amine-functionalized BaYF5:Yb/Er nanoparticles (NPs) for upconversion (UC) fluorescence and in vivo computed X-ray tomography (CT) bioimaging for the first time. High-quality water-soluble amine-functionalized BaYF5:Yb/Er NPs with an average size of 24 nm were synthesized by a facile environmentally friendly hydrothermal method for simultaneous synthesis and surface functionalization. Structure investigation based on the Rietveld refinement method revealed that the as-synthesized BaYF5:Yb/Er NPs present a cubic phase structure, which differs from the previously reported tetragonal structure. Under 980 nm excitation, high-contrast green and red UC emissions were observed from HeLa cells incubated with these amine-functionalized NPs. The UC spectra measured from the NPs incubated with HeLa cells presented only green and red UC emissions without any autofluorescence, further revealing that these NPs are ideal candidates for fluorescent bioimaging. In addition, the cell cytotoxicity test showed low cell toxicity of these NPs. These amine-functionalized NPs were also successfully used as CT agents for in vivo CT imaging because of the efficient X-ray absorption efficiency of Ba and doped Yb ions. A prolonged (2 h) signal enhancement of the spleen in a mouse was observed in CT imaging, which can improve the detection of splenic diseases. More importantly, the simultaneous X-ray and UC in vivo bioimaging was demonstrated in a nude mouse for the first time, indicating the as-prepared UCNPs can be successfully used as dual-modal bioprobes. These results demonstrate that BaYF5:Yb/Er NPs are ideal nanoprobes for dual-modal fluorescent/CT bioimaging with low cytotoxicity, non-autofluorescence, and enhanced detection of the spleen.

  20. Evidence of the direct involvement of the substrate TCP radical in functional switching from oxyferrous O2 carrier to ferric peroxidase in the dual-function hemoglobin/dehaloperoxidase from Amphitrite ornata.

    PubMed

    Sun, Shengfang; Sono, Masanori; Du, Jing; Dawson, John H

    2014-08-05

    The coelomic O2-binding hemoglobin dehaloperoxidase (DHP) from the sea worm Amphitrite ornata is a dual-function heme protein that also possesses a peroxidase activity. Two different starting oxidation states are required for reversible O2 binding (ferrous) and peroxidase (ferric) activity, bringing into question how DHP manages the two functions. In our previous study, the copresence of substrate 2,4,6-trichlorophenol (TCP) and H2O2 was found to be essential for the conversion of oxy-DHP to enzymatically active ferric DHP. On the basis of that study, a functional switching mechanism involving substrate radicals (TCP(•)) was proposed. To further support this mechanism, herein we report details of our investigations into the H2O2-mediated conversion of oxy-DHP to the ferric or ferryl ([TCP] < [H2O2]) state triggered by both biologically relevant [TCP and 4-bromophenol (4-BP)] and nonrelevant (ferrocyanide) compounds. At <50 μM H2O2, all of these conversion reactions are completely inhibited by ferric heme ligands (KCN and imidazole), indicating the involvement of ferric DHP. Furthermore, the spin-trapping reagent 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) effectively inhibits the TCP/4-BP (but not ferrocyanide)-triggered conversion of oxy-DHP to ferric DHP. These results and O2 concentration-dependent conversion rates observed in this study demonstrate that substrate TCP triggers the conversion of oxy-DHP to a peroxidase by TCP(•) oxidation of the deoxyferrous state. TCP(•) is progressively generated, by increasingly produced amounts of ferric DHP, upon H2O2 oxidation of TCP catalyzed initially by trace amounts of ferric enzyme present in the oxy-DHP sample. The data presented herein further address the mechanism of how the halophenolic substrate triggers the conversion of hemoglobin DHP into a peroxidase.

  1. Reassessment of the Genetic Regulation of Fatty Acid Synthesis in Escherichia coli: Global Positive Control by the Dual Functional Regulator FadR

    PubMed Central

    My, L.; Ghandour Achkar, N.; Viala, J. P.

    2015-01-01

    ABSTRACT In Escherichia coli, the FadR transcriptional regulator represses the expression of fatty acid degradation (fad) genes. However, FadR is also an activator of the expression of fabA and fabB, two genes involved in unsaturated fatty acid synthesis. Therefore, FadR plays an important role in maintaining the balance between saturated and unsaturated fatty acids in the membrane. We recently showed that FadR also activates the promoter upstream of the fabH gene (L. My, B. Rekoske, J. J. Lemke, J. P. Viala, R. L. Gourse, and E. Bouveret, J Bacteriol 195:3784–3795, 2013, doi:10.1128/JB.00384-13). Furthermore, recent transcriptomic and proteomic data suggested that FadR activates the majority of fatty acid (FA) synthesis genes. In the present study, we tested the role of FadR in the expression of all genes involved in FA synthesis. We found that FadR activates the transcription of all tested FA synthesis genes, and we identified the FadR binding site for each of these genes. This necessitated the reassessment of the transcription start sites for accA and accB genes described previously, and we provide evidence for the presence of multiple promoters driving the expression of these genes. We showed further that regulation by FadR impacts the amount of FA synthesis enzymes in the cell. Our results show that FadR is a global regulator of FA metabolism in E. coli, acting both as a repressor of catabolism and an activator of anabolism, two directly opposing pathways. IMPORTANCE In most bacteria, a transcriptional regulator tunes the level of FA synthesis enzymes. Oddly, such a global regulator still was missing for E. coli, which nonetheless is one of the prominent model bacteria used for engineering biofuel production using the FA synthesis pathway. Our work identifies the FadR functional dual regulator as a global activator of almost all FA synthesis genes in E. coli. Because FadR also is the repressor of FA degradation, FadR acts both as a repressor and an activator

  2. Dual Wavelength Lasers

    NASA Technical Reports Server (NTRS)

    Walsh, Brian M.

    2010-01-01

    Dual wavelength lasers are discussed, covering fundamental aspects on the spectroscopy and laser dynamics of these systems. Results on Tm:Ho:Er:YAG dual wavelength laser action (Ho at 2.1 m and Er at 2.9 m) as well as Nd:YAG (1.06 and 1.3 m) are presented as examples of such dual wavelength systems. Dual wavelength lasers are not common, but there are criteria that govern their behavior. Based on experimental studies demonstrating simultaneous dual wavelength lasing, some general conclusions regarding the successful operation of multi-wavelength lasers can be made.

  3. Electrochemical immunosensor for simultaneous determination of interleukin-1 beta and tumor necrosis factor alpha in serum and saliva using dual screen printed electrodes modified with functionalized double-walled carbon nanotubes.

    PubMed

    Sánchez-Tirado, E; Salvo, C; González-Cortés, A; Yáñez-Sedeño, P; Langa, F; Pingarrón, J M

    2017-03-22

    Dual screen-printed carbon electrodes modified with 4-carboxyphenyl-functionalized double-walled carbon nanotubes (HOOC-Phe-DWCNTs/SPCEs) have been used as scaffolds for the preparation of electrochemical immunosensors for the simultaneous determination of the cytokines Interleukin-1β (IL-1β) and factor necrosis tumor α (TNF-α). IL-1β. Capture antibodies were immobilized onto HOOC-Phe-DWCNTs/SPCEs in an oriented form making using the commercial polymeric coating Mix&Go™. Sandwich type immunoassays with amperometric signal amplification through the use of poly-HRP-streptavidin conjugates and H2O2 as HRP substrate and hydroquinone as redox mediator were implemented. Upon optimization of the experimental variables affecting the immunosensor performance, the dual immunosensor allows ranges of linearity extending between 0.5 and 100 pg/mL and from 1 to 200 pg/mL for IL-1β and TNF-α, respectively, these ranges being adequate for the determination of the cytokines in clinical samples. The achieved limits of detection were 0.38 pg/mL (IL-1β) and 0.85 pg/mL (TNF-α). In addition, the dual immunosensor exhibits excellent reproducibility of the measurements, storage stability of the anti-IL-Phe-DWCNTs/SPCE and anti-TNF-Phe-DWCNTs/SPCE conjugates, and selectivity as well as negligible cross-talking. The dual immunosensor was applied to the simultaneous determination of IL-1β and TNF-α in human serum spiked at clinically relevant concentration levels and in real saliva samples.

  4. Rapid and sensitive determination of phytosterols in functional foods and medicinal herbs by using UHPLC-MS/MS with microwave-assisted derivatization combined with dual ultrasound-assisted dispersive liquid-liquid microextraction.

    PubMed

    Sun, Jing; Zhao, Xian-En; Dang, Jun; Sun, Xiaoyan; Zheng, Longfang; You, Jinmao; Wang, Xiao

    2017-02-01

    In this work, a hyphenated technique of dual ultrasound-assisted dispersive liquid-liquid microextraction combined with microwave-assisted derivatization followed by ultra high performance liquid chromatography tandem mass spectrometry has been developed for the determination of phytosterols in functional foods and medicinal herbs. Multiple reaction monitoring mode was used for the tandem mass spectrometry detection. A mass spectrometry sensitive reagent, 4'-carboxy-substituted rosamine, has been used as the derivatization reagent for five phytosterols, and internal standard diosgenin was used for the first time. Parameters for the dual microextraction, microwave-assisted derivatization, and ultra high performance liquid chromatography tandem mass spectrometry were all optimized in detail. Satisfactory linearity, recovery, repeatability, accuracy and precision, absence of matrix effect, extremely low limits of detection (0.005-0.015 ng/mL) and limits of quantification (0.030-0.10 ng/mL) were achieved. The proposed method was compared with previously reported methods. It showed better sensitivity, selectivity, and accuracy. The matrix effect was also significantly reduced. The proposed method was successfully applied to the determination of five phytosterols in vegetable oil (sunflower oil, olive oil, corn oil, peanut oil), milk and orange juice (soymilk, peanut milk, orange juice), and medicinal herbs (Ginseng, Ganoderma lucidum, Cordyceps, Polygonum multiflorum) for the quality control of functional foods and medicinal herbs.

  5. Dual Enrollment Academy Programs

    ERIC Educational Resources Information Center

    Gonzalez, Nicolas; Chavez, Guadalupe

    2009-01-01

    Dual Enrollment Engineering (DEEA) and Medical Science (DEMSA) Academies are two-year dual enrollment programs for high school students. Students explore engineering and medical careers through college coursework. Students prepare for higher education in engineering and medical fields while completing associate degrees in biology or engineering…

  6. Investigation of electron density changes at the onset of a chemical reaction using the state-specific dual descriptor from conceptual density functional theory.

    PubMed

    De Proft, Frank; Forquet, Valérian; Ourri, Benjamin; Chermette, Henry; Geerlings, Paul; Morell, Christophe

    2015-04-14

    The electron density changes from reactants towards the transition state of a chemical reaction is expressed as a linear combination of the state-specific dual descriptors (SSDD) of the corresponding reactant complexes. Consequently, the SSDD can be expected to bear important resemblance to the so-called natural orbitals for chemical valence (NOCV), introduced as the orbitals that diagonalize the deformation density matrix of interacting molecules. This agreement is shown for three case studies: the complexation of a Lewis acid with a Lewis base, a SN2 nucleophilic substitution reaction and a Diels-Alder cycloaddition reaction. As such, the SSDD computed for reactant complexes are shown to provide important information about charge transfer interactions during a chemical reaction.

  7. Point-of-care platelet function assays demonstrate reduced responsiveness to clopidogrel, but not aspirin, in patients with Drug-Eluting Stent Thrombosis whilst on dual antiplatelet therapy

    PubMed Central

    Hobson, Alex R; Petley, Graham; Morton, Geraint; Dawkins, Keith D; Curzen, Nick P

    2008-01-01

    Background To test the hypothesis that point-of-care assays of platelet reactivity would demonstrate reduced response to antiplatelet therapy in patients who experienced Drug Eluting Stent (DES) ST whilst on dual antiplatelet therapy compared to matched DES controls. Whilst the aetiology of stent thrombosis (ST) is multifactorial there is increasing evidence from laboratory-based assays that hyporesponsiveness to antiplatelet therapy is a factor in some cases. Methods From 3004 PCI patients, seven survivors of DES ST whilst on dual antiplatelet therapy were identified and each matched with two patients without ST. Analysis was performed using (a) short Thrombelastogram PlateletMapping™ (TEG) and (b) VerifyNow Aspirin and P2Y12 assays. TEG analysis was performed using the Area Under the Curve at 15 minutes (AUC15) as previously described. Results There were no differences in responses to aspirin. There was significantly greater platelet reactivity on clopidogrel in the ST group using the Accumetrics P2Y12 assay (183 ± 51 vs. 108 ± 31, p = 0.02) and a trend towards greater reactivity using TEG AUC15 (910 ± 328 vs. 618 ± 129, p = 0.07). 57% of the ST group by TEG and 43% of the ST cases by Accumetrics PRU had results > two standard deviations above the expected mean in the control group. Conclusion This study demonstrates reduced platelet response to clopidogrel in some patients with DES ST compared to matched controls. The availability of point-of-care assays that can detect these responses raises the possibility of prospectively identifying DES patients at risk of ST and manipulating their subsequent risk. PMID:18312665

  8. Offset dual-shaped reflectors for dual chamber compact ranges

    NASA Technical Reports Server (NTRS)

    Galindo-Israel, Victor; Imbriale, William A.; Rengarajan, Sembiam R.; Mittra, Raj

    1991-01-01

    The application of the theory of the synthesis of offset dual-shaped reflectors to the design of compact ranges is examined. The object of the compact range is to provide a uniform plane wave with minimum amplitude and phase ripple over as large a volume as possible for a given size reflector. Ripple can be lowered by reducing the edge diffraction from the reflector producing the plane wave. This has been done either by serrating or rolling the edge. An alternative approach is to use dual offset-shaped reflector synthesis techniques to produce a reflector aperture distribution that is uniform over most of the aperture, but with a Gaussian taper near the edge. This approach can be used together with rolling and/or serration if desirable. The amount of phase and amplitude ripple obtained with two different dual-shaped reflector designs is studied as a function of position in the plane wave zone and reflector size in wavelengths. The amount of both transverse and longitudinal (z-component) cross polarization is studied.

  9. Dual Credit/Dual Enrollment and Data Driven Policy Implementation

    ERIC Educational Resources Information Center

    Lichtenberger, Eric; Witt, M. Allison; Blankenberger, Bob; Franklin, Doug

    2014-01-01

    The use of dual credit has been expanding rapidly. Dual credit is a college course taken by a high school student for which both college and high school credit is given. Previous studies provided limited quantitative evidence that dual credit/dual enrollment is directly connected to positive student outcomes. In this study, predictive statistics…

  10. Bifocal dual reflector antenna

    NASA Technical Reports Server (NTRS)

    Rao, B. L. J.

    1973-01-01

    A bifocal dual reflector antenna is similar to and has better scan capability than classical cassegrain reflector antenna. The method used in determining the reflector surfaces is a modification of a design method for the dielectric bifocal lens. The three dimensional dual reflector is obtained by first designing an exact (in geometrical optics sense) two-point corrected two dimensional reflector and then rotating it around its axis of symmetry. A point by point technique is used in computing the reflector surfaces. Computed radiation characteristics of the dual reflector are compared with those of a cassegrain reflector. The results confirm that the bifocal antenna has superior performance.

  11. Structural Mapping and Functional Characterization of Zebrafish Class B G-Protein Coupled Receptor (GPCR) with Dual Ligand Selectivity towards GLP-1 and Glucagon

    PubMed Central

    Oren, Deena A.; Wei, Yang; Skrabanek, Luce; Chow, Billy K. C.; Mommsen, Thomas; Mojsov, Svetlana

    2016-01-01

    GLP-1 and glucagon regulate glucose metabolism through a network of metabolic pathways initiated upon binding to their specific receptors that belong to class B G-protein coupled receptors (GPCRs). The therapeutic potential of glucagon is currently being evaluated, while GLP-1 is already used in the treatment of type 2 diabetes and obesity. Development of a second generation of GLP-1 based therapeutics depends on a molecular and structural understanding of the interactions between the GLP-1 receptor (GLP-1R) and its ligand GLP-1. There is considerable sequence conservation between GLP-1 and glucagon and between the hGLP-1R and human glucagon receptor (hGCGR), yet each receptor recognizes only its own specific ligand. Glucagon receptors in fish and frogs also exhibit ligand selectivity only towards glucagon and not GLP-1. Based on competitive binding experiments and assays of increase in intracellular cAMP, we demonstrate here that a GPCR in zebrafish (Danio rerio) exhibits dual ligand selectivity towards GLP-1 and glucagon, a characteristic not found in mammals. Further, many structural features found in hGLP-1R and hGCGR are also found in this zebrafish GPCR (zfGPCR). We show this by mapping of its sequence and structural features onto the hGLP-1R and hGCGR based on their partial and complementary crystal structures. Thus, we propose that zfGPCR represents a dual GLP-1R/GCGR. The main differences between the three receptors are in their stalk regions that connect their N-terminal extracellular domains (NECDs) with their transmembrane domains and the absence of loop 3 in the NECD in zfGLP-1R/GCGR. These observations suggest that the interactions between GLP-1 and glucagon with loop 3 and the stalk regions may induce different conformational changes in hGLP-1R and hGCGR upon ligand binding and activation that lead to selective recognition of their native ligands. PMID:27930690

  12. The first molecular level monitoring of carbohydrate conversion to 5-hydroxymethylfurfural in ionic liquids. B2O3--an efficient dual-function metal-free promoter for environmentally benign applications.

    PubMed

    Khokhlova, Elena A; Kachala, Vadim V; Ananikov, Valentine P

    2012-04-01

    The mechanistic nature of the conversion of carbohydrates to the sustainable platform chemical 5-hydroxymethylfurfural (5-HMF) was revealed at the molecular level. A detailed study of the key sugar units involved in the biomass conversion process has shown that the simple dissolution of fructose in the ionic liquid 1-butyl-3-methylimidazolium chloride significantly changes the anomeric composition and favors the formation of the open fructoketose form. A special NMR approach was developed for the determination of molecular structures and monitoring of chemical reactions directly in ionic liquids. The transformation of glucose to 5-HMF has been followed in situ through the detection of intermediate species. A new environmentally benign, easily available, metal-free promoter with a dual functionality (B(2)O(3)) was developed for carbohydrate conversion to 5-HMF.

  13. Functional magnetic porous silica for T 1-T 2 dual-modal magnetic resonance imaging and pH-responsive drug delivery of basic drugs

    NASA Astrophysics Data System (ADS)

    Li, Ling; Zhang, Run; Guo, Yi; Zhang, Cheng; Zhao, Wei; Xu, Zhiping; Whittaker, Andrew K.

    2016-12-01

    A smart magnetic-targeting drug carrier γ-Fe2O3@p-silica comprising a γ-Fe2O3 core and porous shell has been prepared and characterized. The particles have a uniform size of about 60 nm, and a porous shell of thickness 3 nm. Abundant hydroxyl groups and a large surface area enabled the γ-Fe2O3@p-silica to be readily loaded with a large payload of the basic model drug rhodamine B (RB) (up to 73 mg g-1). Cytotoxicity assays of the γ-Fe2O3@p-silica particles indicated that the particles were biocompatible and suitable for carrying drugs. It was found that the RB was released rapidly at pH 5.5 but at pH 7.4 the rate and extent of release was greatly attenuated. The particles therefore demonstrate an excellent pH-triggered drug release. In addition, the γ-Fe2O3@p-silica particles could be tracked by magnetic resonance imaging (MRI). A clear dose-dependent contrast enhancement in both T 1-weighted and T 2-weighted MR images indicated the potential of the γ-Fe2O3@p-silica particles to act as dual-mode T 1 and T 2 MRI contrast agents.

  14. Functional magnetic porous silica for T 1-T 2 dual-modal magnetic resonance imaging and pH-responsive drug delivery of basic drugs.

    PubMed

    Li, Ling; Zhang, Run; Guo, Yi; Zhang, Cheng; Zhao, Wei; Xu, Zhiping; Whittaker, Andrew K

    2016-12-02

    A smart magnetic-targeting drug carrier γ-Fe2O3@p-silica comprising a γ-Fe2O3 core and porous shell has been prepared and characterized. The particles have a uniform size of about 60 nm, and a porous shell of thickness 3 nm. Abundant hydroxyl groups and a large surface area enabled the γ-Fe2O3@p-silica to be readily loaded with a large payload of the basic model drug rhodamine B (RB) (up to 73 mg g(-1)). Cytotoxicity assays of the γ-Fe2O3@p-silica particles indicated that the particles were biocompatible and suitable for carrying drugs. It was found that the RB was released rapidly at pH 5.5 but at pH 7.4 the rate and extent of release was greatly attenuated. The particles therefore demonstrate an excellent pH-triggered drug release. In addition, the γ-Fe2O3@p-silica particles could be tracked by magnetic resonance imaging (MRI). A clear dose-dependent contrast enhancement in both T 1-weighted and T 2-weighted MR images indicated the potential of the γ-Fe2O3@p-silica particles to act as dual-mode T 1 and T 2 MRI contrast agents.

  15. Single peptide ligand-functionalized uniform hollow mesoporous silica nanoparticles achieving dual-targeting drug delivery to tumor cells and angiogenic blood vessel cells

    PubMed Central

    Liu, Yang; Chen, Qing; Xu, Ming; Guan, Guannan; Hu, Wen; Liang, Ying; Zhao, Xiuli; Qiao, Mingxi; Chen, Dawei; Liu, Hao

    2015-01-01

    Background The purpose of this study was to construct hollow mesoporous silica nanoparticles (HMSN) decorated with tLyp-1 peptide (tHMSN) for dual-targeting drug delivery to tumor cells and angiogenic blood vessel cells. Methods HMSN were synthesized de novo using a novel cationic surfactant-assisted selective etching strategy and were then modified with tLyp-1. Multiple methods, including transmission electron microscopy, X-ray photoelectron spectroscopy, thermogravimetric analysis, bicinchoninic acid assay, and nitrogen adsorption and desorption isotherms, were used to characterize the tHMSN. Doxorubicin were chosen as the model cargo, and the uptake of doxorubicin-loaded tHMSN into MDA-MB-231 cells and human umbilical vein endothelial cells (HUVECs), as models of tumor cells and tumor neovascular endothelial cells, respectively, were observed and detected by confocal laser scanning microscopy and flow cytometry. An in vitro pharmacodynamic study and a study of the mechanism via which the nanoparticles were endocytosed were also performed. Results HMSN with a highly uniform size and well oriented mesopores were synthesized. After tHMSN were characterized, enhanced uptake of the cargo carried by tHMSN into MDA-MB-231 cells and HUVECs compared with that of their unmodified counterparts was validated by confocal laser scanning microscopy and flow cytometry at the qualitative and quantitative levels, respectively. Further, the pharmacodynamic study suggested that, compared with their unmodified counterparts, doxorubicin-loaded tHMSN had an enhanced inhibitory effect on MDA-MB-231 cells and HUVECs in vitro. Finally, a preliminary study on the mechanism by which the nanoparticles were endocytosed indicated that the clathrin-mediated endocytosis pathway has a primary role in the transport of tHMSN into the cytoplasm. Conclusion tHMSN might serve as an effective active targeting nanocarrier strategy for anti-mammary cancer drug delivery. PMID:25834425

  16. Dual-Wavelength Electrochemiluminescence Ratiometry Based on Resonance Energy Transfer between Au Nanoparticles Functionalized g-C3N4 Nanosheet and Ru(bpy)3(2+) for microRNA Detection.

    PubMed

    Feng, Qiu-Mei; Shen, Yi-Zhong; Li, Mei-Xing; Zhang, Zhuo-Lei; Zhao, Wei; Xu, Jing-Juan; Chen, Hong-Yuan

    2016-01-05

    Here, a dual-wavelength ratiometric electrochemiluminescence (ECL) approach is reported based on resonance energy transfer (RET) from graphite-like carbon nitride nanosheet (g-C3N4 NS) to Ru(bpy)3(2+) for sensitive detection of microRNA (miRNA). In this approach, Au nanoparticles (Au NPs) functionalized g-C3N4 NS nanohybrid (Au-g-C3N4 NH) coated on glassy carbon electrode (GCE) could exhibit strong and stable ECL emissions with emission peak centered at 460 nm. The ECL emission at such wavelength matched well with the absorption peak of Ru(bpy)3(2+) as well as impeccably stimulating the emission of Ru(bpy)3(2+) at the wavelength of 620 nm, producing ECL-RET with high efficiency. Thus, based on the ECL signals quenching at 460 nm and increasing at 620 nm, a dual-wavelength ratiometric ECL-RET system was achieved. This system was then utilized for determination of target miRNA. With the attachment of thiol-modified molecular beacon on Au-g-C3N4 NH, target miRNA hybridized with the molecular beacon to form a DNA-RNA duplex. The obtained DNA-RNA duplex could be cleaved by duplex-specific nuclease to release target miRNA which would take part in the next cycle for further hybridization. Finally, the introducing of Ru(bpy)3(2+) was through the probe DNA-Ru(bpy)3(2+) complementary with the rest single-strand DNA on electrode. By measuring the ratio of ECL(460 nm)/ECL(620 nm), we could accurately quantify the concentration of miRNA-21 in a wide range from 1.0 fM to 1.0 nM. This work provides an important reference for the study of dual-wavelength ECL ratiometry and also exhibits potential capability in the detection of nucleic acids.

  17. Effects of selective serotonin reuptake and dual serotonergic-noradrenergic reuptake treatments on attention and executive functions in patients with major depressive disorder.

    PubMed

    Herrera-Guzmán, Ixchel; Herrera-Abarca, Jorge E; Gudayol-Ferré, Esteve; Herrera-Guzmán, Daniel; Gómez-Carbajal, Lizbeth; Peña-Olvira, Miriam; Villuendas-González, Erwin; Joan, Guàrdia-Olmos

    2010-05-30

    Several reports suggest that antidepressants may improve cognitive functioning in patients with major depressive disorder (MDD). The present work aims to study the effects of selective serotonin reuptake inhibitors (SSRIs) and serotonergic-noradrenergic reuptake inhibitors (SNRIs) treatments on the performance of working memory, attention and executive functions in patients with MDD. A total of 73 subjects meeting the Diagnostic and Statistical Manual of Mental Disorders version IV (DSM-IV) criteria for MDD, and 37 control subjects were assessed with the Hamilton Depression Rating Scale and a neuropsychological battery. The subjects were medicated with escitalopram (n=36) or duloxetine (n=37) for 24 weeks. At the end of the trial, the subjects were assessed again with the same tests. The depressed subjects showed alterations in attention and cognitive functions when compared to the control group. The administration of both treatments improved working memory, as well as attention and all the executive functions, but the cognitive functions of depressed patients do not improve enough to reach the levels of performance of the control subjects. Our results suggest that both SSRI and SNRI treatments presented the same efficacy in improving attention and the remaining executive functions.

  18. Dual Causality and the Autonomy of Biology.

    PubMed

    Bock, Walter J

    2017-03-01

    Ernst Mayr's concept of dual causality in biology with the two forms of causes (proximate and ultimate) continues to provide an essential foundation for the philosophy of biology. They are equivalent to functional (=proximate) and evolutionary (=ultimate) causes with both required for full biological explanations. The natural sciences can be classified into nomological, historical nomological and historical dual causality, the last including only biology. Because evolutionary causality is unique to biology and must be included for all complete biological explanations, biology is autonomous from the physical sciences.

  19. Dual-energy contrast-enhanced mammography.

    PubMed

    Travieso Aja, M M; Rodríguez Rodríguez, M; Alayón Hernández, S; Vega Benítez, V; Luzardo, O P

    2014-01-01

    The degree of vascularization in breast lesions is related to their malignancy. For this reason, functional diagnostic imaging techniques have become important in recent years. Dual-energy contrast-enhanced mammography is a new, apparently promising technique in breast cancer that provides information about the degree of vascularization of the lesion in addition to the morphological information provided by conventional mammography. This article describes the state of the art for dual-energy contrast-enhanced mammography. Based on 15 months' clinical experience, we illustrate this review with clinical cases that allow us to discuss the advantages and limitations of this technique.

  20. Structure-function analysis of mouse Sry reveals dual essential roles of the C-terminal polyglutamine tract in sex determination.

    PubMed

    Zhao, Liang; Ng, Ee Ting; Davidson, Tara-Lynne; Longmuss, Enya; Urschitz, Johann; Elston, Marlee; Moisyadi, Stefan; Bowles, Josephine; Koopman, Peter

    2014-08-12

    The mammalian sex-determining factor SRY comprises a conserved high-mobility group (HMG) box DNA-binding domain and poorly conserved regions outside the HMG box. Mouse Sry is unusual in that it includes a C-terminal polyglutamine (polyQ) tract that is absent in nonrodent SRY proteins, and yet, paradoxically, is essential for male sex determination. To dissect the molecular functions of this domain, we generated a series of Sry mutants, and studied their biochemical properties in cell lines and transgenic mouse embryos. Sry protein lacking the polyQ domain was unstable, due to proteasomal degradation. Replacing this domain with irrelevant sequences stabilized the protein but failed to restore Sry's ability to up-regulate its key target gene SRY-box 9 (Sox9) and its sex-determining function in vivo. These functions were restored only when a VP16 transactivation domain was substituted. We conclude that the polyQ domain has important roles in protein stabilization and transcriptional activation, both of which are essential for male sex determination in mice. Our data disprove the hypothesis that the conserved HMG box domain is the only functional domain of Sry, and highlight an evolutionary paradox whereby mouse Sry has evolved a novel bifunctional module to activate Sox9 directly, whereas SRY proteins in other taxa, including humans, seem to lack this ability, presumably making them dependent on partner proteins(s) to provide this function.

  1. kin-19/casein kinase Iα has dual functions in regulating asymmetric division and terminal differentiation in C. elegans epidermal stem cells

    PubMed Central

    Chen, Xin; Lin, Shin Yi; Slack, Frank J

    2010-01-01

    Casein Kinase I (CKI) is a conserved component of the Wnt signaling pathway that regulates cell fate determination in metazoans. We show that post-embryonic asymmetric division and fate specification of C. elegans epidermal stem cells are controlled by a non-canonical Wnt/β-catenin signaling pathway, involving the β-catenins WRM-1 and SYS-1, and that C. elegans kin-19/CKIα functions in this pathway. Furthermore, we find that kin-19 is the only member of the Wnt asymmetry pathway that functions with, or in parallel to, the heterochronic temporal patterning pathway to control withdrawal from self-renewal and subsequent terminal differentiation of epidermal stem cells. We show that, except in the case of kin-19, the Wnt asymmetry pathway and the heterochronic pathway function separately and in parallel to control different aspects of epidermal stem cell fate specification. However, given the function of kin-19/CKIα in both pathways, and that CKI, Wnt signaling pathway and heterochronic pathway genes are widely conserved in animals, our findings suggest that CKIα may function as a regulatory hub through which asymmetric division and terminal differentiation are coordinated in adult stem cells of vertebrates. PMID:21127398

  2. Dual adaptive control: Design principles and applications

    NASA Technical Reports Server (NTRS)

    Mookerjee, Purusottam

    1988-01-01

    The design of an actively adaptive dual controller based on an approximation of the stochastic dynamic programming equation for a multi-step horizon is presented. A dual controller that can enhance identification of the system while controlling it at the same time is derived for multi-dimensional problems. This dual controller uses sensitivity functions of the expected future cost with respect to the parameter uncertainties. A passively adaptive cautious controller and the actively adaptive dual controller are examined. In many instances, the cautious controller is seen to turn off while the latter avoids the turn-off of the control and the slow convergence of the parameter estimates, characteristic of the cautious controller. The algorithms have been applied to a multi-variable static model which represents a simplified linear version of the relationship between the vibration output and the higher harmonic control input for a helicopter. Monte Carlo comparisons based on parametric and nonparametric statistical analysis indicate the superiority of the dual controller over the baseline controller.

  3. Dual-Mode Combustor

    NASA Technical Reports Server (NTRS)

    Trefny, Charles J (Inventor); Dippold, Vance F (Inventor)

    2013-01-01

    A new dual-mode ramjet combustor used for operation over a wide flight Mach number range is described. Subsonic combustion mode is usable to lower flight Mach numbers than current dual-mode scramjets. High speed mode is characterized by supersonic combustion in a free-jet that traverses the subsonic combustion chamber to a variable nozzle throat. Although a variable combustor exit aperture is required, the need for fuel staging to accommodate the combustion process is eliminated. Local heating from shock-boundary-layer interactions on combustor walls is also eliminated.

  4. On the Dual Nature of the Functional Discourse Grammar Model: Context, the Language System/Language Use Distinction, and Indexical Reference in Discourse

    ERIC Educational Resources Information Center

    Cornish, Francis

    2013-01-01

    The Functional Discourse Grammar model has a twofold objective: on the one hand, to provide a descriptively, psychologically and pragmatically adequate account of the forms made available by a typologically diverse range of languages; and on the other, to provide a model of language which is set up to reflect, at one remove, certain of the stages…

  5. Liver extracellular matrix providing dual functions of two-dimensional substrate coating and three-dimensional injectable hydrogel platform for liver tissue engineering.

    PubMed

    Lee, Jung Seung; Shin, Jisoo; Park, Hae-Min; Kim, Yun-Gon; Kim, Byung-Gee; Oh, Jong-Won; Cho, Seung-Woo

    2014-01-13

    Decellularization of tissues or organs can provide an efficient strategy for preparing functional scaffolds for tissue engineering. Microstructures of native extracellular matrices and their biochemical compositions can be retained in the decellularized matrices, providing tissue-specific microenvironments for efficient tissue regeneration. Here, we report the versatility of liver extracellular matrix (LEM) that can be used for two-dimensional (2D) coating and three-dimensional (3D) hydrogel platforms for culture and transplantation of primary hepatocytes. Collagen type I (Col I) has typically been used for hepatocyte culture and transplantation. In this study, LEM was compared with Col I in terms of biophysical and mechanical characteristics and biological performance for enhancing cell viability, differentiation, and hepatic functions. Surface properties of LEM coating and mechanical properties and gelation kinetics of LEM hydrogel could be manipulated by adjusting the LEM concentration. In addition, LEM hydrogel exhibited improved elastic properties, rapid gelation, and volume maintenance compared to Col I hydrogel. LEM coating significantly improved hepatocyte functions such as albumin secretion and urea synthesis. More interestingly, LEM coating upregulated hepatic gene expression of human adipose-derived stem cells, indicating enhanced hepatic differentiation of these stem cells. The viability and hepatic functions of primary hepatocytes were also significantly improved in LEM hydrogel compared to Col I hydrogel both in vitro and in vivo. Albumin and hepatocyte transcription factor expression was upregulated in hepatocytes transplanted in LEM hydrogels. In conclusion, LEM can provide functional biomaterial platforms for diverse applications in liver tissue engineering by promoting survival and maturation of hepatocytes and hepatic commitment of stem cells. This study demonstrates the feasibility of decellularized matrix for both 2D coating and 3D hydrogel in

  6. Hierarchical 3D ZnIn2S4/graphene nano-heterostructures: their in situ fabrication with dual functionality in solar hydrogen production and as anodes for lithium ion batteries.

    PubMed

    Kale, Sayali B; Kalubarme, Ramchandra S; Mahadadalkar, Manjiri A; Jadhav, Harsharaj S; Bhirud, Ashwini P; Ambekar, Jalinder D; Park, Chan-Jin; Kale, Bharat B

    2015-12-21

    Hierarchical 3D ZnIn2S4/graphene (ZnIn2S4/Gr) nano-heterostructures were successfully synthesized using an in-situ hydrothermal method. The dual functionality of these nano-heterostructures i.e. for solar hydrogen production and lithium ion batteries has been demonstrated for the first time. The ZnIn2S4/Gr nano-heterostructures were optimized by varying the concentrations of graphene for utmost hydrogen production. An inspection of the structure shows the existence of layered hexagonal ZnIn2S4 wrapped in graphene. The reduction of graphene oxide (GO) to graphene was confirmed by Raman and XPS analyses. The morphological analysis demonstrated that ultrathin ZnIn2S4 nanopetals are dispersed on graphene sheets. The optical study reveals the extended absorption edge to the visible region due to the presence of graphene and hence is used as a photocatalyst to transform H2S into eco-friendly hydrogen using solar light. The ZnIn2S4/Gr nano-heterostructure that is comprised of graphene and ZnIn2S4 in a weight ratio of 1 : 99 exhibits enhanced photocatalytically stable hydrogen production i.e. ∼6365 μmole h(-1) under visible light irradiation using just 0.2 g of nano-heterostructure, which is much higher as compared to bare hierarchical 3D ZnIn2S4. The heightened photocatalytic activity is attributed to the enhanced charge carrier separation due to graphene which acts as an excellent electron collector and transporter. Furthermore, the usage of nano-heterostructures and pristine ZnIn2S4 as anodes in lithium ion batteries confers the charge capacities of 590 and 320 mA h g(-1) after 220 cycles as compared to their initial reversible capacities of 645 and 523 mA h g(-1), respectively. These nano-heterostructures show high reversible capacity, excellent cycling stability, and high-rate capability indicating their potential as promising anode materials for LIBs. The excellent performance is due to the nanostructuring of ZnIn2S4 and the presence of a graphene layer, which

  7. Dual approximations in optimal control

    NASA Technical Reports Server (NTRS)

    Hager, W. W.; Ianculescu, G. D.

    1984-01-01

    A dual approximation for the solution to an optimal control problem is analyzed. The differential equation is handled with a Lagrange multiplier while other constraints are treated explicitly. An algorithm for solving the dual problem is presented.

  8. The importance of chemistry in creating well-defined nanoscopic embedded therapeutics: devices capable of the dual functions of imaging and therapy.

    PubMed

    Nyström, Andreas M; Wooley, Karen L

    2011-10-18

    Nanomedicine is a rapidly evolving field, for which polymer building blocks are proving useful for the construction of sophisticated devices that provide enhanced diagnostic imaging and treatment of disease, known as theranostics. These well-defined nanoscopic objects have high loading capacities, can protect embedded therapeutic cargo, and offer control over the conditions and rates of release. Theranostics also offer external surface area for the conjugation of ligands to impart stealth characteristics and/or direct their interactions with biological receptors and provide a framework for conjugation of imaging agents to track delivery to diseased site(s). The nanoscopic dimensions allow for extensive biological circulation. The incorporation of such multiple functions is complicated, requiring exquisite chemical control during production and rigorous characterization studies to confirm the compositions, structures, properties, and performance. We are particularly interested in the study of nanoscopic objects designed for treatment of lung infections and acute lung injury, urinary tract infections, and cancer. This Account highlights our work over several years to tune the assembly of unique nanostructures. We provide examples of how the composition, structure, dimensions, and morphology of theranostic devices can tune their performance as drug delivery agents for the treatment of infectious diseases and cancer. The evolution of nanostructured materials from relatively simple overall shapes and internal morphologies to those of increasing complexity is driving the development of synthetic methodologies for the preparation of increasingly complex nanomedicine devices. Our nanomedicine devices are derived from macromolecules that have well-defined compositions, structures, and topologies, which provide a framework for their programmed assembly into nanostructures with controlled sizes, shapes, and morphologies. The inclusion of functional units within selective

  9. Dual Function of the pUL7-pUL51 Tegument Protein Complex in Herpes Simplex Virus 1 Infection

    PubMed Central

    Albecka, Anna; Owen, Danielle J.; Ivanova, Lyudmila; Brun, Juliane; Liman, Rukayya; Davies, Laura; Ahmed, M. Firoz; Colaco, Susanna; Hollinshead, Michael

    2016-01-01

    ABSTRACT The tegument of herpesviruses is a highly complex structural layer between the nucleocapsid and the envelope of virions. Tegument proteins play both structural and regulatory functions during replication and spread, but the interactions and functions of many of these proteins are poorly understood. Here we focus on two tegument proteins from herpes simplex virus 1 (HSV-1), pUL7 and pUL51, which have homologues in all other herpesviruses. We have now identified that HSV-1 pUL7 and pUL51 form a stable and direct protein-protein interaction, their expression levels rely on the presence of each other, and they function as a complex in infected cells. We demonstrate that expression of the pUL7-pUL51 complex is important for efficient HSV-1 assembly and plaque formation. Furthermore, we also discovered that the pUL7-pUL51 complex localizes to focal adhesions at the plasma membrane in both infected cells and in the absence of other viral proteins. The expression of pUL7-pUL51 is important to stabilize focal adhesions and maintain cell morphology in infected cells and cells infected with viruses lacking pUL7 and/or pUL51 round up more rapidly than cells infected with wild-type HSV-1. Our data suggest that, in addition to the previously reported functions in virus assembly and spread for pUL51, the pUL7-pUL51 complex is important for maintaining the attachment of infected cells to their surroundings through modulating the activity of focal adhesion complexes. IMPORTANCE Herpesviridae is a large family of highly successful human and animal pathogens. Virions of these viruses are composed of many different proteins, most of which are contained within the tegument, a complex structural layer between the nucleocapsid and the envelope within virus particles. Tegument proteins have important roles in assembling virus particles as well as modifying host cells to promote virus replication and spread. However, little is known about the function of many tegument proteins

  10. Dual responsive polymeric nanoparticles prepared by direct functionalization of polylactic acid-based polymers via graft-from ring opening metathesis polymerization.

    PubMed

    Veccharelli, Kate M; Tong, Venus K; Young, Jennifer L; Yang, Jerry; Gianneschi, Nathan C

    2016-01-11

    Polylactic acid (PLA) has found widespread use in plastics and in biomedical applications due to its biodegradability into natural benign products. However, PLA-based materials remain limited in usefulness due to difficulty of incorporating functional groups into the polymer backbone. In this paper, we report a strategy for PLA functionalization that establishes the preparation of highly derivatized materials in which ring opening metathesis polymerization (ROMP) is employed as a graft-from polymerization technique utilizing a norbornene-modified handle incorporated into the PLA backbone. As a demonstration of this new synthetic methodology, a PLA-derived nanoparticle bearing imidazole units protected with a photolabile group was prepared. The morphology of this material could be controllably altered in response to exposure of UV light or acidic pH as a stimulus. We anticipate that this graft-from approach to derivatization of PLA could find broad use in the development of modified, biodegradable PLA-based materials.

  11. N and S co-doped porous carbon spheres prepared using L-cysteine as a dual functional agent for high-performance lithium-sulfur batteries.

    PubMed

    Niu, Shuzhang; Lv, Wei; Zhou, Guangmin; He, Yanbing; Li, Baohua; Yang, Quan-Hong; Kang, Feiyu

    2015-12-28

    Nitrogen and sulfur co-doped porous carbon spheres (NS-PCSs) were prepared using L-cysteine to control the structure and functionalization during the hydrothermal reaction of glucose and the subsequent activation process. As the sulfur hosts in Li-S batteries, NS-PCSs combine strong physical confinement and surface chemical interaction to improve the affinity of polysulfides to the carbon matrix.

  12. Dual function of the NK cell receptor 2B4 (CD244) in the regulation of HCV-specific CD8+ T cells.

    PubMed

    Schlaphoff, Verena; Lunemann, Sebastian; Suneetha, Pothakamuri Venkata; Jaroszewicz, Jerzy; Grabowski, Jan; Dietz, Julia; Helfritz, Fabian; Bektas, Hueseyin; Sarrazin, Christoph; Manns, Michael Peter; Cornberg, Markus; Wedemeyer, Heiner

    2011-05-01

    The outcome of viral infections is dependent on the function of CD8+ T cells which are tightly regulated by costimulatory molecules. The NK cell receptor 2B4 (CD244) is a transmembrane protein belonging to the Ig superfamily which can also be expressed by CD8+ T cells. The aim of this study was to analyze the role of 2B4 as an additional costimulatory receptor regulating CD8+ T cell function and in particular to investigate its implication for exhaustion of hepatitis C virus (HCV)-specific CD8+ T cells during persistent infection. We demonstrate that (i) 2B4 is expressed on virus-specific CD8+ T cells during acute and chronic hepatitis C, (ii) that 2B4 cross-linking can lead to both inhibition and activation of HCV-specific CD8+ T cell function, depending on expression levels of 2B4 and the intracellular adaptor molecule SAP and (iii) that 2B4 stimulation may counteract enhanced proliferation of HCV-specific CD8+ T cells induced by PD1 blockade. We suggest that 2B4 is another important molecule within the network of costimulatory/inhibitory receptors regulating CD8+ T cell function in acute and chronic hepatitis C and that 2B4 expression levels could also be a marker of CD8+ T cell dysfunction. Understanding in more detail how 2B4 exerts its differential effects could have implications for the development of novel immunotherapies of HCV infection aiming to achieve immune control.

  13. Dual Function of the pUL7-pUL51 Tegument Protein Complex in Herpes Simplex Virus 1 Infection.

    PubMed

    Albecka, Anna; Owen, Danielle J; Ivanova, Lyudmila; Brun, Juliane; Liman, Rukayya; Davies, Laura; Ahmed, M Firoz; Colaco, Susanna; Hollinshead, Michael; Graham, Stephen C; Crump, Colin M

    2017-01-15

    The tegument of herpesviruses is a highly complex structural layer between the nucleocapsid and the envelope of virions. Tegument proteins play both structural and regulatory functions during replication and spread, but the interactions and functions of many of these proteins are poorly understood. Here we focus on two tegument proteins from herpes simplex virus 1 (HSV-1), pUL7 and pUL51, which have homologues in all other herpesviruses. We have now identified that HSV-1 pUL7 and pUL51 form a stable and direct protein-protein interaction, their expression levels rely on the presence of each other, and they function as a complex in infected cells. We demonstrate that expression of the pUL7-pUL51 complex is important for efficient HSV-1 assembly and plaque formation. Furthermore, we also discovered that the pUL7-pUL51 complex localizes to focal adhesions at the plasma membrane in both infected cells and in the absence of other viral proteins. The expression of pUL7-pUL51 is important to stabilize focal adhesions and maintain cell morphology in infected cells and cells infected with viruses lacking pUL7 and/or pUL51 round up more rapidly than cells infected with wild-type HSV-1. Our data suggest that, in addition to the previously reported functions in virus assembly and spread for pUL51, the pUL7-pUL51 complex is important for maintaining the attachment of infected cells to their surroundings through modulating the activity of focal adhesion complexes.

  14. Metal-Free Radical [2+2+1] Carbocyclization of Benzene-Linked 1,n-Enynes: Dual C(sp(3))-H Functionalization Adjacent to a Heteroatom.

    PubMed

    Hu, Ming; Fan, Jian-Hong; Liu, Yu; Ouyang, Xuan-Hui; Song, Ren-Jie; Li, Jin-Heng

    2015-08-10

    A new metal-free oxidative radical [2+2+1] carbocyclization of benzene-linked 1,n-enynes with two C(sp(3))-H bonds adjacent to the same heteroatom is described. This method achieves two C(sp(3))-H oxidative functionalizations and an annulation, thus providing efficient and general access to a variety of fused five-membered carbocyclic hydrocarbons.

  15. Dual function of a bee (Apis cerana) inhibitor cysteine knot peptide that acts as an antifungal peptide and insecticidal venom toxin.

    PubMed

    Park, Hee Geun; Kyung, Seung Su; Lee, Kwang Sik; Kim, Bo Yeon; Choi, Yong Soo; Yoon, Hyung Joo; Kwon, Hyung Wook; Je, Yeon Ho; Jin, Byung Rae

    2014-12-01

    Inhibitor cysteine knot (ICK) peptides exhibit ion channel blocking, insecticidal, and antimicrobial activities, but currently, no functional roles for bee-derived ICK peptides have been identified. In this study, a bee (Apis cerana) ICK peptide (AcICK) that acts as an antifungal peptide and as an insecticidal venom toxin was identified. AcICK contains an ICK fold that is expressed in the epidermis, fat body, or venom gland and is present as a 6.6-kDa peptide in bee venom. Recombinant AcICK peptide (expressed in baculovirus-infected insect cells) bound directly to Beauveria bassiana and Fusarium graminearum, but not to Escherichia coli or Bacillus thuringiensis. Consistent with these findings, AcICK showed antifungal activity, indicating that AcICK acts as an antifungal peptide. Furthermore, AcICK expression is induced in the fat body and epidermis after injection with B. bassiana. These results provide insight into the role of AcICK during the innate immune response following fungal infection. Additionally, we show that AcICK has insecticidal activity. Our results demonstrate a functional role for AcICK in bees: AcICK acts as an antifungal peptide in innate immune reactions in the body and as an insecticidal toxin in venom. The finding that the AcICK peptide functions with different mechanisms of action in the body and in venom highlights the two-pronged strategy that is possible with the bee ICK peptide.

  16. Dual function of the cytochrome P450 CYP76 family from Arabidopsis thaliana in the metabolism of monoterpenols and phenylurea herbicides.

    PubMed

    Höfer, René; Boachon, Benoît; Renault, Hugues; Gavira, Carole; Miesch, Laurence; Iglesias, Juliana; Ginglinger, Jean-François; Allouche, Lionel; Miesch, Michel; Grec, Sebastien; Larbat, Romain; Werck-Reichhart, Danièle

    2014-11-01

    Comparative genomics analysis unravels lineage-specific bursts of gene duplications related to the emergence of specialized pathways. The CYP76C subfamily of cytochrome P450 enzymes is specific to Brassicaceae. Two of its members were recently associated with monoterpenol metabolism. This prompted us to investigate the CYP76C subfamily genetic and functional diversification. Our study revealed high rates of CYP76C gene duplication and loss in Brassicaceae, suggesting the association of the CYP76C subfamily with species-specific adaptive functions. Gene differential expression and enzyme functional specialization in Arabidopsis thaliana, including metabolism of different monoterpenols and formation of different products, support this hypothesis. In addition to linalool metabolism, CYP76C1, CYP76C2, and CYP76C4 metabolized herbicides belonging to the class of phenylurea. Their ectopic expression in the whole plant conferred herbicide tolerance. CYP76Cs from A. thaliana. thus provide a first example of promiscuous cytochrome P450 enzymes endowing effective metabolism of both natural and xenobiotic compounds. Our data also suggest that the CYP76C gene family provides a suitable genetic background for a quick evolution of herbicide resistance.

  17. Dual Function of the Cytochrome P450 CYP76 Family from Arabidopsis thaliana in the Metabolism of Monoterpenols and Phenylurea Herbicides1[W][OPEN

    PubMed Central

    Höfer, René; Boachon, Benoît; Renault, Hugues; Gavira, Carole; Miesch, Laurence; Iglesias, Juliana; Ginglinger, Jean-François; Allouche, Lionel; Miesch, Michel; Grec, Sebastien; Larbat, Romain; Werck-Reichhart, Danièle

    2014-01-01

    Comparative genomics analysis unravels lineage-specific bursts of gene duplications related to the emergence of specialized pathways. The CYP76C subfamily of cytochrome P450 enzymes is specific to Brassicaceae. Two of its members were recently associated with monoterpenol metabolism. This prompted us to investigate the CYP76C subfamily genetic and functional diversification. Our study revealed high rates of CYP76C gene duplication and loss in Brassicaceae, suggesting the association of the CYP76C subfamily with species-specific adaptive functions. Gene differential expression and enzyme functional specialization in Arabidopsis thaliana, including metabolism of different monoterpenols and formation of different products, support this hypothesis. In addition to linalool metabolism, CYP76C1, CYP76C2, and CYP76C4 metabolized herbicides belonging to the class of phenylurea. Their ectopic expression in the whole plant conferred herbicide tolerance. CYP76Cs from A. thaliana. thus provide a first example of promiscuous cytochrome P450 enzymes endowing effective metabolism of both natural and xenobiotic compounds. Our data also suggest that the CYP76C gene family provides a suitable genetic background for a quick evolution of herbicide resistance. PMID:25082892

  18. Dual beam optical interferometer

    NASA Technical Reports Server (NTRS)

    Gutierrez, Roman C. (Inventor)

    2003-01-01

    A dual beam interferometer device is disclosed that enables moving an optics module in a direction, which changes the path lengths of two beams of light. The two beams reflect off a surface of an object and generate different speckle patterns detected by an element, such as a camera. The camera detects a characteristic of the surface.

  19. OsSUV3 dual helicase functions in salinity stress tolerance by maintaining photosynthesis and antioxidant machinery in rice (Oryza sativa L. cv. IR64).

    PubMed

    Tuteja, Narendra; Sahoo, Ranjan Kumar; Garg, Bharti; Tuteja, Renu

    2013-10-01

    To overcome the salinity-induced loss of crop yield, a salinity-tolerant trait is required. The SUV3 helicase is involved in the regulation of RNA surveillance and turnover in mitochondria, but the helicase activity of plant SUV3 and its role in abiotic stress tolerance have not been reported so far. Here we report that the Oryza sativa (rice) SUV3 protein exhibits DNA and RNA helicase, and ATPase activities. Furthermore, we report that SUV3 is induced in rice seedlings in response to high levels of salt. Its expression, driven by a constitutive cauliflower mosaic virus 35S promoter in IR64 transgenic rice plants, confers salinity tolerance. The T1 and T2 sense transgenic lines showed tolerance to high salinity and fully matured without any loss in yields. The T2 transgenic lines also showed tolerance to drought stress. These results suggest that the introduced trait is functional and stable in transgenic rice plants. The rice SUV3 sense transgenic lines showed lesser lipid peroxidation, electrolyte leakage and H2 O2 production, along with higher activities of antioxidant enzymes under salinity stress, as compared with wild type, vector control and antisense transgenic lines. These results suggest the existence of an efficient antioxidant defence system to cope with salinity-induced oxidative damage. Overall, this study reports that plant SUV3 exhibits DNA and RNA helicase and ATPase activities, and provides direct evidence of its function in imparting salinity stress tolerance without yield loss. The possible mechanism could be that OsSUV3 helicase functions in salinity stress tolerance by improving photosynthesis and antioxidant machinery in transgenic rice.

  20. 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.

  1. FabQ, a dual-function dehydratase/isomerase, circumvents the last step of the classical fatty acid synthesis cycle.

    PubMed

    Bi, Hongkai; Wang, Haihong; Cronan, John E

    2013-09-19

    In the classical anaerobic pathway of unsaturated fatty acid biosynthesis, that of Escherichia coli, the double bond is introduced into the growing acyl chain by the FabA dehydratase/isomerase. Another dehydratase, FabZ, functions in the chain elongation cycle. In contrast, Aerococcus viridans has only a single FabA/FabZ homolog we designate FabQ. FabQ can not only replace the function of E. coli FabZ in vivo, but it also catalyzes the isomerization required for unsaturated fatty acid biosynthesis. Most strikingly, FabQ in combination with E. coli FabB imparts the surprising ability to bypass reduction of the trans-2-acyl-ACP intermediates of classical fatty acid synthesis. FabQ allows elongation by progressive isomerization reactions to form the polyunsaturated fatty acid, 3-hydroxy-cis-5, 7-hexadecadienoic acid, both in vitro and in vivo. FabQ therefore provides a potential pathway for bacterial synthesis of polyunsaturated fatty acids.

  2. FabQ, a Dual-Function Dehydratase/Isomerase, Circumvents the Last Step of the Classical Fatty Acid Synthesis Cycle

    PubMed Central

    Bi, Hongkai; Wang, Haihong; Cronan, John E.

    2015-01-01

    SUMMARY In the classical anaerobic pathway of unsaturated fatty acid biosynthesis, that of Escherichia coli, the double bond is introduced into the growing acyl chain by the FabA dehydratase/isomerase. Another dehydratase, FabZ, functions in the chain elongation cycle. In contrast, Aerococcus viridans has only a single FabA/FabZ homolog we designate FabQ. FabQ can not only replace the function of E. coli FabZ in vivo, but it also catalyzes the isomerization required for unsaturated fatty acid biosynthesis. Most strikingly, FabQ in combination with E. coli FabB imparts the surprising ability to bypass reduction of the trans-2-acyl-ACP intermediates of classical fatty acid synthesis. FabQ allows elongation by progressive isomerization reactions to form the polyunsaturated fatty acid, 3-hydroxy-cis-5, 7-hexadecadienoic acid, both in vitro and in vivo. FabQ therefore provides a potential pathway for bacterial synthesis of polyunsaturated fatty acids. PMID:23972938

  3. Hierarchical Core/Shell NiCo2O4@NiCo2O4 Nanocactus Arrays with Dual-functionalities for High Performance Supercapacitors and Li-ion Batteries.

    PubMed

    Cheng, Jinbing; Lu, Yang; Qiu, Kangwen; Yan, Hailong; Xu, Jinyou; Han, Lei; Liu, Xianming; Luo, Jingshan; Kim, Jang-Kyo; Luo, Yongsong

    2015-07-01

    We report the synthesis of three dimensional (3D) NiCo2O4@NiCo2O4 nanocactus arrays grown directly on a Ni current collector using a facile solution method followed by electrodeposition. They possess a unique 3D hierarchical core-shell structure with large surface area and dual-functionalities that can serve as electrodes for both supercapacitors (SCs) and lithium-ion batteries (LIBs). As the SC electrode, they deliver a remarkable specific capacitance of 1264 F g(-1) at a current density of 2 A g(-1) and ~93.4% of capacitance retention after 5000 cycles at 2 A g(-1). When used as the anode for LIBs, a high reversible capacity of 925 mA h g(-1) is achieved at a rate of 120 mA g(-1) with excellent cyclic stability and rate capability. The ameliorating features of the NiCo2O4 core/shell structure grown directly on highly conductive Ni foam, such as hierarchical mesopores, numerous hairy needles and a large surface area, are responsible for the fast electron/ion transfer and large active sites which commonly contribute to the excellent electrochemical performance of both the SC and LIB electrodes.

  4. Hierarchical Core/Shell NiCo2O4@NiCo2O4 Nanocactus Arrays with Dual-functionalities for High Performance Supercapacitors and Li-ion Batteries

    NASA Astrophysics Data System (ADS)

    Cheng, Jinbing; Lu, Yang; Qiu, Kangwen; Yan, Hailong; Xu, Jinyou; Han, Lei; Liu, Xianming; Luo, Jingshan; Kim, Jang-Kyo; Luo, Yongsong

    2015-07-01

    We report the synthesis of three dimensional (3D) NiCo2O4@NiCo2O4 nanocactus arrays grown directly on a Ni current collector using a facile solution method followed by electrodeposition. They possess a unique 3D hierarchical core-shell structure with large surface area and dual-functionalities that can serve as electrodes for both supercapacitors (SCs) and lithium-ion batteries (LIBs). As the SC electrode, they deliver a remarkable specific capacitance of 1264 F g-1 at a current density of 2 A g-1 and ~93.4% of capacitance retention after 5000 cycles at 2 A g-1. When used as the anode for LIBs, a high reversible capacity of 925 mA h g-1 is achieved at a rate of 120 mA g-1 with excellent cyclic stability and rate capability. The ameliorating features of the NiCo2O4 core/shell structure grown directly on highly conductive Ni foam, such as hierarchical mesopores, numerous hairy needles and a large surface area, are responsible for the fast electron/ion transfer and large active sites which commonly contribute to the excellent electrochemical performance of both the SC and LIB electrodes.

  5. Synthesis of dual-functional targeting probes for cancer theranostics based on iron oxide nanoparticles coated by centipede-like polymer connected with pH-responsive anticancer drug.

    PubMed

    Zhao, Haochen; Li, Zhiping; Yang, Bohan; Wang, Jingyuan; Li, Yapeng

    2015-01-01

    A tumor-targeted and pH-responsive drug release system based on superparamagnetic iron oxide nanoparticles (IONPs) coated by poly(ethylene glycol) (PEG) and dodecylamine (DDA)-modified polyitaconic acid (PIA) connecting with bortezomib (BTZ) (PIA-PEG-DDA-BTZ@IOs) has been constructed and characterized. The anticancer drug BTZ was first conjugated using dopamine as the linker via catechol borate ester bond, which is acid cleavable and used as an ideal pH-responsive drug release system. The IONPs were then coated by PIA-PEG-DDA-BTZ to form micelles with good biocompatibility. The conjugates were further designed to target liver cancer cells overexpressing vascular endothelial growth factor (VEGF) by the targeting molecule anti-vascular endothelial growth factor (anti-VEGF). The magnetic resonance imaging showed that the targeting capability of IONPs-anti-VEGF conjugates to Hep G2 cells was more significant than that of non-anti-VEGF IONPs. From the above, this kind of novel dual-functional targeting probe could provide a new idea for the diagnosis and treatment of cancer.

  6. Hierarchical Core/Shell NiCo2O4@NiCo2O4 Nanocactus Arrays with Dual-functionalities for High Performance Supercapacitors and Li-ion Batteries

    PubMed Central

    Cheng, Jinbing; Lu, Yang; Qiu, Kangwen; Yan, Hailong; Xu, Jinyou; Han, Lei; Liu, Xianming; Luo, Jingshan; Kim, Jang-Kyo; Luo, Yongsong

    2015-01-01

    We report the synthesis of three dimensional (3D) NiCo2O4@NiCo2O4 nanocactus arrays grown directly on a Ni current collector using a facile solution method followed by electrodeposition. They possess a unique 3D hierarchical core-shell structure with large surface area and dual-functionalities that can serve as electrodes for both supercapacitors (SCs) and lithium-ion batteries (LIBs). As the SC electrode, they deliver a remarkable specific capacitance of 1264 F g−1 at a current density of 2 A g−1 and ~93.4% of capacitance retention after 5000 cycles at 2 A g−1. When used as the anode for LIBs, a high reversible capacity of 925 mA h g−1 is achieved at a rate of 120 mA g−1 with excellent cyclic stability and rate capability. The ameliorating features of the NiCo2O4 core/shell structure grown directly on highly conductive Ni foam, such as hierarchical mesopores, numerous hairy needles and a large surface area, are responsible for the fast electron/ion transfer and large active sites which commonly contribute to the excellent electrochemical performance of both the SC and LIB electrodes. PMID:26131926

  7. K4Nb6O17·4.5H2O: a novel dual functional material with quick photoreduction of Cr(VI) and high adsorptive capacity of Cr(III).

    PubMed

    Ma, Yuli; Liu, Xiaoqing; Li, Yang; Su, Yiguo; Chai, Zhanli; Wang, Xiaojing

    2014-08-30

    A series of orthorhombic phase K4Nb6O17·4.5H2O was synthesized via a hydrothermal approach. When presented in an acidic pH range, K4Nb6O17·4.5H2O showed a strong ability in quick reduction from Cr(VI) to Cr(III). The resulted Cr(III) ions were removed by an effective adsorption through simply adjusting the solution pH from strong acidity to near neutrality, owing to the sample's unique nano-sheet structure with a wide layer spacing. The Cr(III) ions adsorbed onto samples were released again for reusing by eluting with 1molL(-1) HCl solution, and K4Nb6O17·4.5H2O regenerated by immersing in a KOH solution. The reduction efficiency of Cr(VI) was still up to 98% after irradiation for 60min, and the removal efficiency of Cr(III) ions was as high as 83% even after five cycles. Therefore, K4Nb6O17·4.5H2O is clearly demonstrated to be an excellent dual functional material with quick photoreduction of Cr(VI) and high adsorptive capacity of Cr(III). The relevant materials reported herein might be found various environment-related applications.

  8. Oxygen/Alcohol Dual Thrust RCS Engines

    NASA Technical Reports Server (NTRS)

    Angstadt, Tara; Hurlbert, Eric

    1999-01-01

    A non-toxic dual thrust RCS engine offers significant operational, safety, and performance advantages to the space shuttle and the next generation RLVs. In this concept, a single engine produces two thrust levels of 25 and 870 lbf. The low thrust level is provided by the spark torch igniter, which, with the addition of 2 extra valves, can also be made to function as a vernier. A dual thrust RCS engine allows 38 verniers to be packaged more efficiently on a vehicle. These 38 vemiers improve translation and reduce cross coupling, thereby providing more pure roll, pitch, and yaw maneuvers of the vehicle. Compared to the 6 vemiers currently on the shuttle, the 38 dual thrust engines would be 25 to 40% more efficient for the same maneuvers and attitude control. The vernier thrust level also reduces plume impingement and contamination concerns. Redundancy is also improved, thereby improving mission success reliability. Oxygen and ethanol are benign propellants which do not create explosive reaction products or contamination, as compared to hypergolic propellants. These characteristics make dual-thrust engines simpler to implement on a non-toxic reaction control system. Tests at WSTF in August 1999 demonstrated a dual-thrust concept that is successful with oxygen and ethanol. Over a variety of inlet pressures and mixture ratios at 22:1 area ratio, the engine produced between 230 and 297 sec Isp, and thrust levels from 8 lbf. to 50 lbf. This paper describes the benefits of dual-thrust engines and the recent results from tests at WSTF.

  9. Reconstitution of Proapoptotic BAK Function in Liposomes Reveals a Dual Role for Mitochondrial Lipids in the BAK-driven Membrane Permeabilization Process*

    PubMed Central

    Landeta, Olatz; Landajuela, Ane; Gil, David; Taneva, Stefka; DiPrimo, Carmelo; Sot, Begoña; Valle, Mikel; Frolov, Vadim A.; Basañez, Gorka

    2011-01-01

    BAK is a key effector of mitochondrial outer membrane permeabilization (MOMP) whose molecular mechanism of action remains to be fully dissected in intact cells, mainly due to the inherent complexity of the intracellular apoptotic machinery. Here we show that the core features of the BAK-driven MOMP pathway can be reproduced in a highly simplified in vitro system consisting of recombinant human BAK lacking the carboxyl-terminal 21 residues (BAKΔC) and tBID in combination with liposomes bearing an appropriate lipid environment. Using this minimalist reconstituted system we established that tBID suffices to trigger BAKΔC membrane insertion, oligomerization, and pore formation. Furthermore, we demonstrate that tBID-activated BAKΔC permeabilizes the membrane by forming structurally dynamic pores rather than a large proteinaceous channel of fixed size. We also identified two distinct roles played by mitochondrial lipids along the molecular pathway of BAKΔC-induced membrane permeabilization. First, using several independent approaches, we showed that cardiolipin directly interacts with BAKΔC, leading to a localized structural rearrangement in the protein that “primes” BAKΔC for interaction with tBID. Second, we provide evidence that selected curvature-inducing lipids present in mitochondrial membranes specifically modulate the energetic expenditure required to create the BAKΔC pore. Collectively, our results support the notion that BAK functions as a direct effector of MOMP akin to BAX and also adds significantly to the growing evidence indicating that mitochondrial membrane lipids are actively implicated in BCL-2 protein family function. PMID:21196599

  10. Enhanced in planta Fitness through Adaptive Mutations in EfpR, a Dual Regulator of Virulence and Metabolic Functions in the Plant Pathogen Ralstonia solanacearum

    PubMed Central

    Rengel, David; Barlet, Xavier; Gouzy, Jérôme

    2016-01-01

    Experimental evolution of the plant pathogen Ralstonia solanacearum, where bacteria were maintained on plant lineages for more than 300 generations, revealed that several independent single mutations in the efpR gene from populations propagated on beans were associated with fitness gain on bean. In the present work, novel allelic efpR variants were isolated from populations propagated on other plant species, thus suggesting that mutations in efpR were not solely associated to a fitness gain on bean, but also on additional hosts. A transcriptomic profiling and phenotypic characterization of the efpR deleted mutant showed that EfpR acts as a global catabolic repressor, directly or indirectly down-regulating the expression of multiple metabolic pathways. EfpR also controls virulence traits such as exopolysaccharide production, swimming and twitching motilities and deletion of efpR leads to reduced virulence on tomato plants after soil drenching inoculation. We studied the impact of the single mutations that occurred in efpR during experimental evolution and found that these allelic mutants displayed phenotypic characteristics similar to the deletion mutant, although not behaving as complete loss-of-function mutants. These adaptive mutations therefore strongly affected the function of efpR, leading to an expanded metabolic versatility that should benefit to the evolved clones. Altogether, these results indicated that EfpR is a novel central player of the R. solanacearum virulence regulatory network. Independent mutations therefore appeared during experimental evolution in the evolved clones, on a crucial node of this network, to favor adaptation to host vascular tissues through regulatory and metabolic rewiring. PMID:27911943

  11. Myxoma virus protein M029 is a dual function immunomodulator that inhibits PKR and also conscripts RHA/DHX9 to promote expanded host tropism and viral replication.

    PubMed

    Rahman, Masmudur M; Liu, Jia; Chan, Winnie M; Rothenburg, Stefan; McFadden, Grant

    2013-01-01

    Myxoma virus (MYXV)-encoded protein M029 is a member of the poxvirus E3 family of dsRNA-binding proteins that antagonize the cellular interferon signaling pathways. In order to investigate additional functions of M029, we have constructed a series of targeted M029-minus (vMyx-M029KO and vMyx-M029ID) and V5-tagged M029 MYXV. We found that M029 plays a pivotal role in determining the cellular tropism of MYXV in all mammalian cells tested. The M029-minus viruses were able to replicate only in engineered cell lines that stably express a complementing protein, such as vaccinia E3, but underwent abortive or abated infection in all other tested mammalian cell lines. The M029-minus viruses were dramatically attenuated in susceptible host European rabbits and caused no observable signs of myxomatosis. Using V5-tagged M029 virus, we observed that M029 expressed as an early viral protein is localized in both the nuclear and cytosolic compartments in virus-infected cells, and is also incorporated into virions. Using proteomic approaches, we have identified Protein Kinase R (PKR) and RNA helicase A (RHA)/DHX9 as two cellular binding partners of M029 protein. In virus-infected cells, M029 interacts with PKR in a dsRNA-dependent manner, while binding with DHX9 was not dependent on dsRNA. Significantly, PKR knockdown in human cells rescued the replication defect of the M029-knockout viruses. Unexpectedly, this rescue of M029-minus virus replication by PKR depletion could then be reversed by RHA/DHX9 knockdown in human monocytic THP1 cells. This indicates that M029 not only inhibits generic PKR anti-viral pathways, but also binds and conscripts RHA/DHX9 as a pro-viral effector to promote virus replication in THP1 cells. Thus, M029 is a critical host range and virulence factor for MYXV that is required for replication in all mammalian cells by antagonizing PKR-mediated anti-viral functions, and also conscripts pro-viral RHA/DHX9 to promote viral replication specifically in myeloid

  12. Myxoma Virus Protein M029 Is a Dual Function Immunomodulator that Inhibits PKR and Also Conscripts RHA/DHX9 to Promote Expanded Host Tropism and Viral Replication

    PubMed Central

    Rahman, Masmudur M.; Liu, Jia; Chan, Winnie M.; Rothenburg, Stefan; McFadden, Grant

    2013-01-01

    Myxoma virus (MYXV)-encoded protein M029 is a member of the poxvirus E3 family of dsRNA-binding proteins that antagonize the cellular interferon signaling pathways. In order to investigate additional functions of M029, we have constructed a series of targeted M029-minus (vMyx-M029KO and vMyx-M029ID) and V5-tagged M029 MYXV. We found that M029 plays a pivotal role in determining the cellular tropism of MYXV in all mammalian cells tested. The M029-minus viruses were able to replicate only in engineered cell lines that stably express a complementing protein, such as vaccinia E3, but underwent abortive or abated infection in all other tested mammalian cell lines. The M029-minus viruses were dramatically attenuated in susceptible host European rabbits and caused no observable signs of myxomatosis. Using V5-tagged M029 virus, we observed that M029 expressed as an early viral protein is localized in both the nuclear and cytosolic compartments in virus-infected cells, and is also incorporated into virions. Using proteomic approaches, we have identified Protein Kinase R (PKR) and RNA helicase A (RHA)/DHX9 as two cellular binding partners of M029 protein. In virus-infected cells, M029 interacts with PKR in a dsRNA-dependent manner, while binding with DHX9 was not dependent on dsRNA. Significantly, PKR knockdown in human cells rescued the replication defect of the M029-knockout viruses. Unexpectedly, this rescue of M029-minus virus replication by PKR depletion could then be reversed by RHA/DHX9 knockdown in human monocytic THP1 cells. This indicates that M029 not only inhibits generic PKR anti-viral pathways, but also binds and conscripts RHA/DHX9 as a pro-viral effector to promote virus replication in THP1 cells. Thus, M029 is a critical host range and virulence factor for MYXV that is required for replication in all mammalian cells by antagonizing PKR-mediated anti-viral functions, and also conscripts pro-viral RHA/DHX9 to promote viral replication specifically in myeloid

  13. The dual role of oxygen functions in coal pretreatment and liquefaction: Crosslinking and cleavage reactions. Seventh quarterly report, September 30, 1992--December 31, 1992

    SciTech Connect

    Serio, M.A.; Kroo, E.; Charpenay, S.; Solomon, P.R.

    1992-12-31

    The work during the past quarter under Task 2 has focused on the investigation of FT-IR methods for measuring carboxyl and phenolic functions. Fourier transform infrared (FT-IR) spectra of coal contain a wealth of information that can be utilized in the development of quantitative analysis routines based on least squares curvefitting. Because of the importance of the carboxylate groups in retrogressive reactions, recent efforts have focused on the C=O stretching region. Raw and modified coal samples (acid washed, demineralized, and cation exchanged) were analyzed in order to validate the proposed band assignments in the C=O stretching region. This parameter set differentiates free carbonyl (B2) and hydrogen-bonded carbonyl (B4) from carboxylic acid carbonyl (B3) and carboxylate (B7). One test of these assignments, which are based on literature data, is to plot B3 versus B7. This should be linear, assuming that the sum of the free carboxyl and carboxylate groups is constant and that the intensity of the overlapped aromatic ring band in B7 is also constant. This relationship was found to hold for a set of raw, acid washed, and acid washed/cation-exchanged Zap coals. The work under Task 3 has involved (1) completion of the synthesis of the -C-C-0- linked, methoxy substituted lignin-network polymer, -- C{sub 6}H{sub 3}(o-OMe)-O-CH{sub 2}CH{sub 2}]{sub {eta}} -- polymer, (2) Analysis of the polymer via depolymerization under pyrolysis-FIMS (Py-FIMS) conditions, and (3) testing of several routes to selective cleavage of the O-Methyl bond so that the relative crosslinking tendencies of the methylated and unmethylated versions of the polymer could be determined.

  14. Multifunctional Photosensitizer Grafted on Polyethylene Glycol and Polyethylenimine Dual-Functionalized Nanographene Oxide for Cancer-Targeted Near-Infrared Imaging and Synergistic Phototherapy.

    PubMed

    Luo, Shenglin; Yang, Zhangyou; Tan, Xu; Wang, Yang; Zeng, Yiping; Wang, Yu; Li, Changming; Li, Rong; Shi, Chunmeng

    2016-07-13

    The integration of photodynamic therapy (PDT) with photothermal therapy (PTT) offers improved efficacy in cancer phototherapy. Herein, a PDT photosensitizer (IR-808) with cancer-targeting ability and near-infrared (NIR) sensitivity was chemically conjugated to both polyethylene glycol (PEG)- and branched polyethylenimine (BPEI)-functionalized nanographene oxide (NGO). Because the optimal laser wavelength (808 nm) of NGO for PTT is consistent with that of IR-808 for PDT, the IR-808-conjugated NGO sheets (NGO-808, 20-50 nm) generated both large amounts of reactive oxygen species (ROS) and local hyperthermia as a result of 808 nm laser irradiation. With PEG- and BPEI-modified NGO as the carrier, the tumor cellular uptake of NGO-808 exhibited higher efficacy than that of strongly hydrophobic free IR-808. Through evaluation with both human and mouse cancer cells, NGO-808 was demonstrated to provide significantly enhanced PDT and PTT effects compared to individual PDT using IR-808 or PTT using NGO. Furthermore, NGO-808 preferentially accumulated in cancer cells as mediated by organic-anion transporting polypeptides (OATPs) overexpressed in many cancer cells, providing the potential for highly specific cancer phototherapy. Using the targeting ability of NGO-808, in vivo NIR fluorescence imaging enabled tumors and their margins to be clearly visualized at 48 h after intravenous injection, providing a theranostic platform for imaging-guided cancer phototherapy. Remarkably, after a single injection of NGO-808 and 808 nm laser irradiation for 5 min, the tumors in two tumor xenograft models were ablated completely, and no tumor recurrence was observed. After treatment with NGO-808, no obvious toxicity was detected in comparison to control groups. Thus, high-performance cancer phototherapy with minimal side effects was afforded from synergistic PDT/PTT treatment and cancer-targeted accumulation of NGO-808.

  15. Dual-function nanostructured lipid carriers to deliver IR780 for breast cancer treatment: Anti-metastatic and photothermal anti-tumor therapy.

    PubMed

    Li, Huipeng; Wang, Kaikai; Yang, Xue; Zhou, Yiwen; Ping, Qineng; Oupicky, David; Sun, Minjie

    2017-02-01

    Cancer treatments that use a combination of approaches with the ability to affect multiple disease pathways have proven highly effective. The present study reports on CXCR4-targeted nanostructured lipid carriers (NLCs) with a CXCR4 antagonist AMD3100 in the shell (AMD-NLCs). AMD-NLCs loaded with IR780 (IR780-AMD-NLCs) reduced the invasiveness of cancer cells, while simultaneously mediating efficient tumor targeting and photothermal therapeutic outcomes. We present the combined effect of encapsulated IR780 on photothermal therapy and of the AMD3100 coating on tumor targeting, CXCR4 antagonism and inhibition of cancer cell invasion and breast cancer lung metastasis in vitro and in vivo. IR780-AMD-NLCs exhibited excellent IR780 loading capacity and AMD3100 coating efficiency. The photothermal properties of IR780 were improved by encapsulation in NLCs. The encapsulated IR780 displayed better heat generating efficiency than free IR780 when exposed to repeated laser irradiation. CXCR4 antagonism and cell invasion assays confirmed that IR780-AMD-NLCs fully inhibited CXCR4 while IR780-NLCs did not function as CXCR4 antagonists. AMD3100-coated NLCs accumulated at high levels in tumors, as judged by in vivo imaging and biodistribution assays. Furthermore, CXCR4-targeted NLCs exhibited an encouraging photothermal anti-tumor effect as well as anti-metastatic efficacy in vivo. These findings suggest that this simple and stable CXCR4-targeted IR780 delivery system holds great promise for prevention of metastasis and for photothermal treatment of tumors.

  16. The dual role of oxygen functions in coal pretreatment and liquefaction: Crosslinking and cleavage reactions. Fifth quarterly report, April 1, 1992--June 30, 1992

    SciTech Connect

    Serio, M.A.; Kroo, E.; Teng, H.; Charpenay, S.; Solomon, P.R.

    1992-12-01

    Preparation of ion-exchanged (including barium, calcium and potassium) demineralized Zap and Wyodak has been completed. Both vacuum dried and moist samples were prepared, using procedures described previously. The modified samples were subjected to functional group analysis as KBr pellets with FT-IR, and programmed pyrolysis analysis with TG-FTIR. Liquefaction experiments of these samples were also performed and products were analyzed. The data show that both the pyrolytic tar and liquefaction yields decrease with the extent of ion-exchange, i.e., in the order of (demineralized) > (ion-exchanged at pH 8) > (ion-exchanged at pH 12.5). For the pyrolysis of vacuum dried samples, the tar yield was higher for the potassium-exchanged coals than the calcium and barium-exchanged samples, suggesting that bivalent cations tighten the coal structure by cross-linking coal fragments and make it more difficult for tar molecules to escape. The liquefaction results show that the potassium-exchanged samples have higher liquefaction yields (especially asphaltenes) than for the barium- and calcium-exchanged samples. This can probably be attributed to the same reason for the high pyrolytic tar yield, i.e., that bivalent cations can serve as a cross-linking agents to tighten the coal structure. Remoisturization of vacuum dried Zap and Wyodak was done in the attempt to understand if moisture uptake for low rank coals is a reversible process and to see if moisture influences the role of the cations. Preliminary results show that the moisture content can reach that of the raw samples by remoisturization for Zap, but not for Wyodak. Furthermore, the chemical structure of the coal samples seems to have been changed by remoisturization, since different C0{sub 2} evolution behaviors were observed.

  17. Dual-Charged Hollow Fiber Membranes for Low-Pressure Nanofiltration Based on Polyelectrolyte Complexes: One-Step Fabrication with Tailored Functionalities.

    PubMed

    Gherasim, Cristina Veronica; Luelf, Tobias; Roth, Hannah; Wessling, Matthias

    2016-07-27

    A new nanofiltration (NF) hollow fiber membrane is developed by using two oppositely charged polyelectrolytes coagulating into a polyelectrolyte complex (PEC) onto polyether sulfone base polymer. The particular membrane architecture emerges during a single-step procedure, allowing setting both the porous negatively charged support of the hollow fiber and the separation layer containing also the positive polyelectrolyte (PEI/PDADMAC) through a single layer dry-jet wet spinning process. The novelty is two-pronged: the composition of the hollow fiber membrane itself and its fabrication procedure (one-step fabrication of membranes employing polyelectrolytes). These result in highly permeable hollow fiber membranes with a stable separation layer and performance at par with the membranes reported in literature obtained by multistep processes. More importantly, the membranes are obtained through a simple, very fast (one-step), and less expensive procedure. The best performance among these newly obtained hollow-fiber membranes is achieved by PD5% hollow fiber (MWCO of 300 Da), which showed 7.6 L/m(2)·h·bar permeability and ∼90% rejection of MgCl2, MgSO4, and Na2SO4 at 2 bar pressure. Thus, the resulting membranes not only have the advantages of the hollow-fiber configuration, but perform very well at extremely low pressures (the lowest reported in the literature). The broad impact of the results presented in this Article lies in the potential to dramatically reduce both the fabrication (duration and complexity) and the price and desalination costs of highly performing NF hollow fiber membranes. These might result in interesting potential applications and open new directions toward designing efficient functional NF hollow fibers for water desalination.

  18. Discrete-continuous variable structural synthesis using dual methods

    NASA Technical Reports Server (NTRS)

    Schmit, L. A.; Fleury, C.

    1980-01-01

    Approximation concepts and dual methods are extended to solve structural synthesis problems involving a mix of discrete and continuous sizing type of design variables. Pure discrete and pure continuous variable problems can be handled as special cases. The basic mathematical programming statement of the structural synthesis problem is converted into a sequence of explicit approximate primal problems of separable form. These problems are solved by constructing continuous explicit dual functions, which are maximized subject to simple nonnegativity constraints on the dual variables. A newly devised gradient projection type of algorithm called DUAL 1, which includes special features for handling dual function gradient discontinuities that arise from the discrete primal variables, is used to find the solution of each dual problem. Computational implementation is accomplished by incorporating the DUAL 1 algorithm into the ACCESS 3 program as a new optimizer option. The power of the method set forth is demonstrated by presenting numerical results for several example problems, including a pure discrete variable treatment of a metallic swept wing and a mixed discrete-continuous variable solution for a thin delta wing with fiber composite skins.

  19. The Mycobacterium tuberculosis IdeR is a dual functional regulator that controls transcription of genes involved in iron acquisition, iron storage and survival in macrophages.

    PubMed

    Gold, B; Rodriguez, G M; Marras, S A; Pentecost, M; Smith, I

    2001-11-01

    In this work, we characterize genes in Mycobacterium tuberculosis that are regulated by IdeR (iron-dependent regulator), an iron-responsive DNA-binding protein of the DtxR family that has been shown to regulate iron acquisition in Mycobacterium smegmatis. To identify some of the genes that constitute the IdeR regulon, we searched the M. tuberculosis genome for promoter regions containing the consensus IdeR/DxR binding sequence. Genes preceded by IdeR boxes included a set encoding proteins necessary for iron acquisition, such as the biosynthesis of siderophores (mbtA, mbtB, mbtI), aromatic amino acids (pheA, hisE, hisB-like) and others annotated to be involved in the synthesis of iron-storage proteins (bfrA, bfrB). Some putative IdeR-regulated genes identified in this search encoded proteins predicted to be engaged in the biosynthesis of lipopolysaccharide (LPS)-like molecules (rv3402c), lipids (acpP) and peptidoglycan (murB). We analysed four promoter regions containing putative IdeR boxes, mbtA-mbtB, mbI, rv3402c and bfrA-bfd, for interaction with IdeR and for iron-dependent expression. Gel retardation experiments and DNase footprinting analyses with purified IdeR showed that IdeR binds to these IdeR boxes in vitro. Analysis of the promoters by primer extension indicated that the IdeR boxes are located near the -10 position of each promoter, suggesting that IdeR acts as a transcriptional repressor by blocking RNA polymerase binding. Using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) coupled to molecular beacons, we showed that mRNA levels of mbtA, mbtB, mbtI, rv3402c and bfd are induced 14- to 49-fold in cultures of M. tuberculosis starved for iron, whereas mRNA levels of bfrA decreased about threefold. We present evidence that IdeR not only acts as a transcriptional repressor but also functions as an activator of bfrA. Three of the IdeR- and iron-repressed genes, mbtB, mbtI and rv3402c, were induced during M. tuberculosis infection of

  20. Dual-Schemata Model

    NASA Astrophysics Data System (ADS)

    Taniguchi, Tadahiro; Sawaragi, Tetsuo

    In this paper, a new machine-learning method, called Dual-Schemata model, is presented. Dual-Schemata model is a kind of self-organizational machine learning methods for an autonomous robot interacting with an unknown dynamical environment. This is based on Piaget's Schema model, that is a classical psychological model to explain memory and cognitive development of human beings. Our Dual-Schemata model is developed as a computational model of Piaget's Schema model, especially focusing on sensori-motor developing period. This developmental process is characterized by a couple of two mutually-interacting dynamics; one is a dynamics formed by assimilation and accommodation, and the other dynamics is formed by equilibration and differentiation. By these dynamics schema system enables an agent to act well in a real world. This schema's differentiation process corresponds to a symbol formation process occurring within an autonomous agent when it interacts with an unknown, dynamically changing environment. Experiment results obtained from an autonomous facial robot in which our model is embedded are presented; an autonomous facial robot becomes able to chase a ball moving in various ways without any rewards nor teaching signals from outside. Moreover, emergence of concepts on the target movements within a robot is shown and discussed in terms of fuzzy logics on set-subset inclusive relationships.

  1. Advances in dual algorithms and convex approximation methods

    NASA Technical Reports Server (NTRS)

    Smaoui, H.; Fleury, C.; Schmit, L. A.

    1988-01-01

    A new algorithm for solving the duals of separable convex optimization problems is presented. The algorithm is based on an active set strategy in conjunction with a variable metric method. This first order algorithm is more reliable than Newton's method used in DUAL-2 because it does not break down when the Hessian matrix becomes singular or nearly singular. A perturbation technique is introduced in order to remove the nondifferentiability of the dual function which arises when linear constraints are present in the approximate problem.

  2. Solution-phase synthesis of single-crystal Cu3Si nanowire arrays on diverse substrates with dual functions as high-performance field emitters and efficient anti-reflective layers

    NASA Astrophysics Data System (ADS)

    Yuan, Fang-Wei; Wang, Chiu-Yen; Li, Guo-An; Chang, Shu-Hao; Chu, Li-Wei; Chen, Lih-Juann; Tuan, Hsing-Yu

    2013-09-01

    There is strong and growing interest in applying metal silicide nanowires as building blocks for a new class of silicide-based applications, including spintronics, nano-scale interconnects, thermoelectronics, and anti-reflective coating materials. Solution-phase environments provide versatile materials chemistry as well as significantly lower production costs compared to gas-phase synthesis. However, solution-phase synthesis of silicide nanowires remains challenging due to the lack of fundamental understanding of silicidation reactions. In this study, single-crystalline Cu3Si nanowire arrays were synthesized in an organic solvent. Self-catalyzed, dense single-crystalline Cu3Si nanowire arrays were synthesized by thermal decomposition of monophenylsilane in the presence of copper films or copper substrates at 420 to 475 °C and 10.3 MPa in supercritical benzene. The solution-grown Cu3Si nanowire arrays serve dual functions as field emitters and anti-reflective layers, which are reported on copper silicide materials for the first time. Cu3Si nanowires exhibit superior field-emission properties, with a turn-on-voltage as low as 1.16 V μm-1, an emission current density of 8 mA cm-2 at 4.9 V μm-1, and a field enhancement factor (β) of 1500. Cu3Si nanowire arrays appear black with optical absorption less than 5% between 400 and 800 nm with minimal reflectance, serving as highly efficient anti-reflective layers. Moreover, the Cu3Si nanowires could be grown on either rigid or flexible substrates (PI). This study shows that solution-phase silicide reactions are adaptable for high-quality silicide nanowire growth and demonstrates their promise towards fabrication of metal silicide-based devices.There is strong and growing interest in applying metal silicide nanowires as building blocks for a new class of silicide-based applications, including spintronics, nano-scale interconnects, thermoelectronics, and anti-reflective coating materials. Solution-phase environments

  3. Dual-Beam ELF/VLF Wave Generation at HAARP

    NASA Astrophysics Data System (ADS)

    Agrawal, D.; Moore, R. C.

    2010-12-01

    A new dual-beam HF heating model is employed to predict the effects of additional HF heating on ELF/VLF wave generation. Modeling predictions are compared with experimental observations performed in February 2008 and in July 2010, at which times the High-frequency Active Auroral Research Program (HAARP) HF heater in Gakona, Alaska performed a series of dual-beam ELF/VLF wave generation experiments. In 2008, HAARP employed a transmission format designed to determine the effect of additional HF heating on ELF/VLF wave amplitudes as a function of HF frequency and peak HF power. Model predictions match observations within reason, considering that the ambient conditions of the ionosphere are not known. In 2010, HAARP transmitted a dual-beam format that allowed for the detection of the total propagation delay between HAARP transmission and ELF/VLF signal detection on the ground. The time-of-arrival (TOA) was measured under dual-beam and single-beam heating conditions for comparative studies. Modeling results for this more recent data set are expected to be unveiled in December. Based on other recent TOA observations, however, it is expected that ionospheric reflections, which can be detected and separated using the TOA technique, may play a more important role than accounted for previously. For each of these cases, the new dual-beam HF heating model makes deterministic predictions (for a variety of ambient ionospheric conditions) regarding the relative change in ELF/VLF amplitude observed on the ground (as a function of HF frequency and power) and the dominant signal TOA. In this paper, we present a complete analysis comparing experimental observations of ELF/VLF wave generation under dual-beam heating conditions with the predictions of the dual-beam HF heating model. Based on the dual-beam TOA observations, we suggest several model improvements to be implemented in the future and furthermore provide several recommendations to guide future dual-beam heating experiments.

  4. Dynamic and static behavior of the H...π and E...π interactions in EH₂ adducts of benzene π-system (E = O, S, Se and Te), elucidated by QTAIM dual functional analysis.

    PubMed

    Hayashi, Satoko; Sugibayashi, Yuji; Nakanishi, Waro

    2016-04-21

    Dynamic and static behavior of the interactions in the EH2 adducts of a benzene π-system (E = O, S, Se and Te) is elucidated by applying QTAIM-DFA (QTAIM dual functional analysis). Two types of H-*-π and E-*-π interactions are detected in the adducts, where the asterisk (*) emphasizes the existence of the bond critical point (BCP) on the interaction in question. Total electron energy densities Hb(rc) are plotted versus Hb(rc) -Vb(rc)/2 [=(ℏ(2)/8m)∇(2)ρb(rc)] at BCPs in QTAIM-DFA, where Vb(rc) are the potential energy densities at BCPs. Data from the fully optimized structures are analyzed by polar (R, θ) coordinate representation. Each plot for an interaction, containing data from the perturbed structures with those of the fully optimized one, shows a specific curve, which provides important information. The plot is expressed by (θp, κp): θp corresponds to the tangent line for the plot and κp is the curvature. θ and θp are measured from the y-axis and y-direction, respectively. Moreover, (R, θ) corresponds to the static nature, (θp, κp) represents the dynamic nature of interactions. While θ classifies the interaction in question, θp characterizes it. Both values are less than 90° for all H-*-π and E-*-π interactions examined in this study; therefore, they are all classified by the pure closed-shell interactions and predicted to have the character of vdW nature. However, it is suggested that E-*-π has the nature of the stronger interaction than the case of H-*-π for dynamic behavior in the same species evaluated at the MP2 and M06-2X levels. The nature of the interactions is well analyzed and specified by applying QTAIM-DFA.

  5. Effects of the antitumor drug OSI-906, a dual inhibitor of IGF-1 receptor and insulin receptor, on the glycemic control, β-cell functions, and β-cell proliferation in male mice.

    PubMed

    Shirakawa, Jun; Okuyama, Tomoko; Yoshida, Eiko; Shimizu, Mari; Horigome, Yuka; Tuno, Takayuki; Hayasaka, Moe; Abe, Shiori; Fuse, Masahiro; Togashi, Yu; Terauchi, Yasuo

    2014-06-01

    The IGF-1 receptor has become a therapeutic target for the treatment of cancer. The efficacy of OSI-906 (linstinib), a dual inhibitor of IGF-1 receptor and insulin receptor, for solid cancers has been examined in clinical trials. The effects of OSI-906, however, on the blood glucose levels and pancreatic β-cell functions have not yet been reported. We investigated the impact of OSI-906 on glycemic control, insulin secretion, β-cell mass, and β-cell proliferation in male mice. Oral administration of OSI-906 worsened glucose tolerance in a dose-dependent manner in the wild-type mice. OSI-906 at a dose equivalent to the clinical daily dose (7.5 mg/kg) transiently evoked glucose intolerance and hyperinsulinemia. Insulin receptor substrate (IRS)-2-deficient mice and mice with diet-induced obesity, both models of peripheral insulin resistance, exhibited more severe glucose intolerance after OSI-906 administration than glucokinase-haploinsufficient mice, a model of impaired insulin secretion. Phloridzin improved the hyperglycemia induced by OSI-906 in mice. In vitro, OSI-906 showed no effect on insulin secretion from isolated islets. After daily administration of OSI-906 for a week to mice, the β-cell mass and β-cell proliferation rate were significantly increased. The insulin signals in the β-cells were apparently unaffected in those mice. Taken together, the results suggest that OSI-906 could exacerbate diabetes, especially in patients with insulin resistance. On the other hand, the results suggest that the β-cell mass may expand in response to chemotherapy with this drug.

  6. Behavior of Halogen Bonds of the Y-X⋅⋅⋅π Type (X, Y=F, Cl, Br, I) in the Benzene π System, Elucidated by Using a Quantum Theory of Atoms in Molecules Dual-Functional Analysis.

    PubMed

    Sugibayashi, Yuji; Hayashi, Satoko; Nakanishi, Waro

    2016-08-18

    The nature of halogen bonds of the Y-X-✶-π(C6 H6 ) type (X, Y=F, Cl, Br, and I) have been elucidated by using the quantum theory of atoms in molecules (QTAIM) dual-functional analysis (QTAIM-DFA), which we proposed recently. Asterisks (✶) emphasize the presence of bond-critical points (BCPs) in the interactions in question. Total electron energy densities, Hb (rc ), are plotted versus Hb (rc )-Vb (rc )/2 [=(ħ(2) /8m)∇(2) ρb (rc )] for the interactions in QTAIM-DFA, in which Vb (rc ) are potential energy densities at the BCPs. Data for perturbed structures around fully optimized structures were used for the plots, in addition to those of the fully optimized ones. The plots were analyzed by using the polar (R, θ) coordinate for the data of fully optimized structures with (θp , κp ) for those that contained the perturbed structures; θp corresponds to the tangent line of the plot and κp is the curvature. Whereas (R, θ) corresponds to the static nature, (θp , κp ) represents the dynamic nature of the interactions. All interactions in Y-X-✶-π(C6 H6 ) are classified by pure closed-shell interactions and characterized to have vdW nature, except for Y-I-✶-π(C6 H6 ) (Y=F, Cl, Br) and F-Br-✶-π(C6 H6 ), which have typical hydrogen-bond nature without covalency. I-I-✶-π(C6 H6 ) has a borderline nature between the two. Y-F-✶-π(C6 H6 ) (Y=Br, I) were optimized as bent forms, in which Y-✶-π interactions were detected. The Y-✶-π interactions in the bent forms are predicted to be substantially weaker than those in the linear F-Y-✶-π(C6 H6 ) forms.

  7. Dual-functional surfactant-templated strategy for synthesis of an in-situ N2-intercalated mesoporous WO3 photoanode for efficient visible-light-driven water oxidation.

    PubMed

    Li, Dong; Chandra, Debraj; Takeuchi, Ryouchi; Togashi, Takanari; Kurihara, Masato; Saito, Kenji; Yui, Tatsuto; Yagi, Masayuki

    2017-03-01

    N2-intercalated crystalline mesoporous tungsten trioxide (WO3) was synthesized by a thermal decomposition technique using dodecylamine (DDA) as a surfactant template with a dual functional role of an N atom source for N2 intercalation, alongside its conventional structure directing role (by micelle formation) to induce a mesoporous structure. N2 physisorption analysis showed that the specific surface area (57.3 m2 g-1) of WO3 (WO3-DDA) templated with DDA is 2.3 times higher than that (24.5 m2 g-1) of WO3 (WO3-bulk) prepared without DDA due to the mesoporous structure of WO3-DDA. The Raman spectra and XPS spectrum of WO3-DDA indicated formation of N2 intercalated into the WO3 lattice above 450 ºC. The UV-visible diffuse reflectance spectra (DRS) exhibited the significant shift of the absorption edge from 459 nm (2.70 eV) to 487 nm (2.54 eV) by 28 nm due to N2-intercalation. This could be explained by the bandgap narrowing of WO3-DDA by formation of a new intermediate N 2p orbital between the conduction band and valance band of WO3. A WO3-DDA coated ITO electrode calcined at 450 ºC generated a photoanodic current under visible light irradiation below 490 nm due to the PEC water oxidation, compared with ITO/WO3-bulk doing so below 470 nm. The incident photon-to-current conversion efficiency (IPCE = 24.5%) at 420 nm and 0.5 V vs Ag/AgCl was higher than that (2.5%) for ITO/WO3-bulk by one order of magnitude due to the N2 intercalation and the mesoporous structure of WO3-DDA.

  8. Solution-phase synthesis of single-crystal Cu3Si nanowire arrays on diverse substrates with dual functions as high-performance field emitters and efficient anti-reflective layers.

    PubMed

    Yuan, Fang-Wei; Wang, Chiu-Yen; Li, Guo-An; Chang, Shu-Hao; Chu, Li-Wei; Chen, Lih-Juann; Tuan, Hsing-Yu

    2013-10-21

    There is strong and growing interest in applying metal silicide nanowires as building blocks for a new class of silicide-based applications, including spintronics, nano-scale interconnects, thermoelectronics, and anti-reflective coating materials. Solution-phase environments provide versatile materials chemistry as well as significantly lower production costs compared to gas-phase synthesis. However, solution-phase synthesis of silicide nanowires remains challenging due to the lack of fundamental understanding of silicidation reactions. In this study, single-crystalline Cu3Si nanowire arrays were synthesized in an organic solvent. Self-catalyzed, dense single-crystalline Cu3Si nanowire arrays were synthesized by thermal decomposition of monophenylsilane in the presence of copper films or copper substrates at 420 to 475 °C and 10.3 MPa in supercritical benzene. The solution-grown Cu3Si nanowire arrays serve dual functions as field emitters and anti-reflective layers, which are reported on copper silicide materials for the first time. Cu3Si nanowires exhibit superior field-emission properties, with a turn-on-voltage as low as 1.16 V μm(-1), an emission current density of 8 mA cm(-2) at 4.9 V μm(-1), and a field enhancement factor (β) of 1500. Cu3Si nanowire arrays appear black with optical absorption less than 5% between 400 and 800 nm with minimal reflectance, serving as highly efficient anti-reflective layers. Moreover, the Cu3Si nanowires could be grown on either rigid or flexible substrates (PI). This study shows that solution-phase silicide reactions are adaptable for high-quality silicide nanowire growth and demonstrates their promise towards fabrication of metal silicide-based devices.

  9. A novel approach to fracture-risk-assessment in osteoporosis by ROI-oriented application of the Minkowski-functionals to dual x-ray absorptiometry scans of the hip

    NASA Astrophysics Data System (ADS)

    Boehm, Holger F.; Panteleon, Alexandra; Vogel, Tobias; Burklein, Dominik; Reiser, Maximilian

    2008-03-01

    Fractures of the proximal femur represent the worst complication in osteoporosis with a mortality rate of up to 50% during the first post-traumatic year. Bone mineral density (BMD) as obtained from dual energy x-ray absorptiometry (DXA) is a good predictor of fracture risk. However, there is a considerable overlap in the BMD-results between individuals who have fractured and those who have not. As DXA uses highly standardized radiographic projection images to obtain the densitometric information, it can be postulated that these images contain much more information than just mineral density. Lately, geometric dimensions, e.g. hip axis length (HAL) or femoral neck axis length (FNAL), are considered in conjunction with BMD, which may allow to enhance the predictive potential of bone mass measurements. In recent studies we sucessfully introduced a novel methodology for topological analysis of multi-dimensional graylevel datasets, that, for instance, allows to predict the ultimate mechanical strength of femoral bone specimens. The new topolocial parameters are based on the so called Minkowski Functionals (MF), which represent a set of topographical descriptors that can be used universally. Since the DXA-images are multi-graylevel datasets in 2D obtained in a standardized way, they are ideally suited to be processed by the new method. In this study we introduce a novel algorithm to evaluate DXA-scans of the proximal femur using quantitative image analysis procedures based on the MF in 2D. The analysis is conducted in four defined regions of interest in analogy to the standard densitometric evaluation. The objective is to provide a tool to identifiy individuals with critically reduced mechanical competence of the hip. The result of the new method is compared with the evaluation bone mineral density obtained by DXA, which - at present - is the clinical standard of reference.

  10. Simultaneous dual-band optical coherence tomography for endoscopic applications

    NASA Astrophysics Data System (ADS)

    Xu, Jianbing; Yu, Luoqin; Wei, Xiaoming; Wang, Xie; Chui, Po Ching; Chan, Kin Tak; Lam, Edmund Y.; Lee, Nikki P.; Wong, Kenneth K. Y.

    2014-12-01

    Dual-band optical coherence tomography (OCT) can greatly enhance the imaging contrast with potential applications in functional (spectroscopic) analysis. A new simultaneous dual-band Fourier domain mode-locked swept laser configuration for dual-band OCT is reported. It was based on a custom-designed dual-channel driver to synchronize two different wavelength bands at 1310 and 1550 nm, respectively. Two lasing wavelengths were swept simultaneously from 1260 to 1364.8 nm for the 1310-nm band and from 1500 to 1604 nm for the 1550-nm band at an A-scan rate of 45 kHz. Broadband wavelength-division multiplexing was utilized to couple two wavelength bands into a common catheter for circumferential scanning to form dual-band OCT. The proposed dual-band OCT scheme was applied to endoscopic OCT imaging of mouse esophageal wall ex vivo and human fingertip in vivo to justify the feasibility of the proposed imaging technique. The proposed dual-band OCT system is fast and easy to be implemented, which allows for in vivo high-speed biomedical imaging with potential applications in spectroscopic investigations for endoscopic imaging.

  11. Dual stage check valve

    NASA Technical Reports Server (NTRS)

    Whitten, D. E. (Inventor)

    1973-01-01

    A dual stage seat valve head arrangement is described which consists of a primary sealing point located between a fixed orifice seat and a valve poppet, and a secondary sealing point between an orifice poppet and a valve poppet. Upstream of the valve orifice is a flexible, convoluted metal diaphragm attached to the orifice poppet. Downstream of the valve orifice, a finger spring exerts a force against the valve poppet, tending to keep the valve in a closed position. The series arrangement of a double seat and poppet is able to tolerate small particle contamination while minimizing chatter by controlling throttling or metering across the secondary seat, thus preserving the primary sealing surface.

  12. Dual modification of biomolecules.

    PubMed

    Maruani, Antoine; Richards, Daniel A; Chudasama, Vijay

    2016-07-14

    With the advent of novel bioorthogonal reactions and "click" chemistry, an increasing number of strategies for the single labelling of proteins and oligonucleotides have emerged. Whilst several methods exist for the site-selective introduction of a single chemical moiety, site-selective and bioorthogonal dual modification of biomolecules remains a challenge. The introduction of multiple modules enables a plethora of permutations and combinations and can generate a variety of bioconjuguates with many potential applications. From de novo approaches on oligomers to the post-translational functionalisation of proteins, this review will highlight the main strategies to dually modify biomolecules.

  13. Dual mode warhead

    SciTech Connect

    Obrsky, J.; Alexander, A.A.; Griffen, O.H.; Foster, J.S.; Shamblen, M.

    1980-12-31

    A dual mode warhead is provided for use against both soft and hard targets and capable of sensing which type of target has been struck comprising a casing made of a ductile material containing an explosive charge and a fuze assembly. The ductile warhead casing will mushroom and later split upon striking a hard target while still confining the explosive. Proper ductility and confinement are necessary for fuze sensing. The fuze assembly contains a pair of parallel firing trains, one initiated only by high and one by low impact deceleration. The firing train actuated by low impact deceleration contains a pyrotechnic delay to allow penetration of soft targets.

  14. Dual Ectopic Thyroid with Normally Located Thyroid: A Case Report

    PubMed Central

    Kumar Choudhury, Bipul; Kaimal Saikia, Uma; Sarma, Dipti; Saikia, Mihir; Dutta Choudhury, Sarojini; Barua, Santanu; Dewri, Swapna

    2011-01-01

    Dual ectopic thyroid is a rare presentation of thyroid ectopia. Only a few cases have been reported in the world literature. Dual ectopic thyroid in the presence of a normally located thyroid is even rarer. We report a case of dual ectopic thyroid in the lingual and submandibular areas in a seventeen-year-old female with hypoplastic thyroid gland in its normal location. The patient presented with a midline swelling at the base of tongue with dysphagia. Thyroid function test revealed primary hypothyroidism. Ultrasonography of the neck showed hypoplastic thyroid in its normal location. A thyroid scan with Technetium-99 m pertechnate showed two intensely hyperfunctioning foci of ectopic thyroid tissue at a higher level in the midline consistent with dual ectopic thyroid, one at the base of tongue and the other in submental region. No uptake was seen in the normal bed. PMID:21765986

  15. Dual-Credit in Kentucky

    ERIC Educational Resources Information Center

    Stephenson, Lisa G.

    2013-01-01

    Credit-based transition programs provide high school students with opportunities to jump start their college education. The Kentucky Community and Technical College System (KCTCS) offers college credit through dual-credit programs. While KCTCS dual-credit offerings have been successful in helping high school students start their college education…

  16. Benefits of Dual Language Education

    ERIC Educational Resources Information Center

    Wallstrum, Kiara

    2009-01-01

    The focus of this paper examines how dual language education (DLE) programs are valuable. The literature shows that children do much more than just thrive in a dual language environment. According to research, children who are bilingual are cognitively, academically, intellectually, socially and verbally more advantaged than their monolingual…

  17. Automatic differentiation using vectorized hyper dual numbers

    NASA Astrophysics Data System (ADS)

    Swaroop, Kshitiz

    Sensitivity analysis is a method to measure the change in a dependent variable with respect to one or more independent variables with uses including optimization, design analysis and risk modeling. Conventional methods like finite difference suffer from both truncation, subtraction errors and cannot be used to simultaneously calculate derivatives of an output with respect to multiple inputs (commonly seen in optimization problems). Automatic Differentiation tackles all these issues successfully allowing us to calculate derivatives of any variable with respect to the independent variables in a computer program up to machine precision without any significant user input. Vectorized Hyper Dual Numbers, an extension of Hyper Dual Numbers, which allows the user to automatically calculate both the Hessian and derivative along with the function evaluation is developed for this thesis. The method is then used for the sizing and layup of a composite wind turbine blade as a proof of concept.

  18. Linear Four-Chalcogen Interactions in Radical Cationic and Dicationic Dimers of 1,5-(Dichalcogena)canes: Nature of the Interactions Elucidated by QTAIM Dual Functional Analysis with QC Calculations.

    PubMed

    Hayashi, Satoko; Nagata, Kengo; Otsuki, Shota; Nakanishi, Waro

    2017-03-15

    The dynamic and static nature of extended hypervalent interactions of the (B)E···(A)E···(A)E···(B)E type are elucidated for four center-seven electron interactions (4c-7e) in the radical cationic dimers (1·(+)) and 4c-6e in the dicationic dimers (1(2+)) of 1,5-(dichalcogena)canes (2: (A)E(CH2CH2CH2)2(B)E: (A)E, (B)E = S, Se, Te, and O). The quantum theory of atoms-in-molecules dual functional analysis (QTAIM-DFA) is applied for the analysis. Total electron energy densities Hb(rc) are plotted versus Hb(rc) - Vb(rc)/2 [= (ℏ(2)/8m)∇(2)ρb(rc)] at bond critical points (BCPs) of the interactions, where Vb(rc) values show potential energy densities at BCPs. Data from the fully optimized structures correspond to the static nature of the interactions. Those from the perturbed structures around the fully optimized ones are also plotted, in addition to those of the fully optimized ones, which represent the dynamic nature of interactions. The (B)E···(A)E-(A)E···(B)E interactions in 1(2+) are stronger than the corresponding ones in 1·(+), respectively. On the one hand, for 1(2+) with (A)E, (B)E = S, Se, and Te, (A)E···(A)E are all classified by the shared shell interactions and predicted to have the weak covalent nature, except for those in 1a(2+) ((A)E = (B)E = S) and 1d(2+) ((A)E = (B)E = Se), which have the nature of regular closed shell (r-CS)/trigonal bipyramidal adduct formation through charge transfer (CT-TBP). On the other hand, (A)E···(B)E are predicted to have the nature of r-CS/molecular complex formation through charge transfer for 1a(2+), 1b(2+) ((A)E = Se; (B)E = S), and 1d(2+) or r-CS/CT-TBP for 1c(2+) ((A)E = Te; (B)E = S), 1e(2+) ((A)E = Te; (B)E = Se), and 1f(2+) ((A)E = (B)E = Te). The (B)E···(A)E-(A)E···(B)E interactions in 1·(+) and 1(2+) are well-analyzed by applying QTAIM-DFA.

  19. Dual broadband metamaterial absorber.

    PubMed

    Kim, Young Ju; Yoo, Young Joon; Kim, Ki Won; Rhee, Joo Yull; Kim, Yong Hwan; Lee, YoungPak

    2015-02-23

    We propose polarization-independent and dual-broadband metamaterial absorbers at microwave frequencies. This is a periodic meta-atom array consisting of metal-dielectric-multilayer truncated cones. We demonstrate not only one broadband absorption from the fundamental magnetic resonances but additional broadband absorption in high-frequency range using the third-harmonic resonance, by both simulation and experiment. In simulation, the absorption was over 90% in 3.93-6.05 GHz, and 11.64-14.55 GHz. The corresponding experimental absorption bands over 90% were 3.88-6.08 GHz, 9.95-10.46 GHz and 11.86-13.84 GHz, respectively. The origin of absorption bands was elucidated. Furthermore, it is independent of polarization angle owing to the multilayered circular structures. The design is scalable to smaller size for the infrared and the visible ranges.

  20. Dual surface interferometer

    DOEpatents

    Pardue, R.M.; Williams, R.R.

    1980-09-12

    A double-pass interferometer is provided which allows direct measurement of relative displacement between opposed surfaces. A conventional plane mirror interferometer may be modified by replacing the beam-measuring path cube-corner reflector with an additional quarterwave plate. The beam path is altered to extend to an opposed plane mirrored surface and the reflected beam is placed in interference with a retained reference beam split from dual-beam source and retroreflected by a reference cube-corner reflector mounted stationary with the interferometer housing. This permits direct measurement of opposed mirror surfaces by laser interferometry while doubling the resolution as with a conventional double-pass plane mirror laser interferometer system.

  1. Dual surface interferometer

    DOEpatents

    Pardue, Robert M.; Williams, Richard R.

    1982-01-01

    A double-pass interferometer is provided which allows direct measurement of relative displacement between opposed surfaces. A conventional plane mirror interferometer may be modified by replacing the beam-measuring path cube-corner reflector with an additional quarter-wave plate. The beam path is altered to extend to an opposed plane mirrored surface and the reflected beam is placed in interference with a retained reference beam split from dual-beam source and retroreflected by a reference cube-corner reflector mounted stationary with the interferometer housing. This permits direct measurement of opposed mirror surfaces by laser interferometry while doubling the resolution as with a conventional double-pass plane mirror laser interferometer system.

  2. Dual-Mode Combustion

    NASA Technical Reports Server (NTRS)

    Goyne, Christopher P.; McDaniel, James C.

    2002-01-01

    The Department of Mechanical and Aerospace Engineering at the University of Virginia has conducted an investigation of the mixing and combustion processes in a hydrogen fueled dual-mode scramjet combustor. The experiment essentially consisted of the "direct connect" continuous operation of a Mach 2 rectangular combustor with a single unswept ramp fuel injector. The stagnation enthalpy of the test flow simulated a flight Mach number of 5. Measurements were obtained using conventional wall instrumentation and laser based diagnostics. These diagnostics included, pressure and wall temperature measurements, Fuel Plume Imaging (FPI) and Particle Image Velocimetry (PIV). A schematic of the combustor configuration and a summary of the measurements obtained are presented. The experimental work at UVa was parallel by Computational Fluid Dynamics (CFD) work at NASA Langley. The numerical and experiment results are compared in this document.

  3. Integrated Dual Imaging Detector

    NASA Technical Reports Server (NTRS)

    Rust, David M.

    1999-01-01

    A new type of image detector was designed to simultaneously analyze the polarization of light at all picture elements in a scene. The integrated Dual Imaging detector (IDID) consists of a lenslet array and a polarizing beamsplitter bonded to a commercial charge coupled device (CCD). The IDID simplifies the design and operation of solar vector magnetographs and the imaging polarimeters and spectroscopic imagers used, for example, in atmosphere and solar research. When used in a solar telescope, the vector magnetic fields on the solar surface. Other applications include environmental monitoring, robot vision, and medical diagnoses (through the eye). Innovations in the IDID include (1) two interleaved imaging arrays (one for each polarization plane); (2) large dynamic range (well depth of 10(exp 5) electrons per pixel); (3) simultaneous readout and display of both images; and (4) laptop computer signal processing to produce polarization maps in field situations.

  4. Dual Tank Fuel System

    DOEpatents

    Wagner, Richard William; Burkhard, James Frank; Dauer, Kenneth John

    1999-11-16

    A dual tank fuel system has primary and secondary fuel tanks, with the primary tank including a filler pipe to receive fuel and a discharge line to deliver fuel to an engine, and with a balance pipe interconnecting the primary tank and the secondary tank. The balance pipe opens close to the bottom of each tank to direct fuel from the primary tank to the secondary tank as the primary tank is filled, and to direct fuel from the secondary tank to the primary tank as fuel is discharged from the primary tank through the discharge line. A vent line has branches connected to each tank to direct fuel vapor from the tanks as the tanks are filled, and to admit air to the tanks as fuel is delivered to the engine.

  5. Modulation of executive control in dual tasks with transcranial direct current stimulation (tDCS).

    PubMed

    Strobach, Tilo; Soutschek, Alexander; Antonenko, Daria; Flöel, Agnes; Schubert, Torsten

    2015-02-01

    Executive processing in dual tasks is primarily associated with activation of the lateral prefrontal cortex (lPFC), which is demonstrated in functional imaging studies (e.g., Szameitat et al., 2006). However, a causal relation between lPFC activity and executive functions in dual tasks has not been demonstrated so far. Here, we used anodal transcranial direct current stimulation (atDCS [1 mA, 20 min] vs. sham stimulation [1 mA, 30s]) over the left inferior frontal junction under conditions of random and fixed task order in dual tasks as well as in single tasks in healthy young individuals (Experiment 1). We found that atDCS, if administered simultaneously to the task, improved performance in random-order dual tasks, but not in fixed-order dual tasks and single tasks. Moreover, dual-task performance under random-order conditions did not improve if atDCS was applied prior to the task performance. The identical procedure in Experiment 2 showed no difference in dual-task performance under random-task order conditions when we compared cathodal tDCS (ctDCS) with sham stimulation. Our findings suggest that dual-task performance is causally related to lPFC activation under conditions that require task-order decisions and high demands on executive functioning. Subsequent studies may now explore if atDCS leads to sustained improvements parallel to the training of dual tasks.

  6. Dual-Phase Nozzle Flow.

    DTIC Science & Technology

    1982-10-01

    Two-phase 20. A T RACT (0.31lmm 401 teV9 i 01 000* u...in #CMIdR@0fr &V WNHI& WARNeJ A revieW or the dual-phase -ower system was made. This study ...pr-et5 ._ lnering Dean of Science and Engineering J* ABSTRACT A review of the dual-phase power system was made. This study focused on the multi...be studied in detail, but first a review of the dual-phase cycle will be carried out from information obtained from References 1 and 2. Reference 1

  7. Dual-Compartment Inflatable Suitlock

    NASA Technical Reports Server (NTRS)

    Howe, Scott; Kennedy, Kriss J.; Guirgis, Peggy L.

    2012-01-01

    A paper discusses a dual-compartment inflatable suitlock (DCIS) for Extra - vehicular Activity (EVA) that will allow for dust control, suit maintenance, and efficient EVA egress/ingress. The expandable (inflatable technologies) aspect of the design will allow the unit to stow in a compact package for transport. The DCIS consists of three hard, in line bulkheads, separating two cylindrical membrane-walled compartments. The inner bulkhead can be fitted with a variety of hatch types, docking flanges, and mating hardware, such as the common berthing mechanism (CBM), for the purpose of mating with vehicles, habitats, and other pressurized modules. The inner bulkhead and center bulkhead function as the end walls of the inner compartment, which, during operations, would stay pressurized, either matching the pressure of the habitat or acting as a lower-pressure transitional volume. The suited crewmember can quickly don a suit, and egress the suitlock without waiting for the compartment to depressurize. The outer compartment can be pressurized infrequently, when a long dwell time is expected prior to the next EVA, or during off-nominal suit maintenance tasks, allowing shirtsleeve inspections and maintenance of the space suits. The outer bulkhead has a pressure-assisted hatch door that stays open and stowed routinely, but can be closed for suit maintenance and pressurization as needed.

  8. ISIFC - dual Biomedical Engineering School.

    PubMed

    Butterlin, Nadia; Soto-Romero, Georges; Duffaud, Jacques; Blagosklonov, Oleg

    2007-01-01

    The Superior Institute for Biomedical Engineering (ISIFC), created in 2001, is part of the Franche-Comté University and is accredited by the French Ministry of National Education. Its originality lies in its innovative course of studies, which trains engineers in the scientific and medical fields to get both competencies. The Institute therefore collaborates with the University Hospital Centre of Besançon (CHU), biomedical companies and National Research Centres (CNRS and INSERM). The dual expertise trainees will have acquired at the end of their 3 years course covers medical and biological skills, scientific and Technical expertises. ISIFC engineers answer to manufacturer needs for skilled scientific and technical staff in instrumentation and techniques adapted to diagnosis, therapeutics and medical control, as well as the needs of potential users for biomedical devices, whether they are doctors, hospital staff, patients, laboratories, etc... Both the skills and the knowledge acquired by an ISIFC engineer will enable him/her to fulfil functions of study, research and development in the industrial sector.

  9. Dual X-ray absorptiometry

    NASA Astrophysics Data System (ADS)

    Altman, Albert; Aaron, Ronald

    2012-07-01

    Dual X-ray absorptiometry is widely used in analyzing body composition and imaging. Both the method and its limitations are related to the Compton and photoelectric contributions to the X-ray attenuation coefficients of materials.

  10. The Man of Dual Nationality.

    ERIC Educational Resources Information Center

    Abe, Yoshio

    1985-01-01

    Presents an English translation of the first few pages, set in a Japanese internment camp in the U.S. during World War II, of a Japanese novel about the problems of dual nationality and personal identity. (KH)

  11. Dual-Compartment Inflatable Suitlock

    NASA Technical Reports Server (NTRS)

    Kennedy, Kriss J.; Guirgis, Peggy L.; Boyle, Robert M.

    2013-01-01

    There is a need for an improvement over current NASA Extravehicular Activity (EVA) technology. The technology must allow the capacity for quicker, more efficient egress/ingress, allow for shirtsleeve suit maintenance, be compact in transport, and be applicable to environments ranging from planetary surface (partial-g) to orbital or deep space zero-g environments. The technology must also be resistant to dust and other foreign contaminants that may be present on or around a planetary surface. The technology should be portable, and be capable of docking with a variety of habitats, ports, stations, vehicles, and other pressurized modules. The Dual-Compartment Inflatable Suitlock (DCIS) consists of three hard inline bulkheads, separating two cylindrical membrane-walled compartments. The Inner Bulkhead can be fitted with a variety of hatch types, docking flanges, and mating hardware, such as the Common Berthing Mechanism (CBM), for the purpose of mating with vehicles, habitats, and other pressurized modules. The Inner Bulkhead and Center Bulkhead function as the end walls of the Inner Compartment, which during operations, would stay pressurized, either matching the pressure of the habitat or acting as a lower-pressure transitional volume. The Inner Compartment contains donning/doffing fixtures and inner suit-port hatches. The Center Bulkhead has two integrated suit-ports along with a maintenance hatch. The Center Bulkhead and Outer Bulkhead function as the end walls of the Outer Compartment, which stays at vacuum during normal operations. This allows the crewmember to quickly don a suit, and egress the suitlock without waiting for the Outer Compartment to depressurize. The Outer Compartment can be pressurized infrequently for both nominal and off-nominal suit maintenance tasks, allowing shirtsleeve inspections and maintenance/repair of the environmental suits. The Outer Bulkhead has a pressure-assisted hatch door that stays open and stowed during EVA operations, but can

  12. Dual-Mode Universities in Higher Education: Way Station or Final Destination?

    ERIC Educational Resources Information Center

    Daniel, John

    2012-01-01

    In the title the author asked whether dual-mode institutions were a stable "final" model for higher education or a step on the way to something else. Only a few institutions seem able to function in dual mode (i.e. with distinct groups of distance and classroom students) in a successful and sustainable way. Some institutions now claim…

  13. Unattended Dual Current Monitor

    SciTech Connect

    Newell, Matthew R.; Parker, Robert F.; Jones, David C.

    2016-08-11

    The Unattended Dual Current Monitor (UDCM) is an ideal solution for current measurement needs such as ion chamber gamma measurements. The UDCM has two independent inputs and each input detects currents in two user selectable ranges, -0.2nA to -20nA or -20nA to -2uA. Measurement results can be retrieved via an Ethernet connection or by monitoring the TTL output pulses with a simple counter. Measurement data is also stored on a user accessible micro-SD card and automatically downloaded to a USB flash drive. A programmable negative High Voltage (HV) power supply provides detector bias voltages from 0 to -1,000V. The UDCM is fully compatible with the IAEA Multi Instrument Collect (MIC) software and responds to the existing MiniGRAND commands. The Ethernet port provides an IAEA RAINSTORM compliant data transfer and data security interface. The UDCM produces TTL pulses at a rate proportional to the input current, 100cps/nA. The UDCM can simplify instrumentation needs by enabling the use of a simple pulse counter for both neutron and gamma measurements. The UDCM is a simple instrument, inexpensive to manufacturer and designed for reliability.

  14. Fast dual tomography

    NASA Astrophysics Data System (ADS)

    Carrion, Philip M.

    1990-09-01

    This paper can be considered as a continuation of the work by Carrion and Carneiro (1989), where a generalized approach to linearized inversion of geophysical data was developed. Their method allows one to incorporate virtually any constraints in the inversion and reformulate the problem in the dual space of Langrangian multipliers (see also Carrion, 1989a). The constrained tomography makes traveltime inversion robust: it automatically rejects “bad data” which correspond to solutions beyond the chosen constraints and allows one to start inversion with an arbitrary chosen initial model.In this paper, I will derive basic formulas for constrained tomographic imaging that can be used in such areas of geophysics as global mapping of the earth interior, exploration geophysics, etc. The method is fast: an example that will be shown in the paper took only 6 min. of VAX CPU time. Had the conventional least-squares matrix inversion been used it would have taken more than 10 hours of the CPU time to solve the same problem.

  15. Neuroretinitis with dual infections

    PubMed Central

    Kiu, Kwong-Han; Hanizasurana, Hashim; Zunaina, Embong

    2015-01-01

    A 22-year-old Malay female presented with left eye floaters for 2 weeks, associated with temporal visual field defect and metamorphopsia for 3 days. She has a guinea pig and a hedgehog at home, but denied being bitten or scratched by them. Her visual acuity at presentation was 6/12 on the left eye and 6/6 on the right eye. Her left eye relative afferent pupillary defect was barely positive with mild anterior chamber reaction. Fundus examination of the left eye showed mild vitritis, swollen optic disc with macular star, crops of active choroidal lesions at superonasal retina with a linear arrangement in the form of migratory track nasally. However, there were no nematodes seen on fundus examination. Investigations showed normal full blood count with no eosinophilia and positive serology test for Bartonella henselae. She was diagnosed to have dual infection – diffuse unilateral subacute neuroretinitis (DUSN), based on the presence of crops of choroidal lesions with migratory track, and cat scratch disease (CSD) based on a positive serological test. She was treated with oral albendazole 400 mg 12 hourly for 6 weeks for DUSN and oral doxycycline 100 mg 12 hourly for 4 weeks for CSD. Focal laser had been applied to the area of migratory track in the left eye. Her left eye vision improved to 6/6 at 1 month after treatment, with resolution of neuroretinitis. PMID:26527902

  16. Dual porphyrias revisited.

    PubMed

    Poblete-Gutiérrez, Pamela; Badeloe, Sadhanna; Wiederholt, Tonio; Merk, Hans F; Frank, Jorge

    2006-09-01

    The porphyrias are clinically and genetically heterogeneous metabolic diseases, which predominantly result from a hereditary dysfunction in the pathway of haeme biosynthesis. Currently, at least eight different forms of porphyrias can be differentiated, all of them characterized by a specific enzyme deficiency that is either inherited in an autosomal-dominant fashion, autosomal recessively or, in the case of porphyria cutanea tarda, might also be acquired. All genes encoding these enzymes have been cloned and several mutations underlying the different types of porphyrias have been reported. Traditionally, the diagnosis of porphyria is made on the basis of clinical symptoms, characteristic biochemical findings and enzyme assays. In some porphyria patients and families, however, these diagnostic tools can reveal simultaneous findings compatible with two different forms of porphyria, a phenomenon referred to as dual porphyria. Here, we give an overview on what is currently known about these peculiar variants of porphyria and suggest that, whenever feasible, molecular genetic analysis should complement the analytical techniques used to characterize patients and families in which a double enzymatic deficiency within the haeme biosynthetic pathway is assumed.

  17. Dual-band dual field-of-view TVWS prototype

    NASA Astrophysics Data System (ADS)

    Bergeron, A.; Jerominek, H.; Doucet, M.; Lagacé, F.; Desnoyers, N.; Bernier, S.; Mercier, L.; Boucher, M.-A.; Jacob, M.; Alain, C.; Pope, T. D.; Laou, P.

    2006-05-01

    A dual band thermal/visible weapon sight (TVWS) prototype was developed by INO in collaboration with DRDC Valcartier. The TVWS operates in the 8-12 μm infrared (IR) and 300-900 nm visible wavebands for enhanced vision capabilities in day and night operations. It is equipped with lightweight athermalized coaxial catadioptric objectives, a bolometric IR imager operating in a microscan mode providing an effective resolution of 320 x 240 pixels and a visible image intensifier of 768 x 493 pixels. The TVWS is equipped with a miniature shutter for automatic offset calibration. Real-time imaging at 30 fps is available. Both the visible and IR images can be toggled with a single touch button and displayed on an integrated color micro liquid crystal display (LCD). The TVWS also has a standard video output via a coaxial connector. An integrated wireless analog RF link can be used to send images to a remote command control. The sight has an adjustable electronic crosshair and two manual focuses from 25 m to infinity. On-board processing capabilities were added to introduce specific functionalities such as image polarity inversion (black hot/white hot) and image enhancement. This TVWS model is also very lightweight (~ 1900 grams) and compact (volume of 142 cubic inches). It offers human size target detection at 800 m and recognition at 200 m (Johnson criteria) with the IR waveband while offering the human recognition at up to 800 m with the visible waveband. The TVWS is adapted for weaver or Picatinny rail mounting.

  18. Assimilation of Dual-Polarimetric Radar Observations with WRF GSI

    NASA Technical Reports Server (NTRS)

    Li, Xuanli; Mecikalski, John; Fehnel, Traci; Zavodsky, Bradley; Srikishen, Jayanthi

    2014-01-01

    Dual-polarimetric (dual-pol) radar typically transmits both horizontally and vertically polarized radio wave pulses. From the two different reflected power returns, more accurate estimate of liquid and solid cloud and precipitation can be provided. The upgrade of the traditional NWS WSR-88D radar to include dual-pol capabilities will soon be completed for the entire NEXRAD network. Therefore, the use of dual-pol radar network will have a broad impact in both research and operational communities. The assimilation of dual-pol radar data is especially challenging as few guidelines have been provided by previous research. It is our goal to examine how to best use dual-pol radar data to improve forecast of severe storm and forecast initialization. In recent years, the Development Testbed Center (DTC) has released the community Gridpoint Statistical Interpolation (GSI) DA system for the Weather Research and Forecasting (WRF) model. The community GSI system runs in independently environment, yet works functionally equivalent to operational centers. With collaboration with the NASA Short-term Prediction Research and Transition (SPoRT) Center, this study explores regional assimilation of the dual-pol radar variables from the WSR-88D radars for real case storms. Our presentation will highlight our recent effort on incorporating the horizontal reflectivity (ZH), differential reflectivity (ZDR), specific differential phase (KDP), and radial velocity (VR) data for initializing convective storms, with a significant focus being on an improved representation of hydrometeor fields. In addition, discussion will be provided on the development of enhanced assimilation procedures in the GSI system with respect to dual-pol variables. Beyond the dual-pol variable assimilation procedure developing within a GSI framework, highresolution (=1 km) WRF model simulations and storm scale data assimilation experiments will be examined, emphasizing both model initialization and short-term forecast

  19. Fostering Radical Conceptual Change through Dual-Situated Learning Model

    ERIC Educational Resources Information Center

    She, Hsiao-Ching

    2004-01-01

    This article examines how the Dual-Situated Learning Model (DSLM) facilitates a radical change of concepts that involve the understanding of matter, process, and hierarchical attributes. The DSLM requires knowledge of students' prior beliefs of science concepts and the nature of these concepts. In addition, DSLM also serves two functions: it…

  20. Dual Sensory Loss and Its Impact on Everyday Competence

    ERIC Educational Resources Information Center

    Brennan, Mark; Horowitz, Amy; Su, Ya-ping

    2005-01-01

    Purpose: This study examined the relation of dual and single sensory impairments, within the context of cognitive function, by using the framework of everyday competence in terms of the probability of difficulty with specific personal and instrumental activities of daily living (ADLs and IADLs, respectively). Design and Methods: The Longitudinal…

  1. Tetrathiafulvalene diindolylquinoxaline: a dual signaling anion receptor with phosphate selectivity†

    PubMed Central

    Bejger, Christopher; Park, Jung Su; Silver, Eric S.; Sessler, Jonathan L.

    2011-01-01

    Incorporation of tetrathiafulvalene into the backbone of a known neutral phosphate receptor, diindolylquinoxaline, yields a dual optical-electrochemical chemosensor for dihydrogen phosphate that functions in dichloromethane. This system shows selectivity for dihydrogen phosphate over other small anions and can be used to detect the presence of this analyte via fluorescence quenching or cyclic voltammetry. PMID:20856940

  2. Exploring Bilingual Pedagogies in Dual Language Preschool Classrooms

    ERIC Educational Resources Information Center

    Gort, Mileidis; Pontier, Ryan W.

    2013-01-01

    In this paper, we present an analysis of the language practices of four Spanish/English dual language (DL) preschool teachers, focusing on the ways in which the teachers mediate bilingual interactions with students and distribute Spanish and English across different classroom discourse functions. Findings reveal teachers' flexible and strategic…

  3. Dual sensor VVIR mode pacing: is it worth it?

    PubMed

    Sulke, N; Tan, K; Kamalvand, K; Bostock, J; Bucknall, C

    1996-11-01

    Dual sensor ventricular demand rate responsive (VVIR mode) pacing was compared with single sensor rate responsive pacing to assess whether this new development should be more widely incorporated in modern pacemaker devices. A within patient randomized, double-blind crossover study involving ten patients, mean age 67.4 years (70% male), had Medtronic Legend Plus dual sensor VVIR pacemakers implanted for high grade AV block and chronic or persistent paroxysmal atrial fibrillation. Performance values were compared to 20 healthy control subjects of a similar age and gender. Patients were both subjectively and objectively assessed after 2 weeks of out-of-hospital activity in VVIR mode (minute ventilation sensing), VVIR mode (activity sensing), VVIR mode (dual sensor), and VVI mode (no rate response). All patients were assessed for subjective preference for, and objective improvement in, any pacing modality as assessed by standardized daily activity protocols and graded exercise treadmill testing. Subjective perception of exercise capacity and functional status was significantly lower in VVI mode (P < 0.05) compared to any of the VVIR modes, which did not differ. After completion of the study 70% of patients chose VVIR as their preferred mode, with 30% expressing no preference. Forty percent preferred activity sensor VVIR mode pacing, 30% preferred dual sensor VVIR mode pacing, and 70% found either dual sensor VVIR mode, minute ventilation sensor VVIR mode, or both modalities least acceptable. No patient found activity sensing VVIR mode least acceptable. Graded treadmill testing revealed significantly lower exercise tolerance during VVI mode pacing (P < 0.01) compared to the VVIR modalities, which did not differ. Overall, chronotropic response was best with dual sensor pacing during standardized daily activity protocols and during the standard car journey. The data from this study suggest that there is no marked clinical advantage obtained from the use of dual sensor

  4. Perspectives on Dual Targeting Delivery Systems for Brain Tumors.

    PubMed

    Gao, Huile

    2017-03-01

    Brain tumor remains one of the most serious threats to human beings. Different from peripheral tumors, drug delivery to brain tumor is largely restricted by the blood brain barrier (BBB). To fully conquer this barrier and specifically deliver drugs to brain tumor, dual targeting delivery systems were explored, which are functionalized with two active targeting ligands: one to the BBB and the other to the brain tumor. The development of dual targeting delivery system is still in its early stage, and attentions need to be paid to issues and concerns that remain unresolved in future studies.

  5. Dual Cauchy rate-distortion model for video coding

    NASA Astrophysics Data System (ADS)

    Zeng, Huanqiang; Chen, Jing; Cai, Canhui

    2014-07-01

    A dual Cauchy rate-distortion model is proposed for video coding. In our approach, the coefficient distribution of the integer transform is first studied. Then, based on the observation that the rate-distortion model of the luminance and that of the chrominance can be well expressed by separate Cauchy functions, a dual Cauchy rate-distortion model is presented. Furthermore, the simplified rate-distortion formulas are deduced to reduce the computational complexity of the proposed model without losing the accuracy. Experimental results have shown that the proposed model is better able to approximate the actual rate-distortion curve for various sequences with different motion activities.

  6. Identification and dual adaptive control of a turbojet engine

    NASA Technical Reports Server (NTRS)

    Merrill, W.; Leininger, G.

    1979-01-01

    The objective of this paper is to utilize the design methods of modern control theory to realize a 'dual-adaptive' feedback control unit for a highly non-linear single spool airbreathing turbojet engine. Using a very detailed and accurate simulation of the non-linear engine as the data source, linear operating point models of unspecified dimension are identified. Feedback control laws are designed at each operating point for a prespecified set of sampling rates using sampled-data output regulator theory. The control system sampling rate is determined by an adaptive sampling algorithm in correspondence with turbojet engine performance. The result is a 'dual-adpative' control law that is functionally dependent upon the sampling rate selected and environmental operating conditions. Simulation transients demonstrate the utility of the dual-adaptive design to improve on-board computer utilization while maintaining acceptable levels of engine performance.

  7. Identification and dual adaptive control of a turbojet engine

    NASA Technical Reports Server (NTRS)

    Merrill, W.; Leininger, G.

    1979-01-01

    The objective of this paper is to utilize the design methods of modern control theory to realize a dual-adaptive feedback control unit for a highly nonlinear single spool airbreathing turbojet engine. Using a very detailed and accurate simulation of the nonlinear engine as the data source, linear operating point models of unspecified dimension are identified. Feedback control laws are designed at each operating point for a prespecified set of sampling rates using sampled-data output regulator theory. The control system sampling rate is determined by an adaptive sampling algorithm in correspondence with turbojet engine performance. The result is a dual-adaptive control law that is functionally dependent upon the sampling rate selected and environmental operating conditions. Simulation transients demonstrate the utility of the dual-adaptive design to improve on-board computer utilization while maintaining acceptable levels of engine performance.

  8. Implications of dual practice for universal health coverage.

    PubMed

    McPake, Barbara; Russo, Giuliano; Hipgrave, David; Hort, Krishna; Campbell, James

    2016-02-01

    Making progress towards universal health coverage (UHC) requires that health workers are adequate in numbers, prepared for their jobs and motivated to perform. In establishing the best ways to develop the health workforce, relatively little attention has been paid to the trends and implications of dual practice - concurrent employment in public and private sectors. We review recent research on dual practice for its potential to guide staffing policies in relation to UHC. Many studies describe the characteristics and correlates of dual practice and speculate about impacts, but there is very little evidence that is directly relevant to policy-makers. No studies have evaluated the impact of policies on the characteristics of dual practice or implications for UHC. We address this lack and call for case studies of policy interventions on dual practice in different contexts. Such research requires investment in better data collection and greater determination on the part of researchers, research funding bodies and national research councils to overcome the difficulties of researching sensitive topics of health systems functions.

  9. UWB dual burst transmit driver

    SciTech Connect

    Dallum, Gregory E; Pratt, Garth C; Haugen, Peter C; Zumstein, James M; Vigars, Mark L; Romero, Carlos E

    2012-04-17

    A dual burst transmitter for ultra-wideband (UWB) communication systems generates a pair of precisely spaced RF bursts from a single trigger event. An input trigger pulse produces two oscillator trigger pulses, an initial pulse and a delayed pulse, in a dual trigger generator. The two oscillator trigger pulses drive a gated RF burst (power output) oscillator. A bias driver circuit gates the RF output oscillator on and off and sets the RF burst packet width. The bias driver also level shifts the drive signal to the level that is required for the RF output device.

  10. Dual porosity gas evolving electrode

    DOEpatents

    Townsend, Carl W.

    1994-01-01

    A dual porosity electrode for use in thermoelectrochemical systems where simultaneous transport of gas and liquid into and/or out of the electrode is required. The electrode includes catalytic electrode particles having diameters ranging from about 25 to 100 angstroms. The catalytic electrode particles are anchored to a support network in clusters which have internal pores ranging in size from 25 to 100 angstroms. The pores between the clusters range in size from between about 1 to 20 microns. A method for making the dual porosity electrodes is also disclosed.

  11. Dual porosity gas evolving electrode

    DOEpatents

    Townsend, C.W.

    1994-11-15

    A dual porosity electrode is described for use in thermoelectrochemical systems where simultaneous transport of gas and liquid into and/or out of the electrode is required. The electrode includes catalytic electrode particles having diameters ranging from about 25 to 100 angstroms. The catalytic electrode particles are anchored to a support network in clusters which have internal pores ranging in size from 25 to 100 angstroms. The pores between the clusters range in size from between about 1 to 20 microns. A method for making the dual porosity electrodes is also disclosed.

  12. Development report for dual-burst disks

    SciTech Connect

    Fusco, A.M.

    1996-11-01

    Burst disks, commonly used in pressure relief applications, were studied as single-use valves. A dual-burst disk design was chosen for primary investigation for systems involving separation of gases of two significantly different pressures. The two disks are used to seal either end of a piston cavity that has a different cross-sectional area on each side. Different piston surface areas are used to maintain hydrostatic equilibrium, P{sub 1}A{sub 1} = P{sub 2}A{sub 2}. The single-use valve functions when the downstream pressure is reduced to approximately atmospheric pressure, creating a pressure differential that causes the burst disks to fail. Several parameters were studied to determine the optimum design of the burst disk. These parameters include thickness, diameter, area/pressure ratio, scoring, and disk geometry. The disk material was limited to 304L stainless steel. Factors that were considered essential to the optimization of the design were robustness, manufacturability, and burst pressure variability. The thicknesses of the disks that were studied range from 0.003 in. to 0.010 in. A model for predicting burst pressures of the burst disks was derived. The model combines membrane stress theory with force/displacement data to predict the burst pressure of various designs to within {+-}10%. This model results from studies that characterize the behavior of individual small and large disks. Welding techniques used to join the dual-disk assembly are discussed. Laser welds are used to join and seal the disks to the bulkhead. These welds were optimized for repeatability and robustness. Resistance upset welding is suggested for joining the dual-disk assembly to the pressure vessel body. Resistance upset weld parameters were developed for this particular design so as to minimize the side effects on the burst-disk performance and to provide high-quality welds.

  13. Gravity dual for a model of perception

    NASA Astrophysics Data System (ADS)

    Nakayama, Yu

    2011-01-01

    One of the salient features of human perception is its invariance under dilatation in addition to the Euclidean group, but its non-invariance under special conformal transformation. We investigate a holographic approach to the information processing in image discrimination with this feature. We claim that a strongly coupled analogue of the statistical model proposed by Bialek and Zee can be holographically realized in scale invariant but non-conformal Euclidean geometries. We identify the Bayesian probability distribution of our generalized Bialek-Zee model with the GKPW partition function of the dual gravitational system. We provide a concrete example of the geometric configuration based on a vector condensation model coupled with the Euclidean Einstein-Hilbert action. From the proposed geometry, we study sample correlation functions to compute the Bayesian probability distribution.

  14. Dual-Doppler Feasibility Study

    NASA Technical Reports Server (NTRS)

    Huddleston, Lisa L.

    2012-01-01

    When two or more Doppler weather radar systems are monitoring the same region, the Doppler velocities can be combined to form a three-dimensional (3-D) wind vector field thus providing for a more intuitive analysis of the wind field. A real-time display of the 3-D winds can assist forecasters in predicting the onset of convection and severe weather. The data can also be used to initialize local numerical weather prediction models. Two operational Doppler Radar systems are in the vicinity of Kennedy Space Center (KSC) and Cape Canaveral Air Force Station (CCAFS); these systems are operated by the 45th Space Wing (45 SW) and the National Weather Service Melbourne, Fla. (NWS MLB). Dual-Doppler applications were considered by the 45 SW in choosing the site for the new radar. Accordingly, the 45th Weather Squadron (45 WS), NWS MLB and the National Aeronautics and Space Administration tasked the Applied Meteorology Unit (AMU) to investigate the feasibility of establishing dual-Doppler capability using the two existing systems. This study investigated technical, hardware, and software requirements necessary to enable the establishment of a dual-Doppler capability. Review of the available literature pertaining to the dual-Doppler technique and consultation with experts revealed that the physical locations and resulting beam crossing angles of the 45 SW and NWS MLB radars make them ideally suited for a dual-Doppler capability. The dual-Doppler equations were derived to facilitate complete understanding of dual-Doppler synthesis; to determine the technical information requirements; and to determine the components of wind velocity from the equation of continuity and radial velocity data collected by the two Doppler radars. Analysis confirmed the suitability of the existing systems to provide the desired capability. In addition, it is possible that both 45 SW radar data and Terminal Doppler Weather Radar data from Orlando International Airport could be used to alleviate any

  15. Increased Brain Activation for Dual Tasking with 70-Days Head-Down Bed Rest

    PubMed Central

    Yuan, Peng; Koppelmans, Vincent; Reuter-Lorenz, Patricia A.; De Dios, Yiri E.; Gadd, Nichole E.; Wood, Scott J.; Riascos, Roy; Kofman, Igor S.; Bloomberg, Jacob J.; Mulavara, Ajitkumar P.; Seidler, Rachael D.

    2016-01-01

    Head-down tilt bed rest (HDBR) has been used as a spaceflight analog to simulate the effects of microgravity exposure on human physiology, sensorimotor function, and cognition on Earth. Previous studies have reported that concurrent performance of motor and cognitive tasks can be impaired during space missions. Understanding the consequences of HDBR for neural control of dual tasking may possibly provide insight into neural efficiency during spaceflight. In the current study, we evaluated how dual task performance and the underlying brain activation changed as a function of HDBR. Eighteen healthy men participated in this study. They remained continuously in the 6° head-down tilt position for 70 days. Functional MRI for bimanual finger tapping was acquired during both single task and dual task conditions, and repeated at 7 time points pre-, during- and post-HDBR. Another 12 healthy males participated as controls who did not undergo HDBR. A widely distributed network involving the frontal, parietal, cingulate, temporal, and occipital cortices exhibited increased activation for dual tasking and increased activation differences between dual and single task conditions during HDBR relative to pre- or post-HDBR. This HDBR-related brain activation increase for dual tasking implies that more neurocognitive control is needed for dual task execution during HDBR compared to pre- and post-HDBR. We observed a positive correlation between pre-to-post HDBR changes in dual-task cost of reaction time and pre-to-post HDBR change in dual-task cost of brain activation in several cerebral and cerebellar regions. These findings could be predictive of changes in dual task processing during spaceflight. PMID:27601982

  16. Dual source and dual detector arrays tetrahedron beam computed tomography for image guided radiotherapy.

    PubMed

    Kim, Joshua; Lu, Weiguo; Zhang, Tiezhi

    2014-02-07

    Cone-beam computed tomography (CBCT) is an important online imaging modality for image guided radiotherapy. But suboptimal image quality and the lack of a real-time stereoscopic imaging function limit its implementation in advanced treatment techniques, such as online adaptive and 4D radiotherapy. Tetrahedron beam computed tomography (TBCT) is a novel online imaging modality designed to improve on the image quality provided by CBCT. TBCT geometry is flexible, and multiple detector and source arrays can be used for different applications. In this paper, we describe a novel dual source-dual detector TBCT system that is specially designed for LINAC radiation treatment machines. The imaging system is positioned in-line with the MV beam and is composed of two linear array x-ray sources mounted aside the electrical portal imaging device and two linear arrays of x-ray detectors mounted below the machine head. The detector and x-ray source arrays are orthogonal to each other, and each pair of source and detector arrays forms a tetrahedral volume. Four planer images can be obtained from different view angles at each gantry position at a frame rate as high as 20 frames per second. The overlapped regions provide a stereoscopic field of view of approximately 10-15 cm. With a half gantry rotation, a volumetric CT image can be reconstructed having a 45 cm field of view. Due to the scatter rejecting design of the TBCT geometry, the system can potentially produce high quality 2D and 3D images with less radiation exposure. The design of the dual source-dual detector system is described, and preliminary results of studies performed on numerical phantoms and simulated patient data are presented.

  17. Dual source and dual detector arrays tetrahedron beam computed tomography for image guided radiotherapy

    NASA Astrophysics Data System (ADS)

    Kim, Joshua; Lu, Weiguo; Zhang, Tiezhi

    2014-02-01

    Cone-beam computed tomography (CBCT) is an important online imaging modality for image guided radiotherapy. But suboptimal image quality and the lack of a real-time stereoscopic imaging function limit its implementation in advanced treatment techniques, such as online adaptive and 4D radiotherapy. Tetrahedron beam computed tomography (TBCT) is a novel online imaging modality designed to improve on the image quality provided by CBCT. TBCT geometry is flexible, and multiple detector and source arrays can be used for different applications. In this paper, we describe a novel dual source-dual detector TBCT system that is specially designed for LINAC radiation treatment machines. The imaging system is positioned in-line with the MV beam and is composed of two linear array x-ray sources mounted aside the electrical portal imaging device and two linear arrays of x-ray detectors mounted below the machine head. The detector and x-ray source arrays are orthogonal to each other, and each pair of source and detector arrays forms a tetrahedral volume. Four planer images can be obtained from different view angles at each gantry position at a frame rate as high as 20 frames per second. The overlapped regions provide a stereoscopic field of view of approximately 10-15 cm. With a half gantry rotation, a volumetric CT image can be reconstructed having a 45 cm field of view. Due to the scatter rejecting design of the TBCT geometry, the system can potentially produce high quality 2D and 3D images with less radiation exposure. The design of the dual source-dual detector system is described, and preliminary results of studies performed on numerical phantoms and simulated patient data are presented.

  18. Dual Enrollment in Spanish: One Working Model

    ERIC Educational Resources Information Center

    Bloom, Melanie; Chambers, Laura

    2009-01-01

    Dual enrollment is now a nation-wide phenomenon as all 50 states currently offer some form of dual-enrollment program to secondary-school students (Karp, Bailey, Hughes, and Fermin 2005). However, dual enrollment itself is often difficult to define as programs vary from school to school (Jordan, Cavalluzzo, and Corallo 2006). Therefore, language…

  19. 7 CFR 247.19 - Dual participation.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 4 2010-01-01 2010-01-01 false Dual participation. 247.19 Section 247.19 Agriculture... CHILD NUTRITION PROGRAMS COMMODITY SUPPLEMENTAL FOOD PROGRAM § 247.19 Dual participation. (a) What must State and local agencies do to prevent and detect dual participation? The State agency must work...

  20. 7 CFR 247.19 - Dual participation.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 4 2011-01-01 2011-01-01 false Dual participation. 247.19 Section 247.19 Agriculture... CHILD NUTRITION PROGRAMS COMMODITY SUPPLEMENTAL FOOD PROGRAM § 247.19 Dual participation. (a) What must State and local agencies do to prevent and detect dual participation? The State agency must work...

  1. Dual Processing and Diagnostic Errors

    ERIC Educational Resources Information Center

    Norman, Geoff

    2009-01-01

    In this paper, I review evidence from two theories in psychology relevant to diagnosis and diagnostic errors. "Dual Process" theories of thinking, frequently mentioned with respect to diagnostic error, propose that categorization decisions can be made with either a fast, unconscious, contextual process called System 1 or a slow, analytical,…

  2. Dual characterizations of optimal systems.

    NASA Technical Reports Server (NTRS)

    Chan, W. L.; Leininger, G. G.

    1972-01-01

    The complementary variational principle developed in a Hilbert space setting provides a duality principle in the calculus of variations with dynamic constraints. This concept is adopted in this paper to investigate dual characterizations of optimal control systems. Systems under consideration include those with dynamics governed by linear ordinary differential equations, linear partial differential equations and non-linear ordinary differential equations.

  3. Dual-Laser-Pulse Ignition

    NASA Technical Reports Server (NTRS)

    Trinh, Huu; Early, James W.; Thomas, Matthew E.; Bossard, John A.

    2006-01-01

    A dual-pulse laser (DPL) technique has been demonstrated for generating laser-induced sparks (LIS) to ignite fuels. The technique was originally intended to be applied to the ignition of rocket propellants, but may also be applicable to ignition in terrestrial settings in which electric igniters may not be suitable.

  4. Dual shell pressure balanced vessel

    DOEpatents

    Fassbender, Alexander G.

    1992-01-01

    A dual-wall pressure balanced vessel for processing high viscosity slurries at high temperatures and pressures having an outer pressure vessel and an inner vessel with an annular space between the vessels pressurized at a pressure slightly less than or equivalent to the pressure within the inner vessel.

  5. Dual x-ray absorptiometry

    NASA Astrophysics Data System (ADS)

    Altman, Albert; Aaron, Ronald

    2011-04-01

    Dual x-ray absorptiometry is widely used in analyzing body composition and imaging. We discuss the physics of the method and exhibit its limitations and show it is related to the Compton and photoelectric contributions to the x-ray absorption coefficients of materials.

  6. Dual channel electrostimulation in pain.

    PubMed

    Devulder, J; De Laat, M; Rolly, G

    1998-06-01

    Spinal cord stimulation is an accepted treatment for neuropathic pain. Technical advances in electrode design and better patient selection have led to better and sustained pain control by these devices. Multilead electrical stimulation is the latest innovation in implantable electrostimulation (Mattrix, Medtronic Minneapolis, USA). Two combined multipolar leads connected to a radiofrequency--coupled system can deliver electrical pulses of various amplitudes and pulse widths at different dermatome levels. Single stimulation is applied with different electrode configurations using both electrodes with identical stimulation parameters. In dual stimulation, the amplitude and the pulse width can vary between the electrode configurations. Dual channel stimulation helps steering stimulation paresthesias. Three patients illustrate the technical advantages of dual channel electrostimulation in the pain relief at multiple sites. Two patients with failed back surgery syndrome obtained more easily stimulation-induced paresthesias in the back and the legs. Dual channel stimulation is cost saving in patients implanted with two electrodes. This is presented in a third patient with an electrode in the thalamus--as pain treatment for cervicobrachialgia and a second in the epidural space--as treatment for the failed back surgery syndrome. These electrodes were connected to the Mattrix stimulator.

  7. Self-Dual Conformal Gravity

    NASA Astrophysics Data System (ADS)

    Dunajski, Maciej; Tod, Paul

    2014-10-01

    We find necessary and sufficient conditions for a Riemannian four-dimensional manifold ( M, g) with anti-self-dual Weyl tensor to be locally conformal to a Ricci-flat manifold. These conditions are expressed as the vanishing of scalar and tensor conformal invariants. The invariants obstruct the existence of parallel sections of a certain connection on a complex rank-four vector bundle over M. They provide a natural generalisation of the Bach tensor which vanishes identically for anti-self-dual conformal structures. We use the obstructions to demonstrate that LeBrun's anti-self-dual metrics on connected sums of s are not conformally Ricci-flat on any open set. We analyze both Riemannian and neutral signature metrics. In the latter case we find all anti-self-dual metrics with a parallel real spinor which are locally conformal to Einstein metrics with non-zero cosmological constant. These metrics admit a hyper-surface orthogonal null Killing vector and thus give rise to projective structures on the space of β-surfaces.

  8. Dual Roles for Immunity in Gastrointestinal Cancers

    PubMed Central

    Ferrone, Cristina; Dranoff, Glenn

    2010-01-01

    Histopathologic examination reveals that most human tumors are associated with diverse immune cell infiltrates, but the roles of host reactions in disease pathogenesis and prognosis remain to be fully clarified. Recent investigations in genetically engineered murine tumor models have uncovered dual functions for immune responses during cancer development and progression. Alterations in tumor cell gene expression profiles and coding sequences may trigger the activation of cytotoxic lymphocytes, which act to restrain tumor growth. In contrast, persistent inflammatory reactions, which may be driven by infection, environmental toxins, or impaired immune regulation, create a microenvironment that fosters tumor cell growth, survival, invasion, and dissemination. The dynamic interplay of these competing responses appears to be a critical event in cancer pathogenesis, with tumor promotion and immune evasion proving dominant in clinically evident disease. Nonetheless, longitudinal studies of patient cohorts have demonstrated that particular histopathologic and genetic signatures of cytotoxic lymphocyte reactions provide important prognostic information. Here, we discuss the dual roles of immunity in cancer development, focusing on gastrointestinal malignancies, given the depth of recent insights into the mechanisms underlying these tumors. PMID:20644090

  9. Jet Noise Scaling in Dual Stream Nozzles

    NASA Technical Reports Server (NTRS)

    Khavaran, Abbas; Bridges, James

    2010-01-01

    Power spectral laws in dual stream jets are studied by considering such flows a superposition of appropriate single-stream coaxial jets. Noise generation in each mixing region is modeled using spectral power laws developed earlier for single stream jets as a function of jet temperature and observer angle. Similarity arguments indicate that jet noise in dual stream nozzles may be considered as a composite of four single stream jets representing primary/secondary, secondary/ambient, transition, and fully mixed zones. Frequency filter are designed to highlight spectral contribution from each jet. Predictions are provided at an area ratio of 2.0--bypass ratio from 0.80 to 3.40, and are compared with measurements within a wide range of velocity and temperature ratios. These models suggest that the low frequency noise in unheated jets is dominated by the fully mixed region at all velocity ratios, while the high frequency noise is dominated by the secondary when the velocity ratio is larger than 0.80. Transition and fully mixed jets equally dominate the low frequency noise in heated jets. At velocity ratios less than 0.50, the high frequency noise from primary/bypass becomes a significant contributing factor similar to that in the secondary/ambient jet.

  10. Dual-stroke heat pump field performance

    NASA Astrophysics Data System (ADS)

    Veyo, S. E.

    1984-11-01

    Two nearly identical proprototype systems, each employing a unique dual-stroke compressor, were built and tested. One was installed in an occupied residence in Jeannette, Pa. It has provided the heating and cooling required from that time to the present. The system has functioned without failure of any prototypical advanced components, although early field experience did suffer from deficiencies in the software for the breadboard micro processor control system. Analysis of field performance data indicates a heating performance factor (HSPF) of 8.13 Stu/Wa, and a cooling energy efficiency (SEER) of 8.35 Scu/Wh. Data indicate that the beat pump is oversized for the test house since the observed lower balance point is 3 F whereas 17 F La optimum. Oversizing coupled with the use of resistance heat ot maintain delivered air temperature warmer than 90 F results in the consumption of more resistance heat than expected, more unit cycling, and therefore lower than expected energy efficiency. Our analysis indicates that with optimal mixing the dual stroke heat pump will yield as HSFF 30% better than a single capacity heat pump representative of high efficiency units in the market place today for the observed weather profile.

  11. Dual-Modality PET/Ultrasound imaging of the Prostate

    SciTech Connect

    Huber, Jennifer S.; Moses, William W.; Pouliot, Jean; Hsu, I.C.

    2005-11-11

    Functional imaging with positron emission tomography (PET)will detect malignant tumors in the prostate and/or prostate bed, as well as possibly help determine tumor ''aggressiveness''. However, the relative uptake in a prostate tumor can be so great that few other anatomical landmarks are visible in a PET image. Ultrasound imaging with a transrectal probe provides anatomical detail in the prostate region that can be co-registered with the sensitive functional information from the PET imaging. Imaging the prostate with both PET and transrectal ultrasound (TRUS) will help determine the location of any cancer within the prostate region. This dual-modality imaging should help provide better detection and treatment of prostate cancer. LBNL has built a high performance positron emission tomograph optimized to image the prostate.Compared to a standard whole-body PET camera, our prostate-optimized PET camera has the same sensitivity and resolution, less backgrounds and lower cost. We plan to develop the hardware and software tools needed for a validated dual PET/TRUS prostate imaging system. We also plan to develop dual prostate imaging with PET and external transabdominal ultrasound, in case the TRUS system is too uncomfortable for some patients. We present the design and intended clinical uses for these dual imaging systems.

  12. Effect of dual-type oligosaccharides on constipation in loperamide-treated rats

    PubMed Central

    Han, Sung Hee; Hong, Ki Bae; Kim, Eun Young; Ahn, So Hyun

    2016-01-01

    BACKGROUND/OBJECTIVES Constipation is a condition that can result from intestinal deformation. Because humans have an upright posture, the effects of gravity can cause this shape deformation. Oligosaccharides are common prebiotics and their effects on bowel health are well known. However, studies of the physiological functionality of a product that contains both lactulose and galactooligosaccharides are insufficient. We investigated the constipation reduction effect of a dual-type oligosaccharide, Dual-Oligo, in loperamide-treated rats. MATERIALS/METHODS Dual-Oligo consists of galactooligosaccharides (15.80%) and lactulose (51.67%). Animals were randomly divided into four groups, the normal group (normal), control group (control), low concentration of Dual-Oligo (LDO) group, and high concentration of Dual-Oligo (HDO) group. After 7 days of oral administration, fecal pellet amount, fecal weight, water content of fecal were measured. Blood chemistry, short-chain fatty acid (SCFA), gastrointestinal transit ratio and length and intestinal mucosa were analyzed. RESULTS Dual-Oligo increased the fecal weight, and water content of feces in rats with loperamide-induced constipation. Gastrointestinal transit ratio and length and area of intestinal mucosa significantly increased after treatment with Dual-Oligo in loperamide-induced rats. A high concentration of Dual-Oligo tended to produce more acetic acid than that observed for the control group, and Dual-Oligo affected the production of total SCFA. Bifidobacteria concentration of cecal contents in the high-concentration oligosaccharide (HDO) and low-concentration oligosaccharide (LDO) groups was similar to the result of the normal group. CONCLUSIONS These results showed that Dual-Oligo is a functional material that is derived from a natural food product and is effective in ameliorating constipation. PMID:27909555

  13. Dual nozzle aerodynamic and cooling analysis study

    NASA Technical Reports Server (NTRS)

    Meagher, G. M.

    1981-01-01

    Analytical models to predict performance and operating characteristics of dual nozzle concepts were developed and improved. Aerodynamic models are available to define flow characteristics and bleed requirements for both the dual throat and dual expander concepts. Advanced analytical techniques were utilized to provide quantitative estimates of the bleed flow, boundary layer, and shock effects within dual nozzle engines. Thermal analyses were performed to define cooling requirements for baseline configurations, and special studies of unique dual nozzle cooling problems defined feasible means of achieving adequate cooling.

  14. Measuring treatment effects on dual-task performance: a framework for research and clinical practice

    PubMed Central

    Plummer, Prudence; Eskes, Gail

    2015-01-01

    The relevance of dual-task walking to everyday ambulation is widely acknowledged, and numerous studies have demonstrated that dual-task interference can significantly impact recovery of functional walking in people with neurological disorders. The magnitude and direction of dual-task interference is influenced by the interaction between the two tasks, including how individuals spontaneously prioritize their attention. Therefore, to accurately interpret and characterize dual-task interference and identify changes over time, it is imperative to evaluate single and dual-task performance in both tasks, as well as the tasks relative to each other. Yet, reciprocal dual-task effects (DTE) are frequently ignored. The purpose of this perspective paper is to present a framework for measuring treatment effects on dual-task interference, specifically taking into account the interactions between the two tasks and how this can provide information on whether overall dual-task capacity has improved or a different attentional strategy has been adopted. In discussing the clinical implications of using this framework, we provide specific examples of using this method and provide some explicit recommendations for research and clinical practice. PMID:25972801

  15. Dual leadership in a hospital practice.

    PubMed

    Thude, Bettina Ravnborg; Thomsen, Svend Erik; Stenager, Egon; Hollnagel, Erik

    2017-02-06

    Purpose Despite the practice of dual leadership in many organizations, there is relatively little research on the topic. Dual leadership means two leaders share the leadership task and are held jointly accountable for the results of the unit. To better understand how dual leadership works, this study aims to analyse three different dual leadership pairs at a Danish hospital. Furthermore, this study develops a tool to characterize dual leadership teams from each other. Design/methodology/approach This is a qualitative study using semi-structured interviews. Six leaders were interviewed to clarify how dual leadership works in a hospital context. All interviews were transcribed and coded. During coding, focus was on the nine principles found in the literature and another principle was found by looking at the themes that were generic for all six interviews. Findings Results indicate that power balance, personal relations and decision processes are important factors for creating efficient dual leaderships. The study develops a categorizing tool to use for further research or for organizations, to describe and analyse dual leaderships. Originality/value The study describes dual leadership in the hospital context and develops a categorizing tool for being able to distinguish dual leadership teams from each other. It is important to reveal if there are any indicators that can be used for optimising dual leadership teams in the health-care sector and in other organisations.

  16. Holographic dual of a time machine

    NASA Astrophysics Data System (ADS)

    Arefeva, Irina; Bagrov, Andrey; Säterskog, Petter; Schalm, Koenraad

    2016-08-01

    Assuming that the AdS/CFT prescription is valid in the case of noncausal backgrounds, we apply it to the simplest possible eternal time machine solution in AdS3 based on two conical defects moving around their center of mass along a circular orbit. Closed timelike curves in this space-time extend all the way to the boundary of AdS3, violating causality of the boundary field theory. By use of the geodesic approximation we address the issue of self-consistent dynamics of the dual 1 +1 dimensional field theory when causality is violated, and calculate the two-point retarded Green function. It has a nontrivial analytical structure both at negative and positive times, providing us with an intuition on how an interacting quantum field could behave once causality is broken.

  17. The cerebellum in dual-task performance in Parkinson’s disease

    PubMed Central

    Gao, Linlin; Zhang, Jiarong; Hou, Yanan; Hallett, Mark; Chan, Piu; Wu, Tao

    2017-01-01

    Parkinson’s disease (PD) patients have difficulty in performing a dual-task. It has been suggested that the cerebellum is important in dual-tasking. We used functional MRI to investigate the role of the cerebellum in performing a dual motor and cognitive task in PD patients. We have examined whether there are any areas additionally activated for dual-task performance, and compared the neural activity and functional connectivity pattern in the cerebellum between PD patients and healthy controls. We found that the right cerebellar vermis and left lobule V of cerebellar anterior lobe were additionally activated for dual-task performance in healthy controls and for motor task in PD patients. We didn’t find any cerebellar regions additionally activated while performing dual-task in PD patients. In addition, the right cerebellar vermis had enhanced connectivity with motor and cognitive associated networks in PD patients. PD patients have limited cerebellar resources that are already utilized for single tasks and, for dual tasks, cannot augment as necessary in order to integrate motor and cognitive networks. PMID:28358358

  18. Dual arm master controller development

    NASA Technical Reports Server (NTRS)

    Kuban, D. P.; Perkins, G. S.

    1985-01-01

    The advanced servomanipulator (ASM) slave was designed with an anthropomorphic stance gear/torque tube power drives, and modular construction. These features resulted in increased inertia, friction, and backlash relative to tape driven manipulators. Studies were performed which addressed to human factor design and performance tradeoffs associated with the corresponding master controller best suited for the ASM. The results of these studies, as well as the conceptual design of the dual arm master controller, are presented.

  19. HELIOS dual swept frequency radiometer

    NASA Technical Reports Server (NTRS)

    White, J. R.

    1975-01-01

    The HELIOS dual swept frequency radiometer, used in conjunction with a dipole antenna, was designed to measure electromagnetic radiation in space. An engineering prototype was fabricated and tested on the HELIOS spacecraft. Two prototypes and two flight units were fabricated and three of the four units were integrated into the HELIOS spacecraft. Two sets of ground support equipment were provided for checkout of the radiometer.

  20. Inverse-Gaussian apodized fiber Bragg grating for dual-wavelength lasing.

    PubMed

    Lin, Bo; Zhang, Han; Tjin, Swee Chuan; Tang, Dingyuan; Hao, Jianzhong; Tay, Chia Meng; Liang, Sheng

    2010-03-10

    A fiber Bragg grating (FBG) with an inverse-Gaussian apodization function is proposed and fabricated. It is shown that such a FBG possesses dual-wavelength narrow transmission peaks and the wavelength spacing between the two peaks is easily controllable during fabrication. Incorporating such a FBG filter into a fiber laser with a linear cavity, we obtain stable dual-wavelength emission with 0.146 nm wavelength spacing. This arrangement provides a simple and low cost way of achieving dual-wavelength fiber laser operation.

  1. Human placenta as a 'dual' biomarker for monitoring fetal and maternal environment with special reference to potentially toxic trace elements. Part 1: physiology, function and sampling of placenta for elemental characterisation.

    PubMed

    Iyengar, G V; Rapp, A

    2001-12-03

    Choice of specimen from human subjects for monitoring pollutants proven to be detrimental to human health depends on the criteria chosen, namely real-time monitoring (RTM) or long-term monitoring (LTM). Specimens such as whole blood, urine, saliva and breast milk are commonly used from living subjects for RTM of toxic metals. However, sampling blood requires an invasive procedure. On the other hand, hair (with some limitations), bone (especially for the assessment of bone seeking elements), adipose tissue (mainly for organic pollutants) and liver (for both organic and inorganic toxicants) are used as specimens for LTM. With the exception of hair, generally these specimens are obtained at post-mortem. In context of health-related biomonitoring, placenta as a specimen has not received as much attention as it deserves. It is a unique sample requiring no invasive procedure, and offers possibilities for RTM, in particular as a dual purpose specimen for evaluating the pollutant burden exerted on the mother as well as on the fetus. Obtaining representative samples of placenta for elemental composition studies is a difficult task, because of heterogeneous mix of placental cells and decidual matter tainted with maternal and fetal blood. Therefore, the present sampling practices for placental tissue, and guidelines to safeguard the validity of the sampled material have been reviewed in part 1 with the following conclusions: medico-legal and ethical matters should be properly addressed before collecting the placenta; it is advisable to collect the entire placenta even if it includes the umbilical cord; further preparatory work is to be carried out in a clean laboratory and depends upon the purpose of the investigation; homogenising the entire sample may prove to be technically challenging but this step is crucial to obtain representative samples, handling the entire sample may be unavoidable; and an alternative method of procuring representative samples would require random

  2. A prospective, randomized, double-blind, placebo-controlled parallel-group dual site trial to evaluate the effects of a Bacillus coagulans-based product on functional intestinal gas symptoms

    PubMed Central

    2009-01-01

    Background This randomized double blind placebo controlled dual site clinical trial compared a probiotic dietary supplement to placebo regarding effects on gastrointestinal symptoms in adults with post-prandial intestinal gas-related symptoms (abdominal pain, distention, flatulence) but no gastrointestinal (GI) diagnoses to explain the symptoms. Methods Sixty-one adults were enrolled (age 36.5 ± 12.6 years; height 165.1 ± 9.2 cm; weight 75.4 ± 17.3 kg) and randomized to either Digestive Advantage™ Gas Defense Formula - (GanedenBC30 Bacillus coagulans GBI-30, 6086): n = 30; or Placebo: n = 31. Study subjects were evaluated every two weeks over a four-week period using validated questionnaires and standard biochemical safety testing. Outcome criteria of interest included change from baseline in Gastrointestinal Symptom Rating Scale (GSRS) abdominal pain, abdominal distention, flatus, and the Severity of Dyspepsia Assessment (SODA) bloating and gas subscores over four weeks of product use. Results Measured against the placebo, subjects in the probiotic group achieved significant improvements in GSRS abdominal pain subscore (p = 0.046) and the GSRS total score (p = 0.048), with a strong trend for improvement on the GSRS abdominal distension subscore (p = 0.061). A strong placebo effect was evident which could explain the lack of statistical significant differences between the groups for many of the efficacy variables. Conclusion In conclusion, the Bacillus coagulans-based product was effective in improving the quality of life and reducing gastrointestinal symptoms in adults with post prandial intestinal gas-related symptoms and no GI diagnoses. Trial Registration ClinicalTrials.gov Identifier: NCT00881322 PMID:19922649

  3. Graphical functions in parametric space

    NASA Astrophysics Data System (ADS)

    Golz, Marcel; Panzer, Erik; Schnetz, Oliver

    2016-12-01

    Graphical functions are positive functions on the punctured complex plane Csetminus {0,1} which arise in quantum field theory. We generalize a parametric integral representation for graphical functions due to Lam, Lebrun and Nakanishi, which implies the real analyticity of graphical functions. Moreover, we prove a formula that relates graphical functions of planar dual graphs.

  4. The Neurocognitive Basis for Impaired Dual-Task Performance in Senior Fallers

    PubMed Central

    Nagamatsu, Lindsay S.; Hsu, C. Liang; Voss, Michelle W.; Chan, Alison; Bolandzadeh, Niousha; Handy, Todd C.; Graf, Peter; Beattie, B. Lynn; Liu-Ambrose, Teresa

    2016-01-01

    Falls are a major health-care concern, and while dual-task performance is widely recognized as being impaired in those at-risk for falls, the underlying neurocognitive mechanisms remain unknown. A better understanding of the underlying mechanisms could lead to the refinement and development of behavioral, cognitive, or neuropharmacological interventions for falls prevention. Therefore, we conducted a cross-sectional study with community-dwelling older adults aged 70–80 years with a history of falls (i.e., two or more falls in the past 12 months) or no history of falls (i.e., zero falls in the past 12 months); n = 28 per group. We compared functional activation during cognitive-based dual-task performance between fallers and non-fallers using functional magnetic resonance imaging (fMRI). Executive cognitive functioning was assessed via Stroop, Trail Making, and Digit Span. Mobility was assessed via the Timed Up and Go test (TUG). We found that non-fallers exhibited significantly greater functional activation compared with fallers during dual-task performance in key regions responsible for resolving dual-task interference, including precentral, postcentral, and lingual gyri. Further, we report slower reaction times during dual-task performance in fallers and significant correlations between level of functional activation and independent measures of executive cognitive functioning and mobility. Our study is the first neuroimaging study to examine dual-task performance in fallers, and supports the notion that fallers have reduced functional brain activation compared with non-fallers. Given that dual-task performance—and the underlying neural concomitants—appears to be malleable with relevant training, our study serves as a launching point for promising strategies to reduce falls in the future. PMID:26903862

  5. Differential invariants of self-dual conformal structures

    NASA Astrophysics Data System (ADS)

    Kruglikov, Boris; Schneider, Eivind

    2017-03-01

    We compute the quotient of the self-duality equation for conformal metrics by the action of the diffeomorphism group. We also determine Hilbert polynomial, counting the number of independent scalar differential invariants depending on the jet-order, and the corresponding Poincaré function. We describe the field of rational differential invariants separating generic orbits of the diffeomorphism pseudogroup action, resolving the local recognition problem for self-dual conformal structures.

  6. A tunable dual frequency dye laser - dual frequency oscillator design

    NASA Technical Reports Server (NTRS)

    Abury, Y.

    1983-01-01

    The pulsed dye laser offers a tunable oscillator, followed by three amplifiers. It is pumped by a dual frequency Nd:YAG laser. Tuning and spectral width are controlled by a holographic network connected to a high power telescope. The modified two wavelength dye laser allows for absorption lidar techniques for remote sensing of the atmosphere. Line switching is achieved by electrooptical commutation. A feasibility experiment was performed with the original oscillator. A model was then built, and tested with different dyes. After a few modifications were made to improve the conversion efficiency, this oscillator was inserted in the laser to check whether the amplifier stages were correctly adjusted.

  7. A dual micro-CT system for small animal imaging

    NASA Astrophysics Data System (ADS)

    Badea, C. T.; Johnston, S.; Johnson, B.; Lin, M.; Hedlund, L. W.; Johnson, G. Allan

    2008-03-01

    Micro-CT is a non-invasive imaging modality usually used to assess morphology in small animals. In our previous work, we have demonstrated that functional micro-CT imaging is also possible. This paper describes a dual micro-CT system with two fixed x-ray/detectors developed to address such challenging tasks as cardiac or perfusion studies in small animals. A two-tube/detector system ensures simultaneous acquisition of two projections, thus reducing scanning time and the number of contrast injections in perfusion studies by a factor of two. The system is integrated with software developed in-house for cardio-respiratory monitoring and gating. The sampling geometry was optimized for 88 microns in such a way that the geometric blur of the focal spot matches the Nyquist sample at the detector. A geometric calibration procedure allows one to combine projection data from the two chains into a single reconstructed volume. Image quality was measured in terms of spatial resolution, uniformity, noise, and linearity. The modulation transfer function (MTF) at 10% is 3.4 lp/mm for single detector reconstructions and 2.3 lp/mm for dual tube/detector reconstructions. We attribute this loss in spatial resolution to the compounding of slight errors in the separate single chain calibrations. The dual micro-CT system is currently used in studies for morphological and functional imaging of both rats and mice.

  8. Wave interaction with dual circular porous plates

    NASA Astrophysics Data System (ADS)

    Mondal, Arpita; Gayen, R.

    2015-12-01

    In this paper we investigated the reflection and the transmission of a system of two symmetric circular-arc-shaped thin porous plates submerged in deep water within the context of linear theory. The hypersingular integral equation technique has been used to analyze the problem mathematically. The integral equations are formulated by applying Green's integral theorem to the fundamental potential function and the scattered potential function into a suitable fluid region, and then using the boundary condition on the porous plate surface. These are solved approximately using an expansion-cum-collocation method using the behaviour of the potential functions at the tips of the plates. This method ultimately produces a very good numerical approximation for the reflection and the transmission coefficients and hydrodynamic force components. The numerical results are depicted graphically against the wave number for a variety of layouts of the arc. Some results are compared with known results for similar configurations of dual rigid plate systems available in the literature with good agreement.

  9. NASA Dual Precipitation Radar Arrives at Goddard

    NASA Video Gallery

    The Dual-frequency Precipitation Radar (DPR) built by the Japan Aerospace Exploration Agency (JAXA) for the Global Precipitation Measurement (GPM) mission's Core Observatory arrived on Friday, Marc...

  10. Dual aperture multispectral Schmidt objective

    NASA Astrophysics Data System (ADS)

    Minott, P. O.

    1984-04-01

    A dual aperture, off-axis catadioptic Schmidt objective is described. It is formed by symmetrically aligning two pairs of Schmidt objectives on opposite sides of a common plane (x,z). Each objective has a spherical primary mirror with a spherical focal plane and center of curvature aligned along an optic axis laterally spaced apart from the common plane. A multiprism beamsplitter with buried dichroic layers and a convex entrance and concave exit surfaces optically concentric to the center of curvature may be positioned at the focal plane. The primary mirrors of each objective may be connected rigidly together and may have equal or unequal focal lengths.

  11. Dual aperture multispectral Schmidt objective

    NASA Technical Reports Server (NTRS)

    Minott, P. O. (Inventor)

    1984-01-01

    A dual aperture, off-axis catadioptic Schmidt objective is described. It is formed by symmetrically aligning two pairs of Schmidt objectives on opposite sides of a common plane (x,z). Each objective has a spherical primary mirror with a spherical focal plane and center of curvature aligned along an optic axis laterally spaced apart from the common plane. A multiprism beamsplitter with buried dichroic layers and a convex entrance and concave exit surfaces optically concentric to the center of curvature may be positioned at the focal plane. The primary mirrors of each objective may be connected rigidly together and may have equal or unequal focal lengths.

  12. Dual intercalating molten electrolyte batteries

    SciTech Connect

    Carlin, R.T.; Long, H.C. De; Fuller, J.; Lauderdale, W.J.; Naughton, T.; Trulove, P.C.; Bahn, C.S.

    1995-12-31

    Dual Intercalating Molten Electrolyte (DIME) electrodes and cells have been examined using a number of low-melting and room-temperature molten salts. A cell with a chloroaluminate melt achieved a cycling efficiency of 85% with a discharge voltage of 2.92 V. Coke-elastomer composite electrodes underwent cation reductive intercalation without experiencing the exfoliation and degradation seen for graphite rods. Theoretical studies for an imidazolium-graphite intercalate predicted the graphite layer spacing expands between 5.18 and 8.01 {angstrom} upon insertion of the imidazolium molecule into the graphite lattice.

  13. Dual laser gyro test program

    NASA Astrophysics Data System (ADS)

    Jones, Malcolm E.; Moore, Kim Eric

    This paper addresses the results of a comparative test evaluation of two similar-sized but otherwise dissimilar ring laser gyroscopes (RLG's). Both units were tested side by side, with the input axes (IA's) parallel, on the same test table. This report describes the rationale and design factors considered important to the test objectives. Emphasis was placed upon the evaluation of the scale factor (SF) linearity, drift rate stability (short term and long term), and derived rate. Conclusions drawn were (1) that dual operation had an observable but insignificant effect on the test results, (2) that the benefits of dual operation outweighed the additional design and analysis efforts required at the outset of the program, and (3) that the performance characteristics of the two test articles were significantly different. The differences between the two test articles (1) led to suggestions which could direct one vendor toward obtaining improved performance and (2) resulted in the creation of a conceptually new method (DELTA TIME-COUNT histogram) for quickly assessing the quality of laser gyros (or any digital sensor device for that matter).

  14. Implementation and applications of dual-modality imaging

    NASA Astrophysics Data System (ADS)

    Hasegawa, Bruce H.; Barber, William C.; Funk, Tobias; Hwang, Andrew B.; Taylor, Carmen; Sun, Mingshan; Seo, Youngho

    2004-06-01

    In medical diagnosis, functional or physiological data can be acquired using radionuclide imaging with positron emission tomography or with single-photon emission computed tomography. However, anatomical or structural data can be acquired using X-ray computed tomography. In dual-modality imaging, both radionuclide and X-ray detectors are incorporated in an imaging system to allow both functional and structural data to be acquired in a single procedure without removing the patient from the imaging system. In a clinical setting, dual-modality imaging systems commonly are used to localize radiopharmaceutical uptake with respect to the patient's anatomy. This helps the clinician to differentiate disease from regions of normal radiopharmaceutical accumulation, to improve diagnosis or cancer staging, or to facilitate planning for radiation therapy or surgery. While initial applications of dual-modality imaging were developed for clinical imaging on humans, it now is recognized that these systems have potentially important applications for imaging small animals involved in experimental studies including basic investigations of mammalian biology and development of new pharmaceuticals for diagnosis or treatment of disease.

  15. Dual parametrization of generalized parton distributions in two equivalent representations

    NASA Astrophysics Data System (ADS)

    Müller, D.; Polyakov, M. V.; Semenov-Tian-Shansky, K. M.

    2015-03-01

    The dual parametrization and the Mellin-Barnes integral approach represent two frameworks for handling the double partial wave expansion of generalized parton distributions (GPDs) in the conformal partial waves and in the t-channel SO(3) partial waves. Within the dual parametrization framework, GPDs are represented as integral convolutions of forward-like functions whose Mellin moments generate the conformal moments of GPDs. The Mellin-Barnes integral approach is based on the analytic continuation of the GPD conformal moments to the complex values of the conformal spin. GPDs are then represented as the Mellin-Barnes-type integrals in the complex conformal spin plane. In this paper we explicitly show the equivalence of these two independently developed GPD representations. Furthermore, we clarify the notions of the J = 0 fixed pole and the D-form factor. We also provide some insight into GPD modeling and map the phenomenologically successful Kumerički-Müller GPD model to the dual parametrization framework by presenting the set of the corresponding forward-like functions. We also build up the reparametrization procedure allowing to recast the double distribution representation of GPDs in the Mellin-Barnes integral framework and present the explicit formula for mapping double distributions into the space of double partial wave amplitudes with complex conformal spin.

  16. A Dual-Stream Neuroanatomy of Singing.

    PubMed

    Loui, Psyche

    2015-02-01

    Singing requires effortless and efficient use of auditory and motor systems that center around the perception and production of the human voice. Although perception and production are usually tightly coupled functions, occasional mismatches between the two systems inform us of dissociable pathways in the brain systems that enable singing. Here I review the literature on perception and production in the auditory modality, and propose a dual-stream neuroanatomical model that subserves singing. I will discuss studies surrounding the neural functions of feedforward, feedback, and efference systems that control vocal monitoring, as well as the white matter pathways that connect frontal and temporal regions that are involved in perception and production. I will also consider disruptions of the perception-production network that are evident in tone-deaf individuals and poor pitch singers. Finally, by comparing expert singers against other musicians and nonmusicians, I will evaluate the possibility that singing training might offer rehabilitation from these disruptions through neuroplasticity of the perception-production network. Taken together, the best available evidence supports a model of dorsal and ventral pathways in auditory-motor integration that enables singing and is shared with language, music, speech, and human interactions in the auditory environment.

  17. Dual mode stereotactic localization method and application

    DOEpatents

    Keppel, Cynthia E.; Barbosa, Fernando Jorge; Majewski, Stanislaw

    2002-01-01

    The invention described herein combines the structural digital X-ray image provided by conventional stereotactic core biopsy instruments with the additional functional metabolic gamma imaging obtained with a dedicated compact gamma imaging mini-camera. Before the procedure, the patient is injected with an appropriate radiopharmaceutical. The radiopharmaceutical uptake distribution within the breast under compression in a conventional examination table expressed by the intensity of gamma emissions is obtained for comparison (co-registration) with the digital mammography (X-ray) image. This dual modality mode of operation greatly increases the functionality of existing stereotactic biopsy devices by yielding a much smaller number of false positives than would be produced using X-ray images alone. The ability to obtain both the X-ray mammographic image and the nuclear-based medicine gamma image using a single device is made possible largely through the use of a novel, small and movable gamma imaging camera that permits its incorporation into the same table or system as that currently utilized to obtain X-ray based mammographic images for localization of lesions.

  18. Towards nanoscale composite particles of dual complexity.

    PubMed

    Wagner, Claudia Simone; Shehata, Samuel; Henzler, Katja; Yuan, Jiayin; Wittemann, Alexander

    2011-03-01

    The fabrication of heteroaggregates comprising inorganic and organic nanoparticles of different sizes is reported. Control over the assembly of nanoscale functional building units is of great significance to many practical applications. Joining together different spherical nanoparticles in a defined manner allows control over the shape of the composites. If two types of constituents are chosen that differ in size, the surfaces of the composites exhibit two specific radii of curvature, yielding aggregates of dual surface roughness. Moreover, if the constituents consist of different materials, the resulting heteroaggregates feature both compositional and interfacial anisotropy, offering unprecedented perspectives for custom-tailored colloids. This study describes a two-step approach towards such designer particles. At first, amine-modified polystyrene particles with 154 nm diameter were assembled into clusters of well-defined configurations. Onto these, oppositely charged inorganic particles with diameters of only a few nanometres were deposited by direct uptake from solution, resulting in numerous functional entities all over the surface of the polymer clusters. Despite the fact that oppositely charged constituents are brought together, charge reversal by uptake of nanoparticles allows for stable suspensions of heterocomposites. Hence, the possibility to assemble particles into nanoscale heterocomposites with full control over shape, composition, and surface roughness is demonstrated.

  19. Sublattice dependent magnetic response of dual Cr doped graphene monolayer: a full potential approach

    NASA Astrophysics Data System (ADS)

    Thakur, Jyoti; Kashyap, Manish K.; Taya, Ankur; Rani, Priti; Saini, Hardev S.

    2017-01-01

    In the present scenario, many researchers are exploring the possibility of inducing a magnetic channel in graphene by introducing various types of defects. To examine the Cr-Cr interactions in dual Cr doped graphene monolayer for magnetic response and spin polarization, the first-principles density functional theory based calculations are performed. Further, the possibility of achieving 100 % spin polarization in various possible configurations of dual Cr-doping have been explored. Dual doping of Cr atoms in graphene monolayer preferring ferromagnetic ordering, generates a spin magnetic state with a local moment of 4.00 µB. Depending upon the relative position of two Cr impurities in graphene, the ground states of doped systems are found be ferromagnetic, antiferromagnetic or paramagnetic. The origin of particular magnetic state observed in all possible dual Cr-doping configurations has been explained on the basis of RKKY indirect exchange interactions.

  20. Support Networks of Dual Career Couples.

    ERIC Educational Resources Information Center

    Lloyd, Sally A.; And Others

    Although social networks play an important role in supporting families under stress, there is some evidence that families living a stressful dual career life style may have limited network resources. To describe support networks of dual career couples and to examine the relationship between the supportiveness of the network and satisfaction with…