Dual wavelength multiple-angle light scattering system for cryptosporidium detection

Science.gov (United States)

Buaprathoom, S.; Pedley, S.; Sweeney, S. J.

2012-06-01

A simple, dual wavelength, multiple-angle, light scattering system has been developed for detecting cryptosporidium suspended in water. Cryptosporidium is a coccidial protozoan parasite causing cryptosporidiosis; a diarrheal disease of varying severity. The parasite is transmitted by ingestion of contaminated water, particularly drinking-water, but also accidental ingestion of bathing-water, including swimming pools. It is therefore important to be able to detect these parasites quickly, so that remedial action can be taken to reduce the risk of infection. The proposed system combines multiple-angle scattering detection of a single and two wavelengths, to collect relative wavelength angle-resolved scattering phase functions from tested suspension, and multivariate data analysis techniques to obtain characterizing information of samples under investigation. The system was designed to be simple, portable and inexpensive. It employs two diode lasers (violet InGaN-based and red AlGaInP-based) as light sources and silicon photodiodes as detectors and optical components, all of which are readily available. The measured scattering patterns using the dual wavelength system showed that the relative wavelength angle-resolved scattering pattern of cryptosporidium oocysts was significantly different from other particles (e.g. polystyrene latex sphere, E.coli). The single wavelength set up was applied for cryptosporidium oocysts'size and relative refractive index measurement and differential measurement of the concentration of cryptosporidium oocysts suspended in water and mixed polystyrene latex sphere suspension. The measurement results showed good agreement with the control reference values. These results indicate that the proposed method could potentially be applied to online detection in a water quality control system.

Dual energy radiography using active detector technology

International Nuclear Information System (INIS)

Seibert, J.A.; Poage, T.F.; Alvarez, R.E.

1996-01-01

A new technology has been implemented using an open-quotes active-detectorclose quotes comprised of two computed radiography (CR) imaging plates in a sandwich geometry for dual-energy radiography. This detector allows excellent energy separation, short exposure time, and high signal to noise ratio (SNR) for clinically robust open-quotes bone-onlyclose quotes and open-quotes soft-tissue onlyclose quotes images with minimum patient motion. Energy separation is achieved by two separate exposures at widely different kVp's: the high energy (120 kVp + 1.5 mm Cu filter) exposure is initiated first, followed by a short burst of intense light to erase the latent image on the front plate, and then a 50 kVp (low energy) exposure. A personal computer interfaced to the x-ray generator, filter wheel, and active detector system orchestrates the acquisition sequence within a time period of 150 msec. The front and back plates are processed using a CR readout algorithm with fixed speed and wide dynamic range. open-quotes Bone-onlyclose quotes and open-quotes soft-tissue onlyclose quotes images are calculated by geometric alignment of the two images and application of dual energy decomposition algorithms on a pixel by pixel basis. Resultant images of a calibration phantom demonstrate an increase of SNR 2 / dose by ∼73 times when compared to a single exposure open-quotes passive-detectorclose quotes comprised of CR imaging plates, and an ∼8 fold increase compared to a screen-film dual-energy cassette comprised of different phosphor compounds. In conclusion, dual energy imaging with open-quotes active detectorclose quotes technology is clinically feasible and can provide substantial improvements over conventional methods for dual-energy radiography

NRG1-Fc improves metabolic health via dual hepatic and central action.

Science.gov (United States)

Zhang, Peng; Kuang, Henry; He, Yanlin; Idiga, Sharon O; Li, Siming; Chen, Zhimin; Yang, Zhao; Cai, Xing; Zhang, Kezhong; Potthoff, Matthew J; Xu, Yong; Lin, Jiandie D

2018-03-08

Neuregulins (NRGs) are emerging as an important family of signaling ligands that regulate glucose and lipid homeostasis. NRG1 lowers blood glucose levels in obese mice, whereas the brown fat-enriched secreted factor NRG4 protects mice from high-fat diet-induced insulin resistance and hepatic steatosis. However, the therapeutic potential of NRGs remains elusive, given the poor plasma half-life of the native ligands. Here, we engineered a fusion protein using human NRG1 and the Fc domain of human IgG1 (NRG1-Fc) that exhibited extended half-life in circulation and improved potency in receptor signaling. We evaluated its efficacy in improving metabolic parameters and dissected the mechanisms of action. NRG1-Fc treatment triggered potent AKT activation in the liver, lowered blood glucose, improved insulin sensitivity, and suppressed food intake in obese mice. NRG1-Fc acted as a potent secretagogue for the metabolic hormone FGF21; however, the latter was largely dispensable for its metabolic effects. NRG1-Fc directly targeted the hypothalamic POMC neurons to promote membrane depolarization and increase firing rate. Together, NRG1-Fc exhibits improved pharmacokinetic properties and exerts metabolic benefits through dual inhibition of hepatic gluconeogenesis and caloric intake.

Therapeutic action of ghrelin in a mouse model of colitis.

Science.gov (United States)

Gonzalez-Rey, Elena; Chorny, Alejo; Delgado, Mario

2006-05-01

Ghrelin is a novel growth hormone-releasing peptide with potential endogenous anti-inflammatory activities ameliorating some pathologic inflammatory conditions. Crohn's disease is a chronic debilitating disease characterized by severe T helper cell (Th)1-driven inflammation of the colon. The aim of this study was to investigate the therapeutic effect of ghrelin in a murine model of colitis. We examined the anti-inflammatory action of ghrelin in the colitis induced by intracolonic administration of trinitrobenzene sulfonic acid. Diverse clinical signs of the disease were evaluated, including weight loss, diarrhea, colitis, and histopathology. We also investigated the mechanisms involved in the potential therapeutic effect of ghrelin, such as inflammatory cytokines and chemokines, Th1-type response, and regulatory factors. Ghrelin ameliorated significantly the clinical and histopathologic severity of the trinitrobenzene sulfonic acid-induced colitis; abrogating body weight loss, diarrhea, and inflammation; and increasing survival. The therapeutic effect was associated with down-regulation of both inflammatory and Th1-driven autoimmune response through the regulation of a wide spectrum of inflammatory mediators. In addition, a partial involvement of interluekin-10/transforming growth factor-beta1-secreting regulatory T cells in this therapeutic effect was demonstrated. Importantly, the ghrelin treatment was therapeutically effective in established colitis and avoided the recurrence of the disease. Our data demonstrate novel anti-inflammatory actions for ghrelin in the gastrointestinal tract, ie, the capacity to deactivate the intestinal inflammatory response and to restore mucosal immune tolerance at multiple levels. Consequently, ghrelin administration represents a novel possible therapeutic approach for the treatment of Crohn's disease and other Th1-mediated inflammatory diseases, such as rheumatoid arthritis and multiple sclerosis.

Dual descriptions of spin-two massive particles in D=2+1 via master actions

Science.gov (United States)

Dalmazi, D.; Mendonça, Elias L.

2009-02-01

In the first part of this work we show the decoupling (up to contact terms) of redundant degrees of freedom which appear in the covariant description of spin-two massive particles in D=2+1. We make use of a master action which interpolates, without solving any constraints, between a first-, second-, and third-order (in derivatives) self-dual model. An explicit dual map between those models is derived. In our approach the absence of ghosts in the third-order self-dual model, which corresponds to a quadratic truncation of topologically massive gravity, is due to the triviality (no particle content) of the Einstein-Hilbert action in D=2+1. In the second part of the work, also in D=2+1, we prove the quantum equivalence of the gauge invariant sector of a couple of self-dual models of opposite helicities (+2 and -2) and masses m+ and m- to a generalized self-dual model which contains a quadratic Einstein-Hilbert action, a Chern-Simons term of first order, and a Fierz-Pauli mass term. The use of a first-order Chern-Simons term instead of a third-order one avoids conflicts with the sign of the Einstein-Hilbert action.

Dual descriptions of spin-two massive particles in D=2+1 via master actions

International Nuclear Information System (INIS)

Dalmazi, D.; Mendonca, Elias L.

2009-01-01

In the first part of this work we show the decoupling (up to contact terms) of redundant degrees of freedom which appear in the covariant description of spin-two massive particles in D=2+1. We make use of a master action which interpolates, without solving any constraints, between a first-, second-, and third-order (in derivatives) self-dual model. An explicit dual map between those models is derived. In our approach the absence of ghosts in the third-order self-dual model, which corresponds to a quadratic truncation of topologically massive gravity, is due to the triviality (no particle content) of the Einstein-Hilbert action in D=2+1. In the second part of the work, also in D=2+1, we prove the quantum equivalence of the gauge invariant sector of a couple of self-dual models of opposite helicities (+2 and -2) and masses m + and m - to a generalized self-dual model which contains a quadratic Einstein-Hilbert action, a Chern-Simons term of first order, and a Fierz-Pauli mass term. The use of a first-order Chern-Simons term instead of a third-order one avoids conflicts with the sign of the Einstein-Hilbert action.

(Glyco)-protein drug carriers with an intrinsic therapeutic activity : The concept of dual targeting

NARCIS (Netherlands)

Meijer, D.K F; Molema, Ingrid; Moolenaar, Frits; de Zeeuw, D; Swart, P.J

Dual targeting can in principle be achieved by using intrinsically active carriers that not only deliver the conjugated drug but also otherwise influence the pathological process. Potential carriers of this kind are monoclonal antibodies, certain interferons and interleukins, as well as certain

Dual multispectral and 3D structured light laparoscope

Science.gov (United States)

Clancy, Neil T.; Lin, Jianyu; Arya, Shobhit; Hanna, George B.; Elson, Daniel S.

2015-03-01

Intraoperative feedback on tissue function, such as blood volume and oxygenation would be useful to the surgeon in cases where current clinical practice relies on subjective measures, such as identification of ischaemic bowel or tissue viability during anastomosis formation. Also, tissue surface profiling may be used to detect and identify certain pathologies, as well as diagnosing aspects of tissue health such as gut motility. In this paper a dual modality laparoscopic system is presented that combines multispectral reflectance and 3D surface imaging. White light illumination from a xenon source is detected by a laparoscope-mounted fast filter wheel camera to assemble a multispectral image (MSI) cube. Surface shape is then calculated using a spectrally-encoded structured light (SL) pattern detected by the same camera and triangulated using an active stereo technique. Images of porcine small bowel were acquired during open surgery. Tissue reflectance spectra were acquired and blood volume was calculated at each spatial pixel across the bowel wall and mesentery. SL features were segmented and identified using a `normalised cut' algoritm and the colour vector of each spot. Using the 3D geometry defined by the camera coordinate system the multispectral data could be overlaid onto the surface mesh. Dual MSI and SL imaging has the potential to provide augmented views to the surgeon supplying diagnostic information related to blood supply health and organ function. Future work on this system will include filter optimisation to reduce noise in tissue optical property measurement, and minimise spot identification errors in the SL pattern.

Research on the speed of light transmission in a dual-frequency laser pumped single fiber with two directions

Science.gov (United States)

Qiu, Wei; Liu, Jianjun; Wang, Yuda; Yang, Yujing; Gao, Yuan; Lv, Pin; Jiang, Qiuli

2018-01-01

In this article a general theory of the coherent population oscillation effect in an erbium-doped fiber at room temperature is presented. We use dual pumping light waves with a simplified two-level system. Thus the time delay equations can be calculated from rate equations and the transmission equation. Using numerical simulation, in the case of dual-frequency pump light waves (1480 nm and 980 nm) with two directions, we analyze the influence of the pump power ratio on the group speed of light propagation. In addition, we compare slow light propagation with a single-pumping light and slow light propagation with a dual-pumping light at room temperature. The discussion shows that a larger time delay of slow light propagation can be obtained with a dual-frequency pumping laser. Compared to previous research methods, a dual-frequency laser pumped fiber with two directions is more controllable. Moreover, we conclude that the group velocity of light can be varied by changing the pump ratio.

Dual-therapeutic reporter genes fusion for enhanced cancer gene therapy and imaging.

Science.gov (United States)

Sekar, T V; Foygel, K; Willmann, J K; Paulmurugan, R

2013-05-01

Two of the successful gene-directed enzyme prodrug therapies include herpes simplex virus-thymidine kinase (HSV1-TK) enzyme-ganciclovir prodrug and the Escherichia coli nitroreductase (NTR) enzyme-CB1954 prodrug strategies; these enzyme-prodrug combinations produce activated cytotoxic metabolites of the prodrugs capable of tumor cell death by inhibiting DNA synthesis and killing quiescent cells, respectively. Both these strategies also affect significant bystander cell killing of neighboring tumor cells that do not express these enzymes. We have developed a dual-combination gene strategy, where we identified HSV1-TK and NTR fused in a particular orientation can effectively kill tumor cells when the tumor cells are treated with a fusion HSV1-TK-NTR gene- along with a prodrug combination of GCV and CB1954. In order to determine whether the dual-system demonstrate superior therapeutic efficacy than either HSV1-TK or NTR systems alone, we conducted both in vitro and in vivo tumor xenograft studies using triple negative SUM159 breast cancer cells, by evaluating the efficacy of cell death by apoptosis and necrosis upon treatment with the dual HSV1-TK genes-GCV-CB1954 prodrugs system, and compared the efficiency to HSV1-TK-GCV and NTR-CB1954. Our cell-based studies, tumor regression studies in xenograft mice, histological analyses of treated tumors and bystander studies indicate that the dual HSV1-TK-NTR-prodrug system is two times more efficient even with half the doses of both prodrugs than the respective single gene-prodrug system, as evidenced by enhanced apoptosis and necrosis of tumor cells in vitro in culture and xenograft of tumor tissues in animals.

Action, outcome, and value: a dual-system framework for morality.

Science.gov (United States)

Cushman, Fiery

2013-08-01

Dual-system approaches to psychology explain the fundamental properties of human judgment, decision making, and behavior across diverse domains. Yet, the appropriate characterization of each system is a source of debate. For instance, a large body of research on moral psychology makes use of the contrast between "emotional" and "rational/cognitive" processes, yet even the chief proponents of this division recognize its shortcomings. Largely independently, research in the computational neurosciences has identified a broad division between two algorithms for learning and choice derived from formal models of reinforcement learning. One assigns value to actions intrinsically based on past experience, while another derives representations of value from an internally represented causal model of the world. This division between action- and outcome-based value representation provides an ideal framework for a dual-system theory in the moral domain.

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

Directory of Open Access Journals (Sweden)

Ayesha Bhatia

2016-01-01

Full Text Available 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.

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

Science.gov (United States)

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.

The mutagenic action of UV-light irradiation on aspergillus terreus in relation to antibacterial activity

International Nuclear Information System (INIS)

Ouda, S.M.

2009-01-01

Four strains of cellulolytic fungi (i.e Penicillium oxalicum, Aspergillus niger, Aspergillus terreus and Trichoderma longibrachiatum) were tested for the production of cellulolytic enzymes and antibiotic action. these fungi were cultured on Czapek Dox's media with different cellulosic substrates. A. terreus. exhibited the highest cellulolytic activity and the highest level of anti-bacterial activity against Staphylococcus aureus. and Escherichia Coli, Ultraviolet light as a mutagenic treatment for A.terreus was investigated. Two treated isolates U.30.12 and U.60.10 were obtained after the treatment at dose 30 and 60 min., respectively with a higher antibiotic activity in comparison with the wild isolate. A compound of fifteen carbon atom of terrecylic acid was isolated from ethyl acetate extract using spectroscopic analysis

Dual Axis Radiographic Hydrodynamic Test Facility mitigation action plan. Annual report for 1998

International Nuclear Information System (INIS)

Haagenstad, T.

1999-01-01

This Mitigation Action Plan Annual Report (MAPAR) has been prepared as part of implementing the Dual Axis Radiographic Hydrodynamic Test Facility (DARHT) Mitigation Action Plan (MAP) to protect workers, soils, water, and biotic and cultural resources in and around the facility

Dual Axis Radiographic Hydrodynamic Test Facility mitigation action plan. Annual report for 1998

Energy Technology Data Exchange (ETDEWEB)

Haagenstad, T.

1999-01-15

This Mitigation Action Plan Annual Report (MAPAR) has been prepared as part of implementing the Dual Axis Radiographic Hydrodynamic Test Facility (DARHT) Mitigation Action Plan (MAP) to protect workers, soils, water, and biotic and cultural resources in and around the facility.

Improving Control Efficiency of Dynamic Street Lighting by Utilizing the Dual Graph Grammar Concept

Directory of Open Access Journals (Sweden)

Igor Wojnicki

2018-02-01

Full Text Available The paper introduces a definition of dual graph grammar. It enables two graphs to share information in a synchronized way. A smart city example application, which is an outdoor lighting control system utilizing the dual graph grammar, is also demonstrated. The system controls dimming of street lights which is based on traffic intensity. Each luminaire’s light level is adjusted individually to comply with the lighting norms to ensure safety. Benefits of applying the dual graph grammar are twofold. First, it increases expressive power of the mathematical model that the system uses. It becomes possible to take into account complex geographical distribution of sensors and logical dependencies among them. Second, it increases the system’s efficiency by reducing the problem size during run-time. Experimental results show a reduction of the computation time by a factor of 2.8. The approach has been verified in practice.

Light-activation through indirect ceramic restorations: does the overexposure compensate for the attenuation in light intensity during resin cement polymerization?

Directory of Open Access Journals (Sweden)

Albano Luis Novaes Bueno

2011-02-01

Full Text Available OBJECTIVES: This study evaluated the effects of light exposure through simulated indirect ceramic restorations (SICR on hardness (KHN of dual-cured resin cements (RCs, immediately after light-activation and 24 h later. MATERIAL AND METHODS: Three dual-cured RCs were evaluated: Eco-Link (Ivoclar Vivadent, Rely X ARC (3M ESPE, and Panavia F (Kuraray Medical Inc.. The RCs were manipulated in accordance to the manufacturers' instructions and were placed into cylindrical acrylic matrixes (1-mm-thick and 4-mm diameter. The RC light-activation (Optilux 501; Demetron Kerr was performed through a glass slide for 120 s (control group, or through 2-mm or 4-mm thick SICRs (IPS Empress II; Ivoclar Vivadent. The specimens were submitted to KHN analysis immediately and 24 h after light-activation. The data obtained at the 2 evaluation intervals were submitted to 2-way ANOVA repeated measures and post-hoc Tukey's test (pre-set alpha of 5%. RESULTS: Lower KHN was observed when light-activation was performed through SICRs for Eco-Link at all evaluation intervals and for Rely X ARC 24 h later. For Panavia F, no significant difference in KHN was observed between control and experimental groups, regardless of evaluation interval. Most groups exhibited higher KHN after 24 h than immediately after light-activation, with the exception of Rely X ARC light-activated through SICR, as no significant difference in KHN was found between evaluation intervals. CONCLUSIONS: Light overexposure did not compensate for light intensity attenuation due to the presence of SICR when Rely X and Eco-Link were used. Although hardness of such RCs increased over a 24-h interval, the RCs subjected to light overexposure did not reach the hardness values exhibited after direct light exposure.

Saturation in dual radiation action

International Nuclear Information System (INIS)

Rossi, H.H.; Zaider, M.

1988-01-01

The theory of dual radiation action (TDRA) was developed with the aim of applying microdosimetry to radiobiology. It therefore can deal only with the first phases in a long chain of events that results in patent effects. It is, however, clear that the initial spatial and temporal pattern of energy deposition has a profound influence on the ultimate outcome. As often happens, the early formulation of the theory contained a number of simplifying assumptions. Although most of these were explicitly stated when the first version of the TDRA was published experimental data obtained when the limitations are important were cited as contrary evidence causing considerable confusion. A more advanced version eliminated some of the restrictions but there remain others, one of which relates to certain aspects of saturation which are addressed here

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

Science.gov (United States)

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

2017-08-22

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

[Predictors of the therapeutic discharge in patients with dual pathology admitted to a therapeutic community with a psychiatric unit].

Science.gov (United States)

Madoz-Gúrpide, Agustín; García Vicent, Vicente; Luque Fuentes, Encarnación; Ochoa Mangado, Enriqueta

2013-01-01

This study aims to analyze the variables on which depends therapeutic discharge, in patients with a severe dual diagnosis admitted to a professional therapeutic community where their pathology is treated. 325 patients admitted between June 2000 and June 2009 to the therapeutic community. This is a retrospective, cross-sectional study with no control group, based on the detailed analysis of the information collected in a model of semi-structured clinical interview designed in the therapeutic community. The 29.5% of the individuals included in the sample were therapeutically discharged. Of all the variables introduced in this analysis the most significant ones were gender, age at the beginning of treatment, education level, opiate dependence, polidrug abuse, and the presence of psychotic disorders and borderline personality disorder. In our study, gender determines the type of discharge, being therapeutic discharge more frequent among women. A higher educational also increases a better prognosis with a higher rate of therapeutic discharge among individuals with higher education level. A later age at the beginning of the treatment reduces the likelihood of therapeutic discharge. Likewise, polidrug abuse, diagnosis of psychotic disorders and borderline personality disorder are associated to a lower rate of therapeutic discharge. Recognizing these characteristics will allow the early identification of those patients more at risk of dropping treatment hastily, while trying to prevent it by increasing the therapeutic intensity.

Simultaneously and separately immobilizing incompatible dual-enzymes on polymer substrate via visible light induced graft polymerization

Science.gov (United States)

Zhu, Xing; He, Bin; Zhao, Changwen; Ma, Yuhong; Yang, Wantai

2018-04-01

Developing facile and mild strategy to construct multi-enzymes immobilization system has attracted considerable attentions in recent years. Here a simple immobilization strategy called visible light induced graft polymerization that can simultaneously and separately encapsulate two kinds of enzymes on one polymer film was proposed. Two incompatible enzymes, trypsin and transglutaminase (TGase) were selected as model dual-enzymes system and simultaneously immobilized on two sides of low-density polyethylene (LDPE) film. After immobilization, it was found that more than 90% of the enzymes can be embedded into dual-enzymes loaded film without leakage. And the activities of both separately immobilized enzymes were higher than the activities of mixed co-immobilized enzymes or the sequential immobilized ones. This dual-enzymes loaded film (DEL film) showed excellent recyclability and can retain >87% activities of both enzymes after 4 cycles of utilization. As an example, this DEL film was used to conjugate a prodrug of cytarabine with a target peptide. The successful preparation of expected product demonstrated that the separately immobilized two enzymes can worked well together to catalyze a two-step reaction.

Discovery of dual-action membrane-anchored modulators of incretin receptors.

Directory of Open Access Journals (Sweden)

Jean-Philippe Fortin

Full Text Available The glucose-dependent insulinotropic polypeptide (GIP and the glucagon-like peptide-1 (GLP-1 receptors are considered complementary therapeutic targets for type 2 diabetes. Using recombinant membrane-tethered ligand (MTL technology, the present study focused on defining optimized modulators of these receptors, as well as exploring how local anchoring influences soluble peptide function.Serial substitution of residue 7 in membrane-tethered GIP (tGIP led to a wide range of activities at the GIP receptor, with [G(7]tGIP showing enhanced efficacy compared to the wild type construct. In contrast, introduction of G(7 into the related ligands, tGLP-1 and tethered exendin-4 (tEXE4, did not affect signaling at the cognate GLP-1 receptor. Both soluble and tethered GIP and GLP-1 were selective activators of their respective receptors. Although soluble EXE4 is highly selective for the GLP-1 receptor, unexpectedly, tethered EXE4 was found to be a potent activator of both the GLP-1 and GIP receptors. Diverging from the pharmacological properties of soluble and tethered GIP, the newly identified GIP-R agonists, (i.e. [G(7]tGIP and tEXE4 failed to trigger cognate receptor endocytosis. In an attempt to recapitulate the dual agonism observed with tEXE4, we conjugated soluble EXE4 to a lipid moiety. Not only did this soluble peptide activate both the GLP-1 and GIP receptors but, when added to receptor expressing cells, the activity persists despite serial washes.These findings suggest that conversion of a recombinant MTL to a soluble membrane anchored equivalent offers a means to prolong ligand function, as well as to design agonists that can simultaneously act on more than one therapeutic target.

Modification of light sources for appropriate biological action

Energy Technology Data Exchange (ETDEWEB)

Kozakov, R; Schoepp, H; Franke, St [Leibniz Institute of Plasma Science and Technology, Felix-Hausdorff-Str. 2, D-17489 Greifswald (Germany); Stoll, C; Kunz, D, E-mail: kozakov@inp-greifswald.d [Charite-Universitymedicine Berlin, Sleep Research and Clinical Chronobiology, Gr. Hamburger Str. 5-11, D-10115 Berlin (Germany)

2010-06-16

The impact of the non-visual action of light on the design of novel light sources is discussed. Therefore possible modifications of lamps dealing with spectral tailoring and their action on melatonin suppression in usual life situations are investigated. The results of melatonin suppression by plasma lamps are presented. It is shown that even short-time exposure to usual light levels in working areas has an influence on the melatonin onset.

Light wavelength dependency of mating activity in the drosophila melanogaster species subgroup

International Nuclear Information System (INIS)

Sakai, Takaomi; Tomaru, Masatoshi; Oguma, Yuzuru; Isono, Kunio; Fukatami, Akishi

2002-01-01

The action spectra of mating activity among the six species of the Drosophila melanogaster species subgroup were compared to understand how light wavelength affects mating activity. The species fell into three groups with respect to the action spectrum of mating activity. We chose one representative species from each of the three types for detailed study: D. melanogaster, D. sechellia and D. yakuba. The mating activities were investigated under three different light intensities of three monochromatic lights stimulus. Each species showed a unique spectral and intensity response. To know the evolutionary meaning of the light wavelength dependency of mating activity, we superimposed the type of action spectrum of mating activity in these six species on a cladogram. Mating inhibition under UV was conserved in evolution among these species. Furthermore we clarified that D. melanogaster showed low mating activity under UV because males courted less under UV. (author)

Screening action potentials: The power of light

Directory of Open Access Journals (Sweden)

Lars eKaestner

2011-07-01

Full Text Available Action potentials reflect the concerted activity of all electrogenic constituents in the plasma membrane during the excitation of a cell. Therefore, the action potential is an integrated readout and a promising parameter to detect electrophysiological failures or modifications thereof in diagnosis as well as in drug screens. Cellular action potentials can be recorded by optical approaches. To fulfill the pre-requirements to scale up for e.g. pharmacological screens the following preparatory work has to be provided: (i model cells under investigation need to represent target cells in the best possible manner; (ii optical sensors that can be either small molecule dyes or genetically encoded potential probes need to provide a reliable readout with minimal interaction with the naive behavior of the cells and (iii devices need to be capable to stimulate the cells, read out the signals with the appropriate speed as well as provide the capacity for a sufficient throughput. Here we discuss several scenarios for all three categories in the field of cardiac physiology and pharmacology and provide a perspective to use the power of light in screening cardiac action potentials.

An artemisinin-mediated ROS evolving and dual protease light-up nanocapsule for real-time imaging of lysosomal tumor cell death.

Science.gov (United States)

Huang, Liwei; Luo, Yingping; Sun, Xian; Ju, Huangxian; Tian, Jiangwei; Yu, Bo-Yang

2017-06-15

Lysosomes are critical organelles for cellular homeostasis and can be used as potential targets to kill tumor cells from inside. Many photo-therapeutic methods have been developed to overproduce reactive oxygen species (ROS) to trigger lysosomal membrane permeabilization (LMP)-associated cell death pathway. However, these technologies rely on extra irradiation to activate the photosensitizers, which limits the applications in treating deep seated tumors and widespread metastatic lesions. This work reports a multifunctional nanocapsule to achieve targeted lysosomal tumor cell death without irradiation and real-time monitoring of drug effect through encapsulating artemisinin and dual protease light-up nanoprobe in a folate-functionalized liposome. The nanocapsule can be specifically uptaken by tumor cells via folate receptor-mediated endocytosis to enter lysosomes, in which artemisinin reacts with ferrous to generate ROS for LMP-associated cell death. By virtue of confocal fluorescence imaging, the artemisinin location in lysosome, ROS-triggered LMP and ultimate cell apoptosis can be visualized with the cathepsin B and caspase-3 activatable nanoprobe. Notably, the artemisinin-mediated ROS evolving for tumor therapy and real-time therapeutic monitoring were successfully implemented by living imaging in tumor-bearing mice, which broaden the nanocapsule for in vivo theranostics and may offer new opportunities for precise medicine. Copyright © 2016 Elsevier B.V. All rights reserved.

Utilizing redox-mediated Bergman cyclization toward the development of dual-action metalloenediyne therapeutics.

Science.gov (United States)

Lindahl, Sarah E; Park, Hyunsoo; Pink, Maren; Zaleski, Jeffrey M

2013-03-13

resulting cisplatin-like byproduct represents an intriguing new strategy for potential dual-threat metalloenediyne therapeutics.

Acting in solidarity : Testing an extended dual pathway model of collective action by bystander group members

NARCIS (Netherlands)

Saab, Rim; Tausch, Nicole; Spears, Russell; Cheung, Wing-Yee

We examined predictors of collective action among bystander group members in solidarity with a disadvantaged group by extending the dual pathway model of collective action, which proposes one efficacy-based and one emotion-based path to collective action (Van Zomeren, Spears, Fischer, & Leach,

Effect of 670-nm Light-Emitting Diode Light On Neuronal Cultures

Science.gov (United States)

Wong-Riley, Margaret T. T.; Whelan, Harry T.

2002-01-01

Light close to and within the near infrared range has documented benefits for promoting wound healing in human and animal studies. Our preliminary results using light-emitting diodes (LEDs) in this range have also demonstrated two-to five-fold increases in growth-phase-specific DNA synthesis in normal fibroblasts, muscle cells, osteoblasts, and mucosal epithelial cells in tissue cultures. However, the mechanisms of action of such light on cells are poorly understood. We hypothesized that the therapeutic effects of such light result from the stimulation of cellular events associated with increases in cytochrome oxidase activity. As a first step in testing our hypothesis, we subjected primary neuronal cultures to impulse blockade by tetrodotoxin (TTX), a voltage-dependent sodium channel blocker, and applied LED light at 670 nm to determine if it could partially or fully reverse the reduction of cytochrome oxidase activity by TTX. The wavelength and parameters were previously tested to be beneficial for wound healing.

Metabolic actions of FGF21: molecular mechanisms and therapeutic implications

Directory of Open Access Journals (Sweden)

Xuan Ge

2012-08-01

Full Text Available Fibroblast growth factor 21 (FGF21 is an atypical member of the FGF family that functions as an endocrine factor. In obese animals, elevation of plasma FGF21 levels by either pharmacological or genetic approaches reduces body weight, decreases hyperglycemia and hyperlipidemia, alleviates fatty liver and increases insulin sensitivity. FGF21 exerts its pleiotropic metabolic effects through its actions on multiple targets, including adipose tissue, liver, brain and pancreas. The expression of FGF21 is under the control of both peroxisome proliferator-activated receptor gamma (PPARγ and peroxisome proliferator-activated receptor alpha (PPARα. A growing body of evidence suggests that the metabolic benefits of these two nuclear receptors are mediated in part by induction of FGF21. In humans, plasma levels of FGF21 are elevated in obese subjects and patients with type 2 diabetes, but are reduced in patients with autoimmune diabetes. This review summarizes recent advances in understanding the physiological roles of FGF21 and the molecular pathways underlying its actions, and also discusses the future prospective of developing FGF21 or its agonists as therapeutic agents for obesity-related medical complications.

A Planar, Chip-Based, Dual-Beam Refractometer Using an Integrated Organic Light Emitting Diode (OLED) Light Source and Organic Photovoltaic (OPV) Detectors

Science.gov (United States)

Ratcliff, Erin L.; Veneman, P. Alex; Simmonds, Adam; Zacher, Brian; Huebner, Daniel

2010-01-01

We present a simple chip-based refractometer with a central organic light emitting diode (OLED) light source and two opposed organic photovoltaic (OPV) detectors on an internal reflection element (IRE) substrate, creating a true dual-beam sensor platform. For first-generation platforms, we demonstrate the use of a single heterojunction OLED based on electroluminescence emission from an Alq3/TPD heterojunction (tris-(8-hydroxyquinoline)aluminum/N,N′-Bis(3-methylphenyl)-N,N′-diphenylbenzidine) and light detection with planar heterojunction pentacene/C60 OPVs. The sensor utilizes the considerable fraction of emitted light from conventional thin film OLEDs that is coupled into guided modes in the IRE instead of into the forward (display) direction. A ray-optics description is used to describe light throughput and efficiency-limiting factors for light coupling from the OLED into the substrate modes, light traversing through the IRE substrate, and light coupling into the OPV detectors. The arrangement of the OLED at the center of the chip provides for two sensing regions, a “sample” and “reference” channel, with detection of light by independent OPV detectors. This configuration allows for normalization of the sensor response against fluctuations in OLED light output, stability, and local fluctuations (temperature) which might influence sensor response. The dual beam configuration permits significantly enhanced sensitivity to refractive index changes relative to single-beam protocols, and is easily integrated into a field-portable instrumentation package. Changes in refractive index (ΔR.I.) between 10−2 and 10−3 R.I. units could be detected for single channel operation, with sensitivity increased to ΔR.I. ≈ 10−4 units when the dual beam configuration is employed. PMID:20218580

Microhardness of light- and dual-polymerizable luting resins polymerized through 7.5-mm-thick endocrowns.

Science.gov (United States)

Gregor, Ladislav; Bouillaguet, Serge; Onisor, Ioana; Ardu, Stefano; Krejci, Ivo; Rocca, Giovanni Tommaso

2014-10-01

The complete polymerization of luting resins through thick indirect restorations is still questioned. The purpose of this study was to evaluate the degree of polymerization of light- and dual-polymerizable luting resins under thick indirect composite resin and ceramic endocrowns by means of Vickers microhardness measurements. The Vickers microhardness measurements of a light-polymerizable microhybrid composite resin and a dual-polymerizable luting cement directly polymerized in a natural tooth mold for 40 seconds with a high-power light-emitting diode lamp (control) were compared with measurements after indirect irradiation through 7.5-mm-thick composite resin and ceramic endocrowns for 3 × 90 seconds. A test-to-control microhardness values ratio of 0.80 at a depth of 0.5 mm below the surface was assumed as the criterion for adequate conversion. For the Vickers microhardness measurements of a dual-polymerizable luting cement, no differences (P>.05) were found between Vickers microhardness control values and values reported after polymerization through composite resin and ceramic endocrowns. For The Vickers microhardness measurements (±SD) of a light-polymerizable microhybrid composite resin, control values were significantly (P.05). Under the conditions of this in vitro study, Vickers microhardness values of the dual-polymerizable resin cement and the light-polymerizable restorative composite resin irradiated for 3 × 90 seconds with a high irradiance light-emitting diode lamp through 7.5-mm-thick endocrowns reached at least 80% of the control Vickers microhardness values, which means that both materials can be adequately polymerized when they are used for luting thick indirect restorations. Copyright © 2014 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Simultaneous live cell imaging using dual FRET sensors with a single excitation light.

Directory of Open Access Journals (Sweden)

Yusuke Niino

Full Text Available Fluorescence resonance energy transfer (FRET between fluorescent proteins is a powerful tool for visualization of signal transduction in living cells, and recently, some strategies for imaging of dual FRET pairs in a single cell have been reported. However, these necessitate alteration of excitation light between two different wavelengths to avoid the spectral overlap, resulting in sequential detection with a lag time. Thus, to follow fast signal dynamics or signal changes in highly motile cells, a single-excitation dual-FRET method should be required. Here we reported this by using four-color imaging with a single excitation light and subsequent linear unmixing to distinguish fluorescent proteins. We constructed new FRET sensors with Sapphire/RFP to combine with CFP/YFP, and accomplished simultaneous imaging of cAMP and cGMP in single cells. We confirmed that signal amplitude of our dual FRET measurement is comparable to of conventional single FRET measurement. Finally, we demonstrated to monitor both intracellular Ca(2+ and cAMP in highly motile cardiac myocytes. To cancel out artifacts caused by the movement of the cell, this method expands the applicability of the combined use of dual FRET sensors for cell samples with high motility.

Light Controls Cytokinin Signaling via Transcriptional Regulation of Constitutively Active Sensor Histidine Kinase CKI1.

Science.gov (United States)

Dobisova, Tereza; Hrdinova, Vendula; Cuesta, Candela; Michlickova, Sarka; Urbankova, Ivana; Hejatkova, Romana; Zadnikova, Petra; Pernisova, Marketa; Benkova, Eva; Hejatko, Jan

2017-05-01

In plants, the multistep phosphorelay (MSP) pathway mediates a range of regulatory processes, including those activated by cytokinins. The cross talk between cytokinin response and light has been known for a long time. However, the molecular mechanism underlying the interaction between light and cytokinin signaling remains elusive. In the screen for upstream regulators we identified a LONG PALE HYPOCOTYL ( LPH ) gene whose activity is indispensable for spatiotemporally correct expression of CYTOKININ INDEPENDENT1 ( CKI1 ), encoding the constitutively active sensor His kinase that activates MSP signaling. lph is a new allele of HEME OXYGENASE1 ( HY1 ) that encodes the key protein in the biosynthesis of phytochromobilin, a cofactor of photoconvertible phytochromes. Our analysis confirmed the light-dependent regulation of the CKI1 expression pattern. We show that CKI1 expression is under the control of phytochrome A (phyA), functioning as a dual (both positive and negative) regulator of CKI1 expression, presumably via the phyA-regulated transcription factors (TF) PHYTOCHROME INTERACTING FACTOR3 and CIRCADIAN CLOCK ASSOCIATED1. Changes in CKI1 expression observed in lph / hy1 - 7 and phy mutants correlate with misregulation of MSP signaling, changed cytokinin sensitivity, and developmental aberrations that were previously shown to be associated with cytokinin and/or CKI1 action. Besides that, we demonstrate a novel role of phyA-dependent CKI1 expression in the hypocotyl elongation and hook development during skotomorphogenesis. Based on these results, we propose that the light-dependent regulation of CKI1 provides a plausible mechanistic link underlying the well-known interaction between light- and cytokinin-controlled plant development. © 2017 American Society of Plant Biologists. All Rights Reserved.

Nicotinic Acid-Mediated Activation of Both Membrane and Nuclear Receptors towards Therapeutic Glucocorticoid Mimetics for Treating Multiple Sclerosis

Directory of Open Access Journals (Sweden)

W. Todd Penberthy

2009-01-01

Full Text Available Acute attacks of multiple sclerosis (MS are most commonly treated with glucocorticoids, which can provide life-saving albeit only temporary symptomatic relief. The mechanism of action (MOA is now known to involve induction of indoleamine 2,3-dioxygenase (IDO and interleukin-10 (IL-10, where IL-10 requires subsequent heme oxygenase-1 (HMOX-1 induction. Ectopic expression studies reveal that even small changes in expression of IDO, HMOX-1, or mitochondrial superoxide dismutase (SOD2 can prevent demyelination in experimental autoimmune encephalomyelitis (EAE animal models of MS. An alternative to glucocorticoids is needed for a long-term treatment of MS. A distinctly short list of endogenous activators of both membrane G-protein-coupled receptors and nuclear peroxisome proliferating antigen receptors (PPARs demonstrably ameliorate EAE pathogenesis by MOAs resembling that of glucocorticoids. These dual activators and potential MS therapeutics include endocannabinoids and the prostaglandin 15-deoxy-Δ12,14-PGJ2. Nicotinamide profoundly ameliorates and prevents autoimmune-mediated demyelination in EAE via maintaining levels of nicotinamide adenine dinucleotide (NAD, without activating PPAR nor any G-protein-coupled receptor. By comparison, nicotinic acid provides even greater levels of NAD than nicotinamide in many tissues, while additionally activating the PPAR-dependent pathway already shown to provide relief in animal models of MS after activation of GPR109a/HM74a. Thus nicotinic acid is uniquely suited for providing therapeutic relief in MS. However nicotinic acid is unexamined in MS research. Nicotinic acid penetrates the blood brain barrier, cures pellagric dementia, has been used for over 50 years clinically without toxicity, and raises HDL concentrations to a greater degree than any pharmaceutical, thus providing unparalleled benefits against lipodystrophy. Summary analysis reveals that the expected therapeutic benefits of high-dose nicotinic

Supersymmetric Dirac-Born-Infeld action with self-dual mass term

International Nuclear Information System (INIS)

Nishino, Hitoshi; Rajpoot, Subhash; Reed, Kevin

2005-01-01

We introduce a Dirac-Born-Infeld action to a self-dual N = 1 supersymmetric vector multiplet in three dimensions. This action is based on the supersymmetric generalized self-duality in odd dimensions developed originally by Townsend, Pilch and van Nieuwenhuizen. Even though such a self-duality had been supposed to be very difficult to generalize to a supersymmetrically interacting system, we show that the Dirac-Born-Infeld action is actually compatible with supersymmetry and self-duality in three dimensions, even though the original self-duality receives corrections by the Dirac-Born-Infeld action. The interactions can be further generalized to arbitrary (non)polynomial interactions. As a by-product, we also show that a third-rank field strength leads to a more natural formulation of self-duality in 3D. We also show an interesting role played by the third-rank field strength leading to supersymmetry breaking, in addition to accommodating a Chern-Simons form

Commissioning of the advanced light source dual-axis streak camera

International Nuclear Information System (INIS)

Hinkson, J.; Keller, R.; Byrd, J.

1997-05-01

A dual-axis camera, Hamamatsu model C5680, has been installed on the Advanced Light Source photon-diagnostics beam-line to investigate electron-beam parameters. During its commissioning process, the camera has been used to measure single-bunch length vs. current, relative bunch charge in adjacent RF buckets, and bunchphase stability. In this paper the authors describe the visible-light branch of the diagnostics beam-line, the streak-camera installation, and the timing electronics. They will show graphical results of beam measurements taken during a variety of accelerator conditions

Evaluation of Nystatin Containing Chitosan Hydrogels as Potential Dual Action Bio-Active Restorative Materials: in Vitro Approach

Directory of Open Access Journals (Sweden)

V. Tamara Perchyonok

2014-11-01

Full Text Available Healing is a specific biological process related to the general phenomenon of growth and tissue regeneration and is a process generally affected by several systemic conditions or as detrimental side-effects of chemotherapy- and radiotherapy-induced inflammation of the oral mucosa. The objectives of this study is to evaluate the novel chitosan based functional drug delivery systems, which can be successfully incorporated into “dual action bioactive restorative materials”, capable of inducing in vitro improved wound healing prototype and containing an antibiotic, such as nystatin, krill oil as an antioxidant and hydroxyapatite as a molecular bone scaffold, which is naturally present in bone and is reported to be successfully used in promoting bone integration when implanted as well as promoting healing. The hydrogels were prepared using a protocol as previously reported by us. The physico-chemical features, including surface morphology (SEM, release behaviors, stability of the therapeutic agent-antioxidant-chitosan, were measured and compared to the earlier reported chitosan-antioxidant containing hydrogels. Structural investigations of the reactive surface of the hydrogel are reported. Release of nystatin was investigated for all newly prepared hydrogels. Bio-adhesive studies were performed in order to assess the suitability of these designer materials. Free radical defense capacity of the biomaterials was evaluated using established in vitro model. The bio-adhesive capacity of the materials in the in vitro system was tested and quantified. It was found that the favorable synergistic effect of free radical built-in defense mechanism of the new functional materials increased sustainable bio-adhesion and therefore acted as a functional multi-dimensional restorative material with potential application in wound healing in vitro.

Dual action of vitamin C versus degradation and supplementation

OpenAIRE

Katarzyna Kaliś

2015-01-01

The article discusses vitamin C from the point of view of its supplementation with food and in the form of oral supplements. The dual action of vitamin C is connected with the presence of oxygen, which may reduce the amount of the vitamin in food products, influence thermal resistance, cause degradation and show an antioxidation effect. Vitamin C stimulates the immune cells and collagen synthesis. It may protect the LDL fraction against oxidation, and therefore it is interesting for cosmetolo...

Therapeutic action and the analyst's responsibility.

Science.gov (United States)

Greenberg, Jay

2015-02-01

Models of the psychoanalytic situation can usefully be thought of as fictions. Viewed this way, the models can be understood as narrative structures that shape what we are able to see and how we are able to think about what happens between us and our analysands. Theories of therapeutic action are elements of what can be called a "controlling fiction," mediating between these theories and our very real responsibilities, both to our preferred method and to a suffering patient. This venture into comparative psychoanalysis is illustrated by a discussion of published case material. © 2015 by the American Psychoanalytic Association.

Gouty arthritis: the diagnostic and therapeutic impact of dual-energy CT

International Nuclear Information System (INIS)

Finkenstaedt, Tim; Manoliou, Andrei; Higashigaito, Kai; Andreisek, Gustav; Guggenberger, Roman; Alkadhi, Hatem; Toniolo, Martin; Michel, Beat

2016-01-01

To determine the diagnostic and therapeutic impact of dual-energy computed tomography (DECT) in gout. Forty-three patients with (n = 20) and without a history of gout (n = 23) showing non-specific soft tissue deposits underwent DECT after unrewarding arthrocentesis. Two blinded, independent readers evaluated DECT for the presence of urate crystals. Clinical diagnosis, clinically suspected urate crystal locations, diagnostic thinking and therapeutic decisions were noted before and after DECT. Clinical 1-month follow-up was obtained. DECT showed urate in 26/43 patients (60 %). After DECT, clinical diagnosis of gout was withdrawn in 17/43 (40 %) and was maintained in 16/43 patients (37 %). In 10/43 patients (23 %) the diagnosis was maintained, but DECT revealed urate in clinically unsuspected locations. In 23/43 patients (53 %), a treatment-change based on DECT occurred. Changes in diagnostic thinking occurred more frequently in patients without a history of gout (p < 0.001), changes in therapeutic decisions more frequently in patients with a history of gout (p = 0.014). Clinical follow-up indicated beneficial effects of DECT-based diagnoses in 83 % of patients. In patients with or without a history of gout and a recent suspicion for gouty arthritis with an unrewarding arthrocentesis, DECT has a marked diagnostic and therapeutic impact when hyperdense soft-tissue deposits are present. (orig.)

Gouty arthritis: the diagnostic and therapeutic impact of dual-energy CT

Energy Technology Data Exchange (ETDEWEB)

Finkenstaedt, Tim; Manoliou, Andrei; Higashigaito, Kai; Andreisek, Gustav; Guggenberger, Roman; Alkadhi, Hatem [University Hospital Zurich and University of Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland); Toniolo, Martin; Michel, Beat [University Hospital Zurich and University of Zurich, Department of Rheumatology, Zurich (Switzerland)

2016-11-15

To determine the diagnostic and therapeutic impact of dual-energy computed tomography (DECT) in gout. Forty-three patients with (n = 20) and without a history of gout (n = 23) showing non-specific soft tissue deposits underwent DECT after unrewarding arthrocentesis. Two blinded, independent readers evaluated DECT for the presence of urate crystals. Clinical diagnosis, clinically suspected urate crystal locations, diagnostic thinking and therapeutic decisions were noted before and after DECT. Clinical 1-month follow-up was obtained. DECT showed urate in 26/43 patients (60 %). After DECT, clinical diagnosis of gout was withdrawn in 17/43 (40 %) and was maintained in 16/43 patients (37 %). In 10/43 patients (23 %) the diagnosis was maintained, but DECT revealed urate in clinically unsuspected locations. In 23/43 patients (53 %), a treatment-change based on DECT occurred. Changes in diagnostic thinking occurred more frequently in patients without a history of gout (p < 0.001), changes in therapeutic decisions more frequently in patients with a history of gout (p = 0.014). Clinical follow-up indicated beneficial effects of DECT-based diagnoses in 83 % of patients. In patients with or without a history of gout and a recent suspicion for gouty arthritis with an unrewarding arthrocentesis, DECT has a marked diagnostic and therapeutic impact when hyperdense soft-tissue deposits are present. (orig.)

Concept of dual-resolution light field imaging using an organic photoelectric conversion film for high-resolution light field photography.

Science.gov (United States)

Sugimura, Daisuke; Kobayashi, Suguru; Hamamoto, Takayuki

2017-11-01

Light field imaging is an emerging technique that is employed to realize various applications such as multi-viewpoint imaging, focal-point changing, and depth estimation. In this paper, we propose a concept of a dual-resolution light field imaging system to synthesize super-resolved multi-viewpoint images. The key novelty of this study is the use of an organic photoelectric conversion film (OPCF), which is a device that converts spectra information of incoming light within a certain wavelength range into an electrical signal (pixel value), for light field imaging. In our imaging system, we place the OPCF having the green spectral sensitivity onto the micro-lens array of the conventional light field camera. The OPCF allows us to acquire the green spectra information only at the center viewpoint with the full resolution of the image sensor. In contrast, the optical system of the light field camera in our imaging system captures the other spectra information (red and blue) at multiple viewpoints (sub-aperture images) but with low resolution. Thus, our dual-resolution light field imaging system enables us to simultaneously capture information about the target scene at a high spatial resolution as well as the direction information of the incoming light. By exploiting these advantages of our imaging system, our proposed method enables the synthesis of full-resolution multi-viewpoint images. We perform experiments using synthetic images, and the results demonstrate that our method outperforms other previous methods.

IMPACT web portal: oncology database integrating molecular profiles with actionable therapeutics.

Science.gov (United States)

Hintzsche, Jennifer D; Yoo, Minjae; Kim, Jihye; Amato, Carol M; Robinson, William A; Tan, Aik Choon

2018-04-20

With the advancement of next generation sequencing technology, researchers are now able to identify important variants and structural changes in DNA and RNA in cancer patient samples. With this information, we can now correlate specific variants and/or structural changes with actionable therapeutics known to inhibit these variants. We introduce the creation of the IMPACT Web Portal, a new online resource that connects molecular profiles of tumors to approved drugs, investigational therapeutics and pharmacogenetics associated drugs. IMPACT Web Portal contains a total of 776 drugs connected to 1326 target genes and 435 target variants, fusion, and copy number alterations. The online IMPACT Web Portal allows users to search for various genetic alterations and connects them to three levels of actionable therapeutics. The results are categorized into 3 levels: Level 1 contains approved drugs separated into two groups; Level 1A contains approved drugs with variant specific information while Level 1B contains approved drugs with gene level information. Level 2 contains drugs currently in oncology clinical trials. Level 3 provides pharmacogenetic associations between approved drugs and genes. IMPACT Web Portal allows for sequencing data to be linked to actionable therapeutics for translational and drug repurposing research. The IMPACT Web Portal online resource allows users to query genes and variants to approved and investigational drugs. We envision that this resource will be a valuable database for personalized medicine and drug repurposing. IMPACT Web Portal is freely available for non-commercial use at http://tanlab.ucdenver.edu/IMPACT .

Acting in solidarity: Testing an extended dual pathway model of collective action by bystander group members.

Science.gov (United States)

Saab, Rim; Tausch, Nicole; Spears, Russell; Cheung, Wing-Yee

2015-09-01

We examined predictors of collective action among bystander group members in solidarity with a disadvantaged group by extending the dual pathway model of collective action, which proposes one efficacy-based and one emotion-based path to collective action (Van Zomeren, Spears, Fischer, & Leach, 2004). Based on two proposed functions of social identity performance (Klein, Spears, & Reicher, 2007), we distinguished between the efficacy of collective action at consolidating the identity of a protest movement and its efficacy at achieving social change (political efficacy). We expected identity consolidation efficacy to positively predict collective action tendencies directly and indirectly via political efficacy. We also expected collective action tendencies to be positively predicted by moral outrage and by sympathy in response to disadvantaged outgroup's suffering. These hypotheses were supported in two surveys examining intentions to protest for Palestine in Britain (Study 1), and intentions to attend the June 4th vigil in Hong Kong to commemorate the Tiananmen massacre among a sample of Hong Kong citizens (Study 2). The contributions of these findings to research on the dual pathway model of collective action and the different functions of collective action are discussed. © 2014 The British Psychological Society.

Dual-wavelength electroluminescence from an n-ZnO/p-GaN heterojunction light emitting diode

International Nuclear Information System (INIS)

Tsai, Bor-Sheng; Chiu, Hung-Jen; Chen, Tai-Hong; Lai, Li-Wen; Ho, Chai-Cheng; Liu, Day-Shan

2015-01-01

Highlights: • The LEDs fabricated by 450 °C- and 700 °C-annealed n-ZnO/p-GaN heterojunction structures were investigated. • The structure annealed at 700 °C emitted yellowish light composed of the dual-wavelength radiations centered at 420 and 610 nm. • The long-wavelength radiation was attributed to emerge from the deep-level emission and the Ga–O interlayer emission. - Abstract: We investigated the electro-optical properties of light emitting diodes (LEDs) fabricated by using the n-ZnO/p-GaN heterojunction structures annealed at 450 °C and 700 °C, in vacuum ambient. A dominant near-UV emission at approximately 420 nm was observed from the LED fabricated by the 450 °C-annealed n-ZnO/p-GaN heterojunction structure, whereas that of the structure annealed at 700 °C emitted a yellowish light composed of the dual-wavelength emissions centered at 420 and 610 nm. The mechanism responsible for the broad long-wavelength radiation was ascribed to the transitions associated with both the deep-level emissions due to the activation of the native defects on the n-ZnO side surface and the formation of the Ga–O interlayer resulting from the in-diffusion of oxygen atoms to the p-GaN side surface of the n-ZnO/p-GaN interface.

Peptides with Dual Antimicrobial and Anticancer Activities

Science.gov (United States)

Felício, Mário R.; Silva, Osmar N.; Gonçalves, Sônia; Santos, Nuno C.; Franco, Octávio L.

2017-02-01

In recent years, the number of people suffering from cancer and multi-resistant infections has increased, such that both diseases are already seen as current and future major causes of death. Moreover, chronic infections are one of the main causes of cancer, due to the instability in the immune system that allows cancer cells to proliferate. Likewise, the physical debility associated with cancer or with anticancer therapy itself often paves the way for opportunistic infections. It is urgent to develop new therapeutic methods, with higher efficiency and lower side effects. Antimicrobial peptides (AMPs) are found in the innate immune system of a wide range of organisms. Identified as the most promising alternative to conventional molecules used nowadays against infections, some of them have been shown to have dual activity, both as antimicrobial and anticancer peptides (ACPs). Highly cationic and amphipathic, they have demonstrated efficacy against both conditions, with the number of nature-driven or synthetically designed peptides increasing year by year. With similar properties, AMPs that can also act as ACPs are viewed as future chemotherapeutic drugs, with the advantage of low propensity to resistance, which started this paradigm in the pharmaceutical market. These peptides have already been described as molecules presenting killing mechanisms at the membrane level, but also acting towards intracellular targets, which increases their success comparatively to specific one-target drugs. This review will approach the desirable characteristics of small peptides that demonstrated dual activity against microbial infections and cancer, as well as the peptides engaged in clinical trials.

Design, synthesis and structure-activity relationships of dual inhibitors of acetylcholinesterase and serotonin transporter as potential agents for Alzheimer's disease.

Science.gov (United States)

Toda, Narihiro; Tago, Keiko; Marumoto, Shinji; Takami, Kazuko; Ori, Mayuko; Yamada, Naho; Koyama, Kazuo; Naruto, Shunji; Abe, Kazumi; Yamazaki, Reina; Hara, Takao; Aoyagi, Atsushi; Abe, Yasuyuki; Kaneko, Tsugio; Kogen, Hiroshi

2003-05-01

We have designed and synthesized a dual inhibitor of acetylcholinesterase (AChE) and serotonin transporter (SERT) as a novel class of treatment drugs for Alzheimer's disease on the basis of a hypothetical model of the AChE active site. Dual inhibitions of AChE and SERT would bring about greater therapeutic effects than AChE inhibition alone and avoid adverse peripheral effects caused by excessive AChE inhibition. Compound (S)-6j exhibited potent inhibitory activities against AChE (IC(50)=101 nM) and SERT (IC(50)=42 nM). Furthermore, (S)-6j showed inhibitory activities of both AChE and SERT in mice brain following oral administration.

Interaction of LED light with coinitiator-containing composite resins: effect of dual peaks.

Science.gov (United States)

Sim, Jae-Seong; Seol, Hyo-Joung; Park, Jeong-Kil; Garcia-Godoy, Franklin; Kim, Hyung-Il; Kwon, Yong Hoon

2012-10-01

Recently the colour stability of composite resins has been an issue due to the emphasis on the aesthetics of restored teeth. The purpose of the present study was to investigate how dual-peak LED units affect the polymerization of coinitiator-containing composite resins. Five composite resins [coinitiator-containing: Aelite LS Posterior (AL), Tetric EvoCeram (TE), and Vit-l-escence (VI); only CQ-containing: Grandio (GD) and Filtek Z350 (Z3)] were light cured using four different light-curing units (LCUs). Among them, Bluephase G2 (BP) and G-light (GL) were dual-peak LED LCUs. Microhardness, polymerization shrinkage, flexural, and compressive properties were measured. BP and GL had no consistent effect on the microhardness of AL, TE, and VI on the top and bottom surfaces of resin specimens. Among the specimens, AL and VI showed the least (9.86-10.41 μm) and greatest (17.58-19.21 μm) polymerization shrinkage, respectively. However, the effect of BP and GL on the shrinkage of specimens was not consistent. Among the specimens, GD showed the greatest flexural properties [strength (FS) and modulus (FM)] and TE showed the lowest flexural and compressive properties [strength (CS) and modulus (CM)]. In same resin product, maximum FS and CS differences due to the different LCUs were 10.3-21.0% and 3.6-9.2%, respectively. Furthermore, the influences of BP and GL on FS and CS were not consistent. The tested dual-peak LED LCUs had no consistent synergic effect on the polymerization of coinitiator-containing composite resins as compared with QTH and single-peak LED LCUs. The dual-peak LED LCUs achieve a similar degree of polymerization in coinitiator-composite resins as QTH and single-peak LED LCUs did. Choice of LCU does not appear to be a determinant of the light curing of coinitiator-composite resins. Copyright © 2012 Elsevier Ltd. All rights reserved.

Fabrication of Ag-decorated BiOBr-mBiVO4 dual heterojunction composite with enhanced visible light photocatalytic performance for degradation of malachite green

Science.gov (United States)

Regmi, Chhabilal; Dhakal, Dipesh; Kim, Tae-Ho; Yamaguchi, Takutaro; Wohn Lee, Soo

2018-04-01

A visible light active Ag-decorated BiVO4-BiOBr dual heterojunction photocatalyst was prepared using a facile hydrothermal method, followed by the photodeposition of Ag. The photocatalytic activity of the synthesized samples was investigated by monitoring the change in malachite green (MG) concentration upon visible light irradiation. The synthesized sample was highly effective for the degradation of non-biodegradable MG. The enhanced activity observed was ascribed to the efficient separation and transfer of charge carriers across the dual heterojunction structure as verified by photoluminescence measurements. The removal of MG was primarily initiated by hydroxyl radicals and holes based on scavenger’s effect. To gain insight into the degradation mechanism, both high performance liquid chromatography and high resolution-quantitative time of flight, electrospray ionization mass spectrometry measurements during the degradation process were carried out. The degradation primarily followed the hydroxylation and N-demethylation process. A possible reaction pathway is proposed on the basis of all the information obtained under various experimental conditions.

Exact effective actions for quarks in pure and self-dual mean fields

International Nuclear Information System (INIS)

Elizalde, E.; Soto, J.

1985-01-01

The QCD effective action for ordinary quarks in the presence of a constant self-dual, pure colormagnetic or pure color-electric background created by themselves is calculated at all loop orders. This is done in a very simple way, by using zeta-function regularization and the fact that the dependence of the effective action on the background can be factorized in these three cases, leaving a well-defined constant factor. The zero mode problem and the imaginary contributions are seen to be mere one-loop artifacts which automatically vanish when the exact calculation is carried out. (orig.)

Gas Flows in Dual Active Galactic Nuclei

Science.gov (United States)

Mueller Sanchez, Francisco; Comerford, Julia M.; Davies, Richard; Treister, Ezequiel; Privon, George C.; Nevin, Becky

2018-06-01

Dual Active Galactic Nuclei (AGN) are the Rosetta stone to understand the role of galaxy mergers in triggering nuclear activity and regulating black hole (BH) and galaxy growth. But very little is known about the physical processes required to effectively trigger AGN activity and regulate the growth of the two BHs. The work I will present here characterizes for the first time the properties of the stars, gas (molecular, ionized, and highly-ionized) and dust in all the confirmed dual AGN at z prototypical merger system NGC 6240: vigorous star formation, two AGNs, outflowing winds of ionized gas, rippling dust and gas lanes, and tidal tails. In this galaxy, we observe for the first time a dual outflow of different species of gas: an AGN-driven outflow of highly-ionized gas to the northeast and a starburst-driven outflow of ionized hydrogen to the northwest. This shows that stellar feedback and supermassive black hole feedback can work in tandem to regulate the stellar growth of a galaxy after a merger event. These results open a new door to studies of dual AGN and AGN pairs in general, and enable dual AGN to be used, for the first time, for studies of galaxy evolution.

Notable light-free catalytic activity for pollutant destruction over flower-like BiOI microspheres by a dual-reaction-center Fenton-like process.

Science.gov (United States)

Wang, Liang; Yan, Dengbiao; Lyu, Lai; Hu, Chun; Jiang, Ning; Zhang, Lili

2018-10-01

BiOI is widely used as photocatalysts for pollutant removal, water splitting, CO 2 reduction and organic transformation due to its excellent photoelectric properties. Here, we report for the first time that a light-free catalyst consisting of the flower-like BiOI microspheres (f-BiOI MSs) exposing (1 0 1) and (1 1 0) crystal planes prepared by a hydrothermal method in ethylene glycol environment can rapidly eliminate the refractory BPA within only ∼3 min through a Fenton-like process. The reaction activity is ∼190 times higher than that of the conventional Fenton catalyst Fe 2 O 3 . A series of characterizations and experiments reveal the formation of the dual reaction centers on f-BiOI MSs. The electron-rich O centers efficiently reduce H 2 O 2 to OH, while the electron-poor oxygen vacancies capture electrons from the adsorbed pollutants and divert them to the electron-rich area during the Fenton-like reactions. By these processes, pollutants are degraded and mineralized quickly in a wide pH range. Our findings address the problems of the classical Fenton reaction and are useful for the development of efficient Fenton-like catalysts through constructing dual reaction centers. Copyright © 2018 Elsevier Inc. All rights reserved.

THE LOW FREQUENCY OF DUAL ACTIVE GALACTIC NUCLEI VERSUS THE HIGH MERGER RATE OF GALAXIES: A PHENOMENOLOGICAL MODEL

International Nuclear Information System (INIS)

Yu Qingjuan; Lu Youjun; Mohayaee, Roya; Colin, Jacques

2011-01-01

Dual active galactic nuclei (AGNs) are natural byproducts of hierarchical mergers of galaxies in the ΛCDM cosmogony. Recent observations have shown that only a small fraction (∼0.1%-2.5%) of AGNs at redshift z ∼< 0.3 are dual with kpc-scale separations, which is rather low compared to the high merger rate of galaxies. Here we construct a phenomenological model to estimate the number density of dual AGNs and its evolution according to the observationally estimated major merger rates of galaxies and various scaling relations on the properties of galaxies and their central massive black holes. We show that our model reproduces the observed frequency and separation distribution of dual AGNs provided that significant nuclear activities are triggered only in gas-rich progenitor galaxies with central massive black holes and only when the nuclei of these galaxies are roughly within the half-light radii of their companion galaxies. Under these constraints, the observed low dual AGN frequency is consistent with the relatively high merger rate of galaxies and supports the hypothesis that major mergers lead to AGN/QSO activities. We also predict that the number of kpc-scale dual AGNs decreases with increasing redshift and only about 0.02%-0.06% of AGNs are dual AGNs with double-peaked narrow line features at redshifts of z ∼ 0.5-1.2. Future observations of high-redshift dual AGNs would provide a solid test for this prediction.

Pharmacological considerations for predicting PK/PD at the site of action for therapeutic proteins.

Science.gov (United States)

Wang, Weirong; Zhou, Honghui

For therapeutic proteins whose sites of action are distal to the systemic circulation, both drug and target concentrations at the tissue sites are not necessarily proportional to those in systemic circulation, highlighting the importance of understanding pharmacokinetic/pharmacodynamic (PK/PD) relationship at the sites of action. This review summarizes the pharmacological considerations for predicting local PK/PD and the importance of measuring PK and PD at site of action. Three case examples are presented to show how mechanistic and physiologically based PK/PD (PBPK/PD) models which incorporated the PK and PD at the tissue site can be used to facilitate understanding the exposure-response relationship for therapeutic proteins. Copyright © 2016. Published by Elsevier Ltd.

Static, self-dual, finite action SU(3) gauge fields in the de Sitter space

International Nuclear Information System (INIS)

Chakrabarti, A.; Comtet, A.; Viswanathan, K.S.; Simon Fraser Univ., Burnaby, British Columbia

1980-01-01

Static, self-dual, finite action SU(3) gauge fields are constructed on the euclidean section of the positive curvature de Sitter metric with periodic time. Their relation to known time dependent flat space solutions is pointed out. Their significances and possible applications are indicated. (orig.)

Dual Axis Radiographic Hydrodynamic Test Facility mitigation action plan. Annual report for 1997

Energy Technology Data Exchange (ETDEWEB)

Haagenstad, H.T.

1998-01-15

This Mitigation Action Plan Annual Report (MAPAR) has been prepared by the US Department of Energy (DOE) as part of implementing the Dual Axis Radiographic Hydrodynamic Test Facility (DARHT) Mitigation Action Plan (MAP). This MAPAR provides a status on specific DARHT facility design- and construction-related mitigation actions that have been initiated in order to fulfill DOE`s commitments under the DARHT MAP. The functions of the DARHT MAP are to (1) document potentially adverse environmental impacts of the Phased Containment Option delineated in the Final EIS, (2) identify commitments made in the Final EIS and ROD to mitigate those potential impacts, and (3) establish Action Plans to carry out each commitment (DOE 1996). The DARHT MAP is divided into eight sections. Sections 1--5 provide background information regarding the NEPA review of the DARHT project and an introduction to the associated MAP. Section 6 references the Mitigation Action Summary Table which summaries the potential impacts and mitigation measures; indicates whether the mitigation is design-, construction-, or operational-related; the organization responsible for the mitigation measure; and the projected or actual completion data for each mitigation measure. Sections 7 and 8 discuss the Mitigation Action Plan Annual Report and Tracking System commitment and the Potential Impacts, Commitments, and Action Plans respectively. Under Section 8, potential impacts are categorized into five areas of concern: General Environment, including impacts to air and water; Soils, especially impacts affecting soil loss and contamination; Biotic Resources, especially impacts affecting threatened and endangered species; Cultural/Paleontological Resources, especially impacts affecting the archeological site known as Nake`muu; and Human Health and Safety, especially impacts pertaining to noise and radiation. Each potential impact includes a brief statement of the nature of the impact and its cause(s). The commitment

Decarboxilase activity and biosynthetic processes in Saccharomyces carlsbergenesis upon the action of light

International Nuclear Information System (INIS)

Chebotarev, L.N.; Shaburova, G.V.; Licyuk, G.M.

1983-01-01

It is established that visible light of 410-520 nm wave-- lengths stimulated decarboxylase activity, protein biosynthesis and increase in the number of cells in the Saccharomyces carlsbergenesis yeast culture. A limiting link of these yeast metabolism is decarboxylizing of pyuvate providing the formation of a substrate for functioning of the di- and pericarboxilic acid cycle. The light effect can activate this process thus eliminating substrate deficiency of the Krebs cycle which results in the increase of anabolic processes intensity

On the derivation of Darboux form for the action- angle dual of trigonometric BCn Sutherland system

International Nuclear Information System (INIS)

Görbe, Tamás F

2014-01-01

Recently Fehér and the author have constructed the action-angle dual of the trigonometric BC n Sutherland system via Hamiltonian reduction. In this paper a reduction- based calculation is carried out to verify the canonical Poisson bracket relations on the phase space of this dual model. Hence the material serves complementary purposes whilst it can also be regarded as a suitable modification of the hyperbolic case previously sorted out by Pusztai

Activity quantification of phantom using dual-head SPECT with two-view planar image

International Nuclear Information System (INIS)

Guo Leiming; Chen Tao; Sun Xiaoguang; Huang Gang

2005-01-01

The absorbed radiation dose from internally deposited radionuclide is a major factor in assessing risk and therapeutic utility in nuclear medicine diagnosis or treatment. The quantification of absolute activity in vivo is necessary procedure of estimating the absorbed dose of organ or tissue. To understand accuracy in the determination of organ activity, the experiments on 99 Tc m activity quantification were made for a body phantom using dual-heat SPECT with the two-view counting technique. Accuracy in the activity quantification is credible and is not affected by depth of source organ in vivo. When diameter of the radiation source is ≤2 cm, the most accurate activity quantification result can be obtained on the basis of establishing the system calibration factor and transmission factor. The use of Buijs's method is preferable, especially at very low source-to-background activity concentration rations. (authors)

Assessing potential targets of calcium action in light-modulated gravitropism

Science.gov (United States)

Roux, S. J.

1995-01-01

Light, through the mediation of the pigment phytochrome, modulates the gravitropic response of the shoots and roots of many plants. The transduction of both light and gravity stimuli appears to involve Ca(2+)-regulated steps, one or more of which may represent points of intersection between the two transduction chains. To be confident that Ca2+ plays a critical role in stimulus-response coupling for gravitropism, it will be important to identify specific targets of Ca2+ action whose function can be clearly linked to the regulation of growth. Calcium typically exerts its influence on cell metabolism through binding to and activating key regulatory proteins. The three best characterized of these proteins in plants are the calmodulins, calcium-dependent protein kinases, and annexins. In this review we summarize what is known about the structure and function of these proteins and speculate on how their activation by Ca2+ could influence the differential growth response of gravitropism.

Therapeutic action of taurine on the postirradiation recovery of the yeast cells

International Nuclear Information System (INIS)

Benevolenskij, V.N.; Yartsev, E.I.; Novosteltseva, S.D.; Yakovlev, V.G.

1975-01-01

It has been shown on X-irradiated Saccharomyces ellipsoides cells that taurine-potassium phosphate applied after the exposure has a therapeutic action, that is, it intensifies the natural process of intracellular dark repair

Visible-light-driven TiO2/Ag3PO4/GO heterostructure photocatalyst with dual-channel for photo-generated charges separation

International Nuclear Information System (INIS)

Lu, Bingqing; Ma, Ni; Wang, Yaping; Qiu, Yiwei; Hu, Haihua; Zhao, Jiahuan; Liang, Dayu; Xu, Sheng; Li, Xiaoyun; Zhu, Zhiyan; Cui, Can

2015-01-01

Highlights: • TiO 2 /Ag 3 PO 4 /GO was synthesized with a facile two-step method. • TiO 2 /Ag 3 PO 4 /GO exhibit superior photocatalytic activity and stability. • TiO 2 /Ag 3 PO 4 /GO has dual-channel for photo-generated charges separation. • TiO 2 /Ag 3 PO 4 /GO composite reduces the consumption of Ag. - Abstract: A novel triple-component TiO 2 /Ag 3 PO 4 /graphene oxide (TiO 2 /Ag 3 PO 4 /GO) photocatalyst with dual channels for photo-generated charges separation has been synthesized to improve the photocatalytic activity and stability of Ag 3 PO 4 under visible light. The synthesis involved in-situ growth of Ag 3 PO 4 nanoparticles on GO sheets to form Ag 3 PO 4 /GO, and then deposited TiO 2 nanocrystals on the surface of Ag 3 PO 4 by hydrolysis of Ti(SO 4 ) 2 at low-temperature hydrothermal condition. The TiO 2 /Ag 3 PO 4 /GO exhibited superior photocatalytic activity and stability to bare Ag 3 PO 4 , TiO 2 /Ag 3 PO 4 and Ag 3 PO 4 /GO in degradation of Rhodamine B and phenol solutions under visible light. It is suggested that the photo-generated electrons in the conduction band of Ag 3 PO 4 can be quickly transferred to GO, while the holes in the valence band of Ag 3 PO 4 can be transferred to the valence band of TiO 2 . The dual transfer channels at the interfaces of TiO 2 /Ag 3 PO 4 /GO result in effective charges separation, leading to enhanced photocatalytic activity and stability. Furthermore, the content of noble metal Ag significantly reduces from 77 wt% in bare Ag 3 PO 4 to 55 wt% in the nanocomposite. The concept of establishing dual channels for charges separation in a triple-component heterostructure provides a promising way to develop photocatalysts with high efficiency

Dissociating action-effect activation and effect-based response selection.

Science.gov (United States)

Schwarz, Katharina A; Pfister, Roland; Wirth, Robert; Kunde, Wilfried

2018-05-25

Anticipated action effects have been shown to govern action selection and initiation, as described in ideomotor theory, and they have also been demonstrated to determine crosstalk between different tasks in multitasking studies. Such effect-based crosstalk was observed not only in a forward manner (with a first task influencing performance in a following second task) but also in a backward manner (the second task influencing the preceding first task), suggesting that action effect codes can become activated prior to a capacity-limited processing stage often denoted as response selection. The process of effect-based response production, by contrast, has been proposed to be capacity-limited. These observations jointly suggest that effect code activation can occur independently of effect-based response production, though this theoretical implication has not been tested directly at present. We tested this hypothesis by employing a dual-task set-up in which we manipulated the ease of effect-based response production (via response-effect compatibility) in an experimental design that allows for observing forward and backward crosstalk. We observed robust crosstalk effects and response-effect compatibility effects alike, but no interaction between both effects. These results indicate that effect activation can occur in parallel for several tasks, independently of effect-based response production, which is confined to one task at a time. Copyright © 2018 Elsevier B.V. All rights reserved.

Peroxisome Proliferator-Activated Receptor Ligands and Their Role in Chronic Myeloid Leukemia: Therapeutic Strategies.

Science.gov (United States)

Yousefi, Bahman; Samadi, Nasser; Baradaran, Behzad; Shafiei-Irannejad, Vahid; Zarghami, Nosratollah

2016-07-01

Imatinib therapy remains the gold standard for treatment of chronic myeloid leukemia; however, the acquired resistance to this therapeutic agent in patients has urged the scientists to devise modalities for overcoming this chemoresistance. For this purpose, initially therapeutic agents with higher tyrosine kinase activity were introduced, which had the potential for inhibiting even mutant forms of Bcr-Abl. Furthermore, coupling imatinib with peroxisome proliferator-activated receptor ligands also showed beneficial effects in chronic myeloid leukemia cell proliferation. These combination protocols inhibited cell growth and induced apoptosis as well as differentiation in chronic myeloid leukemia cell lines. In addition, peroxisome proliferator-activated receptors ligands increased imatinib uptake by upregulating the expression of human organic cation transporter 1. Taken together, peroxisome proliferator-activated receptors ligands are currently being considered as novel promising therapeutic candidates for chronic myeloid leukemia treatment, because they can synergistically enhance the efficacy of imatinib. In this article, we reviewed the potential of peroxisome proliferator-activated receptors ligands for use in chronic myeloid leukemia treatment. The mechanism of action of these therapeutics modalities are also presented in detail. © 2016 John Wiley & Sons A/S.

Peroxisome proliferator-activated receptors (PPARs) as therapeutic target in neurodegenerative disorders

International Nuclear Information System (INIS)

Agarwal, Swati; Yadav, Anuradha; Chaturvedi, Rajnish Kumar

2017-01-01

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors and they serve to be a promising therapeutic target for several neurodegenerative disorders, which includes Parkinson disease, Alzheimer's disease, Huntington disease and Amyotrophic Lateral Sclerosis. PPARs play an important role in the downregulation of mitochondrial dysfunction, proteasomal dysfunction, oxidative stress, and neuroinflammation, which are the major causes of the pathogenesis of neurodegenerative disorders. In this review, we discuss about the role of PPARs as therapeutic targets in neurodegenerative disorders. Several experimental approaches suggest potential application of PPAR agonist as well as antagonist in the treatment of neurodegenerative disorders. Several epidemiological studies found that the regular usage of PPAR activating non-steroidal anti-inflammatory drugs is effective in decreasing the progression of neurodegenerative diseases including PD and AD. We also reviewed the neuroprotective effects of PPAR agonists and associated mechanism of action in several neurodegenerative disorders both in vitro as well as in vivo animal models. - Highlights: • Peroxisome -activated receptors (PPARs) serve to be a promising therapeutic target for several neurodegenerative disorders. • PPAR agonist as well as provides neuroprotection in vitro as well as in vivo animal models of neurodegenerative disorders. • PPAR activating anti-inflammatory drugs use is effective in decreasing progression of neurodegenerative diseases.

Novel N-(pyrimidin-4-ylthiazol-2-amine derivatives as dual-action hypoglycemic agents that activate GK and PPARγ

Directory of Open Access Journals (Sweden)

Hui-peng Song

2011-10-01

Full Text Available A series of novel N-(pyrimidin-4-ylthiazol-2-amine derivatives have been synthesized and evaluated as glucokinase (GK activators. Ethyl 2-(6-(4-(2-hydroxyethylpiperazin-1-yl-2-methylpyrimidin-4-yl-aminothiazole-5-carboxylate was found to be a potent dual-acting hypoglycemic agent activating both GK and PPARγ. When given orally to normal mice, the compound demonstrated significant efficacy in decreasing the glucose level after oral glucose loading.

Spectral matching research for light-emitting diode-based neonatal jaundice therapeutic device light source

Science.gov (United States)

Gan, Ruting; Guo, Zhenning; Lin, Jieben

2015-09-01

To decrease the risk of bilirubin encephalopathy and minimize the need for exchange transfusions, we report a novel design for light source of light-emitting diode (LED)-based neonatal jaundice therapeutic device (NJTD). The bilirubin absorption spectrum in vivo was regarded as target. Based on spectral constructing theory, we used commercially available LEDs with different peak wavelengths and full width at half maximum as matching light sources. Simple genetic algorithm was first proposed as the spectral matching method. The required LEDs number at each peak wavelength was calculated, and then, the commercial light source sample model of the device was fabricated to confirm the spectral matching technology. In addition, the corresponding spectrum was measured and the effect was analyzed finally. The results showed that fitted spectrum was very similar to the target spectrum with 98.86 % matching degree, and the actual device model has a spectrum close to the target with 96.02 % matching degree. With higher fitting degree and efficiency, this matching algorithm is very suitable for light source matching technology of LED-based spectral distribution, and bilirubin absorption spectrum in vivo will be auspicious candidate for the target spectrum of new LED-based NJTD light source.

Low-cost vibration sensor based on dual fiber Bragg gratings and light intensity measurement.

Science.gov (United States)

Gao, Xueqing; Wang, Yongjiao; Yuan, Bo; Yuan, Yinquan; Dai, Yawen; Xu, Gang

2013-09-20

A vibration monitoring system based on light intensity measurement has been constructed, and the designed accelerometer is based on steel cantilever frame and dual fiber Bragg gratings (FBGs). By using numerical simulations for the dual FBGs, the dependence relationship of the area of main lobes on the difference of initial central wavelengths is obtained and the most optimal choice for the initial value and the vibration amplitude of the difference of central wavelengths of two FBGs is suggested. The vibration monitoring experiments are finished, and the measured data are identical to the simulated results.

Dual and multi-stimuli responsive polymeric nanoparticles for programmed site-specific drug delivery.

Science.gov (United States)

Cheng, Ru; Meng, Fenghua; Deng, Chao; Klok, Harm-Anton; Zhong, Zhiyuan

2013-05-01

In the past decades, polymeric nanoparticles have emerged as a most promising and viable technology platform for targeted and controlled drug delivery. As vehicles, ideal nanoparticles are obliged to possess high drug loading levels, deliver drug to the specific pathological site and/or target cells without drug leakage on the way, while rapidly unload drug at the site of action. To this end, various "intelligent" polymeric nanoparticles that release drugs in response to an internal or external stimulus such as pH, redox, temperature, magnetic and light have been actively pursued. These stimuli-responsive nanoparticles have demonstrated, though to varying degrees, improved in vitro and/or in vivo drug release profiles. In an effort to further improve drug release performances, novel dual and multi-stimuli responsive polymeric nanoparticles that respond to a combination of two or more signals such as pH/temperature, pH/redox, pH/magnetic field, temperature/reduction, double pH, pH and diols, temperature/magnetic field, temperature/enzyme, temperature/pH/redox, temperature/pH/magnetic, pH/redox/magnetic, temperature/redox/guest molecules, and temperature/pH/guest molecules have recently been developed. Notably, these combined responses take place either simultaneously at the pathological site or in a sequential manner from nanoparticle preparation, nanoparticle transporting pathways, to cellular compartments. These dual and multi-stimuli responsive polymeric nanoparticles have shown unprecedented control over drug delivery and release leading to superior in vitro and/or in vivo anti-cancer efficacy. With programmed site-specific drug delivery feature, dual and multi-stimuli responsive nanoparticulate drug formulations have tremendous potential for targeted cancer therapy. In this review paper, we highlight the recent exciting developments in dual and multi-stimuli responsive polymeric nanoparticles for precision drug delivery applications, with a particular focus

A green-light-emitting, spontaneously blinking fluorophore based on intramolecular spirocyclization for dual-colour super-resolution imaging.

Science.gov (United States)

Uno, Shin-Nosuke; Kamiya, Mako; Morozumi, Akihiko; Urano, Yasuteru

2017-12-19

We have developed the first green-light-emitting, spontaneously blinking fluorophore (SBF), HEtetTFER. In combination with our near-infrared-light-emitting SBF (HMSiR), HEtetTFER allows dual-colour single-molecule localization microscopy (SMLM) in buffer solution without any additive and without photoactivation.

Silver deposited carboxymethyl chitosan-grafted magnetic nanoparticles as dual action deliverable antimicrobial materials.

Science.gov (United States)

Vo, Duc-Thang; Sabrina, Sabrina; Lee, Cheng-Kang

2017-04-01

Carboxymethyl chitosan (CMCS) was known to have a much better antimicrobial activity than chitosan due to the increased cationic -NH 3 + groups resulted from the intra- and intermolecular interactions between the carboxyl and amino groups. CMCS was grafted onto the surface of silica coated magnetic nanoparticles (MNPs) to obtain magnetically retrievable and deliverable antimicrobial nanoparticles (MNPs@CMCS). The presence of carboxylate groups in CMCS not only enhanced antimicrobial activity but also enabled Ag ions chelating ability to induce the in situ formation of Ag nanoparticles (AgNPs). The deposition of AgNPs on the surface of MNPs@CMCS could significantly increase its antimicrobial activity against planktonic cells due to the dual action of CMCS and AgNPs. Due to its high magnetism, the as-prepared MNPs@CMCS-Ag could be efficiently delivered into an existing biofilm under the guidance of an applied magnetic field. Without direct contact, the Ag ions and/or radical oxygen species (ROS) released from the deposited Ag nanoparticles could effectively kill the bacteria embedded in the extracellular polymeric substances (EPS) matrix of biofilm. Copyright © 2016 Elsevier B.V. All rights reserved.

Depth distributions of light action spectra for skin chromophores

Science.gov (United States)

Barun, V. V.; Ivanov, A. P.

2010-03-01

Light action spectra over wavelengths of 300-1000 nm are calculated for components of the human cutaneous covering: melanin, basal (bloodless) tissue, and blood oxy- and deoxyhemoglobin. The transformation of the spectra with depth in biological tissue results from two factors. The first is the wavelength dependence of the absorption coefficient corresponding to a particular skin chromophore and the second is the spectral selectivity of the radiation flux in biological tissue. This factor is related to the optical properties of all chromophores. A significant change is found to take place in the spectral distribution of absorbed radiant power with increasing depth. The action spectrum of light for the molecular oxygen contained in all components of biological tissue is also studied in the 625-645 nm range. The spectra are found to change with both the volume fraction of blood vessels and the degree of oxygenation of the blood. These results are useful for analyzing processes associated with optical absorption that are possible mechanisms for the interaction of light with biological tissues: photodissociation of oxyhemoglobin and the light-oxygen effect.

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

Science.gov (United States)

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

2017-03-01

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

Motorist actions at a crosswalk with an in-pavement flashing light system.

Science.gov (United States)

Karkee, Ganesh J; Nambisan, Shashi S; Pulugurtha, Srinivas S

2010-12-01

An in-pavement flashing light system is used at crosswalks to alert motorists and pedestrians of possible conflicts and to influence their behavior to enhance safety. The relative behaviors of the drivers and the pedestrians affect safety. An evaluation of motorist behavior at a pedestrian crosswalk with an in-pavement flashing light system is presented in this manuscript. Field observations provide the basis to evaluate motorist behavior at a crosswalk with an in-pavement flashing light system. Outcomes of pedestrian and motorists actions were observed to quantify measures of effectiveness (MOEs) such as yielding behavior of motorists, vehicle speeds, and yielding distance from the crosswalk. A before-and-after study design was used. The before condition was prior to the activation of the in-pavement flashing light system and the after condition was after the activation of the in-pavement flashing light system. The study was conducted on a relatively low-volume roadway located in the Henderson, Nevada. The significance of the differences in the MOEs between the 2 study periods was evaluated using statistical analysis tools such as a one-tailed test for proportions and the Welch-Satterthwaite t-test. The results show that the installation of the in-pavement flashing light system increased the yielding behavior of motorists significantly (P pavement flashing light system is seen to be effective to improve motorists' yielding behavior and the speeds of vehicles were also observed to decrease in the presence of pedestrians.

Degree of conversion of resin-based orthodontic bonding materials cured with single-wave or dual-wave LED light-curing units.

Science.gov (United States)

Santini, Ario; McGuinness, Niall; Nor, Noor Azreen Md

2014-12-01

To evaluate the degree of conversion (DC) of orthodontic adhesives (RBOAs) cured with dual peak or single peak light-emitting diode (LED) light-curing units (LCUs). Standardized samples of RBOAs, APCPlus, Opal® Bond® and LightBond(TM) were prepared (n = 3) and cured with one of two dual peak LCUs (bluephase® G2-Ivoclar-Vivadent or Valo-Ultradent) or a single peak control (bluephase® Ivoclar-Vivadent). The DC was determined using micro-Raman spectroscopy. The presence or absence of initiators other than camphorquinone was confirmed by high-performance liquid chromatography and nuclear magnetic resonance spectroscopy. Data were analysed using general linear model in Minitab 15 (Minitab Inc., State College, PA, USA). There was no significant difference in DC between APCPlus, and Opal® Bond (confidence interval: -3.89- to 2.48); significant difference between APCPlus and LightBond(TM) (-18.55 to -12.18) and Opal® Bond and Lightbond(TM) (-17.85 to -11.48); no significant difference between bluephase (single peak) and dual peak LCUs, bluephase G2 (-4.896 to 1.476) and Valo (-3.935 to 2.437) and between bluephase G2 and Valo (-2.225 to 4.147). APCPlus and Opal® Bond showed higher DC values than LightBond(TM) (P<0.05). Lucirin® TPO was found only in Vit-l-escence. Lucirin® TPO was not identified in the three orthodontic adhesives. All three LCUs performed similarly with the orthodontic adhesives: orthodontic adhesive make had a greater effect on DC than the LCUs. It is strongly suggested that manufacturers of resin-based orthodontic materials test report whether or not dual peak LCUs should be used with their materials. Dual peak LED LCUs, though suitable in the majority of cases, may not be recommended for certain non Lucirin® TPO-containing materials. © 2014 British Orthodontic Society.

Folate decorated dual drug loaded nanoparticle: role of curcumin in enhancing therapeutic potential of nutlin-3a by reversing multidrug resistance.

Directory of Open Access Journals (Sweden)

Manasi Das

Full Text Available Retinoblastoma is the most common intraocular tumor in children. Malfunctioning of many signaling pathways regulating cell survival or apoptosis, make the disease more vulnerable. Notably, resistance to chemotherapy mediated by MRP-1, lung-resistance protein (LRP is the most challenging aspect to treat this disease. Presently, much attention has been given to the recently developed anticancer drug nutlin-3a because of its non-genotoxic nature and potency to activate tumor suppressor protein p53. However, being a substrate of multidrug resistance protein MRP1 and Pgp its application has become limited. Currently, research has step towards reversing Multi drug resistance (MDR by using curcumin, however its clinical relevance is restricted by plasma instability and poor bioavailability. In the present investigation we tried to encapsulate nutlin-3a and curcumin in PLGA nanoparticle (NPs surface functionalized with folate to enhance therapeutic potential of nutlin-3a by modulating MDR. We document that curcumin can inhibit the expression of MRP-1 and LRP gene/protein in a concentration dependent manner in Y79 cells. In vitro cellular cytotoxicity, cell cycle analysis and apoptosis studies were done to compare the effectiveness of native drugs (single or combined and single or dual drug loaded nanoparticles (unconjugated/folate conjugated. The result demonstrated an augmented therapeutic efficacy of targeted dual drug loaded NPs (Fol-Nut-Cur-NPs over other formulation. Enhanced expression or down regulation of proapoptotic/antiapoptotic proteins respectively and down-regulation of bcl2 and NFκB gene/protein by Fol-Nut-Cur-NPs substantiate the above findings. This is the first investigation exploring the role of curcumin as MDR modulator to enhance the therapeutic potentiality of nutlin-3a, which may opens new direction for targeting cancer with multidrug resistance phenotype.

Improvement of energy efficiency and quality of street lighting in South Italy as an action of Sustainable Energy Action Plans. The case study of Comiso (RG)

International Nuclear Information System (INIS)

Beccali, Marco; Bonomolo, Marina; Ciulla, Giuseppina; Galatioto, Alessandra; Lo Brano, Valerio

2015-01-01

Existing street lighting systems, in most of South Italy cities, are often inefficient due to the obsolescence of lamps and luminaires and of ineffective light control systems unable to implement efficient on-off and dimming strategies. Energy efficiency improvement, in street lighting systems, is often one of the key actions to be adopted by Public Administration in their Sustainable Energy Action Plan in the framework of the “Covenant of Majors” activities. As a task of FACTOR 20 project, a set of planning options has been analysed and proposed. Particularly, street lighting efficiency projects have been studied for representative case studies. A detailed survey of the public lighting systems, in Comiso, allowed represent current performance figures such us installed power, luminance and illuminance levels in roads categories, electricity consumption, switching and dimming schedules. A project of system upgrade has been elaborated. To do this, many lighting simulations, energy and economic assessments in three scenarios have been performed. The obtained results show that high improvements of the lighting quality are foreseeable together with large energy and economic saving. An economic sensitivity analysis, has shown how the performance can change. The proposed methodology can be applied in many similar South Italy cities. - Highlights: • Retrofit actions in urban lighting systems of typical South Italy cities are studied. • A methodology for the comparison of baseline and design scenarios is presented. • An analysis of energy and economic savings of different scenarios is performed. • A sensitivity analysis of payback times is presented for different costs of LED and kWhe.

Are gamers better crossers? An examination of action video game experience and dual task effects in a simulated street crossing task.

Science.gov (United States)

Gaspar, John G; Neider, Mark B; Crowell, James A; Lutz, Aubrey; Kaczmarski, Henry; Kramer, Arthur F

2014-05-01

A high-fidelity street crossing simulator was used to test the hypothesis that experienced action video game players are less vulnerable than non-gamers to dual task costs in complex tasks. Previous research has shown that action video game players outperform nonplayers on many single task measures of perception and attention. It is unclear, however, whether action video game players outperform nonplayers in complex, divided attention tasks. Experienced action video game players and nongamers completed a street crossing task in a high-fidelity simulator. Participants walked on a manual treadmill to cross the street. During some crossings, a cognitively demanding working memory task was added. Dividing attention resulted in more collisions and increased decision making time. Of importance, these dual task costs were equivalent for the action video game players and the nongamers. These results suggest that action video game players are equally susceptible to the costs of dividing attention in a complex task. Perceptual and attentional benefits associated with action video game experience may not translate to performance benefits in complex, real-world tasks.

Dual inhibitors of cholinesterases and monoamine oxidases for Alzheimer's disease.

Science.gov (United States)

Knez, Damijan; Sova, Matej; Košak, Urban; Gobec, Stanislav

2017-05-01

Accumulating evidence indicates a solid relationship between several enzymes and Alzheimer's disease. Cholinesterases and monoamine oxidases are closely associated with the disease symptomatology and progression and have been tackled simultaneously using several multifunctional ligands. This design strategy offers great chances to alter the course of Alzheimer's disease, in addition to alleviation of the symptoms. More than 15 years of research has led to the identification of various dual cholinesterase/monoamine oxidase inhibitors, while some showing positive outcomes in clinical trials, thus giving rise to additional research efforts in the field. The aim of this review is to provide an update on the novel dual inhibitors identified recently and to shed light on their therapeutic potential.

Dual-etalon cavity ring-down frequency-comb spectroscopy with broad band light source

Science.gov (United States)

Chandler, David W; Strecker, Kevin E

2014-04-01

In an embodiment, a dual-etalon cavity-ring-down frequency-comb spectrometer system is described. A broad band light source is split into two beams. One beam travels through a first etalon and a sample under test, while the other beam travels through a second etalon, and the two beams are recombined onto a single detector. If the free spectral ranges ("FSR") of the two etalons are not identical, the interference pattern at the detector will consist of a series of beat frequencies. By monitoring these beat frequencies, optical frequencies where light is absorbed may be determined.

Current state of a dual behaviour of antimicrobial peptides-Therapeutic agents and promising delivery vectors.

Science.gov (United States)

Piotrowska, Urszula; Sobczak, Marcin; Oledzka, Ewa

2017-12-01

Micro-organism resistance is an important challenge in modern medicine due to the global uncontrolled use of antibiotics. Natural and synthetic antimicrobial peptides (AMPs) symbolize a new family of antibiotics, which have stimulated research and clinical interest as new therapeutic options for infections. They represent one of the most promising antimicrobial substances, due to their broad spectrum of biological activity, against bacteria, fungi, protozoa, viruses, yeast and even tumour cells. Besides, being antimicrobial, AMPs have been shown to bind and neutralize bacterial endotoxins, as well as possess immunomodulatory, anti-inflammatory, wound-healing, angiogenic and antitumour properties. In contrast to conventional antibiotics, which have very defined and specific molecular targets, host cationic peptides show varying, complex and very rapid mechanisms of actions that make it difficult to form an effective antimicrobial defence. Importantly, AMPs display their antimicrobial activity at micromolar concentrations or less. To do this, many peptide-based drugs are commercially available for the treatment of numerous diseases, such as hepatitis C, myeloma, skin infections and diabetes. Herein, we present an overview of the general mechanism of AMPs action, along with recent developments regarding carriers of AMPs and their potential applications in medical fields. © 2017 John Wiley & Sons A/S.

Confirming the RNAi-mediated mechanism of action of siRNA-based cancer therapeutics in mice.

Science.gov (United States)

Judge, Adam D; Robbins, Marjorie; Tavakoli, Iran; Levi, Jasna; Hu, Lina; Fronda, Anna; Ambegia, Ellen; McClintock, Kevin; MacLachlan, Ian

2009-03-01

siRNAs that specifically silence the expression of cancer-related genes offer a therapeutic approach in oncology. However, it remains critical to determine the true mechanism of their therapeutic effects. Here, we describe the preclinical development of chemically modified siRNA targeting the essential cell-cycle proteins polo-like kinase 1 (PLK1) and kinesin spindle protein (KSP) in mice. siRNA formulated in stable nucleic acid lipid particles (SNALP) displayed potent antitumor efficacy in both hepatic and subcutaneous tumor models. This was correlated with target gene silencing following a single intravenous administration that was sufficient to cause extensive mitotic disruption and tumor cell apoptosis. Our siRNA formulations induced no measurable immune response, minimizing the potential for nonspecific effects. Additionally, RNAi-specific mRNA cleavage products were found in tumor cells, and their presence correlated with the duration of target mRNA silencing. Histological biomarkers confirmed that RNAi-mediated gene silencing effectively inhibited the target's biological activity. This report supports an RNAi-mediated mechanism of action for siRNA antitumor effects, suggesting a new methodology for targeting other key genes in cancer development with siRNA-based therapeutics.

Searching for dual active galactic nuclei

Indian Academy of Sciences (India)

K. Rubinur

2018-02-09

Feb 9, 2018 ... Abstract. Binary or dual active galactic nuclei (DAGN) are expected from galaxy formation theories. How- ... cuss results from the multi-frequency Expanded Very .... mid-IR color using WISE observations where they have.

Internalization, separation-individuation, and the nature of therapeutic action.

Science.gov (United States)

Blatt, S J; Behrends, R S

1987-01-01

Based on the assumption that the mutative factors that facilitate growth in psychoanalysis involve the same fundamental mechanisms that lead to psychological growth in normal development, this paper considers the constant oscillation between gratification and deprivation leading to internalization as the central therapeutic mechanism of the psychoanalytic process. Patients experience the analytic process as a series of gratifying involvements and experienced incompatibilities that facilitate internalization, whereby the patient recovers lost or disrupted regulatory, gratifying interactions with the analyst, which are real or fantasied, by appropriating these interactions, transforming them into their own, enduring, self-generated functions and characteristics. Patients internalize not only the analyst's interpretive activity, but also the analyst's sensitivity, compassion and acceptance, and, in addition, their own activity in relation to the analyst such as free association. Both interpretation and the therapeutic relationship can contain elements of gratifying involvement and experienced incompatibility that lead to internalization and therefore both can be mutative factors in the therapeutic process.

Targeting Microglial Activation States as a Therapeutic Avenue in Parkinson’s Disease

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Sudhakar R. Subramaniam

2017-06-01

Full Text Available Parkinson’s disease (PD is a chronic and progressive disorder characterized neuropathologically by loss of dopamine neurons in the substantia nigra, intracellular proteinaceous inclusions, reduction of dopaminergic terminals in the striatum, and increased neuroinflammatory cells. The consequent reduction of dopamine in the basal ganglia results in the classical parkinsonian motor phenotype. A growing body of evidence suggest that neuroinflammation mediated by microglia, the resident macrophage-like immune cells in the brain, play a contributory role in PD pathogenesis. Microglia participate in both physiological and pathological conditions. In the former, microglia restore the integrity of the central nervous system and, in the latter, they promote disease progression. Microglia acquire different activation states to modulate these cellular functions. Upon activation to the M1 phenotype, microglia elaborate pro-inflammatory cytokines and neurotoxic molecules promoting inflammation and cytotoxic responses. In contrast, when adopting the M2 phenotype microglia secrete anti-inflammatory gene products and trophic factors that promote repair, regeneration, and restore homeostasis. Relatively little is known about the different microglial activation states in PD and a better understanding is essential for developing putative neuroprotective agents. Targeting microglial activation states by suppressing their deleterious pro-inflammatory neurotoxicity and/or simultaneously enhancing their beneficial anti-inflammatory protective functions appear as a valid therapeutic approach for PD treatment. In this review, we summarize microglial functions and, their dual neurotoxic and neuroprotective role in PD. We also review molecules that modulate microglial activation states as a therapeutic option for PD treatment.

Improved anti-tumor activity of a therapeutic melanoma vaccine through the use of the dual COX-2/5-LO inhibitor licofelone

Directory of Open Access Journals (Sweden)

Silke Neumann

2016-12-01

Full Text Available Immune-suppressive cell populations impair anti-tumor immunity and can contribute to the failure of immune therapeutic approaches. We hypothesized that the non-steroidal anti-inflammatory drug (NSAID licofelone, a dual COX-2/5-LO inhibitor, would improve therapeutic melanoma vaccination by reducing immune-suppressive cell populations. Therefore, licofelone was administered after tumor implantation, either alone or in combination with a peptide vaccine containing a long tyrosinase-related protein (TRP2-peptide and the adjuvant α-galactosylceramide, all formulated into cationic liposomes. Mice immunized with the long-peptide vaccine and licofelone showed delayed tumor growth compared to mice given the vaccine alone. This protection was associated with a lower frequency of immature myeloid cells (IMCs in the bone marrow (BM and spleen of tumor-inoculated mice. When investigating the effect of licofelone on IMCs in vitro, we found that the prostaglandin E2-induced generation of IMCs was decreased in the presence of licofelone. Furthermore, pre-incubation of BM cells differentiated under IMC-inducing conditions with licofelone reduced the secretion of cytokines interleukin (IL-10 and -6 upon LPS stimulation as compared to untreated cells. Interestingly, licofelone increased IL-6 and IL-10 secretion when administered after the LPS stimulus, demonstrating an environment-dependent effect of licofelone. Our findings support the use of licofelone to reduce tumor-promoting cell populations.

Solution-Grown ZnO Films toward Transparent and Smart Dual-Color Light-Emitting Diode.

Science.gov (United States)

Huang, Xiaohu; Zhang, Li; Wang, Shijie; Chi, Dongzhi; Chua, Soo Jin

2016-06-22

An individual light-emitting diode (LED) capable of emitting different colors of light under different bias conditions not only allows for compact device integration but also extends the functionality of the LED beyond traditional illumination and display. Herein, we report a color-switchable LED based on solution-grown n-type ZnO on p-GaN/n-GaN heterojunction. The LED emits red light with a peak centered at ∼692 nm and a full width at half-maximum of ∼90 nm under forward bias, while it emits green light under reverse bias. These two lighting colors can be switched repeatedly by reversing the bias polarity. The bias-polarity-switched dual-color LED enables independent control over the lighting color and brightness of each emission with two-terminal operation. The results offer a promising strategy toward transparent, miniaturized, and smart LEDs, which hold great potential in optoelectronics and optical communication.

Xanthone and Flavone Derivatives as Dual Agents with Acetylcholinesterase Inhibition and Antioxidant Activity as Potential Anti-Alzheimer Agents

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Inês Cruz

2017-01-01

Full Text Available Alzheimer’s disease (AD is a multifactorial neurodegenerative disorder that is associated with the elderly. The current therapy that is used to treat AD is based mainly on the administration of acetylcholinesterase (AChE inhibitors. Due to their low efficacy there is a considerable need for other therapeutic strategies. Considering that the malfunctions of different, but interconnected, biochemical complex pathways play an important role in the pathogenesis of this disease, a promising therapy may consist in administration of drugs that act on more than a target on biochemical scenery of AD. In this work, the synthesis and evaluation of xanthone and flavone derivatives as antioxidants with AChE inhibitory activity were accomplished. Among the obtained compounds, Mannich bases 3 and 14 showed capacity to inhibit AChE and antioxidant property, exerting dual activity. Moreover, for the most promising AChE inhibitors, docking studies on the target have been performed aiming to predict the binding mechanism. The results presented here may help to identify new xanthone and flavone derivatives as dual anti-Alzheimer agents with AChE inhibitory and antioxidant activities.

Motivation and justification: a dual-process model of culture in action.

Science.gov (United States)

Vaisey, Stephen

2009-05-01

This article presents a new model of culture in action. Although most sociologists who study culture emphasize its role in post hoc sense making, sociologists of religion and social psychologists tend to focus on the role beliefs play in motivation. The dual-process model integrates justificatory and motivational approaches by distinguishing between "discursive" and "practical" modes of culture and cognition. The author uses panel data from the National Study of Youth and Religion to illustrate the model's usefulness. Consistent with its predictions, he finds that though respondents cannot articulate clear principles of moral judgment, their choice from a list of moral-cultural scripts strongly predicts later behavior.

Effect of curing mode on the hardness of dual-cured composite resin core build-up materials

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César Augusto Galvão Arrais

2010-06-01

Full Text Available This study evaluated the Knoop Hardness (KHN values of two dual-cured composite resin core build-up materials and one resin cement exposed to different curing conditions. Two dual-cured core build-up composite resins (LuxaCore®-Dual, DMG; and FluoroCore®2, Dentsply Caulk, and one dual-cured resin cement (Rely X ARC, 3M ESPE were used in the present study. The composite materials were placed into a cylindrical matrix (2 mm in height and 3 mm in diameter, and the specimens thus produced were either light-activated for 40 s (Optilux 501, Demetron Kerr or were allowed to self-cure for 10 min in the dark (n = 5. All specimens were then stored in humidity at 37°C for 24 h in the dark and were subjected to KHN analysis. The results were submitted to 2-way ANOVA and Tukey's post-hoc test at a pre-set alpha of 5%. All the light-activated groups exhibited higher KHN values than the self-cured ones (p = 0.00001, regardless of product. Among the self-cured groups, both composite resin core build-up materials showed higher KHN values than the dual-cured resin cement (p = 0.00001. LuxaCore®-Dual exhibited higher KHN values than FluoroCore®2 (p = 0.00001 when they were allowed to self-cure, while no significant differences in KHN values were observed among the light-activated products. The results suggest that dual-cured composite resin core build-up materials may be more reliable than dual-cured resin cements when curing light is not available.

Dielectric Meta-Holograms Enabled with Dual Magnetic Resonances in Visible Light.

Science.gov (United States)

Li, Zile; Kim, Inki; Zhang, Lei; Mehmood, Muhammad Q; Anwar, Muhammad S; Saleem, Murtaza; Lee, Dasol; Nam, Ki Tae; Zhang, Shuang; Luk'yanchuk, Boris; Wang, Yu; Zheng, Guoxing; Rho, Junsuk; Qiu, Cheng-Wei

2017-09-26

Efficient transmission-type meta-holograms have been demonstrated using high-index dielectric nanostructures based on Huygens' principle. It is crucial that the geometry size of building blocks be judiciously optimized individually for spectral overlap of electric and magnetic dipoles. In contrast, reflection-type meta-holograms using the metal/insulator/metal scheme and geometric phase can be readily achieved with high efficiency and small thickness. Here, we demonstrate a general platform for design of dual magnetic resonance based meta-holograms based on the geometric phase using silicon nanostructures that are quarter wavelength thick for visible light. Significantly, the projected holographic image can be unambiguously observed without a receiving screen even under the illumination of natural light. Within the well-developed semiconductor industry, our ultrathin magnetic resonance-based meta-holograms may have promising applications in anticounterfeiting and information security.

Light energy transmission and Vickers hardness ratio of bulk-fill resin based composites at different thicknesses cured by a dual-wave or a single-wave light curing unit.

Science.gov (United States)

Santini, Ario; Naaman, Reem Khalil; Aldossary, Mohammed Saeed

2017-04-01

To quantify light energy transmission through two bulk-fill resin-based composites and to measure the top to bottom surface Vickers hardness ratio (VHratio) of samples of various incremental thicknesses, using either a single-wave or dual-wave light curing unit (LCU). Tetric EvoCeram Bulk Fill (TECBF) and SonicFill (SF) were studied. Using MARC-RC, the irradiance delivered to the top surface of the samples 2, 3, 4 and 5 mm thick (n= 5 for each thickness) was adjusted to 800 mW/cm2 for 20 seconds (16 J/cm2) using either a single-wave, Bluephase or a dual-wave, Bluephase G2 LCUs. Light energy transmission through to the bottom surface of the specimens was measured at real time using MARC-RC. The Vickers hardness (VH) was determined using Vickers micro hardness tester and the VHratio was calculated. Data were analyzed using a general linear model in Minitab 16; α= 0.05. TECBF was more translucent than SF (Pwave Bluephase G2). SF showed significantly higher VH ratio than TECBF at all different thickness levels (P 0.05). TECBF showed significantly greater VH ratio when cured with the single-wave Bluephase than when using the dual-wave Bluephase G2 (Penergy through to the bottom surface and the VHratio are material dependent. Although TECBF is more translucent than SF, it showed lower VHratio compared to SF when cured with dual-wave Bluephase G2.

AND logic-like pH- and light-dual controlled drug delivery by surface modified mesoporous silica nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Zhao, Junwei; He, Zhaoshuai; Li, Biao; Cheng, Tanyu, E-mail: tycheng@shnu.edu.cn; Liu, Guohua

2017-04-01

Recently, the controlled drug delivery system has become a potential platform for biomedical application. Herein, we developed a pH and light-dual controlled cargo release system exhibiting AND logic based on MCM-41 mesoporous silica nanoparticles, which was surface modified using β-cyclodextrin (β-CD) with imine bond and azobenzene derivative. The complex of β-CD and azobenzene derivative effectively blocked the cargo delivery in pH = 7.0 phosphate buffered saline (PBS) solution without 365 nm UV light irradiation. The cargo was fully released when both factors of acidic environment (pH = 5.0 PBS) and 365 nm UV light irradiation were satisfied, meanwhile only very little cargo was delivered if one factor was satisfied. The result also demonstrates that the opening/closing of the gate and the release of the cargo in small portions can be controlled. - Highlights: • A pH and light-dual controlled cargo release system exhibiting AND logic is developed. • The delivery system can release the cargo in small potions by controlling the opening/closing of the gate. • The delivery system realizes the controlled release in zebrafish.

Influence of energy density of different light sources on knoop hardness of a dual-cured resin cement

Directory of Open Access Journals (Sweden)

Evandro Piva

2008-06-01

Full Text Available The purpose of this study was to evaluate the Knoop hardness of a dual-cured resin-based luting cement irradiated with different light sources as well energy density through a ceramic sample. Three light-curing unit (LCUs were tested: tungsten halogen light (HAL, light-emitting diode (LED and xenon plasma-arc (PAC lamp. Disc-shaped specimens were fabricated from a resin-based cement (Enforce. Three energy doses were used by modifying the irradiance (I of each LCU and the irradiation time (T: 24 Jcm-2 (I/2x2T, 24 Jcm-2 (IxT and 48 Jcm-2 (Ix2T. Energy doses were applied through a 2.0-mm-thick ceramic sample (Duceram Plus. Three groups underwent direct irradiation over the resin cement with the different LCUs and a chemically-activated group served as a control. Thirteen groups were tested (n=10. Knoop hardness number (KHN means were obtained from cross-sectional areas. Two-way ANOVA and the Holm-Sidak method were used for statistical comparisons of activation mode and energy doses (a=5%. Application of 48 J.cm-2 energy dose through the ceramic using LED (50.5±2.8 and HAL (50.9±3.7 produced significantly higher KHN means (p<0.05 than the control (44.7±3.8. LED showed statistically similar performance to HAL. Only HAL showed a relationship between the increase of LCU energy dose and hardness increase.

Influence of energy density of different light sources on Knoop hardness of a dual-cured resin cement.

Science.gov (United States)

Piva, Evandro; Correr-Sobrinho, Lourenço; Sinhoreti, Mario Alexandre Coelho; Consani, Simonides; Demarco, Flávio Fernando; Powers, John Michael

2008-01-01

The purpose of this study was to evaluate the Knoop hardness of a dual-cured resin-based luting cement irradiated with different light sources as well energy density through a ceramic sample. Three light-curing unit (LCUs) were tested: tungsten halogen light (HAL), light-emitting diode (LED) and xenon plasma-arc (PAC) lamp. Disc-shaped specimens were fabricated from a resin-based cement (Enforce). Three energy doses were used by modifying the irradiance (I) of each LCU and the irradiation time (T): 24 Jcm(-2) (I/2x2T), 24 Jcm(-2) (IxT) and 48 Jcm(-2) (Ix2T). Energy doses were applied through a 2.0-mm-thick ceramic sample (Duceram Plus). Three groups underwent direct irradiation over the resin cement with the different LCUs and a chemically-activated group served as a control. Thirteen groups were tested (n=10). Knoop hardness number (KHN) means were obtained from cross-sectional areas. Two-way ANOVA and the Holm-Sidak method were used for statistical comparisons of activation mode and energy doses (alpha=5%). Application of 48 J.cm(-2) energy dose through the ceramic using LED (50.5+/-2.8) and HAL (50.9+/-3.7) produced significantly higher KHN means (p<0.05) than the control (44.7+/-3.8). LED showed statistically similar performance to HAL. Only HAL showed a relationship between the increase of LCU energy dose and hardness increase.

New Sides of Aldosterone Action in Cardiovascular System as Potential Targets for Therapeutic Intervention.

Science.gov (United States)

Kolodziejczyk, Patrycjusz; Gromotowicz-Poplawska, Anna; Aleksiejczuk, Michal; Chabielska, Ewa; Tutka, Piotr; Miltyk, Wojciech

2018-03-26

Aldosterone, the main mineralocorticoid hormone, plays a crucial role in the regulation of electrolyte homeostasis and blood pressure. Although, this role is undoubtedly important, it is not a hormonal action that attracts the most attention. Aldosterone seems to be very important important as a local messenger in the pathology of cardiovascular diseases (CVD). In the last few years, the attention was focused on the correlation between raised aldosterone level and increased risk of cardiovascular events. It has been demonstrated that aldosterone contributes to fibrosis, inflammation, endothelial dysfunction, fibrinolytic disordes, and oxidative stress leading to CVD development and progression. It used to be thought that the effects of aldosterone are mediated via classic nuclear receptors - mineralocorticoid receptors (MR). Now we know that the mechanism of aldosterone action in cardiovascular system is much more complex, since experimental and clinical studies indicate that MR blockade may be not sufficient to abolish aldosterone-incuced harmful effects in the cardiovascular system. Therefore, the involvement of some other than MR, receptors and factors is suggested. Moreover, in addition to the generally known genomic action of aldosterone, which involves MR activation, the nongenomic pathways are postulated in the mode of hormone action. More and more attention is focused on the membrane-coupled receptors, which mediate the rapid effects of aldosterone and have been already confirmed in different cells and tissues of a cardiovascular system. The confirmation of multiple mechanisms of aldosterone action opens a new perspective for more effective therapeutic intervention in aldosterone-related CVD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Smart worm-like micelles responsive to CO2/N2 and light dual stimuli.

Science.gov (United States)

Jiang, Jianzhong; Wang, Guozheng; Ma, Yuxuan; Cui, Zhenggang; Binks, Bernard P

2017-04-12

CO 2 /N 2 and light dual stimuli-responsive worm-like micelles (WLMs) were obtained by addition of a relatively small amount of a switchable surfactant, 4-butyl-4'-(4-N,N-dimethylhexyloxy-amine) azobenzene bicarbonate (AZO-B6-CO 2 ), sensitive to the same triggers to a binary aqueous solution of cetyltrimethylammonium bromide (CTAB) and sodium salicylate (NaSal).

One-pot solvothermal synthesis of highly efficient, daylight active and recyclable Ag/AgBr coupled photocatalysts with synergistic dual photoexcitation

International Nuclear Information System (INIS)

Zhang, Caihong; Ai, Lunhong; Li, Lili; Jiang, Jing

2014-01-01

Highlights: • Ag/AgBr photocatalysts were controllably synthesized by solvothermal process. • Ag/AgBr composites showed excellent daylight driven photocatalytic activity. • The remarkable activity is attributed to the synergistic dual photoexcitation. -- Abstract: Efficient light harvesting has been considered to be critical for manipulating the photocatalytic behavior of photocatalysts, because it directly determines the generation of reactive redox charge carriers involved in photoreaction process. In this study, we present a successful example on efficient conversion of solar energy by Ag/AgBr coupled photocatalysts that hold unique synergistic dual photoexcitation. A series of Ag/AgBr coupled photocatalysts were controllably synthesized by an easily manipulated mild solvothermal process. The physicochemical properties of the as-prepared Ag/AgBr coupled photocatalysts were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), X-ray energy dispersive spectroscopy (EDS) and UV–vis diffuse reflectance spectroscopy (DRS). The results showed the solvothermal reaction time played key role for control of crystalline structure, morphology, composition, and visible light absorption ability of the resulting photocatalysts. The as-prepared Ag/AgBr coupled photocatalysts exhibited remarkable photocatalytic performance and good reusability for decomposing organic dyes in aqueous solution under the irradiation of commercial 20 W cool daylight fluorescent lamp, owing to the synergistic dual photoexcitation cooperating between plasmonic Ag nanoparticles and narrow-band-gap AgBr

Muscles Activity in the elderly with Balance Impairments in walking under Dual tasks

Directory of Open Access Journals (Sweden)

Elaheh Azadian

2016-09-01

Full Text Available Objectives: Each step during gait requires different attention demands that will affect muscles activity. The study of changes in the timing and intensity of the muscles activity in walking with dual task has received less attention from researchers. The purpose of this study was to evaluate changes in electromyography patterns of gait with cognitive dual tasks in balance impaired elderly. Methods: Thirty older adults were recruited for this study. People were selected through berg balance test. Subjects walked 12-meters in two conditions, normal walking and walking with a cognitive dual task. Spatial-temporal kinematic parameters were recorded through the motion analysis and muscles activities were recorded through electromyography system. The data obtained was analyzed using repeated measures ANOVA at a significant level of p< 0.05.  Results: The results showed that walking under dual tasks would decrease gait speed and increase stride time and stance time. Also muscle activity in Tibialis anterior and Vastus lateralis in stance-phase would decrease significantly in dual tasks as compared with single task (p< 0.05, but timing of muscle activity would not change in dual task conditions.  Conclusions: Based on the results, it can be argued that walking under a dual task can change spatial-temporal parameters and muscle activity in gait pattern in the elderly with balance impairment. One explanation could be that the decreased control of the central nervous system on muscle activity in stance phase due to the performing of a dual task.

CURING EFFICIENCY OF DUAL-CURE RESIN CEMENT UNDER ZIRCONIA WITH TWO DIFFERENT LIGHT CURING UNITS

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Pınar GÜLTEKİN

2015-04-01

Full Text Available Purpose: Adequate polymerization is a crucial factor in obtaining optimal physical properties and a satisfying clinical performance from composite resin materials. The aim of this study was to evaluate the polymerization efficiency of dual-cure resin cement cured with two different light curing units under zirconia structures having differing thicknesses. Materials and Methods: 4 zirconia discs framework in 4 mm diameter and in 0.5 mm, 1 mm and 1.5 mm thickness were prepared using computer-aided design system. One of the 0.5 mm-thick substructures was left as mono-layered whereas others were layered with feldspathic porcelain of same thickness and ceramic samples with 4 different thicknesses (0.5, 1, 1.5 and 2.0 mm were prepared. For each group (n=12 resin cement was light cured in polytetrafluoroethylene molds using Light Emitting Diode (LED or Quartz-Tungsten Halogen (QHT light curing units under each of 4 zirconia based discs (n=96. The values of depth of cure (in mm and the Vickers Hardness Number values (VHN were evaluated for each specimen. Results: The use of LED curing unit produced a greater depth of cure compared to QTH under ceramic discs with 0.5 and 1 mm thickness (p<0.05.At 100μm and 300 μm depth, the LED unit produced significantly greater VHN values compared to the QTH unit (p<0.05. At 500 μm depth, the difference between the VHN values of LED and QTH groups were not statistically significant. Conclusion: Light curing may not result in adequate resin cement polymerization under thick zirconia structures. LED light sources should be preferred over QTH for curing dual-cure resin cements, especially for those under thicker zirconia restorations.

Bruner's Three Forms of Representation Revisited: Action, Pictures and Words for Effective Computer Instruction.

Science.gov (United States)

Presno, Caroline

1997-01-01

Discusses computer instruction in light of Bruner's theory of three forms of representation (action, icons, and symbols). Examines how studies regarding Paivio's dual-coding theory and studies focusing on procedural knowledge support Bruner's theory. Provides specific examples for instruction in three categories: demonstrations, pictures and…

Synergistic Effect of Cu2O and Urea as Modifiers of TiO2 for Enhanced Visible Light Activity

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Marcin Janczarek

2018-06-01

Full Text Available Low cost compounds, i.e., Cu2O and urea, were used as TiO2 modifiers to introduce visible light activity. Simple and cheap methods were applied to synthesize an efficient and stable nanocomposite photocatalytic material. First, the core-shell structure TiO2–polytriazine derivatives were prepared. Thereafter, Cu2O was added as the second semiconductor to form a dual heterojunction system. Enhanced visible light activity was found for the above-mentioned nanocomposite, confirming a synergistic effect of Cu2O and urea (via polytriazine derivatives on titania surface. Two possible mechanisms of visible light activity of the considered material were proposed regarding the type II heterojunction and Z-scheme through the essential improvement of the charge separation effect.

Dual overcharge protection and solid electrolyte interphase-improving action in Li-ion cells containing a bis-annulated dialkoxyarene electrolyte additive

Science.gov (United States)

Zhang, Jingjing; Shkrob, Ilya A.; Assary, Rajeev S.; Zhang, Shuo; Hu, Bin; Liao, Chen; Zhang, Zhengcheng; Zhang, Lu

2018-02-01

1,4-Dialkoxybenzene additives are commonly used as redox active shuttles in lithium-ion batteries in order to prevent runaway oxidation of electrolyte when overcharge conditions set in. During this action the shuttle molecule goes through a futile cycle, becoming oxidized at the cathode and reduced at the anode. Minimizing parasitic reactions in all states of charge is paramount for sustained protective action. Here we demonstrate that recently developed bis-annulated 9,10-bis(2-methoxyethoxy)-1,2,3,4,5,6,7,8-octahydro-1,4:5,8-dimethano-anthracene shuttle molecule (that yields exceptionally stable radical cations) survives over 120 cycles of overcharge abuse with 100% overcharge ratio at C/5 rate. Equally remarkably, in the presence of this additive the cell impedance becomes significantly lower compared to the control cells without the additive; this decrease is observed during the formation, normal cycling, and even under overcharge conditions. This unusual dual action has not been observed in other redox shuttle systems, and it presents considerable practical interest.

Accounting for the contributions of topological excitations in phase transitions through dual actions

International Nuclear Information System (INIS)

Ramos, Rudnei O.

2006-01-01

Topological excitations are believed to play an important role in different areas of physics. For example, cases of topical interest are the study of contributions of nonhomogeneous field configurations, in particular those of topological nature (like kinks, vortices and monopoles) in phase transitions associated to spontaneous symmetry breaking, the use of topological excitations in dual models of QCD to understand properties of its vacuum and confinement through the condensation of magnetic monopoles and vortices and also the relevance of these nonhomogeneous type of configurations in cosmology, again associated to possible phase transitions that are expected to have happened in the early universe. Here we show a derivation of a model dual to the scalar Abelian Higgs model where its topological excitations, namely vortex-strings, become manifest and can be treated in a quantum field theory way. The contribution of these nontrivial vacuum excitations in the phase transition for the scalar Abelian Higgs model in a thermal background is then studied and the results interpreted from the computation of the partition function taking into account the vortice-strings in the functional integration. This is made possible from the derived dual action. The relevance of the obtained results in cosmology, the analogy with phase transitions in superconductors, the relevance also for the study of confinement and other extensions of our calculations are briefly discussed here. (author)

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

Science.gov (United States)

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

2014-12-01

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

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

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Emma eSalo

2015-02-01

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

A longitudinal investigation of older adults' physical activity: Testing an integrated dual-process model.

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Arnautovska, Urska; Fleig, Lena; O'Callaghan, Frances; Hamilton, Kyra

2017-02-01

To assess the effects of conscious and non-conscious processes for prediction of older adults' physical activity (PA), we tested a dual-process model that integrated motivational (behavioural intention) and volitional (action planning and coping planning) processes with non-conscious, automatic processes (habit). Participants (N = 215) comprised community-dwelling older adults (M = 73.8 years). A longitudinal design was adopted to investigate direct and indirect effects of intentions, habit strength (Time 1), and action planning and coping planning (Time 2) on PA behaviour (Time 3). Structural equation modelling was used to evaluate the model. The model provided a good fit to the data, accounting for 44% of the variance in PA behaviour at Time 3. PA was predicted by intentions, action planning, and habit strength, with action planning mediating the intention-behaviour relationship. An effect of sex was also found where males used fewer planning strategies and engaged in more PA than females. By investigating an integration of conscious and non-conscious processes, this study provides a novel understanding of older adults' PA. Interventions aiming to promote PA behaviour of older adults should target the combination of psychological processes.

Mechanistic and structural basis of bioengineered bovine Cathelicidin-5 with optimized therapeutic activity

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Sahoo, Bikash R.; Maruyama, Kenta; Edula, Jyotheeswara R.; Tougan, Takahiro; Lin, Yuxi; Lee, Young-Ho; Horii, Toshihiro; Fujiwara, Toshimichi

2017-03-01

Peptide-drug discovery using host-defense peptides becomes promising against antibiotic-resistant pathogens and cancer cells. Here, we customized the therapeutic activity of bovine cathelicidin-5 targeting to bacteria, protozoa, and tumor cells. The membrane dependent conformational adaptability and plasticity of cathelicidin-5 is revealed by biophysical analysis and atomistic simulations over 200 μs in thymocytes, leukemia, and E. coli cell-membranes. Our understanding of energy-dependent cathelicidin-5 intrusion in heterogeneous membranes aided in designing novel loss/gain-of-function analogues. In vitro findings identified leucine-zipper to phenylalanine substitution in cathelicidin-5 (1-18) significantly enhance the antimicrobial and anticancer activity with trivial hemolytic activity. Targeted mutants of cathelicidin-5 at kink region and N-terminal truncation revealed loss-of-function. We ensured the existence of a bimodal mechanism of peptide action (membranolytic and non-membranolytic) in vitro. The melanoma mouse model in vivo study further supports the in vitro findings. This is the first structural report on cathelicidin-5 and our findings revealed potent therapeutic application of designed cathelicidin-5 analogues.

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

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

2013-01-01

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

Self-action of Bessel wave packets in a system of coupled light guides and formation of light bullets

Energy Technology Data Exchange (ETDEWEB)

Balakin, A. A., E-mail: balakin.alexey@yandex.ru; Mironov, V. A.; Skobelev, S. A., E-mail: sk.sa1981@gmail.com [Russian Academy of Sciences, Institute of Applied Physics (Russian Federation)

2017-01-15

The self-action of two-dimensional and three-dimensional Bessel wave packets in a system of coupled light guides is considered using the discrete nonlinear Schrödinger equation. The features of the self-action of such wave fields are related to their initial strong spatial inhomogeneity. The numerical simulation shows that for the field amplitude exceeding a critical value, the development of an instability typical of a medium with the cubic nonlinearity is observed. Various regimes are studied: the self-channeling of a wave beam in one light guide at powers not strongly exceeding a critical value, the formation of the “kaleidoscopic” picture of a wave packet during the propagation of higher-power radiation along a stratified medium, the formation of light bullets during competition between self-focusing and modulation instabilities in the case of three-dimensional wave packets, etc. In the problem of laser pulse shortening, the situation is considered when the wave-field stratification in the transverse direction dominates. This process is accompanied by the self-compression of laser pulses in well enough separated light guides. The efficiency of conversion of the initial Bessel field distribution to two flying parallel light bullets is about 50%.

Synergistic dual activation catalysis by palladium nanoparticles for epoxide ring opening with phenols.

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Seth, Kapileswar; Roy, Sudipta Raha; Pipaliya, Bhavin V; Chakraborti, Asit K

2013-07-04

Synergistic dual activation catalysis has been devised for epoxide phenolysis wherein palladium nanoparticles induce electrophilic activation via coordination with the epoxide oxygen followed by nucleophilic activation through anion-π interaction with the aromatic ring of the phenol, and water (reaction medium) also renders assistance through 'epoxide-phenol' dual activation.

Strong spectral variation of biomass smoke light absorption and single scattering albedo observed with a novel dual-wavelength photoacoustic instrument

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Kristin Lewis; William P. Arnott; Hans Moosmuller; Cyle E. Wold

2008-01-01

A dual-wavelength photoacoustic instrument operating at 405 and 870 nm was used during the 2006 Fire Lab at Missoula Experiment to measure light scattering and absorption by smoke from the combustion of a variety of biomass fuels. Simultaneous measurements of aerosol light scattering by reciprocal nephelometry within the instrument's acoustic resonator accompany...

Degree of conversion of resin-based materials cured with dual-peak or single-peak LED light-curing units.

Science.gov (United States)

Lucey, Siobhan M; Santini, Ario; Roebuck, Elizabeth M

2015-03-01

There is a lack of data on polymerization of resin-based materials (RBMs) used in paediatric dentistry, using dual-peak light-emitting diode (LED) light-curing units (LCUs). To evaluate the degree of conversion (DC) of RBMs cured with dual-peak or single-peak LED LCUs. Samples of Vit-l-escence (Ultradent) and Herculite XRV Ultra (Kerr) and fissure sealants Delton Clear and Delton Opaque (Dentsply) were prepared (n = 3 per group) and cured with either one of two dual-peak LCUs (bluephase(®) G2; Ivoclar Vivadent or Valo; Ultradent) or a single-peak (bluephase(®) ; Ivoclar Vivadent). High-performance liquid chromatography and nuclear magnetic resonance spectroscopy were used to confirm the presence or absence of initiators other than camphorquinone. The DC was determined using micro-Raman spectroscopy. Data were analysed using general linear model anova; α = 0.05. With Herculite XRV Ultra, the single-peak LCU gave higher DC values than either of the two dual-peak LCUs (P < 0.05). Both fissure sealants showed higher DC compared with the two RBMs (P < 0.05); the DC at the bottom of the clear sealant was greater than the opaque sealant, (P < 0.05). 2,4,6-trimethylbenzoyldiphenylphosphine oxide (Lucirin(®) TPO) was found only in Vit-l-escence. Dual-peak LED LCUs may not be best suited for curing non-Lucirin(®) TPO-containing materials. A clear sealant showed a better cure throughout the material and may be more appropriate than opaque versions in deep fissures. © 2014 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Forced LIGHT expression in prostate tumors overcomes Treg mediated immunosuppression and synergizes with a prostate tumor therapeutic vaccine by recruiting effector T lymphocytes.

Science.gov (United States)

Yan, Lisa; Da Silva, Diane M; Verma, Bhavna; Gray, Andrew; Brand, Heike E; Skeate, Joseph G; Porras, Tania B; Kanodia, Shreya; Kast, W Martin

2015-02-15

LIGHT, a ligand for lymphotoxin-β receptor (LTβR) and herpes virus entry mediator, is predominantly expressed on activated immune cells and LTβR signaling leads to the recruitment of lymphocytes. The interaction between LIGHT and LTβR has been previously shown to activate immune cells and result in tumor regression in a virally-induced tumor model, but the role of LIGHT in tumor immunosuppression or in a prostate cancer setting, where self antigens exist, has not been explored. We hypothesized that forced expression of LIGHT in prostate tumors would shift the pattern of immune cell infiltration toward an anti-tumoral milieu, would inhibit T regulatory cells (Tregs) and would induce prostate cancer tumor associated antigen (TAA) specific T cells that would eradicate tumors. Real Time PCR was used to evaluate expression of forced LIGHT and other immunoregulatory genes in prostate tumors samples. For in vivo studies, adenovirus encoding murine LIGHT was injected intratumorally into TRAMP-C2 prostate cancer cell tumor bearing mice. Chemokine and cytokine concentrations were determined by multiplex ELISA. Flow cytometry was used to phenotype tumor infiltrating lymphocytes and expression of LIGHT on the tumor cell surface. Tumor-specific lymphocytes were quantified via ELISpot assay. Treg induction and Treg suppression assays determined Treg functionality after LIGHT treatment. LIGHT in combination with a therapeutic vaccine, PSCA TriVax, reduced tumor burden. LIGHT expression peaked within 48 hr of infection, recruited effector T cells that recognized mouse prostate stem cell antigen (PSCA) into the tumor microenvironment, and inhibited infiltration of Tregs. Tregs isolated from tumor draining lymph nodes had impaired suppressive capability after LIGHT treatment. Forced LIGHT treatment combined with PSCA TriVax therapeutic vaccination delays prostate cancer progression in mice by recruiting effector T lymphocytes to the tumor and inhibiting Treg mediated

Targeting caspase-3 as dual therapeutic benefits by RNAi facilitating brain-targeted nanoparticles in a rat model of Parkinson's disease.

Science.gov (United States)

Liu, Yang; Guo, Yubo; An, Sai; Kuang, Yuyang; He, Xi; Ma, Haojun; Li, Jianfeng; Lu, Jing; Lv, Jing; Zhang, Ning; Jiang, Chen

2013-01-01

The activation of caspase-3 is an important hallmark in Parkinson's disease. It could induce neuron death by apoptosis and microglia activation by inflammation. As a result, inhibition the activation of caspase-3 would exert synergistic dual effect in brain in order to prevent the progress of Parkinson's disease. Silencing caspase-3 genes by RNA interference could inhibit the activation of caspase-3. We developed a brain-targeted gene delivery system based on non-viral gene vector, dendrigraft poly-L-lysines. A rabies virus glycoprotein peptide with 29 amino-acid linked to dendrigraft poly-L-lysines could render gene vectors the ability to get across the blood brain barrier by specific receptor mediated transcytosis. The resultant brain-targeted vector was complexed with caspase-3 short hairpin RNA coding plasmid DNA, yielding nanoparticles. In vivo imaging analysis indicated the targeted nanoparticles could accumulate in brain more efficiently than non-targeted ones. A multiple dosing regimen by weekly intravenous administration of the nanoparticles could reduce activated casapse-3 levels, significantly improve locomotor activity and rescue dopaminergic neuronal loss and in Parkinson's disease rats' brain. These results indicated the rabies virus glycoprotein peptide modified brain-targeted nanoparticles were promising gene delivery system for RNA interference to achieve anti-apoptotic and anti-inflammation synergistic therapeutic effects by down-regulation the expression and activation of caspase-3.

Targeting caspase-3 as dual therapeutic benefits by RNAi facilitating brain-targeted nanoparticles in a rat model of Parkinson's disease.

Directory of Open Access Journals (Sweden)

Yang Liu

Full Text Available The activation of caspase-3 is an important hallmark in Parkinson's disease. It could induce neuron death by apoptosis and microglia activation by inflammation. As a result, inhibition the activation of caspase-3 would exert synergistic dual effect in brain in order to prevent the progress of Parkinson's disease. Silencing caspase-3 genes by RNA interference could inhibit the activation of caspase-3. We developed a brain-targeted gene delivery system based on non-viral gene vector, dendrigraft poly-L-lysines. A rabies virus glycoprotein peptide with 29 amino-acid linked to dendrigraft poly-L-lysines could render gene vectors the ability to get across the blood brain barrier by specific receptor mediated transcytosis. The resultant brain-targeted vector was complexed with caspase-3 short hairpin RNA coding plasmid DNA, yielding nanoparticles. In vivo imaging analysis indicated the targeted nanoparticles could accumulate in brain more efficiently than non-targeted ones. A multiple dosing regimen by weekly intravenous administration of the nanoparticles could reduce activated casapse-3 levels, significantly improve locomotor activity and rescue dopaminergic neuronal loss and in Parkinson's disease rats' brain. These results indicated the rabies virus glycoprotein peptide modified brain-targeted nanoparticles were promising gene delivery system for RNA interference to achieve anti-apoptotic and anti-inflammation synergistic therapeutic effects by down-regulation the expression and activation of caspase-3.

Translation initiation complex eIF4F is a therapeutic target for dual mTOR kinase inhibitors in non-Hodgkin lymphoma

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Stenson, Mary J.; Maurer, Matthew J.; Wellik, Linda E.; Link, Brian; Hege, Kristen; Dogan, Ahmet; Sotomayor, Eduardo; Witzig, Thomas; Gupta, Mamta

2015-01-01

Deregulated mRNA translation has been implicated in disease development and in part is controlled by a eukaryotic initiation complex eIF4F (composed of eIF4E, eIF4G and eIF4A). We demonstrate here that the cap bound fraction from lymphoma cells was enriched with eIF4G and eIF4E indicating that lymphoma cells exist in an activated translational state. Moreover, 77% (110/142) of diffuse large B cell lymphoma tumors expressed eIF4E and this was associated with an inferior event free survival. Over-expression of wild-type eIF4E (eIF4EWT) but not cap-mutant eIF4E (eIF4Ecap mutant) increased the activation of the eIF4F complex. Treatment with the active-site dual mTOR inhibitor CC214-1 reduced the level of the eIF4F complex by decreasing the cap bound fraction of eIF4G and increasing the levels of 4E-BP1. CC214-1 inhibited both the cap dependent and global protein translation. CC214-1 inhibited c-Myc, and cyclin D3 translation by decreasing polysomal fractions from lymphoma cells. Inhibition of eIF4E with shRNA further decreased the CC214-1 induced inhibition of the eIF4F complex, c-Myc, cyclin D3 translation, and colony formation. These studies demonstrate that the eIF4F complex is deregulated in aggressive lymphoma and that dual mTOR therapy has therapeutic potential in these patients. PMID:25839159

Mechanisms and Implications of Dual-Acting Methotrexate in Folate-Targeted Nanotherapeutic Delivery

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Pamela T. Wong

2015-01-01

Full Text Available The rational design of a nanoplatform in drug delivery plays a crucial role in determining its targeting specificity and efficacy in vivo. A conventional approach relies on the surface conjugation of a nanometer-sized particle with two functionally distinct types of molecules, one as a targeting ligand, and the other as a therapeutic agent to be delivered to the diseased cell. However, an alternative simplified approach can be used, in which a single type of molecule displaying dual function as both a targeting ligand and therapeutic agent is conjugated to the nanoparticle. In this review, we evaluate the validity of this new strategy by using methotrexate, which displays multifunctional mechanisms of action. Methotrexate binds to the folate receptor, a surface biomarker frequently overexpressed in tumor cells, and also inhibits dihydrofolate reductase, an enzyme critical for cell survival and division. Thus we describe a series of fifth generation poly(amido amine dendrimers conjugated with methotrexate, and discuss several lines of evidence supporting the efficacy of this new platform strategy based on surface plasmon resonance spectroscopy, enzyme activity assays, and cell-based studies with folate receptor (+ KB cancer cells.

Dual PI3K/mTOR inhibitor BEZ235 as a promising therapeutic strategy against paclitaxel-resistant gastric cancer via targeting PI3K/Akt/mTOR pathway.

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Chen, Dongshao; Lin, Xiaoting; Zhang, Cheng; Liu, Zhentao; Chen, Zuhua; Li, Zhongwu; Wang, Jingyuan; Li, Beifang; Hu, Yanting; Dong, Bin; Shen, Lin; Ji, Jiafu; Gao, Jing; Zhang, Xiaotian

2018-01-26

Paclitaxel (PTX) is widely used in the front-line chemotherapy for gastric cancer (GC), but resistance limits its use. Due to the lack of proper models, mechanisms underlying PTX resistance in GC were not well studied. Using established PTX-resistant GC cell sublines HGC-27R, we for the first time integrated biological traits and molecular mechanisms of PTX resistance in GC. Data revealed that PTX-resistant GC cells were characterized by microtubular disorders, an EMT phenotype, reduced responses to antimitotic drugs, and resistance to apoptosis (marked by upregulated β-tubulin III, vimentin, attenuated changes in G 2 /M molecules or pro-apoptotic factors in response to antimitotic drugs or apoptotic inducers, respectively). Activation of the phosphoinositide 3-kinase, the serine/threonine kinase Akt and mammalian target of rapamycin (PI3K/Akt/mTOR) and mitogen-activated protein kinase (MAPK) pathways were also observed, which might be the reason for above phenotypic alternations. In vitro data suggested that targeting these pathways were sufficient to elicit antitumor responses in PTX-resistant GC, in which the dual PI3K/mTOR inhibitor BEZ235 displayed higher therapeutic efficiency than the mTOR inhibitor everolimus or the MEK inhibitor AZD6244. Antitumor effects of BEZ235 were also confirmed in mice bearing HGC-27R tumors. Thus, these data suggest that PI3K/Akt/mTOR and MAPK pathway inhibition, especially PI3K/mTOR dual blockade, might be a promising therapeutic strategy against PTX-resistant GC.

From Chemotherapy-Induced Emesis to Neuroprotection: Therapeutic Opportunities for 5-HT3 Receptor Antagonists.

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Fakhfouri, Gohar; Mousavizadeh, Kazem; Mehr, Sharam Ejtemaei; Dehpour, Ahmad Reza; Zirak, Mohammad Reza; Ghia, Jean-Eric; Rahimian, Reza

2015-12-01

5-HT3 receptor antagonists are extensively used as efficacious agents in counteracting chemotherapy-induced emesis. Recent investigations have shed light on other potential effects (analgesic, anxiolytic, and anti-psychotic). Some studies have reported neuroprotective properties for the 5-HT3 receptor antagonists in vitro and in vivo. When administered to Aβ-challenged rat cortical neurons, 5-HT3 receptor antagonists substantially abated apoptosis, elevation of cytosolic Ca(2), glutamate release, reactive oxygen species (ROS) generation, and caspase-3 activity. In addition, in vivo studies show that 5-HT3 receptor antagonists possess, alongside their anti-emetic effects, notable immunomodulatory properties in CNS. We found that pretreatment with tropisetron significantly improved neurological deficits and diminished leukocyte transmigration into the brain, TNF-α level, and brain infarction in a murine model of embolic stroke. Our recent investigation revealed that tropisetron protects against Aβ-induced neurotoxicity in vivo through both 5-HT3 receptor-dependent and -independent pathways. Tropisetron, in vitro, was found to be an efficacious inhibitor of the signaling pathway leading to the activation of pro-inflammatory NF-κB, a transcription factor pivotal to the upregulation of several neuroinflammatory mediators in brain. This mini review summarizes novel evidence concerning effects of 5-HT3 antagonists and their possible mechanisms of action in ameliorating neurodegenerative diseases including Alzheimer, multiple sclerosis, and stroke. Further, we discuss some newly synthesized 5-HT3 receptor antagonists with dual properties of 5-HT3 receptor blockade/alpha-7 nicotinic receptor activator and their potential in management of memory impairment. Since 5-HT3 receptor antagonists possess a large therapeutic window, they can constitute a scaffold for design and synthesis of new neuroprotective medications.

Brain Activations for Vestibular Stimulation and Dual Tasking Change with Spaceflight

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Yuan, Peng; Koppelmans, Vincent; Reuter-Lorenz, Patricia; De Dios, Yiri; Gadd, Nichole; Wood, Scott; Riascos, Roy; Kofman, Igor; Bloomberg, Jacob; Mulavara, Ajitkumar;

Dual-controlled release system of drugs for bone regeneration.

Science.gov (United States)

Kim, Yang-Hee; Tabata, Yasuhiko

2015-11-01

Controlled release systems have been noted to allow drugs to enhance their ability for bone regeneration. To this end, various biomaterials have been used as the release carriers of drugs, such as low-molecular-weight drugs, growth factors, and others. The drugs are released from the release carriers in a controlled fashion to maintain their actions for a long time period. Most research has been focused on the controlled release of single drugs to demonstrate the therapeutic feasibility. Controlled release of two combined drugs, so-called dual release systems, are promising and important for tissue regeneration. This is because the tissue regeneration process of bone formation is generally achieved by multiple bioactive molecules, which are produced from cells by other molecules. If two types of bioactive molecules, (i.e., drugs), are supplied in an appropriate fashion, the regeneration process of living bodies will be efficiently promoted. This review focuses on the bone regeneration induced by dual-controlled release of drugs. In this paper, various dual-controlled release systems of drugs aiming at bone regeneration are overviewed explaining the type of drugs and their release materials. Copyright © 2015 Elsevier B.V. All rights reserved.

Formation of Offset and Dual Active Galactic Nuclei

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Barrows, Scott; Comerford, Julia M.; Greene, Jenny E.

2018-06-01

Galaxy mergers are effective mechanisms for triggering accretion onto supermassive black holes (SMBHs) and thereby powering active galactic nuclei (AGN). In the merger scenario, when the SMBH from only one galaxy is accreting we observe a spatially offset AGN, and when the SMBHs from both galaxies are accreting we observe a dual AGN. Understanding the merger conditions that lead to the formation of offset AGN versus dual AGN is fundamental to informing models of hierarchical SMBH growth and the physics leading to the accretion of matter onto SMBHs. However, while the role of galaxy mergers for AGN triggering has been well-studied, the efficiency with which these events trigger offset AGN versus dual AGN is currently unclear. One reason for this gap in knowledge can be attributed to the observational difficulties in distinguishing between offset and dual AGN since doing so requires high spatial resolution, especially in the small separation regime where merger-driven AGN triggering is most likely to occur. To overcome this hurdle, we have utilized the spatial resolution of the Chandra X-ray Observatory to develop a unique sample of AGN hosted by late-stage galaxy mergers. Moreover, we have recently acquired Hubble Space Telescope imaging for a subset of these systems to examine the role that their merger morphologies play in SMBH growth and the formation of offset and dual AGN. We find that offset AGN are predominately found in minor mergers, whereas dual AGN are usually hosted by major mergers and galaxies with large morphological asymmetries. Furthermore, in both offset and dual AGN, the rate of SMBH growth increases toward more major mergers and larger morphological asymmetries. These results are in agreement with numerical simulations predicting that merger morphology is a relevant parameter governing SMBH merger-driven growth, and these results are the first to observationally confirm these trends at small pair separations.

Action of methotrexate and tofacitinib on directly stimulated and bystander-activated lymphocytes.

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Piscianz, Elisa; Candilera, Vanessa; Valencic, Erica; Loganes, Claudia; Paron, Greta; De Iudicibus, Sara; Decorti, Giuliana; Tommasini, Alberto

2016-07-01

Chronic inflammation associated with autoimmune activation is characteristic of rheumatic diseases from childhood to adulthood. In recent decades, significant improvements in the treatment of these types of disease have been achieved using disease modifying anti-rheumatic drugs (DMARDs), such as methotrexate (MTX) and, more recently, using biologic inhibitors. The recent introduction of kinase inhibitors (for example, tofacitinib; Tofa) further increases the available ARDs. However, there are patients that do not respond to any treatment strategies, for whom combination therapies are proposed. The data regarding the combined action of different drugs is lacking and the knowledge of the mechanisms of ARDs and their actions upon pathogenic lymphocytes, which are hypothesized to sustain disease, is poor. An in vitro model of inflammation was developed in the current study, in which stimulated and unstimulated lymphocytes were cultured together, but tracked separately, to investigate the action of MTX and Tofa on the two populations. By analysing lymphocyte proliferation and activation, and cytokine secretion in the culture supernatants, it was established that, due to the presence of activated cells, unstimulated cells underwent a bystander activation that was modulated by the ARDs. Additionally, varying administration schedules were demonstrated to affect lymphocytes differently in vitro, either directly or via bystander activation. Furthermore, MTX and Tofa exerted different effects; while MTX showed an antiproliferative effect, Tofa marginally effected activation, although only a slight antiproliferative action, which could be potentiated by sequential treatment with MTX. Thus, it was hypothesized that these differences may be exploited in sequential therapeutic strategies, to maximize the anti‑rheumatic effect. These findings are notable and must be accounted for, as bystander‑activated cells in vivo could contribute to the spread of autoimmune activation

PirocarbotrateTM: A new radiopharamaceutical labelled with 32P for the treatment of solid tumours. Therapeutic action and radiodosimetric calculations

International Nuclear Information System (INIS)

Zubillaga, M.; Boccio, J.; Calmanovici, G.; Goldman, C.; Caro, R.; Nicolini, J.; Ughetti, R.; Sapia, S.; Frahm, I.; Gamboni, M.

2001-01-01

Pirocarbotrat TM is a gelatin protected charcoal suspension labelled with chromic [ 32 P] pyrophosphate. To evaluate its effectiveness as a therapeutic agent for the treatment of solid tumours, studies of therapeutic action and dose calculations, were carried out after an intratumoural single dose of this radiopharmaceutical. We used 28 female Sprague Dawley rats in which experimental mammary adenocarcinomas were induced. The tumours were injected with a single dose of 18.5 MBq. Once the experiment was finished, animals were sacrificed to extract their organs and the injected tumours, the activity of which were measured by the Bremsstrahlung photons of 32 P. Representative pieces of tissues from the treated and control tumours were selected for histolopathological examination. The results show that after 32 days of treatment, the percentage of activity found in the tumour was 84.50 ± 2.60%, while the percentage of activity found in the other evaluated organs was almost negligible. The therapeutic action was evaluated by the percentage of tumour regression (P.T.R.) which was 78.3%. The treated tumours showed closely packed black charcoal particles at the injection point, which are shown always in sharply demarcated big clusters, always associated with necrotic debris from the neoplastic tissue. The extension of the necrotic tissue in the tumour vicinity is variable, ranging from 1 to 4 mm. Radiodosimetric calculations, carried out according to the Medical Internal Radiation Dose Committee (MIRD) of the Society of Nuclear Medicine, demonstrate that the dose absorbed by the tumours was 6200 Gy. The dose absorbed by the rest of the organism is 0.533 Gy. The ratio dose to the tumour/dose to the rest of the organism is 1.17x10 4 . We can conclude that Pirocarbotrat TM , a non-sealed beta radiation source, behaves very closely to a sealed beta radiation source when it is intratumourally injected into solid tumours. (author)

Photodynamic Action of LED-Activated Curcumin against Staphylococcus aureus Involving Intracellular ROS Increase and Membrane Damage

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Yuan Jiang

2014-01-01

Full Text Available Aim. To investigate the effect of photodynamic action of LED-activated curcumin on cell viability, membrane permeability, and intracellular reactive oxygen species of Staphylococcus aureus. Methods. Staphylococcus aureus was incubated with the different concentrations of curcumin for 60 min and then irradiated by blue light with the wavelength of 470 nm and with light dose of 3 J/cm2. The colony forming unit assay was used to investigate photocytotoxicity of curcumin on Staphylococcus aureus, confocal laser scanning microscopy (CLSM and flow cytometry (FCM for assaying membrane permeability, FCM analysis with DCFH-DA staining for measuring the intracellular ROS level, and transmission electron microscopy (TEM for observing morphology and structure. Results. Blue light-activated curcumin significantly killed Staphylococcus aureus in a curcumin dose-dependent manner. TEM observed remarkable structural damages in S. aureus after light-activated curcumin. More red fluorescence of PI dye was found in S. aureus treated by blue light-activated curcumin than in those of the controlled bacterial cells. Intracellular ROS increase was observed after light-activated curcumin. Conclusion. Blue light-activated curcumin markedly damaged membrane permeability, resulting in cell death of Staphylococcus aureus and highlighted that intracellular ROS increase might be an important event in photodynamic killing of Staphylococcus aureus in the presence of curcumin.

Mixed heavy–light matching in the Universal One-Loop Effective Action

International Nuclear Information System (INIS)

Ellis, Sebastian A.R.; Quevillon, Jérémie; You, Tevong; Zhang, Zhengkang

2016-01-01

Recently, a general result for evaluating the path integral at one loop was obtained in the form of the Universal One-Loop Effective Action. It may be used to derive effective field theory operators of dimensions up to six, by evaluating the traces of matrices in this expression, with the mass dependence encapsulated in the universal coefficients. Here we show that it can account for loops of mixed heavy–light particles in the matching procedure. Our prescription for computing these mixed contributions to the Wilson coefficients is conceptually simple. Moreover it has the advantage of maintaining the universal structure of the effective action, which we illustrate using the example of integrating out a heavy electroweak triplet scalar coupling to a light Higgs doublet. Finally we also identify new structures that were previously neglected in the universal results.

Therapeutic actions for the compensation on postural changes in athletes of Race walking

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Annia Gómez Valdés

2017-07-01

Full Text Available The research that is presented refers to the importance of having a control on the posture alterations that can be appreciated in athletes of sport march (12-15 years old in the sport formation school “Ormani Arenado", Pinar del Río; especially according to the age of these walkers. Its objective is aimed at proposing therapeutic actions for the compensation of the posture alterations, treated from planning physical preparation, based on indications as the positions and convenient movements, treatment goals and exercises for each deformity; addressing individual characteristics. For the realization of the investigation it was used theoretical, empiric and statistical methods which were facilitated to conclude that the adoption of incorrect postures during the training and the intensive use of the skeletal-muscle and locomotive systems impacts in the occurrence of the posture alterations that they rebound negatively in working of the athletes study object, standing out in them cavus feet, varus knees, lordosis and scoliosis; with the result that it is necessary their compensation and / or correction from the training of the physical preparation; so the application of therapeutic actions proposed to confirm their effectiveness in order to extend the study to other categories is recommended.

Fiberoptic microneedles: novel optical diffusers for interstitial delivery of therapeutic light.

Science.gov (United States)

Kosoglu, Mehmet A; Hood, Robert L; Rossmeisl, John H; Grant, David C; Xu, Yong; Robertson, John L; Rylander, Marissa Nichole; Rylander, Christopher G

2011-11-01

Photothermal therapies have limited efficacy and application due to the poor penetration depth of light inside tissue. In earlier work, we described the development of novel fiberoptic microneedles to provide a means to mechanically penetrate dermal tissue and deliver light directly into a localized target area.This paper presents an alternate fiberoptic microneedle design with the capability of delivering more diffuse, but therapeutically useful photothermal energy. Laser lipolysis is envisioned as a future clinical application for this design. A novel fiberoptic microneedle was developed using hydrofluoric acid etching of optical fiber to permit diffuse optical delivery. Microneedles etched for 10, 30, and 50 minutes, and an optical fiber control were compared with three techniques. First, red light delivery from the microneedles was evaluated by imaging the reflectance of the light from a white paper.Second, spatial temperature distribution of the paper in response to near-IR light (1,064 nm, 1 W CW) was recorded using infrared thermography. Third, ex vivo adipose tissue response during 1,064 nm, (5 W CW)irradiation was recorded with bright field microscopy. Acid etching exposed a 3 mm length of the fiber core, allowing circumferential delivery of light along this length. Increasing etching time decreased microneedle diameter, resulting in increased uniformity of red and 1,064 nm light delivery along the microneedle axis. For equivalent total energy delivery, thinner microneedles reduced carbonization in the adipose tissue experiments. We developed novel microscale optical diffusers that provided a more homogeneous light distribution from their surfaces, and compared performance to a flat-cleaved fiber, a device currently utilized in clinical practice. These fiberoptic microneedles can potentially enhance clinical laser procedures by providing direct delivery of diffuse light to target chromophores, while minimizing undesirable photothermal damage in adjacent

Biological Activity of Lenalidomide and Its Underlying Therapeutic Effects in Multiple Myeloma

Directory of Open Access Journals (Sweden)

Roberta Martiniani

2012-01-01

Full Text Available Lenalidomide is a synthetic compound derived by modifying the chemical structure of thalidomide. It belongs to the second generation of immunomodulatory drugs (IMiDs and possesses pleiotropic properties. Even if lenalidomide has been shown to be active in the treatment of several hematologic malignancies, this review article is mostly focalized on its mode of action in multiple myeloma. The present paper is about the direct and indirect antitumor effects of lenalidomide on malignant plasmacells, bone marrow microenvironment, bone resorption and host’s immune response. The molecular mechanisms and targets of lenalidomide remain largely unknown, but recent evidence shows cereblon (CRBN as a possible mediator of its therapeutical effects.

Synthetic (+)-antroquinonol exhibits dual actions against insulin resistance by triggering AMP kinase and inhibiting dipeptidyl peptidase IV activities.

Science.gov (United States)

Hsu, C Y; Sulake, R S; Huang, P-K; Shih, H-Y; Sie, H-W; Lai, Y-K; Chen, C; Weng, C F

2015-01-01

The fungal product (+)-antroquinonol activates AMP kinase (AMPK) activity in cancer cell lines. The present study was conducted to examine whether chemically synthesized (+)-antroquinonol exhibited beneficial metabolic effects in insulin-resistant states by activating AMPK and inhibiting dipeptidyl peptidase IV (DPP IV) activity. Effects of (+)-antroquinonol on DPP IV activity were measured with a DPPIV Assay Kit and effects on GLP-1-induced PKA were measured in AR42J cells. Translocation of the glucose transporter 4, GLUT4, induced either by insulin-dependent PI3K/AKT signalling or by insulin-independent AMPK activation, was assayed in differentiated myotubes. Glucose uptake and GLUT4 translocation were assayed in L6 myocytes. Mice with diet-induced obesity were used to assess effects of acute and chronic treatment with (+)-antroquinonol on glycaemic control in vivo. The results showed that of (+)-antroquinonol (100 μM ) inhibited the DPP IV activity as effectively as the clinically used inhibitor, sitagliptin. The phosphorylation of AMPK Thr(172) in differentiated myotubes was significantly increased by (+)-antroquinonol. In cells simultaneously treated with S961 (insulin receptor antagonist), insulin and (+)-antroquinonol, the combination of (+)-antroquinonol plus insulin still increased both GLUT4 translocation and glucose uptake. Further, (+)-antroquinonol and sitagliptin reduced blood glucose, when given acutely or chronically to DIO mice. Chemically synthesized (+)-antroquinonol exhibits dual effects to ameliorate insulin resistance, by increasing AMPK activity and GLUT4 translocation, along with inhibiting DPP IV activity. © 2014 The British Pharmacological Society.

Dual-Band Modulation of Visible and Near-Infrared Light Transmittance in an All-Solution-Processed Hybrid Micro-Nano Composite Film.

Science.gov (United States)

Liang, Xiao; Chen, Mei; Guo, Shumeng; Zhang, Lanying; Li, Fasheng; Yang, Huai

2017-11-22

Smart windows with controllable visible and near-infrared light transmittance can significantly improve the building's energy efficiency and inhabitant comfort. However, most of the current smart window technology cannot achieve the target of ideal solar control. Herein, we present a novel all-solution-processed hybrid micronano composite smart material that have four optical states to separately modulate the visible and NIR light transmittance through voltage and temperature, respectively. This dual-band optical modulation was achieved by constructing a phase-separated polymer framework, which contains the microsized liquid crystals domains with a negative dielectric constant and tungsten-doped vanadium dioxide (W-VO 2 ) nanocrystals (NCs). The film with 2.5 wt % W-VO 2 NCs exhibits transparency at normal condition, and the passage of visible light can be reversibly and actively regulated between 60.8% and 1.3% by external applied voltage. Also, the transmittance of NIR light can be reversibly and passively modulated between 59.4% and 41.2% by temperature. Besides, the film also features easy all-solution processability, fast electro-optical (E-O) response time, high mechanical strength, and long-term stability. The as-prepared film provides new opportunities for next-generation smart window technology, and the proposed strategy is conductive to engineering novel hybrid inorganic-organic functional matters.

Ultraviolet light and ultraviolet light-activated composite resins

International Nuclear Information System (INIS)

Murray, G.A.; Yates, J.L.; Newman, S.M.

1981-01-01

In a comparison of the UV light--activated composite resins, Estilux was polymerized to a significantly greater depth than the other composite resins. In general, Lee-fill polymerized the least. When comparing the UV light sources, the Lee light and the Duralux light did not significantly differ from each other, but both polymerized the materials tested to a significantly greater depth than the other light sources. Of the two time exposures, 60-second exposure provided a significantly greater depth of polymerization than 20 seconds for each light with each material

Rat Urinary Bladder Carcinogenesis by Dual-Acting PPARα+γ Agonists

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Martin B. Oleksiewicz

2008-01-01

Full Text Available Despite clinical promise, dual-acting activators of PPARα and γ (here termed PPARα+γ agonists have experienced high attrition rates in preclinical and early clinical development, due to toxicity. In some cases, discontinuation was due to carcinogenic effect in the rat urothelium, the epithelial layer lining the urinary bladder, ureters, and kidney pelvis. Chronic pharmacological activation of PPARα is invariably associated with cancer in rats and mice. Chronic pharmacological activation of PPARγ can in some cases also cause cancer in rats and mice. Urothelial cells coexpress PPARα as well as PPARγ, making it plausible that the urothelial carcinogenicity of PPARα+γ agonists may be caused by receptor-mediated effects (exaggerated pharmacology. Based on previously published mode of action data for the PPARα+γ agonist ragaglitazar, and the available literature about the role of PPARα and γ in rodent carcinogenesis, we propose a mode of action hypothesis for the carcinogenic effect of PPARα+γ agonists in the rat urothelium, which combines receptor-mediated and off-target cytotoxic effects. The proposed mode of action hypothesis is being explored in our laboratories, towards understanding the human relevance of the rat cancer findings, and developing rapid in vitro or short-term in vivo screening approaches to faciliate development of new dual-acting PPAR agonist compounds.

Light-activated polymethylmethacrylate nanofibers with antibacterial activity

Energy Technology Data Exchange (ETDEWEB)

Elashnikov, Roman [Department of Solid State Engineering, University of Chemistry and Technology, 16628 Prague (Czech Republic); Lyutakov, Oleksiy, E-mail: lyutakoo@vscht.cz [Department of Solid State Engineering, University of Chemistry and Technology, 16628 Prague (Czech Republic); Ulbrich, Pavel [Department of Biochemistry and Microbiology, University of Chemistry and Technology, 16628 Prague (Czech Republic); Svorcik, Vaclav [Department of Solid State Engineering, University of Chemistry and Technology, 16628 Prague (Czech Republic)

2016-07-01

The creation of an antibacterial material with triggerable properties enables us to avoid the overuse or misuse of antibacterial substances and, thus, prevent the emergence of resistant bacterial strains. As a potential light-activated antibacterial material, polymethylmethacrylate (PMMA) nanofibers doped with silver nanoparticles (AgNPs) and meso-tetraphenylporphyrin (TPP) were prepared by electrospinning. TPP was chosen as an effectively reactive oxygen species (ROS) producer. Antibacterial tests on Staphylococcus epidermidis (S. epidermidis) and Enterococcus faecalis (E. faecalis) showed the excellent light-triggerable antibacterial activity of the doped materials. Upon light irradiation at the wavelength corresponding to the TPP absorption peak (405 nm), antibacterial activity dramatically increased, mostly due to the release of AgNPs from the polymer matrix. Furthermore, under prolonged light irradiation, the AgNPs/TPP/PMMA nanofibers, displayed enhanced longevity and photothermal stability. Thus, our results suggest that the proposed material is a promising option for the photodynamic inactivation of bacteria. - Highlights: • The novelty of proposed work can be summared as follow: • Silver nanoparticles/meso-tetraphenylporphyrin embedded polymethylmethacrylate nanofibers were obtained for the first time. • Light triggering of PMMA fibers leads to sufficient release of AgNPs or their agglomeration, depending on the light source. • Release of AgNPs leads to appearance of pronounced antimicrobial activity, which can be switched on/off by the illumination.

Generalized Fermat's principle and action for light rays in a curved spacetime

Science.gov (United States)

Frolov, Valeri P.

2013-09-01

We start with formulation of the generalized Fermat’s principle for light propagation in a curved spacetime. We apply Pontryagin’s minimum principle of the optimal control theory and obtain an effective Hamiltonian for null geodesics in a curved spacetime. We explicitly demonstrate that dynamical equations for this Hamiltonian correctly reproduce null geodesic equations. Other forms of the action for light rays in a curved spacetime are also discussed.

In vivo electroporation enhances vaccine-mediated therapeutic control of human papilloma virus-associated tumors by the activation of multifunctional and effector memory CD8+ T cells.

Science.gov (United States)

Sales, Natiely S; Silva, Jamile R; Aps, Luana R M M; Silva, Mariângela O; Porchia, Bruna F M M; Ferreira, Luís Carlos S; Diniz, Mariana O

2017-12-19

In vivo electroporation (EP) has reignited the clinical interest on DNA vaccines as immunotherapeutic approaches to control different types of cancer. EP has been associated with increased immune response potency, but its capacity in influencing immunomodulation remains unclear. Here we evaluated the impact of in vivo EP on the induction of cellular immune responses and therapeutic effects of a DNA vaccine targeting human papillomavirus-induced tumors. Our results demonstrate that association of EP with the conventional intramuscular administration route promoted a more efficient activation of multifunctional and effector memory CD8 + T cells with enhanced cytotoxic activity. Furthermore, EP increased tumor infiltration of CD8 + T cells and avoided tumor recurrences. Finally, our results demonstrated that EP promotes local migration of antigen presenting cells that enhances with vaccine co-delivery. Altogether the present evidences shed further light on the in vivo electroporation action and its impact on the immunogenicity of DNA vaccines. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pulsed Light Stimulation Increases Boundary Preference and Periodicity of Episodic Motor Activity in Drosophila melanogaster.

Directory of Open Access Journals (Sweden)

Shuang Qiu

Full Text Available There is considerable interest in the therapeutic benefits of long-term sensory stimulation for improving cognitive abilities and motor performance of stroke patients. The rationale is that such stimulation would activate mechanisms of neural plasticity to promote enhanced coordination and associated circuit functions. Experimental approaches to characterize such mechanisms are needed. Drosophila melanogaster is one of the most attractive model organisms to investigate neural mechanisms responsible for stimulation-induced behaviors with its powerful accessibility to genetic analysis. In this study, the effect of chronic sensory stimulation (pulsed light stimulation on motor activity in w1118 flies was investigated. Flies were exposed to a chronic pulsed light stimulation protocol prior to testing their performance in a standard locomotion assay. Flies responded to pulsed light stimulation with increased boundary preference and travel distance in a circular arena. In addition, pulsed light stimulation increased the power of extracellular electrical activity, leading to the enhancement of periodic electrical activity which was associated with a centrally-generated motor pattern (struggling behavior. In contrast, such periodic events were largely missing in w1118 flies without pulsed light treatment. These data suggest that the sensory stimulation induced a response in motor activity associated with the modifications of electrical activity in the central nervous system (CNS. Finally, without pulsed light treatment, the wild-type genetic background was associated with the occurrence of the periodic activity in wild-type Canton S (CS flies, and w+ modulated the consistency of periodicity. We conclude that pulsed light stimulation modifies behavioral and electrophysiological activities in w1118 flies. These data provide a foundation for future research on the genetic mechanisms of neural plasticity underlying such behavioral modification.

A novel oral dual amylin and calcitonin receptor agonist (KBP-042) exerts antiobesity and antidiabetic effects in rats

DEFF Research Database (Denmark)

Andreassen, Kim V; Feigh, Michael; Hjuler, Sara T

2014-01-01

-induced obese (DIO) and Zucker diabetic fatty (ZDF) rats. In vitro, KBP-042 demonstrated superior binding affinity and activation of amylin and calcitonin receptors, and ex vivo, KBP-042 exerted inhibitory action on stimulated insulin and glucagon release from isolated islets. In vivo, KBP-042 induced...... a superior and pronounced reduction in food intake in conjunction with a sustained pair-fed corrected weight loss in DIO rats. Concomitantly, KBP-042 improved glucose homeostasis and reduced hyperinsulinemia and hyperleptinemia in conjunction with enhanced insulin sensitivity. In ZDF rats, KBP-042 induced...... antiobesity and antidiabetic efficacy by dual modulation of insulin sensitivity and directly decelerating stress on the pancreatic α- and β-cells. These results could provide the basis for oral KBP-042 as a novel therapeutic agent in type 2 diabetes....

The Botulinum Toxin as a Therapeutic Agent: Molecular Structure and Mechanism of Action in Motor and Sensory Systems.

Science.gov (United States)

Kumar, Raj; Dhaliwal, Harkiran Preet; Kukreja, Roshan Vijay; Singh, Bal Ram

2016-02-01

Botulinum neurotoxin (BoNT) produced by Clostridium botulinum is the most potent molecule known to mankind. Higher potency of BoNT is attributed to several factors, including structural and functional uniqueness, target specificity, and longevity. Although BoNT is an extremely toxic molecule, it is now increasingly used for the treatment of disorders related to muscle hyperactivity and glandular hyperactivity. Weakening of muscles due to peripheral action of BoNT produces a therapeutic effect. Depending on the target tissue, BoNT can block the cholinergic neuromuscular or cholinergic autonomic innervation of exocrine glands and smooth muscles. In recent observations of the analgesic properties of BoNT, the toxin modifies the sensory feedback loop to the central nervous system. Differential effects of BoNT in excitatory and inhibitory neurons provide a unique therapeutic tool. In this review the authors briefly summarize the structure and mechanism of actions of BoNT on motor and sensory neurons to explain its therapeutic effects and future potential. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

[Suppression of visceral pain by action of the low intensity polarized light on acupuncture antinociceptive points].

Science.gov (United States)

Lymans'kyĭ, Iu P; Tamarova, Z A; Huliar, S O

2003-01-01

In experiments on mice, statistically authentic weakening of visceral pain has been shown after an action of low intensity polarized light from a device Bioptron on antinociceptive acupuncture points (AP). Pain was caused by an intraperitoneal injection of 2% acetic acid (0.1 ml/10 g). The intensity of pain was judged on duration and frequency of painful behavioral reactions (writhing, licking of abdomen), as well as on duration of sleep, eating and motor activity. In animals which immediately after injections of acetic acid were exposed to polarized light of low intensity for 10 min, applied on any of antinociceptive APs (E-36, E-43, VC-8, RP-6), the duration of painful behavioral reaction was determined to be reduced, while that of non-painful one increased. The comparison of the total duration of the writhing at control and experimental mice showed that an activation of AP E-43 induced the greatest analgesic effect (76.5%), from AP VC-8 it was 76.3%, from RP-6--46.8%, and from E-36--41.4%. We have concluded that the effect of polarized light of low intensity on APs was a convenient non-pharmacological method of treating visceral pain.

Effect of Light-Activated Hypocrellin B on the Growth and Membrane Permeability of Gram-Negative Escherichia coli Cells

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Yuan Jiang

2014-01-01

Full Text Available Aim. To investigate the effect of light-activated hypocrellin B on the growth and membrane permeability of Gram-negative bacteria. Methods. Escherichia coli (E. coli as a model bacterium of Gram-negative bacteria was incubated with various concentrations of hypocrellin B for 60 min and was subsequently irradiated by blue light with wavelength of 470 nm at the dose of 12 J/cm2. Colony forming units were counted and the growth inhibition rate of E. coli cells was calculated after light-activated hypocrellin B. Membrane permeability was measured using flow cytometry and confocal laser scanning microscopy (CLSM with propidium iodide (PI staining. Bacterial morphology was observed using transmission electron microscopy (TEM. Reactive oxygen species in bacterial cells were measured using flow cytometry with DCFH-DA staining. Results. Significant growth inhibition rate of E. coli cells was observed after photodynamic action of hypocrellin B. Remarkable damage to the ultrastructure of E. coli was also observed by TEM. Flow cytometry and CLSM observation showed that light-activated hypocrellin B markedly increased membrane permeability of E. coli. Flow cytometry showed the intracellular ROS increase in E. coli treated by photodynamic action of hypocrellin B. Conclusion. Light-activated hypocrellin B caused intracellular ROS increase and structural damages and inhibited the growth of Gram-negative E. coli cells.

Radiosensitizers action on Iodine 131 therapeutical effect

International Nuclear Information System (INIS)

Agote, Marcos; Kreimann, Erica L.; Bocanera, Laura V.; Dagrosa, Maria A.; Juvenal, Guillermo J.; Pisarev, Mario A.

1999-01-01

Present studies were aimed to research the possible application of a radiosensitizer, nicotinamide, to increase the therapeutical effect of radioiodine. There were used goitrous and normal rats with growing dose of Iodine 131, with and without simultaneous treatment with nicotinamide. The obtained results show that the nicotinamide treatment importantly increases the thyroid radio destructive effect induced by radioiodine. Under these experimental conditions, nicotinamide induces to a significant increase of thyroid vascularisation, without changes in the proteins ADP-ribosylation activity. These results show, for the first time, the radiosensitizer effect of nicotinamide in front of Iodine 131 and give the possibility of using it in the treatment of hyperthyroid or thyroid difference cancer patients. (author)

Restricted access magnetic materials prepared by dual surface modification for selective extraction of therapeutic drugs from biological fluids

Energy Technology Data Exchange (ETDEWEB)

Wang Yu; Wang Yuxia; Chen Lei [School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072 (China); Wan Qianhong, E-mail: qhwan@tju.edu.cn [School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072 (China)

2012-02-15

Magnetic porous particles with dual functionality have been prepared by a two-step procedure and evaluated as novel restricted access materials for extraction of therapeutic agents from biological fluids. The magnetic silica particles served as scaffolds were first modified with diol groups, which were then converted to octadecyl esters through reaction with stearoyl chloride. In the second step, the octadecyl esters on the exterior surface were hydrolyzed by the action of lipase to yield magnetic particles with hydrophobic reversed-phase ligands on the inner surface and biocompatible diol groups on the outer surface. The restricted access behavior of the resulting materials was confirmed by differential binding of small molecules such as methotrexate (MTX), leucovorin (LV) and folic acid (FA) relative to bovine serum albumin. While MTX, LV and FA were all bound to the magnetic particles with high affinity, the adsorption of the protein was markedly reduced due to size exclusion effect. The utility of the magnetic particles for sample preparation was tested in solid-phase extraction of MTX, LV and FA from spiked human serum and the effects of the SPE conditions on the recovery of the analytes were systematically studied. Moreover, the magnetic particle-based sample preparation procedure coupled with reversed-phase liquid chromatography analysis was validated in terms of specificity, linearity and reproducibility. The method was shown to be free from interference of endogenous compounds and linear over the concentration range of 0.5-10 {mu}g/mL for the three drugs studied. The limits of detection for the three drugs in serum were in the range of 0.160-0.302 {mu}g/mL. Reproducibility expressed as the RSD of the recovery for ten replicated extractions at three different concentrations was found to be less than 8.93%. With a unique combination of surface functionality with magnetic cores, the restricted access magnetic particles may be adapted in automated and high

Action of UV-A and blue light on enzymes activity and accumulation of lipid peroxidation products in attached and detached frog retinas

Science.gov (United States)

Lapina, Victoria A.; Doutsov, Alexander E.

1994-07-01

The effect of the UV-A and blue light on the accumulation of lipid peroxidation products and activities of succinate dehydrogenase and superoxide dismutase in the retina was examined in eye cup model of dark and light adapted frogs R. temporaria. Retinas were exposed to UV-A radiation (8 mW/cm2) and blue light (10 to 150 mW/cm2) for periods from 5 min to 1 hr. We have measured TBA-active products both in the retina homogenates and in the reaction media. Enzyme activities was measured in the retina homogenates only. The measurements revealed a significant increase in the endogenous and exogenous forms of lipid peroxidation products in the retina of dark adapted frog (1.6+/- 0.4; 1.4+/- 0.3 nmole TBA-active products per mg protein, respectively) compared to light adapted (0.85+/- 0.16; 0.32+/- 0.06 nmole TBA-active products per mg protein, respectively). In the same conditions succinate dehydrogenase activity was decline more than 50% but superoxide dismutase activity didn't decrease. Disorganized inner and outer segments were observed after 40 min exposures. No light microscopic changes were detected after 5 min exposures. Light damage was significantly higher in the retina of dark adapted frog. The results indicate that the retina from eye cup of dark adapted frog is more susceptible to UV-A and blue light damages.

QCD as a dual superconductor

International Nuclear Information System (INIS)

Zachariasen, F.

1986-01-01

The author describes the construction of an effective action describing long-range Yang-Mills theory. This action is motivated by a study of the system of Dyson equations and Ward identities, but cannot (yet) be derived from the underlying quantum theory. The effective action turns out to describe a medium very much like a dual relativistic superconductor; that is, with electric and magnetic fields interchanged. There is a dual Meissner effect, which serves to compress color electric fields into flux tubes, containing quantized units of color electric flux. This produces electric confinement. There is a magnetic condensate, resulting from a spontaneous symmetry breaking analogous to that in the relativistic superconductor, as in the Abelian Higgs model. He gives the motivation leading to the effective action, and describes the quantized electric flux tube solutions. Finally, he mentions briefly some other applications

A Prokinetic Agent with a Dual Effect – Itopride – In the Treatment of Dysmotility

OpenAIRE

Petr Dite; Martin Rydlo; Milan Dockal; Arnost Martinek

2014-01-01

A wide range of dyspeptic symptoms in clinical practice reflect the high prevalence of functional disorders of the gastrointestinal (GI) tract. Prokinetic agents are the current mainstay in the therapy of functional dyspepsia. One of these drugs is itopride. We evaluated therapeutic efficacy of itopride according to the literature review. The therapeutic potential of itopride is connected with a dual effect: influencing of enzyme acetylcholinesterase activity and blocking dopamine D2 receptor...

The therapeutic action of psychoanalysis: abstinence and informative experiences.

Science.gov (United States)

Chused, J F

1996-01-01

In recent years a number of analytic concepts have been subject to scrutiny, with the value of interpretations, the usefulness of abstinence, the possibility of neutrality, all questioned. One reason for the skepticism about interpretations, in particular, is that before a patient can use an interpretation for psychic change, his perceptual frame must change, a process that is rarely initiated by the verbal content of an interpretation alone. Instead, alterations in perception usually require experiences which are discordant with expectations. In this paper the author demonstrates how the nonverbal elements of an intervention, the action communications, provide informative experiences, creating the dissonance between expectation and eventuality which makes psychic change possible. Case vignettes are presented to illustrate this point as well as to support the idea that when nonverbal experiences contribute to lasting change within a patient, the therapeutic benefit does not accrue primarily from the gratification provided by the experience, but from how the experience informs the patient about his mode of thinking, perceiving, and reacting.

Inducing fluorescence of uranyl acetate as a dual-purpose contrast agent for correlative light-electron microscopy with nanometre precision.

Science.gov (United States)

Tuijtel, Maarten W; Mulder, Aat A; Posthuma, Clara C; van der Hoeven, Barbara; Koster, Abraham J; Bárcena, Montserrat; Faas, Frank G A; Sharp, Thomas H

2017-09-05

Correlative light-electron microscopy (CLEM) combines the high spatial resolution of transmission electron microscopy (TEM) with the capability of fluorescence light microscopy (FLM) to locate rare or transient cellular events within a large field of view. CLEM is therefore a powerful technique to study cellular processes. Aligning images derived from both imaging modalities is a prerequisite to correlate the two microscopy data sets, and poor alignment can limit interpretability of the data. Here, we describe how uranyl acetate, a commonly-used contrast agent for TEM, can be induced to fluoresce brightly at cryogenic temperatures (-195 °C) and imaged by cryoFLM using standard filter sets. This dual-purpose contrast agent can be used as a general tool for CLEM, whereby the equivalent staining allows direct correlation between fluorescence and TEM images. We demonstrate the potential of this approach by performing multi-colour CLEM of cells containing equine arteritis virus proteins tagged with either green- or red-fluorescent protein, and achieve high-precision localization of virus-induced intracellular membrane modifications. Using uranyl acetate as a dual-purpose contrast agent, we achieve an image alignment precision of ~30 nm, twice as accurate as when using fiducial beads, which will be essential for combining TEM with the evolving field of super-resolution light microscopy.

Topologically massive gauge theories and their dual factorized gauge-invariant formulation

International Nuclear Information System (INIS)

Bertrand, Bruno; Govaerts, Jan

2007-01-01

There exists a well-known duality between the Maxwell-Chern-Simons theory and the 'self-dual' massive model in (2 + 1) dimensions. This dual description may be extended to topologically massive gauge theories (TMGT) for forms of arbitrary rank and in any dimension. This communication introduces the construction of this type of duality through a reparametrization of the 'master' theory action. The dual action thereby obtained preserves the full gauge symmetry structure of the original theory. Furthermore, the dual action is factorized into a propagating sector of massive gauge-invariant variables and a decoupled sector of gauge-variant variables defining a pure topological field theory. Combining the results obtained within the Lagrangian and Hamiltonian formulations, a completed structure for a gauge-invariant dual factorization of TMGT is thus achieved. (fast track communication)

Engineering Cellular Resistance to HIV-1 Infection In Vivo Using a Dual Therapeutic Lentiviral Vector

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Bryan P Burke

2015-01-01

Full Text Available We described earlier a dual-combination anti-HIV type 1 (HIV-1 lentiviral vector (LVsh5/C46 that downregulates CCR5 expression of transduced cells via RNAi and inhibits HIV-1 fusion via cell surface expression of cell membrane-anchored C46 antiviral peptide. This combinatorial approach has two points of inhibition for R5-tropic HIV-1 and is also active against X4-tropic HIV-1. Here, we utilize the humanized bone marrow, liver, thymus (BLT mouse model to characterize the in vivo efficacy of LVsh5/C46 (Cal-1 vector to engineer cellular resistance to HIV-1 pathogenesis. Human CD34+ hematopoietic stem/progenitor cells (HSPC either nonmodified or transduced with LVsh5/C46 vector were transplanted to generate control and treatment groups, respectively. Control and experimental groups displayed similar engraftment and multilineage hematopoietic differentiation that included robust CD4+ T-cell development. Splenocytes isolated from the treatment group were resistant to both R5- and X4-tropic HIV-1 during ex vivo challenge experiments. Treatment group animals challenged with R5-tropic HIV-1 displayed significant protection of CD4+ T-cells and reduced viral load within peripheral blood and lymphoid tissues up to 14 weeks postinfection. Gene-marking and transgene expression were confirmed stable at 26 weeks post-transplantation. These data strongly support the use of LVsh5/C46 lentiviral vector in gene and cell therapeutic applications for inhibition of HIV-1 infection.

Multitarget Therapeutic Leads for Alzheimer's Disease: Quinolizidinyl Derivatives of Bi- and Tricyclic Systems as Dual Inhibitors of Cholinesterases and β-Amyloid (Aβ) Aggregation.

Science.gov (United States)

Tonelli, Michele; Catto, Marco; Tasso, Bruno; Novelli, Federica; Canu, Caterina; Iusco, Giovanna; Pisani, Leonardo; Stradis, Angelo De; Denora, Nunzio; Sparatore, Anna; Boido, Vito; Carotti, Angelo; Sparatore, Fabio

2015-06-01

Multitarget therapeutic leads for Alzheimer's disease were designed on the models of compounds capable of maintaining or restoring cell protein homeostasis and of inhibiting β-amyloid (Aβ) oligomerization. Thirty-seven thioxanthen-9-one, xanthen-9-one, naphto- and anthraquinone derivatives were tested for the direct inhibition of Aβ(1-40) aggregation and for the inhibition of electric eel acetylcholinesterase (eeAChE) and horse serum butyrylcholinesterase (hsBChE). These compounds are characterized by basic side chains, mainly quinolizidinylalkyl moieties, linked to various bi- and tri-cyclic (hetero)aromatic systems. With very few exceptions, these compounds displayed inhibitory activity on both AChE and BChE and on the spontaneous aggregation of β-amyloid. In most cases, IC50 values were in the low micromolar and sub-micromolar range, but some compounds even reached nanomolar potency. The time course of amyloid aggregation in the presence of the most active derivative (IC50 =0.84 μM) revealed that these compounds might act as destabilizers of mature fibrils rather than mere inhibitors of fibrillization. Many compounds inhibited one or both cholinesterases and Aβ aggregation with similar potency, a fundamental requisite for the possible development of therapeutics exhibiting a multitarget mechanism of action. The described compounds thus represent interesting leads for the development of multitarget AD therapeutics. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Highly Efficient and Visible Light Responsive Heterojunction Composites as Dual Photoelectrodes for Photocatalytic Fuel Cell

Directory of Open Access Journals (Sweden)

Honghui Pan

2018-01-01

Full Text Available In the present work, a novel photocatalytic fuel cell (PFC system involving a dual heterojunction photoelectrodes, viz. polyaniline/TiO2 nanotubes (PANI/TiO2 NTs photoanode and CuO/Co3O4 nanorods (CuO/Co3O4 NRs photocathode, has been designed. Compared to TiO2 NTs electrode of PFC, the present heterojunction design not only enhances the visible light absorption but also offers the higher efficiency in degrading Rhodamine B–a model organic pollutant. The study includes an evaluation of the dual performance of the photoelectrodes as well. Under visible-light irradiation of 3 mW cm−2, the cell composed of the photoanode PANI/TiO2 NTs and CuO/Co3O4 NRs photocathode forms an interior bias of +0.24 V within the PFC system. This interior bias facilitated the transfer of electrons from the photoanode to photocathode across the external circuit and combined with the holes generated therein along with a simultaneous power production. In this manner, the separation of electron/hole pair was achieved in the photoelectrodes by releasing the holes and electrons of PANI/TiO2 NTs photoanode and CuO/Co3O4 NRs photocathode, respectively. Using this PFC system, the degradation of Rhodamine B in aqueous media was achieved to an extent of 68.5% within a reaction duration of a four-hour period besides a simultaneous power generation of 85 μA cm−2.

Being Active and Impulsive: The Role of Goals for Action and Inaction in Self-Control.

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Hepler, Justin; Albarracin, Dolores; McCulloch, Kathleen C; Noguchi, Kenji

2012-12-01

Although self-control often requires behavioral inaction (i.e., not eating a piece of cake), the process of inhibiting impulsive behavior is commonly characterized as cognitively active (i.e., actively exerting self-control). Two experiments examined whether motivation for action or inaction facilitates self-control behavior in the presence of tempting stimuli. Experiment 1 used a delay discounting task to assess the ability to delay gratification with respect to money. Experiment 2 used a Go/No-Go task to assess the ability to inhibit a dominant but incorrect motor response to the words "condom" and "sex". The results demonstrate that goals for inaction promote self-control, whereas goals for action promote impulsive behavior. These findings are discussed in light of recent evidence suggesting that goals for action and inaction modulate physiological resources that promote behavioral execution.

The Philosophy and Feasibility of Dual Readout Calorimetry

International Nuclear Information System (INIS)

Hauptman, John

2006-01-01

I will discuss the general physical ideas behind dual-readout calorimetry, their implementation in DREAM (Dual REAdout Module) with exact separation of scintillation and Cerenkov light, implementation with mixed light in DREAM fibers, anticipated implementation in PbWO4 crystals with applications to the 4th Concept detector and to CMS, use in high energy gamma-ray and cosmic ray astrophysics with Cerenkov and N2 fluorescent light, and implementation in the 4th Concept detector for muon identification

Near Infrared Fluorescence Imaging in Nano-Therapeutics and Photo-Thermal Evaluation

Science.gov (United States)

Vats, Mukti; Mishra, Sumit Kumar; Baghini, Mahdieh Shojaei; Chauhan, Deepak S.; Srivastava, Rohit; De, Abhijit

2017-01-01

The unresolved and paramount challenge in bio-imaging and targeted therapy is to clearly define and demarcate the physical margins of tumor tissue. The ability to outline the healthy vital tissues to be carefully navigated with transection while an intraoperative surgery procedure is performed sets up a necessary and under-researched goal. To achieve the aforementioned objectives, there is a need to optimize design considerations in order to not only obtain an effective imaging agent but to also achieve attributes like favorable water solubility, biocompatibility, high molecular brightness, and a tissue specific targeting approach. The emergence of near infra-red fluorescence (NIRF) light for tissue scale imaging owes to the provision of highly specific images of the target organ. The special characteristics of near infra-red window such as minimal auto-fluorescence, low light scattering, and absorption of biomolecules in tissue converge to form an attractive modality for cancer imaging. Imparting molecular fluorescence as an exogenous contrast agent is the most beneficial attribute of NIRF light as a clinical imaging technology. Additionally, many such agents also display therapeutic potentials as photo-thermal agents, thus meeting the dual purpose of imaging and therapy. Here, we primarily discuss molecular imaging and therapeutic potentials of two such classes of materials, i.e., inorganic NIR dyes and metallic gold nanoparticle based materials. PMID:28452928

Potentiating therapeutic effects by enhancing synergism based on active constituents from traditional medicine.

Science.gov (United States)

Zhang, Aihua; Sun, Hui; Wang, Xijun

2014-04-01

Shifting current drug discovery tide from 'finding new drugs' to 'screening natural products' may be helpful for overcoming the 'more investment, fewer drugs' challenge. Traditional Chinese medicine (TCM), relying on natural products, has been playing a very important role in health protection and disease control for thousands of years in Asia, whose therapeutic efficacy is based on the 'synergism', that is, the combinational effects to be greater than that of the individual drug. Based on syndromes and patient characteristics and guided by the theories of TCM, formulae are designed to contain a combination of various kinds of crude drugs that, when combined, generally assume that a synergism of all ingredients will bring about the maximum of therapeutic efficacy. The increasing evidence has shown that multiple active component combinations of TCM could amplify the therapeutic efficacy of each agent, representing a new trend for modern medicine. However, the precise mechanism of synergistic action remains poorly understood. The present review highlights the concept of synergy and gives some examples of synergistic effects of TCM, and provides an overview of the recent and potential developments of advancing drug discovery towards more agile development of targeted combination therapies from TCM. Copyright © 2013 John Wiley & Sons, Ltd.

Structural and biochemical analysis of atypically low dephosphorylating activity of human dual-specificity phosphatase 28.

Directory of Open Access Journals (Sweden)

Bonsu Ku

Full Text Available Dual-specificity phosphatases (DUSPs constitute a subfamily of protein tyrosine phosphatases, and are intimately involved in the regulation of diverse parameters of cellular signaling and essential biological processes. DUSP28 is one of the DUSP subfamily members that is known to be implicated in the progression of hepatocellular and pancreatic cancers, and its biological functions and enzymatic characteristics are mostly unknown. Herein, we present the crystal structure of human DUSP28 determined to 2.1 Å resolution. DUSP28 adopts a typical DUSP fold, which is composed of a central β-sheet covered by α-helices on both sides and contains a well-ordered activation loop, as do other enzymatically active DUSP proteins. The catalytic pocket of DUSP28, however, appears hardly accessible to a substrate because of the presence of nonconserved bulky residues in the protein tyrosine phosphatase signature motif. Accordingly, DUSP28 showed an atypically low phosphatase activity in the biochemical assay, which was remarkably improved by mutations of two nonconserved residues in the activation loop. Overall, this work reports the structural and biochemical basis for understanding a putative oncological therapeutic target, DUSP28, and also provides a unique mechanism for the regulation of enzymatic activity in the DUSP subfamily proteins.

[Treatment program for dual-diagnosis substance abusers].

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Kandel, Isack

2007-01-01

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

Ghost free dual vector theories in 2+1 dimensions

International Nuclear Information System (INIS)

Dalmazi, Denis

2006-01-01

We explore here the issue of duality versus spectrum equivalence in dual theories generated through the master action approach. Specifically we examine a generalized self-dual (GSD) model where a Maxwell term is added to the self-dual model. A gauge embedding procedure applied to the GSD model leads to a Maxwell-Chern-Simons (MCS) theory with higher derivatives. We show here that the latter contains a ghost mode contrary to the original GSD model. By figuring out the origin of the ghost we are able to suggest a new master action which interpolates between the local GSD model and a nonlocal MCS model. Those models share the same spectrum and are ghost free. Furthermore, there is a dual map between both theories at classical level which survives quantum correlation functions up to contact terms. The remarks made here may be relevant for other applications of the master action approach

Hybrid Modulation of Bidirectional Three-Phase Dual-Active-Bridge DC Converters for Electric Vehicles

Directory of Open Access Journals (Sweden)

Yen-Ching Wang

2016-06-01

Full Text Available Bidirectional power converters for electric vehicles (EVs have received much attention recently, due to either grid-supporting requirements or emergent power supplies. This paper proposes a hybrid modulation of the three-phase dual-active bridge (3ΦDAB converter for EV charging systems. The designed hybrid modulation allows the converter to switch its modulation between phase-shifted and trapezoidal modes to increase the conversion efficiency, even under light-load conditions. The mode transition is realized in a real-time manner according to the charging or discharging current. The operation principle of the converter is analyzed in different modes and thus design considerations of the modulation are derived. A lab-scaled prototype circuit with a 48V/20Ah LiFePO4 battery is established to validate the feasibility and effectiveness.

Dual learning processes in interactive skill acquisition.

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Fu, Wai-Tat; Anderson, John R

2008-06-01

Acquisition of interactive skills involves the use of internal and external cues. Experiment 1 showed that when actions were interdependent, learning was effective with and without external cues in the single-task condition but was effective only with the presence of external cues in the dual-task condition. In the dual-task condition, actions closer to the feedback were learned faster than actions farther away but this difference was reversed in the single-task condition. Experiment 2 tested how knowledge acquired in single and dual-task conditions would transfer to a new reward structure. Results confirmed the two forms of learning mediated by the secondary task: A declarative memory encoding process that simultaneously assigned credits to actions and a reinforcement-learning process that slowly propagated credits backward from the feedback. The results showed that both forms of learning were engaged during training, but only at the response selection stage, one form of knowledge may dominate over the other depending on the availability of attentional resources. (c) 2008 APA, all rights reserved

White light generation tuned by dual hybridization of nanocrystals and conjugated polymers

International Nuclear Information System (INIS)

Demir, Hilmi Volkan; Nizamoglu, Sedat; Ozel, Tuncay; Mutlugun, Evren; Huyal, Ilkem Ozge; Sari, Emre; Holder, Elisabeth; Tian Nan

2007-01-01

Dual hybridization of highly fluorescent conjugated polymers and highly luminescent nanocrystals (NCs) is developed and demonstrated in multiple combinations for controlled white light generation with high color rendering index (CRI) (> 80) for the first time. The generated white light is tuned using layer-by-layer assembly of CdSe/ZnS core-shell NCs closely packed on polyfluorene, hybridized on near-UV emitting nitride-based light emitting diodes (LEDs). The design, synthesis, growth, fabrication and characterization of these hybrid inorganic-organic white LEDs are presented. The following experimental realizations are reported: (i) layer-by-layer hybridization of yellow NCs (λ PL =580 nm) and blue polyfluorene (λ PL =439 nm) with tristimulus coordinates of (x, y)=(0.31, 0.27), correlated color temperature of T c =6962 K and CRI of R a =53.4; (ii) layer-by-layer assembly of yellow and green NCs (λ PL =580 and 540 nm) and blue polyfluorene (λ PL =439 nm) with (x, y)=(0.23, 0.30), T c =14395 K and R a =65.7; and (iii) layer-by-layer deposition of yellow, green and red NCs (λ PL =580, 540 and 620 nm) and blue polyfluorene (λ PL =439 nm) with (x, y)=(0.38, 0.39), T c =4052 K and R a = 83.0. The CRI is demonstrated to be well controlled and significantly improved by increasing multi-chromaticity of the NC and polymer emitters

Slowdown of group velocity of light in dual-frequency laser-pumped cascade structure of Er3+-doped optical fiber at room temperature

Science.gov (United States)

Qiu, Wei; Yang, Yujing; Gao, Yuan; Liu, Jianjun; Lv, Pin; Jiang, Qiuli

2018-04-01

Slow light is demonstrated in the cascade structure of an erbium-doped fiber with two forward propagation pumps. The results of the numerical simulation of the time delay and the optimum modulation frequency complement each other. The time delay and the optimum modulation frequency depend on the pump ratio G (G  =  {{P}1480}:{{P}980} ). The discussion results of this paper show that a larger time delay of slow light propagation can be obtained in the cascade structure of Er3+-doped optical fibers with dual-frequency laser pumping. Compared to previous research methods, the dual-frequency laser-pumped cascade structure of an Er3+-doped optical fiber is more controllable. Based on our discussion the pump ratio G should be selected in order to obtain a more appropriate time delay and the slowdown of group velocity.

Dual regulatory switch confers tighter control on HtrA2 proteolytic activity.

Science.gov (United States)

Singh, Nitu; D'Souza, Areetha; Cholleti, Anuradha; Sastry, G Madhavi; Bose, Kakoli

2014-05-01

High-temperature requirement protease A2 (HtrA2), a multitasking serine protease that is involved in critical biological functions and pathogenicity, such as apoptosis and cancer, is a potent therapeutic target. It is established that the C-terminal post-synaptic density protein, Drosophila disc large tumor suppressor, zonula occludens-1 protein (PDZ) domain of HtrA2 plays pivotal role in allosteric modulation, substrate binding and activation, as commonly reported in other members of this family. Interestingly, HtrA2 exhibits an additional level of functional modulation through its unique N-terminus, as is evident from 'inhibitor of apoptosis proteins' binding and cleavage. This phenomenon emphasizes multiple activation mechanisms, which so far remain elusive. Using conformational dynamics, binding kinetics and enzymology studies, we addressed this complex behavior with respect to defining its global mode of regulation and activity. Our findings distinctly demonstrate a novel N-terminal ligand-mediated triggering of an allosteric switch essential for transforming HtrA2 to a proteolytically competent state in a PDZ-independent yet synergistic activation process. Dynamic analyses suggested that it occurs through a series of coordinated structural reorganizations at distal regulatory loops (L3, LD, L1), leading to a population shift towards the relaxed conformer. This precise synergistic coordination among different domains might be physiologically relevant to enable tighter control upon HtrA2 activation for fostering its diverse cellular functions. Understanding this complex rheostatic dual switch mechanism offers an opportunity for targeting various disease conditions with tailored site-specific effector molecules. © 2014 FEBS.

Analysis of light scattering from human breast tissue using a custom dual-optical scanning near-field optical microscope.

Science.gov (United States)

Kyle, Jennifer Reiber; Kyle, Michael D; Raghavan, Ravi; Budak, Gurer; Ozkan, Cengiz S; Ozkan, Mihrimah

2011-03-01

In this paper we introduce a custom scanning near-field optical microscope (SNOM) that simultaneously collects reflection and transmission near-field images along with topography. This dual-optical SNOM uses a bent probe, which allows for axial reflection imaging, accurate surface scanning, and easy identification of topographic artifacts. Using this novel dual-optical SNOM, we image desiccated and non-desiccated human breast epithelial tissue. By comparing the simultaneous SNOM images, we isolate the effects of tissue morphology and variations in refractive indices on the forward- and back-scattering of light from the tissue. We find that the reduction in back-scattering from tissue, relative to the glass slide, is caused by dense packing of the scattering sites in the cytoplasm (morphology) in the desiccated tissue and a thin-film of water adhering to the glass slide (refractive index) in the non-desiccated tissue sample. Our work demonstrates the potential of our customized dual-optical SNOM system for label-free tissue diagnostics. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Light Regulation of Gibberellin Biosynthesis and Mode of Action.

Science.gov (United States)

García-Martinez, José Luis; Gil, Joan

2001-12-01

Some phenotypic effects produced in plants by light are very similar to those induced by hormones. In this review, the light-gibberellin (GA) interaction in germination, de-etiolation, stem growth, and tuber formation (process regulated by GAs) are discussed. Germination of lettuce and Arabidopsis seeds depends on red irradiation (R), which enhances the expression of GA 3-oxidase genes (GA3ox) and leads to an increase in active GA content. De-etiolation of pea seedling alters the expression of GA20ox and GA3ox genes and induces a rapid decrease of GA1 content. Stem growth of green plants is also affected by diverse light irradiation characteristics. Low light intensity increases stem elongation and active GA content in pea and Brassica. Photoperiod controls active GA levels in long-day rosette (spinach and Silene) and in woody plants (Salix and hybrid aspen) by regulating different steps of GA biosynthesis, mainly through transcript levels of GA20ox and GA3ox genes. Light modulation of stem elongation in light-grown plants is controlled by phytochrome, which modifies GA biosynthesis and catabolism (tobacco, potato, cowpea, Arabidopsis) and GA-response (pea, cucumber, Arabidopsis). In Arabidopsis and tobacco, ATH1 (a gene encoding an homeotic transcription factor) is a positive mediator of a phyB-specific signal transduction cascade controlling GA levels by regulating the expression of GA20ox and GA3ox. Tuber formation in potato is controlled by photoperiod (through phyB) and GAs. Inductive short-day conditions alter the diurnal rhythm of GA20ox transcript abundance, and increases the expression of a new protein (PHOR1) that plays a role in the photoperiod-GA interaction.

Evidence of the immunomodulatory role of dual PI3K/mTOR inhibitors in transplantation: an experimental study in mice.

Science.gov (United States)

Vilchez, Valery; Turcios, Lilia; Butterfield, David A; Mitov, Mihail I; Coquillard, Cristin L; Brandon, Ja Anthony; Cornea, Virgilius; Gedaly, Roberto; Marti, Francesc

2017-10-01

The PI3K/mTOR signaling cascade is fundamental in T-cell activation and fate decisions. We showed the distinct regulation of PI3K/mTOR in regulatory and effector T-cells and proposed the potential therapeutic benefit of targeting this pathway to control the balance between effector and regulatory T-cell activities. Substantial adverse effects in long-term clinical usage of rapamycin suggest the use of alternative treatments in restraining effector T-cell function in transplant patients. We hypothesize that dual PI3K/mTOR inhibitors may represent an immunosuppressant alternative. Here we show that dual PI3K/mTOR PI-103 and PKI-587 inhibitors interfered IL-2-dependent responses in T-cells. However, in contrast to the inhibitory effects in non-Treg T-cell proliferation and effector functions, dual inhibitors increased the differentiation, preferential expansion, and suppressor activity of iTregs. Rapamycin, PI-103, and PKI-587 targeted different signaling events and induced different metabolic patterns in primary T-cells. Similar to rapamycin, in vivo administration of PI-103 and PKI-587 controlled effectively the immunological response against allogeneic skin graft. These results characterize specific regulatory mechanisms of dual PI3K/mTOR inhibitors in T-cells and support their potential as a novel therapeutic option in transplantation. © 2017 Steunstichting ESOT.

Multirate delivery of multiple therapeutic agents from metal-organic frameworks

Directory of Open Access Journals (Sweden)

Alistair C. McKinlay

2014-12-01

Full Text Available The highly porous nature of metal-organic frameworks (MOFs offers great potential for the delivery of therapeutic agents. Here, we show that highly porous metal-organic frameworks can be used to deliver multiple therapeutic agents—a biologically active gas, an antibiotic drug molecule, and an active metal ion—simultaneously but at different rates. The possibilities offered by delivery of multiple agents with different mechanisms of action and, in particular, variable timescales may allow new therapy approaches. Here, we show that the loaded MOFs are highly active against various strains of bacteria.

Therapeutic potential of a dual mTORC1/2 inhibitor for the prevention of posterior capsule opacification: An in vitro study.

Science.gov (United States)

Feng, Hao; Yang, Zhibo; Bai, Xue; Yang, Meirong; Fang, Yuan; Zhang, Xiaonan; Guo, Qiqiang; Ning, Hong

2018-04-01

Mammalian target of rapamycin (mTOR) serves a central role in regulating cell growth and survival, and has been demonstrated to be involved in the pathological progression of posterior capsule opacification (PCO). In the present study, the potency of PP242, a novel dual inhibitor of mTOR complex 1/2 (mTORC1/2), in the suppression of the growth of human lens epithelial cells (HLECs) was investigated. Using a Cell Counting Kit‑8 and a wound healing assay, it was demonstrated that PP242 inhibited the proliferation and migration of HLECs. In addition, western blot analysis indicated that PP242 completely inhibited mTORC1 and mTORC2 downstream signaling activities, whereas rapamycin only partially inhibited mTORC1 activity within LECs. Furthermore, PP242 treatment led to an upregulation of the expression levels of p53 and B cell lymphoma‑2 (Bcl‑2)‑associated X and downregulation of Bcl‑2. In addition, flow cytometric analysis demonstrated that PP242 induced the cell cycle arrest at the G0/G1 phase, which may have caused apoptosis and induced autophagy within the LECs. The results of the present study suggested that administration of PP242 may potentially offer a novel therapeutic approach for the prevention of PCO.

[Phenibut potentiation of the therapeutic action of antiparkinson agents].

Science.gov (United States)

Gol'dblat, Iu V; Lapin, I P

1986-01-01

It was observed in experiments on mice that the central action of phenibut (beta-phenyl-gamma-aminobutyric acid) diminished after destruction of brain dopaminergic neurons by 6-hydroxydopamine and after pretreatment with the dopamine receptor blocker haloperidol which suggests the dopaminergic component in the action of phenibut. In 13 of 16 patients receiving long-term treatment with antiparkinsonic drugs, addition of phenibut (0.25 g thrice daily for 10 days) resulted in marked clinical improvement with a significant increase of motor activity, as well as diminution of both rigidity and tremor. Follow-up showed a significant lowering of muscle tone of rigid muscles, augmentation of their strength and amplitude of movements. In 8 patients receiving phenibut without antiparkinsonic drugs the results were negligible.

Revisiting the Therapeutic Potential of Bothrops jararaca Venom: Screening for Novel Activities Using Connectivity Mapping

Directory of Open Access Journals (Sweden)

Carolina Alves Nicolau

2018-02-01

Full Text Available Snake venoms are sources of molecules with proven and potential therapeutic applications. However, most activities assayed in venoms (or their components are of hemorrhagic, hypotensive, edematogenic, neurotoxic or myotoxic natures. Thus, other relevant activities might remain unknown. Using functional genomics coupled to the connectivity map (C-map approach, we undertook a wide range indirect search for biological activities within the venom of the South American pit viper Bothrops jararaca. For that effect, venom was incubated with human breast adenocarcinoma cell line (MCF7 followed by RNA extraction and gene expression analysis. A list of 90 differentially expressed genes was submitted to biosimilar drug discovery based on pattern recognition. Among the 100 highest-ranked positively correlated drugs, only the antihypertensive, antimicrobial (both antibiotic and antiparasitic, and antitumor classes had been previously reported for B. jararaca venom. The majority of drug classes identified were related to (1 antimicrobial activity; (2 treatment of neuropsychiatric illnesses (Parkinson’s disease, schizophrenia, depression, and epilepsy; (3 treatment of cardiovascular diseases, and (4 anti-inflammatory action. The C-map results also indicated that B. jararaca venom may have components that target G-protein-coupled receptors (muscarinic, serotonergic, histaminergic, dopaminergic, GABA, and adrenergic and ion channels. Although validation experiments are still necessary, the C-map correlation to drugs with activities previously linked to snake venoms supports the efficacy of this strategy as a broad-spectrum approach for biological activity screening, and rekindles the snake venom-based search for new therapeutic agents.

Defining the action spectrum of potential PGC-1α activators on a mitochondrial and cellular level in vivo.

Science.gov (United States)

Hofer, Annette; Noe, Natalie; Tischner, Christin; Kladt, Nikolay; Lellek, Veronika; Schauß, Astrid; Wenz, Tina

2014-05-01

Previous studies have demonstrated a therapeutic benefit of pharmaceutical PGC-1α activation in cellular and murine model of disorders linked to mitochondrial dysfunction. While in some cases, this effect seems to be clearly associated with boosting of mitochondrial function, additional alterations as well as tissue- and cell-type-specific effects might play an important role. We initiated a comprehensive analysis of the effects of potential PGC-1α-activating drugs and pharmaceutically targeted the PPAR (bezafibrate, rosiglitazone), AMPK (AICAR, metformin) and Sirt1 (resveratrol) pathways in HeLa cells, neuronal cells and PGC-1α-deficient MEFs to get insight into cell type specificity and PGC-1α dependence of their working action. We used bezafibrate as a model drug to assess the effect on a tissue-specific level in a murine model. Not all analyzed drugs activate the PGC pathway or alter mitochondrial protein levels. However, they all affect supramolecular assembly of OXPHOS complexes and OXPHOS protein stability. In addition, a clear drug- and cell-type-specific influence on several cellular stress pathways as well as on post-translational modifications could be demonstrated, which might be relevant to fully understand the action of the analyzed drugs in the disease state. Importantly, the effect on the activation of mitochondrial biogenesis and stress response program upon drug treatment is PGC-1α dependent in MEFs demonstrating not only the pleiotropic effects of this molecule but points also to the working mechanism of the analyzed drugs. The definition of the action spectrum of the different drugs forms the basis for a defect-specific compensation strategy and a future personalized therapeutic approach.

Emotional Readiness and Music Therapeutic Activities

Science.gov (United States)

Drossinou-Korea, Maria; Fragkouli, Aspasia

2016-01-01

The purpose of this study is to understand the children's expression with verbal and nonverbal communication in the Autistic spectrum. We study the emotional readiness and the music therapeutic activities which exploit the elements of music. The method followed focused on the research field of special needs education. Assumptions on the parameters…

Restricted access magnetic materials prepared by dual surface modification for selective extraction of therapeutic drugs from biological fluids

International Nuclear Information System (INIS)

Wang Yu; Wang Yuxia; Chen Lei; Wan Qianhong

2012-01-01

Magnetic porous particles with dual functionality have been prepared by a two-step procedure and evaluated as novel restricted access materials for extraction of therapeutic agents from biological fluids. The magnetic silica particles served as scaffolds were first modified with diol groups, which were then converted to octadecyl esters through reaction with stearoyl chloride. In the second step, the octadecyl esters on the exterior surface were hydrolyzed by the action of lipase to yield magnetic particles with hydrophobic reversed-phase ligands on the inner surface and biocompatible diol groups on the outer surface. The restricted access behavior of the resulting materials was confirmed by differential binding of small molecules such as methotrexate (MTX), leucovorin (LV) and folic acid (FA) relative to bovine serum albumin. While MTX, LV and FA were all bound to the magnetic particles with high affinity, the adsorption of the protein was markedly reduced due to size exclusion effect. The utility of the magnetic particles for sample preparation was tested in solid-phase extraction of MTX, LV and FA from spiked human serum and the effects of the SPE conditions on the recovery of the analytes were systematically studied. Moreover, the magnetic particle-based sample preparation procedure coupled with reversed-phase liquid chromatography analysis was validated in terms of specificity, linearity and reproducibility. The method was shown to be free from interference of endogenous compounds and linear over the concentration range of 0.5-10 μg/mL for the three drugs studied. The limits of detection for the three drugs in serum were in the range of 0.160-0.302 μg/mL. Reproducibility expressed as the RSD of the recovery for ten replicated extractions at three different concentrations was found to be less than 8.93%. With a unique combination of surface functionality with magnetic cores, the restricted access magnetic particles may be adapted in automated and high

LIGHT BRIDGE IN A DEVELOPING ACTIVE REGION. I. OBSERVATION OF LIGHT BRIDGE AND ITS DYNAMIC ACTIVITY PHENOMENA

International Nuclear Information System (INIS)

Toriumi, Shin; Katsukawa, Yukio; Cheung, Mark C. M.

2015-01-01

Light bridges, the bright structures that divide the umbra of sunspots and pores into smaller pieces, are known to produce a wide variety of activity events in solar active regions (ARs). It is also known that the light bridges appear in the assembling process of nascent sunspots. The ultimate goal of this series of papers is to reveal the nature of light bridges in developing ARs and the occurrence of activity events associated with the light bridge structures from both observational and numerical approaches. In this first paper, exploiting the observational data obtained by Hinode, the Interface Region Imaging Spectrograph, and the Solar Dynamics Observatory, we investigate the detailed structure of the light bridge in NOAA AR 11974 and its dynamic activity phenomena. As a result, we find that the light bridge has a weak, horizontal magnetic field, which is transported from the interior by a large-scale convective upflow and is surrounded by strong, vertical fields of adjacent pores. In the chromosphere above the bridge, a transient brightening occurs repeatedly and intermittently, followed by a recurrent dark surge ejection into higher altitudes. Our analysis indicates that the brightening is the plasma heating due to magnetic reconnection at lower altitudes, while the dark surge is the cool, dense plasma ejected from the reconnection region. From the observational results, we conclude that the dynamic activity observed in a light bridge structure such as chromospheric brightenings and dark surge ejections are driven by magnetoconvective evolution within the light bridge and its interaction with the surrounding magnetic fields

LIGHT BRIDGE IN A DEVELOPING ACTIVE REGION. I. OBSERVATION OF LIGHT BRIDGE AND ITS DYNAMIC ACTIVITY PHENOMENA

Energy Technology Data Exchange (ETDEWEB)

Toriumi, Shin; Katsukawa, Yukio [National Astronomical Observatory of Japan, 2-21-1 Osawa, Mitaka, Tokyo 181-8588 (Japan); Cheung, Mark C. M., E-mail: shin.toriumi@nao.ac.jp [Lockheed Martin Solar and Astrophysics Laboratory, 3251 Hanover Street, Building/252, Palo Alto, CA 94304 (United States)

2015-10-01

Light bridges, the bright structures that divide the umbra of sunspots and pores into smaller pieces, are known to produce a wide variety of activity events in solar active regions (ARs). It is also known that the light bridges appear in the assembling process of nascent sunspots. The ultimate goal of this series of papers is to reveal the nature of light bridges in developing ARs and the occurrence of activity events associated with the light bridge structures from both observational and numerical approaches. In this first paper, exploiting the observational data obtained by Hinode, the Interface Region Imaging Spectrograph, and the Solar Dynamics Observatory, we investigate the detailed structure of the light bridge in NOAA AR 11974 and its dynamic activity phenomena. As a result, we find that the light bridge has a weak, horizontal magnetic field, which is transported from the interior by a large-scale convective upflow and is surrounded by strong, vertical fields of adjacent pores. In the chromosphere above the bridge, a transient brightening occurs repeatedly and intermittently, followed by a recurrent dark surge ejection into higher altitudes. Our analysis indicates that the brightening is the plasma heating due to magnetic reconnection at lower altitudes, while the dark surge is the cool, dense plasma ejected from the reconnection region. From the observational results, we conclude that the dynamic activity observed in a light bridge structure such as chromospheric brightenings and dark surge ejections are driven by magnetoconvective evolution within the light bridge and its interaction with the surrounding magnetic fields.

Challenges in searching for therapeutics against Botulinum Neurotoxins.

Science.gov (United States)

Pirazzini, Marco; Rossetto, Ornella

2017-05-01

Botulinum neurotoxins (BoNTs) are the most potent toxins known. BoNTs are responsible for botulism, a deadly neuroparalytic syndrome caused by the inactivation of neurotransmitter release at peripheral nerve terminals. Thanks to their specificity and potency, BoNTs are both considered potential bio-weapons and therapeutics of choice for a variety of medical syndromes. Several variants of BoNTs have been identified with individual biological properties and little antigenic relation. This expands greatly the potential of BoNTs as therapeutics but poses a major safety problem, increasing the need for finding appropriate antidotes. Areas covered: The authors describe the multi-step molecular mechanism through which BoNTs enter nerve terminals and discuss the many levels at which the toxins can be inhibited. They review the outcomes of the different strategies adopted to limit neurotoxicity and counter intoxication. Potential new targets arising from the last discoveries of the mechanism of action and the approaches to promote neuromuscular junction recovery are also discussed. Expert opinion: Current drug discovery efforts have mainly focused on BoNT type A and addressed primarily light chain proteolytic activity. Development of pan-BoNT inhibitors acting independently of BoNT immunological properties and targeting a common step of the intoxication process should be encouraged.

White light generation tuned by dual hybridization of nanocrystals and conjugated polymers

Energy Technology Data Exchange (ETDEWEB)

Demir, Hilmi Volkan [Devices and Sensors Group and Nanotechnology Research Center, Bilkent University, Ankara 06800 (Turkey); Nizamoglu, Sedat [Devices and Sensors Group and Nanotechnology Research Center, Bilkent University, Ankara 06800 (Turkey); Ozel, Tuncay [Devices and Sensors Group and Nanotechnology Research Center, Bilkent University, Ankara 06800 (Turkey); Mutlugun, Evren [Devices and Sensors Group and Nanotechnology Research Center, Bilkent University, Ankara 06800 (Turkey); Huyal, Ilkem Ozge [Devices and Sensors Group and Nanotechnology Research Center, Bilkent University, Ankara 06800 (Turkey); Sari, Emre [Devices and Sensors Group and Nanotechnology Research Center, Bilkent University, Ankara 06800 (Turkey); Holder, Elisabeth [Functional Polymers Group and Institute of Polymer Technology, University of Wuppertal, Gaussstrasse 20, D-42097 Wuppertal (Germany); Tian Nan [Functional Polymers Group and Institute of Polymer Technology, University of Wuppertal, Gaussstrasse 20, D-42097 Wuppertal (Germany)

2007-10-15

Dual hybridization of highly fluorescent conjugated polymers and highly luminescent nanocrystals (NCs) is developed and demonstrated in multiple combinations for controlled white light generation with high color rendering index (CRI) (> 80) for the first time. The generated white light is tuned using layer-by-layer assembly of CdSe/ZnS core-shell NCs closely packed on polyfluorene, hybridized on near-UV emitting nitride-based light emitting diodes (LEDs). The design, synthesis, growth, fabrication and characterization of these hybrid inorganic-organic white LEDs are presented. The following experimental realizations are reported: (i) layer-by-layer hybridization of yellow NCs ({lambda}{sub PL}=580 nm) and blue polyfluorene ({lambda}{sub PL}=439 nm) with tristimulus coordinates of (x, y)=(0.31, 0.27), correlated color temperature of T{sub c}=6962 K and CRI of R{sub a}=53.4; (ii) layer-by-layer assembly of yellow and green NCs ({lambda}{sub PL}=580 and 540 nm) and blue polyfluorene ({lambda}{sub PL}=439 nm) with (x, y)=(0.23, 0.30), T{sub c}=14395 K and R{sub a}=65.7; and (iii) layer-by-layer deposition of yellow, green and red NCs ({lambda}{sub PL}=580, 540 and 620 nm) and blue polyfluorene ({lambda}{sub PL}=439 nm) with (x, y)=(0.38, 0.39), T{sub c}=4052 K and R{sub a}= 83.0. The CRI is demonstrated to be well controlled and significantly improved by increasing multi-chromaticity of the NC and polymer emitters.

The OSp(32 vertical stroke 1) versus OSp(8 vertical stroke 2) supersymmetric M-brane action from self-dual (2,2) strings

International Nuclear Information System (INIS)

Ketov, S.V.

1996-09-01

Taking the (2,2) strings as a starting point, we discuss the equivalent self-dual field theories and analyze their symmetry structure in 2+2 dimensions from the viewpoint of string/membrane unification. Requiring the 'Lorentz' invariance and supersymmetry in the (2,2) string target space leads to an extension of the (2,2) string theory to a theory of 2+2 dimensional supermembranes (M-branes) propagating in a higher dimensional target space. The origin of the hidden target space dimensions of the M-brane is related to the maximally extended supersymmetry implied by the 'Lorentz' covariance and dimensional reasons. The Kaehler-Chern-Simons-type action describing the self-dual gravity in 2+2 dimensions is proposed. Its maximal supersymmetrization (of the Green-Schwarz-type) naturally leads to the 2+10 (or higher) dimensions for the M-brane target space. The proposed OSp(32 vertical stroke 1) supersymmetric action gives the pre-geometrical description of M-branes, which may be useful for a fundamental formulation of F and M theory. (orig.)

AMPK activation: a therapeutic target for type 2 diabetes?

Directory of Open Access Journals (Sweden)

Coughlan KA

2014-06-01

Full Text Available Kimberly A Coughlan, Rudy J Valentine, Neil B Ruderman, Asish K Saha Endocrinology and Diabetes, Department of Medicine, Boston University Medical Center, Boston, MA, USA Abstract: Type 2 diabetes (T2D is a metabolic disease characterized by insulin resistance, β-cell dysfunction, and elevated hepatic glucose output. Over 350 million people worldwide have T2D, and the International Diabetes Federation projects that this number will increase to nearly 600 million by 2035. There is a great need for more effective treatments for maintaining glucose homeostasis and improving insulin sensitivity. AMP-activated protein kinase (AMPK is an evolutionarily conserved serine/threonine kinase whose activation elicits insulin-sensitizing effects, making it an ideal therapeutic target for T2D. AMPK is an energy-sensing enzyme that is activated when cellular energy levels are low, and it signals to stimulate glucose uptake in skeletal muscles, fatty acid oxidation in adipose (and other tissues, and reduces hepatic glucose production. There is substantial evidence suggesting that AMPK is dysregulated in animals and humans with metabolic syndrome or T2D, and that AMPK activation (physiological or pharmacological can improve insulin sensitivity and metabolic health. Numerous pharmacological agents, natural compounds, and hormones are known to activate AMPK, either directly or indirectly – some of which (for example, metformin and thiazolidinediones are currently used to treat T2D. This paper will review the regulation of the AMPK pathway and its role in T2D, some of the known AMPK activators and their mechanisms of action, and the potential for future improvements in targeting AMPK for the treatment of T2D. Keywords: adenosine monophosphate-activated protein kinase, type 2 diabetes, insulin resistance, drug therapy

DC-bias Cancellation for Phase Shift Controlled Dual Active Bridge

DEFF Research Database (Denmark)

Alzola, Rafael Pena; Mathe, Laszlo; Liserre, Marco

2013-01-01

The dual active bridge topology allows bidirectional power flow and galvanic isolation for DC/DC energy conversion. These features have made it the possible backbone of the future smart transformer for distribution. The different voltage drops and commutation dead-times of the semiconductor...

Near-Infrared Light Activation of Proteins Inside Living Cells Enabled by Carbon Nanotube-Mediated Intracellular Delivery.

Science.gov (United States)

Li, He; Fan, Xinqi; Chen, Xing

2016-02-01

Light-responsive proteins have been delivered into the cells for controlling intracellular events with high spatial and temporal resolution. However, the choice of wavelength is limited to the UV and visible range; activation of proteins inside the cells using near-infrared (NIR) light, which has better tissue penetration and biocompatibility, remains elusive. Here, we report the development of a single-walled carbon nanotube (SWCNT)-based bifunctional system that enables protein intracellular delivery, followed by NIR activation of the delivered proteins inside the cells. Proteins of interest are conjugated onto SWCNTs via a streptavidin-desthiobiotin (SA-DTB) linkage, where the protein activity is blocked. SWCNTs serve as both a nanocarrier for carrying proteins into the cells and subsequently a NIR sensitizer to photothermally cleave the linkage and release the proteins. The released proteins become active and exert their functions inside the cells. We demonstrated this strategy by intracellular delivery and NIR-triggered nuclear translocation of enhanced green fluorescent protein, and by intracellular delivery and NIR-activation of a therapeutic protein, saporin, in living cells. Furthermore, we showed that proteins conjugated onto SWCNTs via the SA-DTB linkage could be delivered to the tumors, and optically released and activated by using NIR light in living mice.

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

Science.gov (United States)

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

2018-01-01

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

Structure-activity relationships of the antimicrobial peptide arasin 1 - and mode of action studies of the N-terminal, proline-rich region.

Directory of Open Access Journals (Sweden)

Victoria S Paulsen

Full Text Available Arasin 1 is a 37 amino acid long proline-rich antimicrobial peptide isolated from the spider crab, Hyas araneus. In this work the active region of arasin 1 was identified through structure-activity studies using different peptide fragments derived from the arasin 1 sequence. The pharmacophore was found to be located in the proline/arginine-rich NH(2 terminus of the peptide and the fragment arasin 1(1-23 was almost equally active to the full length peptide. Arasin 1 and its active fragment arasin 1(1-23 were shown to be non-toxic to human red blood cells and arasin 1(1-23 was able to bind chitin, a component of fungal cell walls and the crustacean shell. The mode of action of the fully active N-terminal arasin 1(1-23 was explored through killing kinetic and membrane permeabilization studies. At the minimal inhibitory concentration (MIC, arasin 1(1-23 was not bactericidal and had no membrane disruptive effect. In contrast, at concentrations of 5×MIC and above it was bactericidal and interfered with membrane integrity. We conclude that arasin 1(1-23 has a different mode of action than lytic peptides, like cecropin P1. Thus, we suggest a dual mode of action for arasin 1(1-23 involving membrane disruption at peptide concentrations above MIC, and an alternative mechanism of action, possibly involving intracellular targets, at MIC.

Imaging enabled platforms for development of therapeutics

Science.gov (United States)

Celli, Jonathan; Rizvi, Imran; Blanden, Adam R.; Evans, Conor L.; Abu-Yousif, Adnan O.; Spring, Bryan Q.; Muzikansky, Alona; Pogue, Brian W.; Finkelstein, Dianne M.; Hasan, Tayyaba

2011-03-01

Advances in imaging and spectroscopic technologies have enabled the optimization of many therapeutic modalities in cancer and noncancer pathologies either by earlier disease detection or by allowing therapy monitoring. Amongst the therapeutic options benefiting from developments in imaging technologies, photodynamic therapy (PDT) is exceptional. PDT is a photochemistry-based therapeutic approach where a light-sensitive molecule (photosensitizer) is activated with light of appropriate energy (wavelength) to produce reactive molecular species such as free radicals and singlet oxygen. These molecular entities then react with biological targets such as DNA, membranes and other cellular components to impair their function and lead to eventual cell and tissue death. Development of PDT-based imaging also provides a platform for rapid screening of new therapeutics in novel in vitro models prior to expensive and labor-intensive animal studies. In this study we demonstrate how an imaging platform can be used for strategizing a novel combination treatment strategy for multifocal ovarian cancer. Using an in vitro 3D model for micrometastatic ovarian cancer in conjunction with quantitative imaging we examine dose and scheduling strategies for PDT in combination with carboplatin, a chemotherapeutic agent presently in clinical use for management of this deadly form of cancer.

Evaluation of dual γ-ray imager with active collimator using various types of scintillators.

Science.gov (United States)

Lee, Wonho; Lee, Taewoong; Jeong, Manhee; Kim, Ho Kyung

2011-10-01

The performance of a specialized dual γ-ray imager using both mechanical and electronic collimation was evaluated by Monte Carlo simulation (MCNP5). The dual imager consisted of an active collimator and a planar detector that were made from scintillators. The active collimator served not only as a coded aperture for mechanical collimation but also as a first detector for electronic collimation. Therefore, a single system contained both mechanical and electronic collimation. Various types of scintillators were tested and compared with each other in terms of their angular resolution, efficiency, and background noise. In general, a BGO active collimator had the best mechanical collimation performance, and an LaCl₃(Ce) active collimator provided the best electronic collimation performance. However, for low radiation energies, the mechanical collimation images made from both scintillators showed the same quality, and, for high radiation energies, electronic collimation images made from both scintillators also show similar quality. Therefore, if mechanical collimation is used to detect low-energy radiation and electronic collimation is applied to reconstruct a high-energy source, either LaCl₃(Ce) or BGO would be appropriate for the active collimator of a dual γ-ray imager. These results broaden the choice of scintillators for the active collimator of the dual γ-ray imager, which makes it possible to consider other factors, such as machinability and cost, in making the imager. As a planar detector, BGO showed better performance than other scintillators since its radiation detection efficiency was highest of all. Copyright © 2011 Elsevier Ltd. All rights reserved.

Natural Translating Locomotion Modulates Cortical Activity at Action Observation

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Thierry Pozzo

2017-11-01

Full Text Available The present study verified if the translational component of locomotion modulated cortical activity recorded at action observation. Previous studies focusing on visual processing of biological motion mainly presented point light walker that were fixed on a spot, thus removing the net translation toward a goal that yet remains a critical feature of locomotor behavior. We hypothesized that if biological motion recognition relies on the transformation of seeing in doing and its expected sensory consequences, a significant effect of translation compared to centered displays on sensorimotor cortical activity is expected. To this aim, we explored whether EEG activity in the theta (4–8 Hz, alpha (8–12 Hz, beta 1 (14–20 Hz and beta 2 (20–32 Hz frequency bands exhibited selectivity as participants viewed four types of stimuli: a centered walker, a centered scrambled, a translating walker and a translating scrambled. We found higher theta synchronizations for observed stimulus with familiar shape. Higher power decreases in the beta 1 and beta 2 bands, indicating a stronger motor resonance was elicited by translating compared to centered stimuli. Finally, beta bands modulation in Superior Parietal areas showed that the translational component of locomotion induced greater motor resonance than human shape. Using a Multinomial Logistic Regression classifier we found that Dorsal-Parietal and Inferior-Frontal regions of interest (ROIs, constituting the core of action-observation system, were the only areas capable to discriminate all the four conditions, as reflected by beta activities. Our findings suggest that the embodiment elicited by an observed scenario is strongly mediated by horizontal body displacement.

Tunability of the circadian action of tetrachromatic solid-state light sources

International Nuclear Information System (INIS)

Žukauskas, A.; Vaicekauskas, R.

2015-01-01

An approach to the optimization of the spectral power distribution of solid-state light sources with the tunable non-image forming photobiological effect on the human circadian rhythm is proposed. For tetrachromatic clusters of model narrow-band (direct-emission) light-emitting diodes (LEDs), the limiting tunability of the circadian action factor (CAF), which is the ratio of the circadian efficacy to luminous efficacy of radiation, was established as a function of constraining color fidelity and luminous efficacy of radiation. For constant correlated color temperatures (CCTs), the CAF of the LED clusters can be tuned above and below that of the corresponding blackbody radiators, whereas for variable CCT, the clusters can have circadian tunability covering that of a temperature-tunable blackbody radiator

Tunability of the circadian action of tetrachromatic solid-state light sources

Energy Technology Data Exchange (ETDEWEB)

Žukauskas, A., E-mail: arturas.zukauskas@ff.vu.lt [Institute of Applied Research, Vilnius University, Saulėtekio al. 9-III, LT-10222 Vilnius (Lithuania); Vaicekauskas, R. [Department of Computer Science, Vilnius University, Didlaukio g. 47, Vilnius LT-08303 (Lithuania)

2015-01-26

An approach to the optimization of the spectral power distribution of solid-state light sources with the tunable non-image forming photobiological effect on the human circadian rhythm is proposed. For tetrachromatic clusters of model narrow-band (direct-emission) light-emitting diodes (LEDs), the limiting tunability of the circadian action factor (CAF), which is the ratio of the circadian efficacy to luminous efficacy of radiation, was established as a function of constraining color fidelity and luminous efficacy of radiation. For constant correlated color temperatures (CCTs), the CAF of the LED clusters can be tuned above and below that of the corresponding blackbody radiators, whereas for variable CCT, the clusters can have circadian tunability covering that of a temperature-tunable blackbody radiator.

Adaptive Lighting Design – Staged Experiences of Light

DEFF Research Database (Denmark)

Søndergaard, Karin; Petersen, Kjell Yngve

2015-01-01

involved in the negotiations of how the lighting design unfolds. Each installation stages a specified place, where participants perform their own experiences of being and moving in dynamically changing lighting settings. Through investigative actions participants test the ways that the lighting...... compositions influence their ability to orient themselves within the geography of the space and how the balances in light colours and luminous intensities affect their experience of directionality, distances, and scales. In short, the experience of being present in the space as well as one’s experience......Adaptive Lighting Design – Staged Experiences of Light The two installations, White Cube and White Box, enable experience-based studies as a form of perceptual activity, wherein lighting conditions are examined in a dialectical exchange between the system and the people participating. Adaptive...

Supercontinuum optimization for dual-soliton based light sources using genetic algorithms in a grid platform.

Science.gov (United States)

Arteaga-Sierra, F R; Milián, C; Torres-Gómez, I; Torres-Cisneros, M; Moltó, G; Ferrando, A

2014-09-22

We present a numerical strategy to design fiber based dual pulse light sources exhibiting two predefined spectral peaks in the anomalous group velocity dispersion regime. The frequency conversion is based on the soliton fission and soliton self-frequency shift occurring during supercontinuum generation. The optimization process is carried out by a genetic algorithm that provides the optimum input pulse parameters: wavelength, temporal width and peak power. This algorithm is implemented in a Grid platform in order to take advantage of distributed computing. These results are useful for optical coherence tomography applications where bell-shaped pulses located in the second near-infrared window are needed.

Generation of activity-rest patterns by dual circadian pacemaker systems : a model

NARCIS (Netherlands)

Beersma, Domien G.M.; Daan, Serge

1992-01-01

Activity-rest patterns displayed by an animal under various circumstances are suggested to result from the combined influences of two virtually identical circadian pacemaker components. Increased output of each component proportionally increases the probability of activity of the animal. Such a dual

Dual antiretroviral therapy for HIV infection.

Science.gov (United States)

Soriano, Vicente; Fernandez-Montero, Jose Vicente; Benitez-Gutierrez, Laura; Mendoza, Carmen de; Arias, Ana; Barreiro, Pablo; Peña, José M; Labarga, Pablo

2017-08-01

For two decades, triple combinations of antiretrovirals have been the standard treatment for HIV infection. The challenges of such lifelong therapy include long-term side effects, high costs and reduced drug adherence. The recent advent of more potent and safer antiretrovirals has renewed the interest for simpler HIV regimens. Areas covered: We discuss the pros and cons of dual antiretroviral therapies in both drug-naïve and in treatment-experienced patients with viral suppression (switch strategy). Expert opinion: Some dual antiretroviral regimens are safe and efficacious, particularly as maintenance therapy. At this time, combinations of dolutegravir plus rilpivirine represent the best dual regimen. Longer follow-up and larger study populations are needed before supporting dolutegravir plus lamivudine. In contrast, dual therapy based on maraviroc is less effective. Although dual regimens with boosted protease inhibitors plus either lamivudine or raltegravir may be effective, they are penalized by metabolic side effects and risk for drug interactions. The newest dual regimens could save money, reduce toxicity and spare drug options for the future. For the first time in HIV therapeutics, less can be more. Dual therapy switching has set up a new paradigm in HIV treatment that uses induction-maintenance.

Preventive and therapeutic effects of SkQ1-containing Visomitin eye drops against light-induced retinal degeneration.

Science.gov (United States)

Novikova, Yu P; Gancharova, O S; Eichler, O V; Philippov, P P; Grigoryan, E N

2014-10-01

The human retina is constantly affected by light of varying intensity, this being especially true for photoreceptor cells and retinal pigment epithelium. Traditionally, photoinduced damages of the retina are induced by visible light of high intensity in albino rats using the LIRD (light-induced retinal degeneration) model. This model allows study of pathological processes in the retina and the search for retinoprotectors preventing retinal photodamage. In addition, the etiology and mechanisms of retina damage in the LIRD model have much in common with the mechanisms of the development of age-related retinal disorders, in particular, with age-related macular degeneration (AMD). We have studied preventive and therapeutic effects of Visomitin eye drops (based on the mitochondria-targeted antioxidant SkQ1) on albino rat retinas damaged by bright light. In the first series of experiments, rats receiving Visomitin for two weeks prior to illumination demonstrated significantly less expressed atrophic and degenerative changes in the retina compared to animals receiving similar drops with no SkQ1. In the second series, the illuminated rats were treated for two weeks with Visomitin or similar drops without SkQ1. The damaged retinas of the experimental animals were repaired much more effectively than those of the control animals. Therefore, we conclude that Visomitin SkQ1-containing eye drops have pronounced preventive and therapeutic effects on the photodamaged retina and might be recommended as a photoprotector and a pharmaceutical preparation for the treatment of AMD in combination with conventional medicines.

Assessing delivery and quantifying efficacy of small interfering ribonucleic acid therapeutics in the skin using a dual-axis confocal microscope

Science.gov (United States)

Ra, Hyejun; Gonzalez-Gonzalez, Emilio; Smith, Bryan R.; Gambhir, Sanjiv S.; Kino, Gordon S.; Solgaard, Olav; Kaspar, Roger L.; Contag, Christopher H.

2010-05-01

Transgenic reporter mice and advances in imaging instrumentation are enabling real-time visualization of cellular mechanisms in living subjects and accelerating the development of novel therapies. Innovative confocal microscope designs are improving their utility for microscopic imaging of fluorescent reporters in living animals. We develop dual-axis confocal (DAC) microscopes for such in vivo studies and create mouse models where fluorescent proteins are expressed in the skin for the purpose of advancing skin therapeutics and transdermal delivery tools. Three-dimensional image volumes, through the different skin compartments of the epidermis and dermis, can be acquired in several seconds with the DAC microscope in living mice, and are comparable to histologic analyses of reporter protein expression patterns in skin sections. Intravital imaging with the DAC microscope further enables visualization of green fluorescent protein (GFP) reporter gene expression in the skin over time, and quantification of transdermal delivery of small interfering RNA (siRNA) and therapeutic efficacy. Visualization of transdermal delivery of nucleic acids will play an important role in the development of innovative strategies for treating skin pathologies.

Artificial light and nocturnal activity in gammarids

Directory of Open Access Journals (Sweden)

Elizabeth K. Perkin

2014-03-01

Full Text Available Artificial light is gaining attention as a potential stressor to aquatic ecosystems. Artificial lights located near streams increase light levels experienced by stream invertebrates and we hypothesized light would depress night drift rates. We also hypothesized that the effect of light on drift rates would decrease over time as the invertebrates acclimated to the new light level over the course of one month’s exposure. These hypotheses were tested by placing Gammarus spp. in eight, 75 m × 1 m artificial flumes. One flume was exposed to strong (416 lx artificial light at night. This strong light created a gradient between 4.19 and 0.04 lx over the neighboring six artificial flumes, while a control flume was completely covered with black plastic at night. Night-time light measurements taken in the Berlin area confirm that half the flumes were at light levels experienced by urban aquatic invertebrates. Surprisingly, no light treatment affected gammarid drift rates. In contrast, physical activity measurements of in situ individually caged G. roeseli showed they increased short-term activity levels in nights of complete darkness and decreased activity levels in brightly lit flumes. Both nocturnal and diurnal drift increased, and day drift rates were unexpectadly higher than nocturnal drift.

Mental simulation of drawing actions enhances delayed recall of a complex figure.

Science.gov (United States)

De Lucia, Natascia; Trojano, Luigi; Senese, Vincenzo Paolo; Conson, Massimiliano

2016-10-01

Motor simulation implies that the same motor representations involved in action execution are re-enacted during observation or imagery of actions. Neurofunctional data suggested that observation of letters or abstract paintings can elicit simulation of writing or drawing gestures. We performed four behavioural experiments on right-handed healthy participants to test whether observation of a static and complex geometrical figure implies re-enactment of drawing actions. In Experiment 1, participants had to observe the stimulus without explicit instruction (observation-only condition), while performing irrelevant finger tapping (motor dual task), or while articulating irrelevant verbal material (verbal dual task). Delayed drawing of the stimulus was less accurate in the motor dual-task (interfering with simulation of hand actions) than in verbal dual-task and observation-only conditions. In Experiment 2, delayed drawing in the observation only was as accurate as when participants encoded the stimulus by copying it; in both conditions, accuracy was higher than when participants were instructed to observe the stimulus to recall it later verbally (observe to recall), thus being discouraged from engaging motor simulation. In Experiment 3, delayed drawing was as accurate in the observation-only condition as when participants imagined copying the stimulus; accuracy in both conditions was higher than in the observe-to-recall condition. In Experiment 4, in the observe-only condition participants who observed the stimulus with their right arm hidden behind their back were significantly less accurate than participants who had their left arm hidden. These findings converge in suggesting that mere observation of a geometrical stimulus can activate motor simulation and re-enactment of drawing actions.

Integrated or dual vocational training focused on the operations of a nuclear power plant; La formacion profesional integrada y/o dual enfocada a la operativa de una central nuclear

Energy Technology Data Exchange (ETDEWEB)

Roca, F.

2014-10-01

Dual vocational training is understood to be all the mixed employment and training actions and initiatives, the purpose of which in the vocational qualification of workers in a system alternating a job in a company with the training activity received in the framework of the vocational training system for employment of the educational system. The dual vocational training that results from this mixed strategy is provided via the following modality: Shared training between the training center and the company, which consists of coparticipation to varying degrees in the teaching and learning processes in the company and the training center. (Author)

Low-level light therapy of the eye and brain

Directory of Open Access Journals (Sweden)

Rojas JC

2011-10-01

Full Text Available Julio C Rojas1,2, F Gonzalez-Lima1 1Departments of Psychology, Pharmacology and Toxicology, University of Texas at Austin, Austin, TX; 2Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA Abstract: Low-level light therapy (LLLT using red to near-infrared light energy has gained attention in recent years as a new scientific approach with therapeutic applications in ophthalmology, neurology, and psychiatry. The ongoing therapeutic revolution spearheaded by LLLT is largely propelled by progress in the basic science fields of photobiology and bioenergetics. This paper describes the mechanisms of action of LLLT at the molecular, cellular, and nervous tissue levels. Photoneuromodulation of cytochrome oxidase activity is the most important primary mechanism of action of LLLT. Cytochrome oxidase is the primary photoacceptor of light in the red to near-infrared region of the electromagnetic spectrum. It is also a key mitochondrial enzyme for cellular bioenergetics, especially for nerve cells in the retina and the brain. Evidence shows that LLLT can secondarily enhance neural metabolism by regulating mitochondrial function, intraneuronal signaling systems, and redox states. Current knowledge about LLLT dosimetry relevant for its hormetic effects on nervous tissue, including noninvasive in vivo retinal and transcranial effects, is also presented. Recent research is reviewed that supports LLLT potential benefits in retinal disease, stroke, neurotrauma, neurodegeneration, and memory and mood disorders. Since mitochondrial dysfunction plays a key role in neurodegeneration, LLLT has potential significant applications against retinal and brain damage by counteracting the consequences of mitochondrial failure. Upon transcranial delivery in vivo, LLLT induces brain metabolic and antioxidant beneficial effects, as measured by increases in cytochrome oxidase and superoxide dismutase activities. Increases

Dynamic operator actions analysis for inherently safe fast reactors and light water reactors

International Nuclear Information System (INIS)

Ho, V.; Apostolakis, G.

1988-01-01

A comparative dynamic human actions analysis of inherently safe fast reactors (ISFRs) and light water reactors (LWRs) in terms of systems response and estimated human error rates is presented. Brief overviews of the ISFR and LWR systems are given to illustrate the design differences. Key operator actions required by the ISFR reactor shutdown and decay heat removal systems are identified and are compared with those of the LWR. It is observed that, because of the passive nature of the ISFR safety-related systems, a large time window is available for operator actions during transient events. Furthermore, these actions are fewer in number, are less complex, and have lower error rates and less severe consequences than those of the LWRs. We expect the ISFR operator errors' contribution to risk is smaller (at least in the context of the existing human reliability models) than that of the LWRs. (author)

Intracellular delivery of potential therapeutic genes: prospects in cancer gene therapy.

Science.gov (United States)

Bakhtiar, Athirah; Sayyad, Mustak; Rosli, Rozita; Maruyama, Atsushi; Chowdhury, Ezharul H

2014-01-01

Conventional therapies for malignant cancer such as chemotherapy and radiotherapy are associated with poor survival rates owing to the development of cellular resistance to cancer drugs and the lack of targetability, resulting in unwanted adverse effects on healthy cells and necessitating the lowering of therapeutic dose with consequential lower efficacy of the treatment. Gene therapy employing different types of viral and non-viral carriers to transport gene(s) of interest and facilitating production of the desirable therapeutic protein(s) has tremendous prospects in cancer treatments due to the high-level of specificity in therapeutic action of the expressed protein(s) with diminished off-target effects, although cancer cell-specific delivery of transgene(s) still poses some challenges to be addressed. Depending on the potential therapeutic target genes, cancer gene therapy could be categorized into tumor suppressor gene replacement therapy, immune gene therapy and enzyme- or prodrug-based therapy. This review would shed light on the current progress of delivery of potentially therapeutic genes into various cancer cells in vitro and animal models utilizing a variety of viral and non-viral vectors.

pH/Ultrasound Dual-Responsive Gas Generator for Ultrasound Imaging-Guided Therapeutic Inertial Cavitation and Sonodynamic Therapy.

Science.gov (United States)

Feng, Qianhua; Zhang, Wanxia; Yang, Xuemei; Li, Yuzhen; Hao, Yongwei; Zhang, Hongling; Hou, Lin; Zhang, Zhenzhong

2018-03-01

Herein, a pH/ultrasound dual-responsive gas generator is reported, which is based on mesoporous calcium carbonate (MCC) nanoparticles by loading sonosensitizer (hematoporphyrin monomethyl ether (HMME)) and modifying surface hyaluronic acid (HA). After pinpointing tumor regions with prominent targeting efficiency, HMME/MCC-HA decomposes instantaneously under the cotriggering of tumoral inherent acidic condition and ultrasound (US) irradiation, concurrently accompanying with CO 2 generation and HMME release with spatial/temporal resolution. Afterward, the CO 2 bubbling and bursting effect under US stimulus results in cavitation-mediated irreversible cell necrosis, as well as the blood vessel destruction to further occlude the blood supply, providing a "bystander effect." Meanwhile, reactive oxygen species generated from HMME can target the apoptotic pathways for effective sonodynamic therapy. Thus, the combination of apoptosis/necrosis with multimechanisms consequently results in a remarkable antitumor therapeutic efficacy, simultaneously minimizing the side effects on major organs. Moreover, the echogenic property of CO 2 make the nanoplatform as a powerful ultrasound contrast agent to identify cancerous lesions. Based on the above findings, such all-in-one drug delivery platform of HMME/MCC-HA is utilized to provide the US imaging guidance for therapeutic inertial cavitation and sonodynamic therapy simultaneously, which highlights possibilities of advancing cancer theranostics in biomedical fields. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Therapeutic efficacy and mechanism of action of ethamsylate, a long-standing hemostatic agent.

Science.gov (United States)

Garay, Ricardo P; Chiavaroli, Carlo; Hannaert, Patrick

2006-01-01

Ethamsylate (2,5-dihydroxy-benzene-sulfonate diethylammonium salt) is a synthetic hemostatic drug indicated in cases of capillary bleeding. This review covers more than 40 years of intensive clinical and fundamental research with ethamsylate. First, we summarize the large medical literature concerning its clinical efficacy. Of these, well-controlled clinical trials clearly showed the therapeutic efficacy of ethamsylate in dysfunctional uterine bleeding, with the magnitude of blood-loss reduction being directly proportional to the severity of the menorrhagia. Other well-controlled clinical trials showed therapeutic efficacy of ethamsylate in periventricular hemorrhage in very low birth weight babies and surgical or postsurgical capillary bleeding. Second, we review the numerous investigations performed to elucidate the mechanism of action of ethamsylate. Ethamsylate acts on the first step of hemostasis by improving platelet adhesiveness and restoring capillary resistance. Recent studies showed that ethamsylate promotes P-selectin-dependent, platelet adhesive mechanisms. Finally, we compare ethamsylate with other recent hemostatic agents. It is suggested that the place of ethamsylate as a hemostatic agent is that of a mild but well-tolerated drug, particularly useful in dysfunctional uterine bleeding when contraception is not needed.

Naturally occurring immunomodulators with antitumor activity: An insight on their mechanisms of action.

Science.gov (United States)

Mohamed, Shimaa Ibrahim Abdelmonym; Jantan, Ibrahim; Haque, Md Areeful

2017-09-01

Natural products with immunomodulatory activity are widely used in treatment of many diseases including autoimmune diseases, inflammatory disorders in addition to cancer. They gained a great interest in the last decades as therapeutic agents since they provide inexpensive and less toxic products than the synthetic chemotherapeutic agents. Immunomodulators are the agents that have the ability to boost or suppress the host defense response that can be used as a prophylaxis as well as in combination with other therapeutic modalities. The anticancer activity of these immunomodulators is due to their anti-inflammatory, antioxidant, and induction of apoptosis, anti-angiogenesis, and anti-metastasis effect. These natural immunomodulators such as genistein, curcumin, and resveratrol can be used as prophylaxis against the initiation of cancer besides the inhibition of tumor growth and proliferation. Whereas, immunostimulants can elicit and activate humoral and cell-mediated immune responses against the tumor that facilitate the recognition and destruction of the already existing tumor. This review represents the recent studies on various natural immunomodulators with antitumor effects. We have focused on the relationship between their anticancer activity and immunomodulatory mechanisms. The mechanisms of action of various immunomodulators such as polyphenolic compounds, flavonoids, organosulfur compounds, capsaicin, vinca alkaloids, bromelain, betulinic acid and zerumbone, the affected cancerous cell lines in addition to the targeted molecules and transcriptional pathways have been review and critically analyzed. Copyright © 2017 Elsevier B.V. All rights reserved.

Dual role for plasminogen activator inhibitor type 1 as soluble and as matricellular regulator of epithelial alveolar cell wound healing.

Science.gov (United States)

Maquerlot, François; Galiacy, Stephane; Malo, Michel; Guignabert, Christophe; Lawrence, Daniel A; d'Ortho, Maria-Pia; Barlovatz-Meimon, Georgia

2006-11-01

Epithelium repair, crucial for restoration of alveolo-capillary barrier integrity, is orchestrated by various cytokines and growth factors. Among them keratinocyte growth factor plays a pivotal role in both cell proliferation and migration. The urokinase plasminogen activator (uPA) system also influences cell migration through proteolysis during epithelial repair. In addition, the complex formed by uPAR-uPA and matrix-bound plasminogen activator inhibitor type-1 (PAI-1) exerts nonproteolytic roles in various cell types. Here we present new evidence about the dual role of PAI-1 under keratinocyte growth factor stimulation using an in vitro repair model of rat alveolar epithelial cells. Besides proteolytic involvement of the uPA system, the availability of matrix-bound-PAI-1 is also required for an efficient healing. An unexpected decrease of healing was shown when PAI-1 activity was blocked. However, the proteolytic action of uPA and plasmin were still required. Moreover, immediately after wounding, PAI-1 was dramatically increased in the newly deposited matrix at the leading edge of wounds. We thus propose a dual role for PAI-1 in epithelial cell wound healing, both as a soluble inhibitor of proteolysis and also as a matrix-bound regulator of cell migration. Matrix-bound PAI-1 could thus be considered as a new member of the matricellular protein family.

Non-trivial self-dual gluon configurations in lattice QCD

International Nuclear Information System (INIS)

Bilson-Thompson, S.; Bowman, P.; Bonnet, F.; Leinweber, D.; Williams, A.; Dunne, G.

2000-01-01

Full text: We have investigated the smoothing of gauge fields in SU(3) using a variety of cooling algorithms. A topic of particular interest to such investigations is the behaviour of self-dual field configurations over a large number of cooling sweeps. It is well known that cooling based upon the standard Wilson action is affected by excessively large discretisation errors, leading in the long-term to trivial configurations. This has shifted the research emphasis onto improved actions, which are designed to minimise the discretisation errors that arise on the lattice. The cooling schemes we have investigated have been designed to eliminate O(a 2 ) and O(a 4 ) discretization errors producing an action accurate to order O(a 6 ). An analogously defined improved topological charge operator is used to investigate vacuum instanton dynamics. We used these operators to construct self-dual gluon configurations by cooling until the duality condition S/S 0 |Q| (where S 0 is the single instanton action and Q is the topological charge) is reached. As it is expected from theoretical grounds that Q is always an integer, a range of different actions and topological charge operators are assessed to determine which combination produced a result closest to what we would expect in the continuum. As our lattices have (untwisted) periodic boundary conditions we are particularly interested in investigating the relevance of the Nahm transformation to our results. This is a duality transformation which maps a self-dual SU(N) configuration with topological charge Q on the 4-torus to a self-dual SU(Q) configuration with topological charge N on the dual 4-torus. As there are no instanton solutions in SU(1), the Nahm transformation appears to preclude the existence of a |Q| = 1 self-dual solution on the 4-torus. We have investigated this on the lattice by finding |Q| = 1 configurations and assessing the behaviour of the action and the stability of the topological charge as they cool towards

Central as well as peripheral attentional bottlenecks in dual-task performance activate lateral prefrontal cortices

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Andre J Szameitat

2016-03-01

Full Text Available Human information processing suffers from severe limitations in parallel processing. In particular, when required to respond to two stimuli in rapid succession, processing bottlenecks may appear at central and peripheral stages of task processing. Importantly, it has been suggested that executive functions are needed to resolve the interference arising at such bottlenecks. The aims of the present study were to test whether central attentional limitations (i.e., bottleneck at the decisional response selection stage as well as peripheral limitations (i.e., bottleneck at response initiation both demand executive functions located in the lateral prefrontal cortex. For this, we re-analysed two previous studies, in which a total of 33 participants performed a dual-task according to the paradigm of the psychological refractory period (PRP during fMRI. In one study (N=17, the PRP task consisted of two two-choice response tasks known to suffer from a central bottleneck (CB group. In the other study (N=16, the PRP task consisted of two simple-response tasks known to suffer from a peripheral bottleneck (PB group. Both groups showed considerable dual-task costs in form of slowing of the second response in the dual-task (PRP effect. Imaging results are based on the subtraction of both single-tasks from the dual-task within each group. In the CB group, the bilateral middle frontal gyri and inferior frontal gyri were activated. Higher activation in these areas was associated with lower dual-task costs. In the PB group, the right middle frontal and inferior frontal gyrus were activated. Here, higher activation was associated with higher dual-task costs. In conclusion we suggest that central and peripheral bottlenecks both demand executive functions located in lateral prefrontal cortices. Differences between the CB and PB groups with respect to the exact prefrontal areas activated and the correlational patterns suggest that the executive functions resolving

Synthesis of the light/pH responsive polymer for immobilization of α-amylase

Energy Technology Data Exchange (ETDEWEB)

Yang, Long [Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi' an 710119 (China); Lei, Ming [School of Material Science and Engineering, Shaanxi Normal University, Xi' an 710119 (China); Zhao, Min [Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi' an 710119 (China); Yang, Hong [Basic Experimental Teaching Center, Shaanxi Normal University, Xi' an 710062 (China); Zhang, Hong; Li, Yan; Zhang, Kehu [Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi' an 710119 (China); Lei, Zhongli, E-mail: lzl2016@snnu.edu.cn [Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi' an 710119 (China)

2017-02-01

In this study, light/pH responsive methoxy poly (ethylene glycol)-(5-propargylether-2-nitrobenzyl bromoisobutyrate)-poly methylacrylic acid-b-polystyrene (mPEG-ONB-PMAA-b-PS) polymers were synthesized, and successfully utilized to fabricate micelles and immobilize α-amylase. The critical micelle concentrations (CMC) of the polymers were measured with Pyrene Fluorescent Probe Technique. The morphology and diameter of micelles were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS). In addition, the effects of pH, temperature and light-responsive on the catalytic activity were investigated. The optimized fabrication conditions of α-amylase-loaded micelles which α-amylase gave the higher activity were as follows: Immobilization time, 60 min; Immobilization temperature, 50 °C; enzyme concentration, 10 U mL{sup −1}; PBS buffer, pH = 5.4. α-Amylase immobilized in these micelles was much more stable than that free α-amylase. - Highlights: • Light/pH dual-responsive polymer mPEG-ONB-PMAA-b-PS was developed. • The polymer mPEG-ONB-PMAA-b-PS was characterized and utilized to immobilized α-amylase. • A systematic study of dual-responsive polymer influence on α-amylase active was performed.

A Superconducting Dual-Channel Photonic Switch.

Science.gov (United States)

Srivastava, Yogesh Kumar; Manjappa, Manukumara; Cong, Longqing; Krishnamoorthy, Harish N S; Savinov, Vassili; Pitchappa, Prakash; Singh, Ranjan

2018-06-05

The mechanism of Cooper pair formation and its underlying physics has long occupied the investigation into high temperature (high-T c ) cuprate superconductors. One of the ways to unravel this is to observe the ultrafast response present in the charge carrier dynamics of a photoexcited specimen. This results in an interesting approach to exploit the dissipation-less dynamic features of superconductors to be utilized for designing high-performance active subwavelength photonic devices with extremely low-loss operation. Here, dual-channel, ultrafast, all-optical switching and modulation between the resistive and the superconducting quantum mechanical phase is experimentally demonstrated. The ultrafast phase switching is demonstrated via modulation of sharp Fano resonance of a high-T c yttrium barium copper oxide (YBCO) superconducting metamaterial device. Upon photoexcitation by femtosecond light pulses, the ultrasensitive cuprate superconductor undergoes dual dissociation-relaxation dynamics, with restoration of superconductivity within a cycle, and thereby establishes the existence of dual switching windows within a timescale of 80 ps. Pathways are explored to engineer the secondary dissociation channel which provides unprecedented control over the switching speed. Most importantly, the results envision new ways to accomplish low-loss, ultrafast, and ultrasensitive dual-channel switching applications that are inaccessible through conventional metallic and dielectric based metamaterials. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Carrageenan activates monocytes via type-specific binding with interleukin-8: an implication for design of immuno-active biomaterials.

Science.gov (United States)

Chan, Weng-I; Zhang, Guangpan; Li, Xin; Leung, Chung-Hang; Ma, Dik-Lung; Dong, Lei; Wang, Chunming

2017-02-28

Polymers that can activate the immune system may become useful biomaterials tools, given that the mechanisms underlying their actions are well understood. Herein, we report a novel type of interaction between polymers and immune cells - in studying the influence of the three major types of carrageenan (CGN) polysaccharides on monocyte behaviour in vitro, we found only the λ-type induced monocyte adhesion and this action requires the presence of an adequate amount of serum. Further analyses indicated λ-CGN bound interleukin-8 (IL-8) in the serum and activated the cultured monocytes through an IL-8-dependent pathway. This is the first demonstration that a polymer, with a renowned immunostimulatory effect, activates the immune system via binding and harnessing the function of a specific cytokine in the microenvironment. This is a new mechanism underlying polymer-immunity interactions that may shed light on future design and application of biomaterials tools targeting the immune system for a wide variety of therapeutic applications.

A rewritable, reprogrammable, dual light-responsive polymer actuator

NARCIS (Netherlands)

Gelebart, A.H.; Mulder, D.J.; Vantomme, G.; Schenning, A.P.H.J.; Broer, D.J.

2017-01-01

We report on the fabrication of a rewritable and reprogrammable dual-photoresponsive liquid crystalline-based actuator containing an azomerocyanine dye that can be locally converted into the hydroxyazopyridinium form by acid treatment. Each dye absorbs at a different wavelength giving access to

Metabolic activity, urease production, antibiotic resistance and virulence in dual species biofilms of Staphylococcus epidermidis and Staphylococcus aureus

Science.gov (United States)

Vandecandelaere, Ilse; Van Nieuwerburgh, Filip; Deforce, Dieter

2017-01-01

In this paper, the metabolic activity in single and dual species biofilms of Staphylococcus epidermidis and Staphylococcus aureus isolates was investigated. Our results demonstrated that there was less metabolic activity in dual species biofilms compared to S. aureus biofilms. However, this was not observed if S. aureus and S. epidermidis were obtained from the same sample. The largest effect on metabolic activity was observed in biofilms of S. aureus Mu50 and S. epidermidis ET-024. A transcriptomic analysis of these dual species biofilms showed that urease genes and genes encoding proteins involved in metabolism were downregulated in comparison to monospecies biofilms. These results were subsequently confirmed by phenotypic assays. As metabolic activity is related to acid production, the pH in dual species biofilms was slightly higher compared to S. aureus Mu50 biofilms. Our results showed that S. epidermidis ET-024 in dual species biofilms inhibits metabolic activity of S. aureus Mu50, leading to less acid production. As a consequence, less urease activity is required to compensate for low pH. Importantly, this effect was biofilm-specific. Also S. aureus Mu50 genes encoding virulence-associated proteins (Spa, SplF and Dps) were upregulated in dual species biofilms compared to monospecies biofilms and using Caenorhabditis elegans infection assays, we demonstrated that more nematodes survived when co-infected with S. epidermidis ET-024 and S. aureus mutants lacking functional spa, splF or dps genes, compared to nematodes infected with S. epidermidis ET-024 and wild- type S. aureus. Finally, S. epidermidis ET-024 genes encoding resistance to oxacillin, erythromycin and tobramycin were upregulated in dual species biofilms and increased resistance was subsequently confirmed. Our data indicate that both species in dual species biofilms of S. epidermidis and S. aureus influence each other’s behavior, but additional studies are required necessary to elucidate the exact

Quercetin: A wonder bioflvonoid with therapeutic potential in disease management

Directory of Open Access Journals (Sweden)

Alka Gupta

2016-03-01

Full Text Available In the last decade, considerable efforts have been made to develop health promising nutritional supplements. Quercetin is a plant-derived bioflavonoid which is recently gaining scientific interest for its antioxidant free radical scavenging effects and anti-inflammatory properties. This wonder flavanol exhibits therapeutic potential in various ailments like cancer, coronary artery, asthma and alzheimer (neurodegeneration diseases. Additional clinical uses include treatment of inflammatory conditions like gout, pancreatitis and prostatitis. It has been extensively studied for its gastroprotective effects, anti-obesity action, immune booster, reducing risk of cataract and reduction of diabetic complications. The present review briefly discusses about biological activity, mechanism of action and therapeutic potential of quercetin in prevention and mitigation of diseases.

Brain activation during dual-task processing is associated with cardiorespiratory fitness and performance in older adults

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Chelsea N Wong

2015-08-01

Full Text Available Higher cardiorespiratory fitness is associated with better cognitive performance and enhanced brain activation. Yet, the extent to which cardiorespiratory fitness-related brain activation is associated with better cognitive performance is not well understood. In this cross-sectional study, we examined whether the association between cardiorespiratory fitness and executive function was mediated by greater prefrontal cortex activation in healthy older adults. Brain activation was measured during dual-task performance with functional magnetic resonance imaging in a sample of 128 healthy older adults (59-80 years. Higher cardiorespiratory fitness was associated with greater activation during dual-task processing in several brain areas including the anterior cingulate and supplementary motor cortex (ACC/SMA, thalamus and basal ganglia, right motor/somatosensory cortex and middle frontal gyrus, and left somatosensory cortex, controlling for age, sex, education, and gray matter volume. Of these regions, greater ACC/SMA activation mediated the association between cardiorespiratory fitness and dual-task performance. We provide novel evidence that cardiorespiratory fitness may support cognitive performance by facilitating brain activation in a core region critical for executive function.

A survey of dual active galactic nuclei in simulations of galaxy mergers: frequency and properties

Science.gov (United States)

Capelo, Pedro R.; Dotti, Massimo; Volonteri, Marta; Mayer, Lucio; Bellovary, Jillian M.; Shen, Sijing

2017-08-01

We investigate the simultaneous triggering of active galactic nuclei (AGN) in merging galaxies, using a large suite of high-resolution hydrodynamical simulations. We compute dual-AGN observability time-scales using bolometric, X-ray and Eddington-ratio thresholds, confirming that dual activity from supermassive black holes (BHs) is generally higher at late pericentric passages, before a merger remnant has formed, especially at high luminosities. For typical minor and major mergers, dual activity lasts ˜20-70 and ˜100-160 Myr, respectively. We also explore the effects of X-ray obscuration from gas, finding that the dual-AGN time decreases at most by a factor of ˜2, and of contamination from star formation. Using projected separations and velocity differences rather than three-dimensional quantities can decrease the dual-AGN time-scales by up to ˜4, and we apply filters that mimic current observational-resolution limitations. In agreement with observations, we find that for a sample of major and minor mergers hosting at least one AGN, the fraction harbouring dual AGN is ˜20-30 and ˜1-10 per cent, respectively. We quantify the effects of merger mass ratio (0.1 to 1), geometry (coplanar, prograde and retrograde, and inclined), disc gas fraction and BH properties, finding that the mass ratio is the most important factor, with the difference between minor and major mergers varying between factors of a few to orders of magnitude, depending on the luminosity and filter used. We also find that a shallow imaging survey will require very high angular resolution whereas a deep imaging survey will be less resolution-dependent.

Assessment of Dual Life Stage Antiplasmodial Activity of British Seaweeds

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Deniz Tasdemir

2013-10-01

Full Text Available Terrestrial plants have proven to be a prolific producer of clinically effective antimalarial drugs, but the antimalarial potential of seaweeds has been little explored. The main aim of this study was to assess the in vitro chemotherapeutical and prophylactic potential of the extracts of twenty-three seaweeds collected from the south coast of England against blood stage (BS and liver stage (LS Plasmodium parasites. The majority (14 of the extracts were active against BS of P. falciparum, with brown seaweeds Cystoseira tamariscifolia, C. baccata and the green seaweed Ulva lactuca being the most active (IC50s around 3 μg/mL. The extracts generally had high selectivity indices (>10. Eight seaweed extracts inhibited the growth of LS parasites of P. berghei without any obvious effect on the viability of the human hepatoma (Huh7 cells, and the highest potential was exerted by U. lactuca and red seaweeds Ceramium virgatum and Halopitys incurvus (IC50 values 14.9 to 28.8 μg/mL. The LS-active extracts inhibited one or more key enzymes of the malarial type-II fatty acid biosynthesis (FAS-II pathway, a drug target specific for LS. Except for the red seaweed Halopitys incurvus, all LS-active extracts showed dual activity versus both malarial intracellular stage parasites. This is the first report of LS antiplasmodial activity and dual stage inhibitory potential of seaweeds.

Parallel optical control of spatiotemporal neuronal spike activity using high-frequency digital light processingtechnology

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Jason eJerome

2011-08-01

Full Text Available Neurons in the mammalian neocortex receive inputs from and communicate back to thousands of other neurons, creating complex spatiotemporal activity patterns. The experimental investigation of these parallel dynamic interactions has been limited due to the technical challenges of monitoring or manipulating neuronal activity at that level of complexity. Here we describe a new massively parallel photostimulation system that can be used to control action potential firing in in vitro brain slices with high spatial and temporal resolution while performing extracellular or intracellular electrophysiological measurements. The system uses Digital-Light-Processing (DLP technology to generate 2-dimensional (2D stimulus patterns with >780,000 independently controlled photostimulation sites that operate at high spatial (5.4 µm and temporal (>13kHz resolution. Light is projected through the quartz-glass bottom of the perfusion chamber providing access to a large area (2.76 x 2.07 mm2 of the slice preparation. This system has the unique capability to induce temporally precise action potential firing in large groups of neurons distributed over a wide area covering several cortical columns. Parallel photostimulation opens up new opportunities for the in vitro experimental investigation of spatiotemporal neuronal interactions at a broad range of anatomical scales.

Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

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Danbo Yang

2010-12-01

Full Text Available The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(L-g-glutamylglutamine-paclitaxel nano-conjugate (PGG-PTX. PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic.

Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

International Nuclear Information System (INIS)

Yang, Danbo; Yu, Lei; Van, Sang

2010-01-01

The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(l-γ-glutamylglutamine)-paclitaxel nano-conjugate (PGG-PTX). PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic

Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

Energy Technology Data Exchange (ETDEWEB)

Yang, Danbo [Biomedical Engineering and Technology Institute, Institutes for Advanced Interdisciplinary Research, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062 (China); Yu, Lei, E-mail: yu-lei@gg.nitto.co.jp [Biomedical Engineering and Technology Institute, Institutes for Advanced Interdisciplinary Research, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062 (China); Biomedical Group, Nitto Denko Technical Corporation, 501 Via Del Monte, Oceanside, CA 92058 (United States); Van, Sang [Biomedical Group, Nitto Denko Technical Corporation, 501 Via Del Monte, Oceanside, CA 92058 (United States)

2010-12-23

The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(l-γ-glutamylglutamine)-paclitaxel nano-conjugate (PGG-PTX). PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic.

TNFSF14 (LIGHT Exhibits Inflammatory Activities in Lung Fibroblasts Complementary to IL-13 and TGF-β

Directory of Open Access Journals (Sweden)

Ricardo da Silva Antunes

2018-03-01

Full Text Available The cytokine TNFSF14 [homologous to Lymphotoxin, exhibits Inducible expression and competes with HSV Glycoprotein D for binding to HVEM, a receptor expressed on T lymphocytes (LIGHT] has been shown in mouse models to be important for development of lung tissue remodeling that is characteristic of asthma, idiopathic pulmonary fibrosis (IPF, and systemic sclerosis (SSc. However, its cellular targets are not fully delineated. In the present report, we show that LTβR and HVEM, the receptors for LIGHT, are constitutively expressed in primary human lung fibroblasts (HLFs. We asked whether LIGHT could promote inflammatory and remodeling-relevant activity in HLFs and how this was similar to, or distinct from, IL-13 or TGF-β, two cytokines strongly implicated in the pathogenesis of asthma, IPF, and SSc. Accumulation of myofibroblasts expressing alpha smooth muscle actin is a feature of lung inflammatory diseases. LIGHT promoted cell cycle progression and proliferation of HLFs, but not alpha smooth muscle actin expression. In contrast, TGF-β upregulated alpha smooth muscle actin but did not drive their proliferation. LIGHT also increased the gene or protein expression of a number of proinflammatory mediators, including ICAM-1 and VCAM-1, IL-6 and GM-CSF, the chemokines CCL5 and 20, and CXCL5, 11, and 12, and lung remodeling-associated proteinases MMP-9 and ADAM8. These were dependent on LTβR but not HVEM. LIGHT displayed overlapping and synergistic activities with IL-13 for a number of the activities, but LIGHT additionally enhanced the gene expression of several molecules, including the innate cytokines IL-33 and TSLP, which were not upregulated by IL-13. Our results highlight the varied and pleiotropic effects of LIGHT in HLFs. LIGHT might then be a therapeutic target for modulation of inflammation and remodeling associated with asthma and other similar diseases of the lung that involve fibroblasts.

Simultaneous surface and depth neural activity recording with graphene transistor-based dual-modality probes.

Science.gov (United States)

Du, Mingde; Xu, Xianchen; Yang, Long; Guo, Yichuan; Guan, Shouliang; Shi, Jidong; Wang, Jinfen; Fang, Ying

2018-05-15

Subdural surface and penetrating depth probes are widely applied to record neural activities from the cortical surface and intracortical locations of the brain, respectively. Simultaneous surface and depth neural activity recording is essential to understand the linkage between the two modalities. Here, we develop flexible dual-modality neural probes based on graphene transistors. The neural probes exhibit stable electrical performance even under 90° bending because of the excellent mechanical properties of graphene, and thus allow multi-site recording from the subdural surface of rat cortex. In addition, finite element analysis was carried out to investigate the mechanical interactions between probe and cortex tissue during intracortical implantation. Based on the simulation results, a sharp tip angle of π/6 was chosen to facilitate tissue penetration of the neural probes. Accordingly, the graphene transistor-based dual-modality neural probes have been successfully applied for simultaneous surface and depth recording of epileptiform activity of rat brain in vivo. Our results show that graphene transistor-based dual-modality neural probes can serve as a facile and versatile tool to study tempo-spatial patterns of neural activities. Copyright © 2018 Elsevier B.V. All rights reserved.

Synergistically enhanced photocatalytic hydrogen evolution performance of ZnCdS by co-loading graphene quantum dots and PdS dual cocatalysts under visible light

Science.gov (United States)

Wang, Fang; Su, Yanhong; Min, Shixiong; Li, Yanan; Lei, Yonggang; Hou, Jianhua

2018-04-01

Here, we report that the co-loading of graphene quantum dots (GQDs) and PdS dual cocatalysts on ZnCdS surface achieves a high efficiency photocatalytic H2 evolution under visible light (≥420 nm). The GQDs/ZnCdS/PdS photocatalyst was prepared by a facile two steps: hydrothermal coupling of GQDs on ZnCdS surface followed by an in-situ chemical deposition of PdS. The resulted GQDs/ZnCdS/PdS exhibits a H2 evolution rate of 517 μmol h-1, which is 15, 7, and 1.7 times higher than that of pure ZnCdS, GQDs/ZnCdS, and ZnCdS/PdS, respectively, demonstrating the synergistic effects of GQDs and PdS dual cocatalysts. A high apparent quantum efficiency (AQE) up to 22.4% can be achieved over GQDs/ZnCdS/PdS at 420 nm. GQDs/ZnCdS/PdS also has a relatively good stability. Such a considerable enhancement of photocatalytic activity was attributable to the co-loading of the GQDs and PdS as respective reduction and oxidation cocatalysts, leading to an efficient charge separation and surface reactions.

Dual Targeting of Intracellular Pathogenic Bacteria with a Cleavable Conjugate of Kanamycin and an Antibacterial Cell-Penetrating Peptide.

Science.gov (United States)

Brezden, Anna; Mohamed, Mohamed F; Nepal, Manish; Harwood, John S; Kuriakose, Jerrin; Seleem, Mohamed N; Chmielewski, Jean

2016-08-31

Bacterial infection caused by intracellular pathogens, such as Mycobacterium, Salmonella, and Brucella, is a burgeoning global health epidemic that necessitates urgent action. However, the therapeutic value of a number of antibiotics, including aminoglycosides, against intracellular pathogenic bacteria is compromised due to their inability to traverse eukaryotic membranes. For this significant problem to be addressed, a cleavable conjugate of the antibiotic kanamycin and a nonmembrane lytic, broad-spectrum antimicrobial peptide with efficient mammalian cell penetration, P14LRR, was prepared. This approach allows kanamycin to enter mammalian cells as a conjugate linked via a tether that breaks down in the reducing environment within cells. Potent antimicrobial activity of the P14KanS conjugate was demonstrated in vitro, and this reducible conjugate effectively cleared intracellular pathogenic bacteria within macrophages more potently than that of a conjugate lacking the disulfide moiety. Notably, successful clearance of Mycobacterium tuberculosis within macrophages was observed with the dual antibiotic conjugate, and Salmonella levels were significantly reduced in an in vivo Caenorhabditis elegans model.

Comparison of a wellpoint vacuum pump system to dual pump recovery system effectiveness for the extraction of light non-aqueous phase liquids

International Nuclear Information System (INIS)

Koll, C.S.; Palmerton, D.L. Jr.; Kunzel, R.G.

1994-01-01

The effectiveness of two light non-aqueous phase liquid (LNAPL) extraction systems is compared at a site in the Mid-New Jersey Atlantic Coastal Plains Region: an existing dual pump recovery system and a wellpoint vacuum pump system. Home heating oil was released to a shallow sand and gravel aquifer by a leaky underground distribution system in the early 1970s. Eight-inch-diameter dual pump recovery wells were used for the last nine years, to lower the water table and extract LNAPL at several spill sites located throughout a residential community of 1,500 homes. Several small LNAPL plumes still exist today with surface areas ranging from 400 ft 2 to over 28,000 ft 2 . LNAPL recovery peaked in 1985 using dual pump recovery systems, averaging 33 gallons per day (gpd). In 1987, four 24-inch wells were replaced by 11 8-inch-diameter recovery wells at six sites, and LNAPL recovery rates averaged 5 gpd. In recent years, the recovery of LNAPL has declined and when graphed, is asymptotic. In 1993, dual pump recovery of LNAPL averaged 0.3 gpd for all six sites

Dual stage active magnetic regenerator and method

Science.gov (United States)

Pecharsky, Vitalij K.; Gschneidner, Jr., Karl A.

1999-03-30

A dual stage active magnetic regenerator refrigerator as well as method using the Joule-Brayton thermodynamic cycle includes a high temperature stage refrigerant comprising DyAl.sub.2 or (Dy.sub.1-x Er.sub.x)Al.sub.2 where x is selected to be greater than 0 and less than about 0.3 in combination with a low temperature stage comprising (Dy.sub.1-x Er.sub.x)Al.sub.2 where x is selected to be greater than about 0.5 and less than 1 to provide significantly improved refrigeration efficiency in the liquefaction of gaseous hydrogen.

The nuclear receptor PPARγ as a therapeutic target for cerebrovascular and brain dysfunction in Alzheimer's disease

Directory of Open Access Journals (Sweden)

Nektaria Nicolakakis

2010-05-01

Full Text Available Peroxisome proliferator-activated receptors (PPARs are ligand-activated nuclear transcription factors that regulate peripheral lipid and glucose metabolism. Three subtypes make up the PPAR family (α, γ, β/δ, and synthetic ligands for PPARα (fibrates and PPARγ (Thiazolidinediones, TZDs are currently prescribed for the respective management of dyslipidemia and type 2 diabetes. In contrast to the well characterized action of PPARs in the periphery, little was known about the presence or function of these receptors in the brain and cerebral vasculature, until fairly recently. Indeed, research in the last decade has uncovered these receptors in most brain cell types, and has shown that their activation, particularly that of PPARγ, is implicated in normal brain and cerebrovascular physiology, and confers protection under pathological conditions. Notably, accumulating evidence has highlighted the therapeutic potential of PPARγ ligands in the treatment of brain disorders such as Alzheimer’s disease (AD, leading to the testing of the TZDs pioglitazone and rosiglitazone in AD clinical trials. This review will focus on the benefits of PPARγ agonists for vascular, neuronal and glial networks, and assess the value of these compounds as future AD therapeutics in light of evidence from transgenic mouse models and recent clinical trials.

Vicarious motor activation during action perception: beyond correlational evidence

Directory of Open Access Journals (Sweden)

Alessio eAvenanti

2013-05-01

Full Text Available Neurophysiological and imaging studies have shown that seeing the actions of other individuals brings about the vicarious activation of motor regions involved in performing the same actions. While this suggests a simulative mechanism mediating the perception of others’ actions, one cannot use such evidence to make inferences about the functional significance of vicarious activations. Indeed, a central aim in social neuroscience is to comprehend how vicarious activations allow the understanding of other people’s behavior, and this requires to use stimulation or lesion methods to establish causal links from brain activity to cognitive functions. In the present work we review studies investigating the effects of transient manipulations of brain activity or stable lesions in the motor system on individuals’ ability to perceive and understand the actions of others. We conclude there is now compelling evidence that neural activity in the motor system is critical for such cognitive ability. More research using causal methods, however, is needed in order to disclose the limits and the conditions under which vicarious activations are required to perceive and understand actions of others as well as their emotions and somatic feelings.

Development of Optically Active Nanostructures for Potential Applications in Sensing, Therapeutics and Imaging

Science.gov (United States)

Joshi, Padmanabh

Materials at nanoscale are finding manifold applications in the various fields like sensing, plasmonics, therapeutics, to mention a few. Large amount of development has taken place regarding synthesis and exploring the novel applications of the various types of nanomaterials like organic, inorganic and hybrid of both. Yet, it is believed that the full potential of different nanomaterials is yet to be fully established stimulating researchers to explore more in the field of nanotechnology. Building on the same premise, in the following studies we have developed the nanomaterials in the class of optically active nanoparticles. First part of the study we have successfully designed, synthesized, and characterized Ag-Fe3O4 nanocomposite substrate for potential applications in quantitative Surface Enhanced Raman Scattering (SERS) measurements. Quantitative SERS-based detection of dopamine was performed successfully. In subsequent study, facile, single-step synthesis of polyethyleneimine (PEI) coated lanthanide based NaYF4 (Yb, Er) nanoparticles was developed and their application as potential photodynamic therapy agent was studied using excitations by light in near infra-red and visible region. In the following and last study, synthesis and characterization of the conjugated polymer nanoparticles was attempted successfully. Functionalization of the conjugated nanoparticles, which is a bottleneck for their potential applications, was successfully performed by encapsulating them in the silica nanoparticles, surface of which was then functionalized by amine group. Three types of optically active nanoparticles were developed for potential applications in sensing, therapeutics and imaging.

Peculiarities of near-ultraviolet (365 nm) and visible light effects in Paramecium Caudatum cells

International Nuclear Information System (INIS)

Samoilova, K.A.; Sushchenko, N.B.

1977-01-01

After treatment with 365 nm or visible light Paramecium caudatum cells fail to divide and die shortly after irradiation; no death occurs long after irradiation, as well as after several cell cycles, unlike the situation after the action of 254 nm or 300-380 nm. Irradiation inhibits mainly the first cell cycle following which the recovery of cells starts. Thus no after-effects take place after the action of 365 nm and visible light, and the patterns of their effects are rather similar. The photoreactivation of damages induced by 365 nm is quite small, being about 2 times less than that for 254 nm and 300-380 nm. Similarity of the action of 254, 300-380, 365 nm and visible light was established by the stimulation of cell division by low doses and increase in viability of infusoria from cultures with low survival and depressed rate of multiplication. This effect of 365 nm is not eliminated by visible light; moreover, the latter promotes the 'therapeutic' effect of the 365 nm line. (author)

Hexahydroquinolines are antimalarial candidates with potent blood-stage and transmission-blocking activity.

Science.gov (United States)

Vanaerschot, Manu; Lucantoni, Leonardo; Li, Tao; Combrinck, Jill M; Ruecker, Andrea; Kumar, T R Santha; Rubiano, Kelly; Ferreira, Pedro E; Siciliano, Giulia; Gulati, Sonia; Henrich, Philipp P; Ng, Caroline L; Murithi, James M; Corey, Victoria C; Duffy, Sandra; Lieberman, Ori J; Veiga, M Isabel; Sinden, Robert E; Alano, Pietro; Delves, Michael J; Lee Sim, Kim; Winzeler, Elizabeth A; Egan, Timothy J; Hoffman, Stephen L; Avery, Vicky M; Fidock, David A

2017-10-01

Antimalarial compounds with dual therapeutic and transmission-blocking activity are desired as high-value partners for combination therapies. Here, we report the identification and characterization of hexahydroquinolines (HHQs) that show low nanomolar potency against both pathogenic and transmissible intra-erythrocytic forms of the malaria parasite Plasmodium falciparum. This activity translates into potent transmission-blocking potential, as shown by in vitro male gamete formation assays and reduced oocyst infection and prevalence in Anopheles mosquitoes. In vivo studies illustrated the ability of lead HHQs to suppress Plasmodium berghei blood-stage parasite proliferation. Resistance selection studies, confirmed by CRISPR-Cas9-based gene editing, identified the digestive vacuole membrane-spanning transporter PfMDR1 (P. falciparum multidrug resistance gene-1) as a determinant of parasite resistance to HHQs. Haemoglobin and haem fractionation assays suggest a mode of action that results in reduced haemozoin levels and might involve inhibition of host haemoglobin uptake into intra-erythrocytic parasites. Furthermore, parasites resistant to HHQs displayed increased susceptibility to several first-line antimalarial drugs, including lumefantrine, confirming that HHQs have a different mode of action to other antimalarials drugs for which PfMDR1 is known to confer resistance. This work evokes therapeutic strategies that combine opposing selective pressures on this parasite transporter as an approach to countering the emergence and transmission of multidrug-resistant P. falciparum malaria.

Hexahydroquinolines are Antimalarial Candidates with Potent Blood Stage and Transmission-Blocking Activity

Science.gov (United States)

Vanaerschot, Manu; Lucantoni, Leonardo; Li, Tao; Combrinck, Jill M.; Ruecker, Andrea; Kumar, T.R. Santha; Rubiano, Kelly; Ferreira, Pedro E.; Siciliano, Giulia; Gulati, Sonia; Henrich, Philipp P.; Ng, Caroline L.; Murithi, James M.; Corey, Victoria C.; Duffy, Sandra; Lieberman, Ori J.; Veiga, M. Isabel; Sinden, Robert E.; Alano, Pietro; Delves, Michael J.; Sim, Kim Lee; Winzeler, Elizabeth A.; Egan, Timothy J.; Hoffman, Stephen L.; Avery, Vicky M.; Fidock, David A.

2017-01-01

Antimalarial compounds with dual therapeutic and transmission-blocking activity are desired as high-value partners for combination therapies. Here, we report the identification and characterization of hexahydroquinolines (HHQs) that show low nanomolar potency against both pathogenic and transmissible intra-erythrocytic forms of the malaria parasite Plasmodium falciparum. This activity translates into potent transmission-blocking potential, as shown by in vitro male gamete formation assays and reduced oocyst infection and prevalence in Anopheles mosquitoes. In vivo studies illustrated the ability of lead HHQs to suppress P. berghei blood-stage parasite proliferation. Resistance selection studies, confirmed by CRISPR/Cas9-based gene editing, identified the digestive vacuole membrane-spanning transporter PfMDR1 as a determinant of parasite resistance to HHQs. Hemoglobin and heme fractionation assays suggest a mode of action that results in reduced hemozoin levels and might involve inhibition of host hemoglobin uptake into intra-erythrocytic parasites. Furthermore, parasites resistant to HHQs displayed increased susceptibility to several first-line antimalarial drugs including lumefantrine, confirming that HHQs have a different mode of action than other antimalarials drugs for which PfMDR1 is known to confer resistance. This work evokes therapeutic strategies that combine opposing selective pressures on this parasite transporter as an approach to countering the emergence and transmission of multidrug-resistant P. falciparum malaria. PMID:28808258

Cannabis and endocannabinoid modulators: Therapeutic promises and challenges

Science.gov (United States)

Grant, Igor; Cahn, B. Rael

2008-01-01

The discovery that botanical cannabinoids such as delta-9 tetrahydrocannabinol exert some of their effect through binding specific cannabinoid receptor sites has led to the discovery of an endocannabinoid signaling system, which in turn has spurred research into the mechanisms of action and addiction potential of cannabis on the one hand, while opening the possibility of developing novel therapeutic agents on the other. This paper reviews current understanding of CB1, CB2, and other possible cannabinoid receptors, their arachidonic acid derived ligands (e.g. anandamide; 2 arachidonoyl glycerol), and their possible physiological roles. CB1 is heavily represented in the central nervous system, but is found in other tissues as well; CB2 tends to be localized to immune cells. Activation of the endocannabinoid system can result in enhanced or dampened activity in various neural circuits depending on their own state of activation. This suggests that one function of the endocannabinoid system may be to maintain steady state. The therapeutic action of botanical cannabis or of synthetic molecules that are agonists, antagonists, or which may otherwise modify endocannabinoid metabolism and activity indicates they may have promise as neuroprotectants, and may be of value in the treatment of certain types of pain, epilepsy, spasticity, eating disorders, inflammation, and possibly blood pressure control. PMID:18806886

Comparing double string theory actions

International Nuclear Information System (INIS)

De Angelis, L.; Gionti, S.J.G.; Marotta, R.; Pezzella, F.

2014-01-01

Aimed to a deeper comprehension of a manifestly T-dual invariant formulation of string theory, in this paper a detailed comparison between the non-covariant action proposed by Tseytlin and the covariant one proposed by Hull is done. These are obtained by making both the string coordinates and their duals explicitly appear, on the same footing, in the world-sheet action, so “doubling” the string coordinates along the compact dimensions. After a discussion on the nature of the constraints in both the models and the relative quantization, it results that the string coordinates and their duals behave like “non-commuting” phase space coordinates but their expressions in terms of Fourier modes generate the oscillator algebra of the standard bosonic string. A proof of the equivalence of the two formulations is given. Furthermore, open-string solutions are also discussed

Comparing double string theory actions

Energy Technology Data Exchange (ETDEWEB)

De Angelis, L. [Dipartimento di Fisica, Università degli Studi “Federico II” di Napoli,Complesso Universitario Monte S. Angelo ed. 6, via Cintia, 80126 Napoli (Italy); Gionti, S.J.G. [Specola Vaticana, Vatican City, V-00120, Vatican City State and Vatican Observatory Research Group, Steward Observatory, The University Of Arizona, 933 North Cherry Avenue, Tucson, Arizona 85721 (United States); Marotta, R.; Pezzella, F. [Istituto Nazionale di Fisica Nucleare, Sezione di Napoli,Complesso Universitario di Monte S. Angelo ed. 6, via Cintia, 80126 Napoli (Italy)

2014-04-28

Aimed to a deeper comprehension of a manifestly T-dual invariant formulation of string theory, in this paper a detailed comparison between the non-covariant action proposed by Tseytlin and the covariant one proposed by Hull is done. These are obtained by making both the string coordinates and their duals explicitly appear, on the same footing, in the world-sheet action, so “doubling” the string coordinates along the compact dimensions. After a discussion on the nature of the constraints in both the models and the relative quantization, it results that the string coordinates and their duals behave like “non-commuting” phase space coordinates but their expressions in terms of Fourier modes generate the oscillator algebra of the standard bosonic string. A proof of the equivalence of the two formulations is given. Furthermore, open-string solutions are also discussed.

A dual Lewis base activation strategy for enantioselective carbene-catalyzed annulations.

Science.gov (United States)

Izquierdo, Javier; Orue, Ane; Scheidt, Karl A

2013-07-24

A dual activation strategy integrating N-heterocyclic carbene (NHC) catalysis and a second Lewis base has been developed. NHC-bound homoenolate equivalents derived from α,β-unsaturated aldehydes combine with transient reactive o-quinone methides in an enantioselective formal [4 + 3] fashion to access 2-benzoxopinones. The overall approach provides a general blueprint for the integration of carbene catalysis with additional Lewis base activation modes.

Model predictive control for a dual active bridge inverter with a floating bridge

OpenAIRE

Chowdhury, Shajjad; Wheeler, Patrick W.; Gerada, C.; Patel, Chintan

2016-01-01

This paper presents a Model Predictive Control technique applied to a dual active bridge inverter where one of the bridges is floating. The proposed floating bridge topology eliminates the need for isolation transformer in a dual inverter system and therefore reduces the size, weight and losses in the system. To achieve multilevel output voltage waveforms the floating inverter DC link capacitor is charged to the half of the main DC link voltage. A finite-set Model Predictive Control technique...

Nuclear piping criteria for Advanced Light-Water Reactors, Volume 1--Failure mechanisms and corrective actions

International Nuclear Information System (INIS)

Anon.

1993-01-01

This WRC Bulletin concentrates on the major failure mechanisms observed in nuclear power plant piping during the past three decades and on corrective actions taken to minimize or eliminate such failures. These corrective actions are applicable to both replacement piping and the next generation of light-water reactors. This WRC Bulletin was written with the objective of meeting a need for piping criteria in Advanced Light-Water Reactors, but there is application well beyond the LWR industry. This Volume, in particular, is equally applicable to current nuclear power plants, fossil-fueled power plants, and chemical plants including petrochemical. Implementation of the recommendations for mitigation of specific problems should minimize severe failures or cracking and provide substantial economic benefit. This volume uses a case history approach to high-light various failure mechanisms and the corrective actions used to resolve such failures. Particular attention is given to those mechanisms leading to severe piping failures, where severe denotes complete severance, large ''fishmouth'' failures, or long throughwall cracks releasing a minimum of 50 gpm. The major failure mechanisms causing severe failure are erosion-corrosion and vibrational fatigue. Stress corrosion cracking also has been a common problem in nuclear piping systems. In addition thermal fatigue due to mixing-tee and to thermal stratification also is discussed as is microbiologically-induced corrosion. Finally, water hammer, which represents the ultimate in internally-generated dynamic high-energy loads, is discussed

RBEOER: a FORTRAN program for the computation of RBEs, OERs, survival ratios, and the effects of fractionation using the theory of dual radiation action

International Nuclear Information System (INIS)

Zaider, M.; Dicello, J.F.

1978-05-01

The computer code RBEOER calculates RBEs, OERs and survival curves as a function of the dose delivered to a biological system and the temporal distribution of the dose (fractionation). The method of calculation is based on the theory of dual radiation action. The basic formalism and the input parameters are described. A sample output is presented

Single-species versus dual-species probiotic supplementation as an emerging therapeutic strategy for obesity.

Science.gov (United States)

Karimi, G; Jamaluddin, R; Mohtarrudin, N; Ahmad, Z; Khazaai, H; Parvaneh, M

2017-10-01

Recent studies have reported beneficial effects of specific probiotics on obesity. However, the difference in the anti-obesity effects of probiotics as single species and dual species is still uncertain. Therefore, we aimed to compare the efficacy of single and dual species of bacteria on markers of obesity in high-fat diet-induced obese rats. A total of 40 male Sprague-Dawley rats were assigned to one of five groups of varying diets as follows: standard diet, high fat diet (HFD), HFD supplemented with Lactobacillus casei strain Shirota, HFD supplemented with Bifidobacterium longum and HFD supplemented with a mixture of these two bacterial species. After 15 weeks of supplementation, the animals were examined for changes in body weight, body fat, total count of bacteria in fecal, blood serum lipid profile, leptin, adiponectin and inflammatory biomarkers. Histological analysis of the liver and adipose tissue was performed and the hepatic mRNA expression levels of genes related to lipid metabolism were measured. It was found that probiotic supplementation of either B. longum or a mixture of B. longum and LcS bacteria significantly reduced weight and triglycerides in the HFD groups. Supplementation of B. longum bacteria showed better results in terms of modulating leptin level, fat mass, adipocyte size and lipoprotein lipase expression, as well as increasing adiponectin and peroxisome proliferator-activated receptors-γ expression compared to dual species of bacteria. No significant differences were observed in the total count of fecal bacteria, glucose and inflammatory biomarker levels between supplemented groups. B. longum supplementation in obesity was more beneficial in metabolic profile changes than the mixture species. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B

Winding design of series AC inductor for dual active bridge converters

DEFF Research Database (Denmark)

Shen, Zhan; Wang, Huai; Shen, Yanfeng

2018-01-01

The ac resistance and parasitic capacitance of the inductor are the primary considerations in the winding design for the dual-active bridge converter (DAB). They are dependent of up to four independent structure variables. The interactive restrictions between those variables makes the design diff...

pH Dependent Antimicrobial Peptides and Proteins, Their Mechanisms of Action and Potential as Therapeutic Agents

Directory of Open Access Journals (Sweden)

Erum Malik

2016-11-01

Full Text Available Antimicrobial peptides (AMPs are potent antibiotics of the innate immune system that have been extensively investigated as a potential solution to the global problem of infectious diseases caused by pathogenic microbes. A group of AMPs that are increasingly being reported are those that utilise pH dependent antimicrobial mechanisms, and here we review research into this area. This review shows that these antimicrobial molecules are produced by a diverse spectrum of creatures, including vertebrates and invertebrates, and are primarily cationic, although a number of anionic examples are known. Some of these molecules exhibit high pH optima for their antimicrobial activity but in most cases, these AMPs show activity against microbes that present low pH optima, which reflects the acidic pH generally found at their sites of action, particularly the skin. The modes of action used by these molecules are based on a number of major structure/function relationships, which include metal ion binding, changes to net charge and conformational plasticity, and primarily involve the protonation of histidine, aspartic acid and glutamic acid residues at low pH. The pH dependent activity of pore forming antimicrobial proteins involves mechanisms that generally differ fundamentally to those used by pH dependent AMPs, which can be described by the carpet, toroidal pore and barrel-stave pore models of membrane interaction. A number of pH dependent AMPs and antimicrobial proteins have been developed for medical purposes and have successfully completed clinical trials, including kappacins, LL-37, histatins and lactoferrin, along with a number of their derivatives. Major examples of the therapeutic application of these antimicrobial molecules include wound healing as well as the treatment of multiple cancers and infections due to viruses, bacteria and fungi. In general, these applications involve topical administration, such as the use of mouth washes, cream formulations

Enhanced activation of motor execution networks using action observation combined with imagination of lower limb movements.

Directory of Open Access Journals (Sweden)

Michael Villiger

Full Text Available The combination of first-person observation and motor imagery, i.e. first-person observation of limbs with online motor imagination, is commonly used in interactive 3D computer gaming and in some movie scenes. These scenarios are designed to induce a cognitive process in which a subject imagines himself/herself acting as the agent in the displayed movement situation. Despite the ubiquity of this type of interaction and its therapeutic potential, its relationship to passive observation and imitation during observation has not been directly studied using an interactive paradigm. In the present study we show activation resulting from observation, coupled with online imagination and with online imitation of a goal-directed lower limb movement using functional MRI (fMRI in a mixed block/event-related design. Healthy volunteers viewed a video (first-person perspective of a foot kicking a ball. They were instructed to observe-only the action (O, observe and simultaneously imagine performing the action (O-MI, or imitate the action (O-IMIT. We found that when O-MI was compared to O, activation was enhanced in the ventralpremotor cortex bilaterally, left inferior parietal lobule and left insula. The O-MI and O-IMIT conditions shared many activation foci in motor relevant areas as confirmed by conjunction analysis. These results show that (i combining observation with motor imagery (O-MI enhances activation compared to observation-only (O in the relevant foot motor network and in regions responsible for attention, for control of goal-directed movements and for the awareness of causing an action, and (ii it is possible to extensively activate the motor execution network using O-MI, even in the absence of overt movement. Our results may have implications for the development of novel virtual reality interactions for neurorehabilitation interventions and other applications involving training of motor tasks.

Interdisciplinary Action in Halls of EJA: the projects work in the light of focus-cultural history

Directory of Open Access Journals (Sweden)

Cyntia Graziella Guizelim Simões Girotto

2009-11-01

Full Text Available This article aims to discuss the organization of work teaching in classrooms of Pejão (Program of Education for Youth and Adult - Unesp - Linda through the Work Projects, which underlie actions from the perspective of interdisciplinary Theory History-Culture. Pointing to the pedagogical implications of this conception of education, considering the formation of educating young adults and forth the use of time and space for education, production of knowledge, the procedure to information given to school subjects, the development / implementation / development / evaluation of projects of interdisciplinary work in the light of the focus vygotiskiano. Therefore, our gaze is theoretical and methodological back-up for a particular context: the classes of its shares in EJA interdisciplinary. Discuss such issues as follows: the first section, we present the general theory, discussing key concepts such as mediation, activity, learning, development, and then inserted the actions of students and educators of EJA. In a second section, we draw some lessons of that theory, to (re present and (re thinking projects in the EJA, resignified and resizing them by vygotiskiano bias.

Partially massless higher-spin theory II: one-loop effective actions

Energy Technology Data Exchange (ETDEWEB)

Brust, Christopher [Perimeter Institute for Theoretical Physics,31 Caroline St. N, Waterloo, Ontario, N2L 2Y5 (Canada); Hinterbichler, Kurt [CERCA, Department of Physics, Case Western Reserve University,10900 Euclid Ave, Cleveland, OH, 44106 (United States)

2017-01-30

We continue our study of a generalization of the D-dimensional linearized Vasiliev higher-spin equations to include a tower of partially massless (PM) fields. We compute one-loop effective actions by evaluating zeta functions for both the “minimal” and “non-minimal” parity-even versions of the theory. Specifically, we compute the log-divergent part of the effective action in odd-dimensional Euclidean AdS spaces for D=7 through 19 (dual to the a-type conformal anomaly of the dual boundary theory), and the finite part of the effective action in even-dimensional Euclidean AdS spaces for D=4 through 8 (dual to the free energy on a sphere of the dual boundary theory). We pay special attention to the case D=4, where module mixings occur in the dual field theory and subtlety arises in the one-loop computation. The results provide evidence that the theory is UV complete and one-loop exact, and we conjecture and provide evidence for a map between the inverse Newton’s constant of the partially massless higher-spin theory and the number of colors in the dual CFT.

Partially massless higher-spin theory II: one-loop effective actions

International Nuclear Information System (INIS)

Brust, Christopher; Hinterbichler, Kurt

2017-01-01

We continue our study of a generalization of the D-dimensional linearized Vasiliev higher-spin equations to include a tower of partially massless (PM) fields. We compute one-loop effective actions by evaluating zeta functions for both the “minimal” and “non-minimal” parity-even versions of the theory. Specifically, we compute the log-divergent part of the effective action in odd-dimensional Euclidean AdS spaces for D=7 through 19 (dual to the a-type conformal anomaly of the dual boundary theory), and the finite part of the effective action in even-dimensional Euclidean AdS spaces for D=4 through 8 (dual to the free energy on a sphere of the dual boundary theory). We pay special attention to the case D=4, where module mixings occur in the dual field theory and subtlety arises in the one-loop computation. The results provide evidence that the theory is UV complete and one-loop exact, and we conjecture and provide evidence for a map between the inverse Newton’s constant of the partially massless higher-spin theory and the number of colors in the dual CFT.

[Dual action of vitamin C versus degradation and supplementation].

Science.gov (United States)

Kaliś, Katarzyna

2015-11-17

The article discusses vitamin C from the point of view of its supplementation with food and in the form of oral supplements. The dual action of vitamin C is connected with the presence of oxygen, which may reduce the amount of the vitamin in food products, influence thermal resistance, cause degradation and show an antioxidation effect. Vitamin C stimulates the immune cells and collagen synthesis. It may protect the LDL fraction against oxidation, and therefore it is interesting for cosmetology, rheumatology, immunology and dietetics. The latest research with respect to vitamin C proved that it has the ability to dissolve neurotoxic senile plaques. Equally effective in the treatment of Alzheimer's disease is the oxidised form of vitamin C, i.e. dehydroascorbic acid. Vitamin C may be used in a combined vitamin E supplementation to avoid the pro-oxidative effect and reduce the risk of diabetes mellitus type 2 complications. In the review there is a description of the types of vitamin C degradation depending on a specific factor such as pH, temperature, oxygen, enzyme and the impact of diet on the quantity of the supplied vitamin. The literature data confirmed the positive influence of vitamin C as an addition to food. The last part of the article presents the methods of vitamin C protection used in food processing technology and of determining its content in food products. Additionally, the article describes the problems related to vitamin C oxidation processes during food processing and storage. The presented research results indicate that an adequate diet contains a sufficient amount of vitamin C for healthy people. In the case of chronic patients it is better to use supplementation.

The dual of the Carroll-Field-Jackiw model

International Nuclear Information System (INIS)

Guimaraes, M.S.; Grigorio, L.; Wotzasek, C.

2006-01-01

In this work we apply different duality techniques, both the dual projection, based on the soldering formalism and the master action, in order to obtain and study the dual description of the Carroll- Field-Jackiw model [1], a theory with a Chern-Simons-like explicitly Lorentz and CPT violating term, including the interaction with external charges. This Maxwell-Chern-Simons-like model may be rewritten in terms of the interacting modes of a massless scalar model and a topologically massive model [2], that are mapped, through duality, into interacting massless Maxwell and massive self-dual modes [3]. It is also shown that these dual modes might be represented into an unified rank-two self-dual model that represents the direct dual of the vector Maxwell-Chern-Simons-like model

Translocation of labelled assimilates, ion uptake and nucleic acids contents in zea mays plants as influenced by application of the herbicide dual and the bioregulaators GA3 and kinetin

International Nuclear Information System (INIS)

Hassanein, R.AA.; Khodary, S.E.A.; Abdel-Aziz, S.M.

2001-01-01

Maize seedlings, grown hydroponic for one month, were undertaken o investigate the effect of dual (metolachlor), bio regulators (GA 3 and kinetin) and their interaction with dual on translocation rate of assimilates, nucleic acids content. ion uptake and the activities of protease and nitrate reductase enzymes. Dual at all concentrations decreased the rate of assimilates translocation and nucleic acids levels. Also reduction in the ability of the treated plants to absorb ions from the growth medium as well as the activities of nitrate reductase and protease enzymes were retarded upon dual application. The results also revealed that treatment with either GA 3 or kinetin in combination with dual, reversed the adverse action of the herbicide on zea mays plants

Molecular substrates of action control in cortico-striatal circuits.

Science.gov (United States)

Shiflett, Michael W; Balleine, Bernard W

2011-09-15

The purpose of this review is to describe the molecular mechanisms in the striatum that mediate reward-based learning and action control during instrumental conditioning. Experiments assessing the neural bases of instrumental conditioning have uncovered functional circuits in the striatum, including dorsal and ventral striatal sub-regions, involved in action-outcome learning, stimulus-response learning, and the motivational control of action by reward-associated cues. Integration of dopamine (DA) and glutamate neurotransmission within these striatal sub-regions is hypothesized to enable learning and action control through its role in shaping synaptic plasticity and cellular excitability. The extracellular signal regulated kinase (ERK) appears to be particularly important for reward-based learning and action control due to its sensitivity to combined DA and glutamate receptor activation and its involvement in a range of cellular functions. ERK activation in striatal neurons is proposed to have a dual role in both the learning and performance factors that contribute to instrumental conditioning through its regulation of plasticity-related transcription factors and its modulation of intrinsic cellular excitability. Furthermore, perturbation of ERK activation by drugs of abuse may give rise to behavioral disorders such as addiction. Copyright © 2011 Elsevier Ltd. All rights reserved.

When dual identity becomes a liability: identity and political radicalism among migrants.

Science.gov (United States)

Simon, Bernd; Reichert, Frank; Grabow, Olga

2013-03-01

This article examines the role of dual identity in political radicalism among migrants. Dual identity is defined as identification with both one's ethnocultural minority in-group and one's society of residence. We employed a longitudinal research design using members of the two largest migrant groups in Germany (Turkish migrants and Russian migrants) as participants. We reasoned that when dual identity is burdened with incompatibility between component identifications, it may foster controversial or even destructive forms of political mobilization, such as radicalism. Multiple regression analysis controlling for other influences confirmed the hypothesized moderated relationship between dual identification and sympathy for radical action. When accompanied by high, as opposed to low, perceived identity incompatibility, dual identification predicted increases in sympathy for radical action among both Turkish migrants and Russian migrants. The implications for public life in ethnically and culturally heterogeneous societies are discussed.

Integrated or dual vocational training focused on the operations of a nuclear power plant

International Nuclear Information System (INIS)

Roca, F.

2014-01-01

Dual vocational training is understood to be all the mixed employment and training actions and initiatives, the purpose of which in the vocational qualification of workers in a system alternating a job in a company with the training activity received in the framework of the vocational training system for employment of the educational system. The dual vocational training that results from this mixed strategy is provided via the following modality: Shared training between the training center and the company, which consists of coparticipation to varying degrees in the teaching and learning processes in the company and the training center. (Author)

Biological and therapeutic activities, and anticancer properties of curcumin.

Science.gov (United States)

Perrone, Donatella; Ardito, Fatima; Giannatempo, Giovanni; Dioguardi, Mario; Troiano, Giuseppe; Lo Russo, Lucio; DE Lillo, Alfredo; Laino, Luigi; Lo Muzio, Lorenzo

2015-11-01

Curcumin (diferuloylmethane) is a polyphenol derived from the Curcuma longa plant. Curcumin has been used extensively in Ayurvedic medicine, as it is nontoxic and exhibits a variety of therapeutic properties, including antioxidant, analgesic, anti-inflammatory and antiseptic activities. Recently, certain studies have indicated that curcumin may exert anticancer effects in a variety of biological pathways involved in mutagenesis, apoptosis, tumorigenesis, cell cycle regulation and metastasis. The present study reviewed previous studies in the literature, which support the therapeutic activity of curcumin in cancer. In addition, the present study elucidated a number of the challenges concerning the use of curcumin as an adjuvant chemotherapeutic agent. All the studies reviewed herein suggest that curcumin is able to exert anti-inflammatory, antiplatelet, antioxidative, hepatoprotective and antitumor activities, particularly against cancers of the liver, skin, pancreas, prostate, ovary, lung and head neck, as well as having a positive effect in the treatment of arthritis.

STANDARDIZATION OF CUPPING THERAPY POINTS AND MECHANISM OF ACTION IN THE LIGHT OF SCIENCE

OpenAIRE

Dr. Izharul Hasan

2018-01-01

Now a day’s cupping therapy is an established therapeutic modality among Indian system of medicine as well as worldwide. Inspite of that, standard operative procedure (SOPs) for cupping therapy is yet to develop. In this paper author comprises the possible indications of cupping therapy along with procedures, application points, safety concerns, historical perspective, surgical operative standards described in traditional system of medicine as well as in the light of science. Cupping may be d...

Light-regulation of enzyme activity in anacystis nidulans (Richt.).

Science.gov (United States)

Duggan, J X; Anderson, L E

1975-01-01

The effect of light on the levels of activity of six enzymes which are light-modulated in higher plants was examined in the photosynthetic procaryot Anacystis nidulans. Ribulose-5-phosphate kinase (EC 2.7.1.19) was found to be light-activated in vivo and dithiothreitol-activated in vitro while glucose-6-phosphate dehydrogenase (EC 1.1.1.49) was light-inactivated and dithiothreitol-inactivated. The enzymes fructose-1,6-diphosphate phosphatase (EC 3.1.3.11), sedoheptulose-1,7-diphosphate phosphatase, NAD- and NADP-linked glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.12; EC 1.2.1.13) were not affected by light treatment of the intact algae, but sedoheptulose-diphosphate phosphatase and the glyceraldehyde-3-phosphate dehydrogenases were dithiothreitol-activated in crude extracts. Light apparently controls the activity of the reductive and oxidative pentose phosphate pathway in this photosynthetic procaryot as in higher plants, through a process which probably involves reductive modulation of enzyme activity.

The lipid dependence of melittin action investigated by dual-color fluorescence burst analysis

NARCIS (Netherlands)

Bogaart, Geert van den; Mika, Jacek T.; Krasnikov, Viktor; Poolman, Bert

Dual-color fluorescence-burst analysis was used to study melittin-induced leakage of macromolecules from liposomes of various lipid compositions. To perform dual-color fluorescence-burst analysis, fluorescently labeled size-marker molecules were encapsulated into liposomes, labeled with a second

Dual-task performance involving hand dexterity and cognitive tasks and daily functioning in people with schizophrenia: a pilot study.

Science.gov (United States)

Lin, Keh-chung; Wu, Yi-fang; Chen, I-chen; Tsai, Pei-luen; Wu, Ching-yi; Chen, Chia-ling

2015-01-01

This study investigated separate and concurrent performance on cognitive and hand dexterity tasks and the relationship to daily functioning in 16 people with schizophrenia and 16 healthy control participants. Participants performed the Purdue Pegboard Test and the Serial Seven Subtraction Test under single- and dual-task conditions and completed two daily functioning evaluations. The hand dexterity of all participants declined in the dual-task condition, but the discrepancy between single-task and dual-task hand dexterity was greater in the schizophrenia group than in the control group (p.70, for all). The extent of discrepancy in hand dexterity was negatively correlated with daily functioning in the schizophrenia group (rs=-.3 to -.5, ps=.04-.26). Ability to perform dual tasks may be an indicator of daily functioning in people with schizophrenia. Use of dual-task training may be considered as a therapeutic activity with these clients. Copyright © 2015 by the American Occupational Therapy Association, Inc.

Light curing through glass ceramics: effect of curing mode on micromechanical properties of dual-curing resin cements.

Science.gov (United States)

Flury, Simon; Lussi, Adrian; Hickel, Reinhard; Ilie, Nicoleta

2014-04-01

The aim of this study was to investigate micromechanical properties of five dual-curing resin cements after different curing modes including light curing through glass ceramic materials. Vickers hardness (VH) and indentation modulus (Y HU) of Panavia F2.0, RelyX Unicem 2 Automix, SpeedCEM, BisCem, and BeautiCem SA were measured after 1 week of storage (37 °C, 100 % humidity). The resin cements were tested following self-curing or light curing with the second-generation light-emitting diode (LED) curing unit Elipar FreeLight 2 in Standard Mode (1,545 mW/cm(2)) or with the third-generation LED curing unit VALO in High Power Mode (1,869 mW/cm(2)) or in XtraPower Mode (3,505 mW/cm(2)). Light curing was performed directly or through glass ceramic discs of 1.5 or 3 mm thickness of IPS Empress CAD or IPS e.max CAD. VH and Y HU were analysed with Kruskal-Wallis tests followed by pairwise Wilcoxon rank sum tests (α = 0.05). RelyX Unicem 2 Automix resulted in the highest VH and Y HU followed by BeautiCem SA, BisCem, SpeedCEM, and finally Panavia F2.0. Self-curing of RelyX Unicem 2 Automix and SpeedCEM lowered VH and Y HU compared to light curing whereas self-curing of Panavia F2.0, BisCem, and BeautiCem SA led to similar or significantly higher VH and Y HU compared to light curing. Generally, direct light curing resulted in similar or lower VH and Y HU compared to light curing through 1.5-mm-thick ceramic discs. Light curing through 3-mm-thick discs of IPS e.max CAD generally reduced VH and Y HU for all resin cements except SpeedCEM, which was the least affected by light curing through ceramic discs. The resin cements responded heterogeneously to changes in curing mode. The applied irradiances and light curing times adequately cured the resin cements even through 1.5-mm-thick ceramic discs. When light curing resin cements through thick glass ceramic restorations, clinicians should consider to prolong the light curing times even with LED curing units providing high

The design of the light-flash warning light

Science.gov (United States)

Wang, Junli

2018-05-01

In today's society, the warning light has been used widely in people's daily life and various industries and agricultures. It is important to protect people's life and security. Light-flashing warning light is a kind of warning light control equipment which can control warning light automatically open and work in the state of blinking after dark, and it can automatically shut down after the dawn. It can achieve the flashing light automatic control and dual function. At present, light-flashing warning lights are mainly used in the projects of municipal construction. It is helpful to warn people and vehicles that passed in the construction site and ensure personal safety through using light-flashing warning light. Its design is simple, its performance is stable and it is also very convince to use it.

Dual-Task Performance: Influence of Frailty, Level of Physical Activity, and Cognition.

Science.gov (United States)

Giusti Rossi, Paulo; Pires de Andrade, Larissa; Hotta Ansai, Juliana; Silva Farche, Ana Claudia; Carnaz, Leticia; Dalpubel, Daniela; Ferriolli, Eduardo; Assis Carvalho Vale, Francisco; de Medeiros Takahashi, Anielle Cristhine

2018-03-08

Cognition and level of physical activity have been associated with frailty syndrome. The development of tools that assess deficits related to physical and cognitive frailties simultaneously are of common interest. However, little is known about how much these aspects influence the performance of dual-task tests. Our aims were (a) to verify the influence of frailty syndrome and objectively measured physical activity and cognition on the Timed Up and Go (TUG) test and Timed Up and Go associated with dual-task (TUG-DT) performances; and (b) to compare TUG and TUG-DT performances between older adults who develop frailty syndrome. Sixty-four community-dwelling older adults were divided into frail, prefrail, and nonfrail groups, according to frailty phenotype. Assessments included anamnesis, screening of frailty syndrome, cognitive assessment (Addenbrooke's cognitive examination), placement of a triaxial accelerometer to assess level of physical activity, and TUG and TUG-DT (TUG associated with a motor-cognitive task of calling a phone number) performances. After 7 days, the accelerometer was removed. A multiple linear regression was applied to identify which independent variables could explain performances in the TUG and TUG-DT. Subsequently, the analysis of covariance test, adjusted for age, cognition, and level of physical activity covariates, was used to compare test performances. There were no differences in cognition between groups. Significant differences in the level of physical activity were found in the frail group. Compared with the frail group, the nonfrail group required less time and fewer steps to complete the TUG. Regarding the TUG-DT, cognition and age influenced the time spent and number of steps, respectively; however, no differences were found between groups. Frail older adults presented worse performance in the TUG when compared with nonfrail older adults. The dual-task test does not differentiate older adults with frailty syndrome, regardless of

Anti-dengue virus serotype 2 activity and mode of action of a novel peptide.

Science.gov (United States)

Chew, M-F; Tham, H-W; Rajik, M; Sharifah, S H

2015-10-01

To identify a novel antiviral peptide against dengue virus serotype 2 (DENV-2) by screening a phage display peptide library and to evaluate its in vitro antiviral activity and mode of action. A phage display peptide library was biopanned against purified DENV-2 and resulted in the identification and selection of a peptide (peptide gg-ww) for further investigation. ELISA was performed, and peptide gg-ww was shown to possess the highest binding affinity against DENV-2. Thus, peptide gg-ww was synthesized for cytotoxicity and antiviral assays. Virus plaque reduction assay, real-time PCR and immunofluorescence assay were used to investigate the inhibitory effect of peptide gg-ww on DENV-2 infection in Vero cells. Three different assays (pre-, simultaneous and post-treatments assays) were performed to investigate the peptide's mode of action. Results indicated that peptide gg-ww possessed strong antiviral activity with a ~96% inhibition rate, which was achieved at 250 μmol l(-1) . Viral replication was inhibited during a simultaneous treatment assay, indicating that the entry of the virus was impeded by this peptide. Peptide gg-ww displayed antiviral action against DENV-2 by targeting an early stage of viral replication (i.e. during viral entry). Peptide gg-ww may represent a new therapeutic candidate for the treatment of DENV infections and is a potential candidate to be developed as a peptide drug. © 2015 The Society for Applied Microbiology.

Training Changes Professionals’ Attitudes Towards Dual Diagnosis

DEFF Research Database (Denmark)

Pinderup, Pernille

2016-01-01

Studies have shown that mental health professionals in many cases have counterproductive attitudes towards patients with mental illnesses and comorbid substance use disorders (dual diagnosis). This is problematic because professionals’ attitudes are important for both the therapeutic alliance...... and treatment outcome. This study tested whether providing training in dual diagnosis treatment to mental health professionals will affect their attitudes positively. Twenty-one professionals completed a questionnaire on attitudes towards working with dual diagnosis (Comorbidity Problems Perceptions...... Questionnaire, CMPPQ) pre-training and post-training. Results showed that there was a significant positive change in total CMPPQ scores and a positive change in all six subscales of the CMPPQ following training, indicating that the training resulted in more positive attitudes. The study suggests that training...

Physiology of inactivation of microbial cells by near-ultraviolet light: mode of action and application for the enrichment of mutants of Escherichia coli and saccharomyces cerevisiae

International Nuclear Information System (INIS)

Peters, J.

1976-01-01

The mode of action of near-ultraviolet (NUV) light was studied in Escherichia coli. NUV light (maximum emission at 365 nm) caused the photodestruction of ribonucleoside diphosphate (RDP) reductase activity in vivo. Evidence was presented for a model suggesting that the loss of RDP-reductase resulted in a metabolic state analogous to that produced during starvation for thymine. Some important properties of cells irradiated by NUV light, cell death, loss of the ability to support the replication of DNA phages and a delay in the onset of cell division in sublethally irradiated cells, were accounted for in terms of photoinactivation of RDP-reductase. Conditions were described under which NUV light was an effective counterselective agent for the enrichment of mutants of Escherichia coli and Saccharomyces cerevisiae

Kaehler-Dirac ghosts for self-dual fields

International Nuclear Information System (INIS)

Labastida, J.M.F.; Pernici, M.

1988-01-01

We present the generalization to spacetime dimension D=4n+2 of the Lorentz covariant quadratic lagrangian for pairs of (anti)self-dual fields previously obtained by the authors in D=2. In the process of BRST quantizing this lagrangian a first-order quadratic lagrangian for ghost (anti)self-dual fields is found which, after gauge fixing, can be written in terms of bispinors and it turns out to be a Kaehler-Dirac lagrangian. The coupling to gravity is straightforward and the gravitational anomaly due to (anti)self-dual fields is obtained directly from an action principle. (orig.)

Novel robust cellulose-based foam with pH and light dual-response for oil recovery

Science.gov (United States)

Wang, Qian; Meng, Guihua; Wu, Jianning; Wang, Yixi; Liu, Zhiyong; Guo, Xuhong

2018-05-01

We fabricated pH and light dual-responsive adsorption materials which could induce the transition of surface wettability between hydrophobicity and hydrophilicity by using ATRP. The structure and morphology of adsorption materials were confirmed by ATR-FTIR, XPS, TGA and SEM. It showed that the modified cellulose (CE)-based foam was hydrophobic, which can adsorb a range of oils and organic solvents in water under pH = 7.0 or visible light irradiation (λ > 500 nm). Meanwhile, the wettability of robust CE-based foam can convert hydrophobicity into hydrophilicity and underwater oleophobicity under pH = 3.0 or UV irradiation (λ = 365 nm), giving rise to release oils and organic solvents. Most important of all, the adsorption and desorption processes of the modified CE-based foam could be switched by external stimuli. Furthermore, the modified CE-based foam was not damaged and still retained original performance after reversible cycle repeated for many times with variation of surface wettability. In short, it indicates that CE-based foam materials with switchable surface wettability are new responsive absorbent materials and have owned potential application in the treatment of oil recovery.

Evaluation of compatibility between different types of adhesives and dual-cured resin cement.

Science.gov (United States)

Franco, Eduardo B; Lopes, Lawrence G; D'alpino, Paulo H P; Pereira, José C; Mondelli, Rafael F L; Navarro, Maria F L

2002-01-01

The objective of this in vitro study was to evaluate the bonding compatibility between different adhesives and a dual-cured resin cement, using a conventional tensile bond test. The adhesives used were: Prime & Bond (PB) (Dentsply) (PB), Scotchbond Multi Purpose (SB) (3M), and the activator Self Cure (SC) (Dentsply). The dual-curing resin cement used was Enforce (EF) (Dentsply). Six groups with five specimens in each were tested: G1: EF/PB/EF (light cured); G2: EF/SB/EF (light cured); G3: EF/PB+SC/EF (light cured); G4: EF/PB+SC/EF (only chemically cured); G5: EF/EF (light cured); G6: EF/EF (only chemically cured). The resin cement was applied in two stainless steel molds with a cone-shaped perforation measuring 4 mm in diameter and 1 mm in thickness, and the adhesive was applied between them. Ten minutes after specimens were cured, the tensile strength was measured in a universal testing machine at a crosshead speed of 0.5 mm/min. The mean values (MPa) +/- SD obtained in each experimental group were: G1: 1.4 +/- 0.2; G2: 1.3 +/- 0.2; G3: 1.2 +/- 0.4; G4: 0.8 +/- 0.2; G5: 1.2 +/- 0.1; G6: 0.7 +/- 0.1. The results were statistically evaluated using nonparametric Kruskal-Wallis and Dunn tests (p adhesives used with dual-cured resin cement. The lowest tensile bond strength values occurred in the absence of photoactivation.

Eye-independent, light-activated chromatophore expansion (LACE) and expression of phototransduction genes in the skin of Octopus bimaculoides.

Science.gov (United States)

Ramirez, M Desmond; Oakley, Todd H

2015-05-15

Cephalopods are renowned for changing the color and pattern of their skin for both camouflage and communication. Yet, we do not fully understand how cephalopods control the pigmented chromatophore organs in their skin and change their body pattern. Although these changes primarily rely on eyesight, we found that light causes chromatophores to expand in excised pieces of Octopus bimaculoides skin. We call this behavior light-activated chromatophore expansion (or LACE). To uncover how octopus skin senses light, we used antibodies against r-opsin phototransduction proteins to identify sensory neurons that express r-opsin in the skin. We hypothesized that octopus LACE relies on the same r-opsin phototransduction cascade found in octopus eyes. By creating an action spectrum for the latency to LACE, we found that LACE occurred most quickly in response to blue light. We fit our action spectrum data to a standard opsin curve template and estimated the λmax of LACE to be 480 nm. Consistent with our hypothesis, the maximum sensitivity of the light sensors underlying LACE closely matches the known spectral sensitivity of opsin from octopus eyes. LACE in isolated preparations suggests that octopus skin is intrinsically light sensitive and that this dispersed light sense might contribute to their unique and novel patterning abilities. Finally, our data suggest that a common molecular mechanism for light detection in eyes may have been co-opted for light sensing in octopus skin and then used for LACE. © 2015. Published by The Company of Biologists Ltd.

Smart Fluid System Dually Responsive to Light and Electric Fields: An Electrophotorheological Fluid.

Science.gov (United States)

Yoon, Chang-Min; Jang, Yoonsun; Noh, Jungchul; Kim, Jungwon; Jang, Jyongsik

2017-10-24

Electrophotorheological (EPR) fluids, whose rheological activity is dually responsive to light and electric fields (E fields), is formulated by mixing photosensitive spiropyran-decorated silica (SP-sSiO 2 ) nanoparticles with zwitterionic lecithin and mineral oil. A reversible photorheological (PR) activity of the EPR fluid is developed via the binding and releasing mechanism of lecithin and merocyanine (MC, a photoisomerized form of SP) under ultraviolet (UV) and visible (VIS) light applications. Moreover, the EPR fluid exhibits an 8-fold higher electrorheological (ER) performance compared to the SP-sSiO 2 nanoparticle-based ER fluid (without lecithin) under an E field, which is attributed to the enhanced dielectric properties facilitated by the binding of the lecithin and SP molecules. Upon dual application of UV light and an E field, the EPR fluid exhibits high EPR performance (ca. 115.3 Pa) that far exceeds its separate PR (ca. 0.8 Pa) and ER (ca. 57.5 Pa) activities, because of the synergistic contributions of the PR and ER effects through rigid and fully connected fibril-like structures. Consequently, this study offers a strategy on formulation of dual-stimuli responsive smart fluid systems.

AMDE-1 is a dual function chemical for autophagy activation and inhibition.

Directory of Open Access Journals (Sweden)

Min Li

Full Text Available 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.

A smart upconversion-based light-triggered polymer for synergetic chemo-photodynamic therapy and dual-modal MR/UCL imaging.

Science.gov (United States)

Du, Bin; Han, Shuping; Zhao, Feifei; Lim, Kok Hwa; Xi, Hongwei; Su, Xiangjie; Yao, Hanchun; Zhou, Jie

2016-10-01

We have developed a novel nanocomposite to achieve effective therapy and live surveillance of tumor tissue. In this study, fullerene (C 60 ) with iron oxide (Fe 3 O 4 ) nanoparticles and upconversion nanophosphors (UCNPs) was loaded into N-succinyl-N'-4-(2-nitrobenzyloxy)-succinyl-chitosan micelles (SNSC) with good biocompatibility. In addition, hydrophobic anticancer drug docetaxel (DTX) was also loaded into the nanocomposites. The experiments conducted in vitro and in vivo demonstrated that C 60 /Fe 3 O 4 -UCNPs@DTX@SNSC can act synergistically to kill tumor cells by releasing chemotherapy drugs at specific target site as well as generating reactive oxygen using 980nm. In addition, it can also be used for non-invasive deep magnetic resonance and upconversion fluorescence dual-mode imaging. The results indicated that this system provided an efficient method to surmount the drawback of UV or visible light-responsive polymeric systems for controlled drug release and generated reactive oxygen in deep tissues and ultimately realized the integration of dual-modal imaging and treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

Cryptochrome and phytochrome cooperatively but independently reduce active gibberellin content in rice seedlings under light irradiation.

Science.gov (United States)

Hirose, Fumiaki; Inagaki, Noritoshi; Hanada, Atsushi; Yamaguchi, Shinjiro; Kamiya, Yuji; Miyao, Akio; Hirochika, Hirohiko; Takano, Makoto

2012-09-01

In contrast to a wealth of knowledge about the photoregulation of gibberellin metabolism in dicots, that in monocots remains largely unclear. In this study, we found that a blue light signal triggers reduction of active gibberellin content in rice seedlings with simultaneous repression of two gibberellin 20-oxidase genes (OsGA20ox2 and OsGA20ox4) and acute induction of four gibberellin 2-oxidase genes (OsGA2ox4-OsGA2ox7). For further examination of the regulation of these genes, we established a series of cryptochrome-deficient lines through reverse genetic screening from a Tos17 mutant population and construction of knockdown lines based on an RNA interference technique. By using these lines and phytochrome mutants, we elucidated that cryptochrome 1 (cry1), consisting of two species in rice plants (cry1a and cry1b), is indispensable for robust induction of the GA2ox genes. On the other hand, repression of the GA20ox genes is mediated by phytochromes. In addition, we found that the phytochromes also mediate the repression of a gibberellin 3-oxidase gene (OsGA3ox2) in the light. These results imply that, in rice seedlings, phytochromes mediate the repression of gibberellin biosynthesis capacity, while cry1 mediates the induction of gibberellin inactivation capacity. The cry1 action was demonstrated to be dominant in the reduction of active gibberellin content, but, in rice seedlings, the cumulative effects of these independent actions reduced active gibberellin content in the light. This pathway design in which different types of photoreceptors independently but cooperatively regulate active gibberellin content is unique from the viewpoint of dicot research. This redundancy should provide robustness to the response in rice plants.

Dual-channel operation in a synchronously pumped optical parametric oscillator for the generation of broadband mid-infrared coherent light sources.

Science.gov (United States)

Liu, Pei; Wang, Sicong; He, Puyuan; Zhang, Zhaowei

2018-05-01

We report, to the best of our knowledge, a novel approach for generating broadband mid-infrared (mid-IR) light by implementing a dual-channel scheme in a synchronously pumped optical parametric oscillator (SPOPO). Two-channel operation was achieved by inserting a prism pair and two reflection mirrors inside an optical parametric oscillator (OPO) cavity. Pumped by a Yb-fiber laser, the OPO generated an idler wave at ∼3150  nm with a -10  dB bandwidth of ∼13.2  THz, which was twice as much as that of the pump source. This scheme represents a promising technical route to transform conventional SPOPOs into a device capable of generating mid-IR light with very broad instantaneous bandwidth.

Restricted access magnetic materials prepared by dual surface modification for selective extraction of therapeutic drugs from biological fluids

Science.gov (United States)

Wang, Yu; Wang, Yuxia; Chen, Lei; Wan, Qian-Hong

2012-02-01

Magnetic porous particles with dual functionality have been prepared by a two-step procedure and evaluated as novel restricted access materials for extraction of therapeutic agents from biological fluids. The magnetic silica particles served as scaffolds were first modified with diol groups, which were then converted to octadecyl esters through reaction with stearoyl chloride. In the second step, the octadecyl esters on the exterior surface were hydrolyzed by the action of lipase to yield magnetic particles with hydrophobic reversed-phase ligands on the inner surface and biocompatible diol groups on the outer surface. The restricted access behavior of the resulting materials was confirmed by differential binding of small molecules such as methotrexate (MTX), leucovorin (LV) and folic acid (FA) relative to bovine serum albumin. While MTX, LV and FA were all bound to the magnetic particles with high affinity, the adsorption of the protein was markedly reduced due to size exclusion effect. The utility of the magnetic particles for sample preparation was tested in solid-phase extraction of MTX, LV and FA from spiked human serum and the effects of the SPE conditions on the recovery of the analytes were systematically studied. Moreover, the magnetic particle-based sample preparation procedure coupled with reversed-phase liquid chromatography analysis was validated in terms of specificity, linearity and reproducibility. The method was shown to be free from interference of endogenous compounds and linear over the concentration range of 0.5-10 μg/mL for the three drugs studied. The limits of detection for the three drugs in serum were in the range of 0.160-0.302 μg/mL. Reproducibility expressed as the RSD of the recovery for ten replicated extractions at three different concentrations was found to be less than 8.93%. With a unique combination of surface functionality with magnetic cores, the restricted access magnetic particles may be adapted in automated and high

Energy Efficient Hybrid Dual Axis Solar Tracking System

Directory of Open Access Journals (Sweden)

Rashid Ahammed Ferdaus

2014-01-01

Full Text Available This paper describes the design and implementation of an energy efficient solar tracking system from a normal mechanical single axis to a hybrid dual axis. For optimizing the solar tracking mechanism electromechanical systems were evolved through implementation of different evolutional algorithms and methodologies. To present the tracker, a hybrid dual-axis solar tracking system is designed, built, and tested based on both the solar map and light sensor based continuous tracking mechanism. These light sensors also compare the darkness and cloudy and sunny conditions assisting daily tracking. The designed tracker can track sun’s apparent position at different months and seasons; thereby the electrical controlling device requires a real time clock device for guiding the tracking system in seeking solar position for the seasonal motion. So the combination of both of these tracking mechanisms made the designed tracker a hybrid one. The power gain and system power consumption are compared with a static and continuous dual axis solar tracking system. It is found that power gain of hybrid dual axis solar tracking system is almost equal to continuous dual axis solar tracking system, whereas the power saved in system operation by the hybrid tracker is 44.44% compared to the continuous tracking system.

Dual action of vitamin C versus degradation and supplementation

Directory of Open Access Journals (Sweden)

Katarzyna Kaliś

2015-11-01

Full Text Available The article discusses vitamin C from the point of view of its supplementation with food and in the form of oral supplements. The dual action of vitamin C is connected with the presence of oxygen, which may reduce the amount of the vitamin in food products, influence thermal resistance, cause degradation and show an antioxidation effect. Vitamin C stimulates the immune cells and collagen synthesis. It may protect the LDL fraction against oxidation, and therefore it is interesting for cosmetology, rheumatology, immunology and dietetics. The latest research with respect to vitamin C proved that it has the ability to dissolve neurotoxic senile plaques. Equally effective in the treatment of Alzheimer’s disease is the oxidised form of vitamin C, i.e. dehydroascorbic acid. Vitamin C may be used in a combined vitamin E supplementation to avoid the pro-oxidative effect and reduce the risk of diabetes mellitus type 2 complications. In the review there is a description of the types of vitamin C degradation depending on a specific factor such as pH, temperature, oxygen, enzyme and the impact of diet on the quantity of the supplied vitamin. The literature data confirmed the positive influence of vitamin C as an addition to food. The last part of the article presents the methods of vitamin C protection used in food processing technology and of determining its content in food products. Additionally, the article describes the problems related to vitamin C oxidation processes during food processing and storage. The presented research results indicate that an adequate diet contains a sufficient amount of vitamin C for healthy people. In the case of chronic patients it is better to use supplementation.

Phototropin 1 and dim-blue light modulate the red light de-etiolation response.

Science.gov (United States)

Wang, Yihai; M Folta, Kevin

2014-01-01

Light signals regulate seedling morphological changes during de-etiolation through the coordinated actions of multiple light-sensing pathways. Previously we have shown that red-light-induced hypocotyl growth inhibition can be reversed by addition of dim blue light through the action of phototropin 1 (phot1). Here we further examine the fluence-rate relationships of this blue light effect in short-term (hours) and long-term (days) hypocotyl growth assays. The red stem-growth inhibition and blue promotion is a low-fluence rate response, and blue light delays or attenuates both the red light and far-red light responses. These de-etiolation responses include blue light reversal of red or far-red induced apical hook opening. This response also requires phot1. Cryptochromes (cry1 and cry2) are activated by higher blue light fluence-rates and override phot1's influence on hypocotyl growth promotion. Exogenous application of auxin transport inhibitor naphthylphthalamic acid abolished the blue light stem growth promotion in both hypocotyl growth and hook opening. Results from the genetic tests of this blue light effect in auxin transporter mutants, as well as phytochrome kinase substrate mutants indicated that aux1 may play a role in blue light reversal of red light response. Together, the phot1-mediated adjustment of phytochrome-regulated photomorphogenic events is most robust in dim blue light conditions and is likely modulated by auxin transport through its transporters.

Reconsidering the concept of 'dual-use' in the context of neuroscience research

Directory of Open Access Journals (Sweden)

Voarino, Nathalie

2014-11-01

Full Text Available The concept of ‘dual-use’ research usually refers to research with both civilian (e.g., therapeutic and military applications. I argue here that this dichotomy can and should be reconsidered and thus that the concept of dual-use can be helpful in examining other potential misuses, such as neuroenhancement or neuromarketing.

Co-lateralized bilingual mechanisms for reading in single and dual language contexts: evidence from visual half-field processing of action words in proficient bilinguals

Directory of Open Access Journals (Sweden)

Marlena eKrefta

2015-08-01

Full Text Available When reading, proficient bilinguals seem to engage the same cognitive circuits regardless of the language in use. Yet, whether or not such ‘bilingual’ mechanisms would be lateralized in the same way in distinct – single or dual – language contexts is a question for debate. To fill this gap, we tested 18 highly proficient Polish (L1 – English (L2 childhood bilinguals whose task was to read aloud one of the two laterally presented action verbs, one stimulus per visual half field. While in the single-language blocks only L1 or L2 words were shown, in the subsequent mixed-language blocks words from both languages were concurrently displayed. All stimuli were presented for 217 ms followed by masks in which letters were replaced with hash marks. Since in non-simultaneous bilinguals the control of language, skilled actions (including reading, and representations of action concepts are typically left lateralized, the vast majority of our participants showed the expected, significant right visual field advantage for L1 and L2, both for accuracy and response times. The observed effects were nevertheless associated with substantial variability in the strength of the lateralization of the mechanisms involved. Moreover, although it could be predicted that participants’ performance should be better in a single-language context, accuracy was significantly higher and response times were significantly shorter in a dual-language context, irrespective of the language tested. Finally, for both accuracy and response times, there were significant positive correlations between the laterality indices (LIs of both languages independent of the context, with a significantly greater left-sided advantage for L1 vs. L2 in the mixed-language blocks, based on LIs calculated for response times. Thus, despite similar representations of the two languages in the bilingual brain, these results also point to the functional separation of L1 and L2 in the dual

Colorimetry and SERS dual-mode detection of telomerase activity: combining rapid screening with high sensitivity.

Science.gov (United States)

Zong, Shenfei; Wang, Zhuyuan; Chen, Hui; Hu, Guohua; Liu, Min; Chen, Peng; Cui, Yiping

2014-01-01

As an important biomarker and therapeutic target, telomerase has attracted considerable attention concerning its detection and monitoring. Here, we present a colorimetry and surface enhanced Raman scattering (SERS) dual-mode telomerase activity detection method, which has several distinctive advantages. First, colorimetric functionality allows rapid preliminary discrimination of telomerase activity by the naked eye. Second, the employment of SERS technique results in greatly improved detection sensitivity. Third, the combination of colorimetry and SERS into one detection system can ensure highly efficacious and sensitive screening of numerous samples. Besides, the avoidance of polymerase chain reaction (PCR) procedures further guarantees fine reliability and simplicity. Generally, the presented method is realized by an "elongate and capture" procedure. To be specific, gold nanoparticles modified with Raman molecules and telomeric repeat complementary oligonucleotide are employed as the colorimetric-SERS bifunctional reporting nanotag, while magnetic nanoparticles functionalized with telomerase substrate oligonucleotide are used as the capturing substrate. Telomerase can synthesize and elongate telomeric repeats onto the capturing substrate. The elongated telomeric repeats subsequently facilitate capturing of the reporting nanotag via hybridization between telomeric repeat and its complementary strand. The captured nanotags can cause a significant difference in the color and SERS intensity of the magnetically separated sediments. Thus both the color and SERS can be used as indicators of the telomerase activity. With fast screening ability and outstanding sensitivity, we anticipate that this method would greatly promote practical application of telomerase-based early-stage cancer diagnosis.

Dual Logic and Cerebral Coordinates for Reciprocal Interaction in Eye Contact

Science.gov (United States)

Lee, Ray F.

2015-01-01

In order to scientifically study the human brain’s response to face-to-face social interaction, the scientific method itself needs to be reconsidered so that both quantitative observation and symbolic reasoning can be adapted to the situation where the observer is also observed. In light of the recent development of dyadic fMRI which can directly observe dyadic brain interacting in one MRI scanner, this paper aims to establish a new form of logic, dual logic, which provides a theoretical platform for deductive reasoning in a complementary dual system with emergence mechanism. Applying the dual logic in the dfMRI experimental design and data analysis, the exogenous and endogenous dual systems in the BOLD responses can be identified; the non-reciprocal responses in the dual system can be suppressed; a cerebral coordinate for reciprocal interaction can be generated. Elucidated by dual logic deductions, the cerebral coordinate for reciprocal interaction suggests: the exogenous and endogenous systems consist of the empathy network and the mentalization network respectively; the default-mode network emerges from the resting state to activation in the endogenous system during reciprocal interaction; the cingulate plays an essential role in the emergence from the exogenous system to the endogenous system. Overall, the dual logic deductions are supported by the dfMRI experimental results and are consistent with current literature. Both the theoretical framework and experimental method set the stage to formally apply the scientific method in studying complex social interaction. PMID:25885446

Dual logic and cerebral coordinates for reciprocal interaction in eye contact.

Directory of Open Access Journals (Sweden)

Ray F Lee

Full Text Available In order to scientifically study the human brain's response to face-to-face social interaction, the scientific method itself needs to be reconsidered so that both quantitative observation and symbolic reasoning can be adapted to the situation where the observer is also observed. In light of the recent development of dyadic fMRI which can directly observe dyadic brain interacting in one MRI scanner, this paper aims to establish a new form of logic, dual logic, which provides a theoretical platform for deductive reasoning in a complementary dual system with emergence mechanism. Applying the dual logic in the dfMRI experimental design and data analysis, the exogenous and endogenous dual systems in the BOLD responses can be identified; the non-reciprocal responses in the dual system can be suppressed; a cerebral coordinate for reciprocal interaction can be generated. Elucidated by dual logic deductions, the cerebral coordinate for reciprocal interaction suggests: the exogenous and endogenous systems consist of the empathy network and the mentalization network respectively; the default-mode network emerges from the resting state to activation in the endogenous system during reciprocal interaction; the cingulate plays an essential role in the emergence from the exogenous system to the endogenous system. Overall, the dual logic deductions are supported by the dfMRI experimental results and are consistent with current literature. Both the theoretical framework and experimental method set the stage to formally apply the scientific method in studying complex social interaction.

Comparative evaluation of bidirectional dual active bridge DC-DC converter variants

NARCIS (Netherlands)

Sfakianakis, G.; Everts, J.; Huisman, H.; Lomonova, E.A.

2016-01-01

For the realization of DC-DC converters in automotive industry, the Dual Active Bridge (DAB) converter seems to be a promising choice because of its soft-switching and high-power-density capability. Contrary to the traditional 3 level - 3 level (3-3L) DAB, a 3 level - 5 level (3-5L) DAB can operate

The Theory of Action in the light of the schizo experience: an study of insane epistemology

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Gabriel Peters

2016-12-01

device that has proven fruitful in a variety of research domains, namely the plunge into the realm of the “pathological” as a pathway to illuminate “normal” modalities of action and experience. Resorting to this strategy on the plane of sociological characterizations of human conduct, the article harnesses phenomenological and existential descriptions of schizoid and schizophrenic experiences, not only to understand these in the light of the praxeological theory of action, but also to deepen the praxeological theory of action in the light of what such descriptions teach us about the multiplicity of ways of being-in-the-world displayed by the anthropos. The study defends that these transformations, despite their psychic costs, must not be conceived as mere functional deficits, but rather as complex existential attitudes which defy, in practice, certain postulates of the praxeological theory of action: the grounding upon tacit beliefs is replaced with a hyper-reflexive compulsion, the pragmatic relationship with material objects gives way to a quasi-philosophical perplexity in face of their mere reality, the inter-subjective agreements that offer familiarity and order to social reality in a given culture are perceived in their radical ontological arbitrariness, and the estrangement from one’s own body ceases to be a playful Cartesian skepticism so as to become a profound existential experience.

Exploiting light chains for the scalable generation and platform purification of native human bispecific IgG

Science.gov (United States)

Fischer, Nicolas; Elson, Greg; Magistrelli, Giovanni; Dheilly, Elie; Fouque, Nicolas; Laurendon, Amélie; Gueneau, Franck; Ravn, Ulla; Depoisier, Jean-François; Moine, Valery; Raimondi, Sylvain; Malinge, Pauline; Di Grazia, Laura; Rousseau, François; Poitevin, Yves; Calloud, Sébastien; Cayatte, Pierre-Alexis; Alcoz, Mathias; Pontini, Guillemette; Fagète, Séverine; Broyer, Lucile; Corbier, Marie; Schrag, Delphine; Didelot, Gérard; Bosson, Nicolas; Costes, Nessie; Cons, Laura; Buatois, Vanessa; Johnson, Zoe; Ferlin, Walter; Masternak, Krzysztof; Kosco-Vilbois, Marie

2015-01-01

Bispecific antibodies enable unique therapeutic approaches but it remains a challenge to produce them at the industrial scale, and the modifications introduced to achieve bispecificity often have an impact on stability and risk of immunogenicity. Here we describe a fully human bispecific IgG devoid of any modification, which can be produced at the industrial scale, using a platform process. This format, referred to as a κλ-body, is assembled by co-expressing one heavy chain and two different light chains, one κ and one λ. Using ten different targets, we demonstrate that light chains can play a dominant role in mediating specificity and high affinity. The κλ-bodies support multiple modes of action, and their stability and pharmacokinetic properties are indistinguishable from therapeutic antibodies. Thus, the κλ-body represents a unique, fully human format that exploits light-chain variable domains for antigen binding and light-chain constant domains for robust downstream processing, to realize the potential of bispecific antibodies. PMID:25672245

Dual-Drive Production Prototype Project

Science.gov (United States)

2009-06-01

This project was an initiative to engineer, develop and build a plug-in hybrid-electric vehicle using the Dual-Drive system. The project aimed to build a plug-in hybrid utilitarian vehicle on a light commercial vehicle platform. The hybrid vehicle wi...

The lateralization of motor cortex activation to action words

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Olaf eHauk

2011-11-01

Full Text Available What determines the laterality of activation in motor cortex for words whose meaning is related to bodily actions? It has been suggested that the neuronal representation of the meaning of action-words is shaped by individual experience. However, core language functions are left-lateralized in the majority of both right- and left-handers. It is still an open question to what degree connections between left-hemispheric core language areas and right-hemispheric motor areas can play a role in semantics. We investigated laterality of brain activation using fMRI in right- and left-handed participants in response to visually presented hand-related action-words, namely uni- and bi-manual actions (such as "throw" and "clap". These stimulus groups were matched with respect to general (hand-action-relatedness, but differed with respect to whether they are usually performed with the dominant hand or both hands. We may expect generally more left-hemispheric motor-cortex activation for hand-related words in both handedness groups, with possibly more bilateral activation for bimanual words as well as left-handers. In our study, both participant groups activated motor cortex bilaterally for bi-manual words. Interestingly, both groups also showed a left-lateralized activation pattern to uni-manual words. We argue that this reflects the effect of left-hemispheric language dominance on the formation of semantic brain circuits on the basis of Hebbian correlation learning.

Establishment of animal model of dual liver transplantation in rat.

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Ying Zhang

Full Text Available The animal model of the whole-size and reduced-size liver transplantation in both rat and mouse has been successfully established. Because of the difficulties and complexities in microsurgical technology, the animal model of dual liver transplantation was still not established for twelve years since the first human dual liver transplantation has been made a success. There is an essential need to establish this animal model to lay a basic foundation for clinical practice. To study the physiological and histopathological changes of dual liver transplantation, "Y" type vein from the cross part between vena cava and two iliac of donor and "Y' type prosthesis were employed to recanalize portal vein and the bile duct between dual liver grafts and recipient. The dual right upper lobes about 45-50% of the recipient liver volume were taken as donor, one was orthotopically implanted at its original position, the other was rotated 180° sagitally and heterotopically positioned in the left upper quadrant. Microcirculation parameters, liver function, immunohistochemistry and survival were analyzed to evaluate the function of dual liver grafts. No significant difference in the hepatic microcirculatory flow was found between two grafts in the first 90 minutes after reperfusion. Light and electronic microscope showed the liver architecture was maintained without obvious features of cellular destruction and the continuity of the endothelium was preserved. Only 3 heterotopically positioned graft appeared patchy desquamation of endothelial cell, mitochondrial swelling and hepatocytes cytoplasmic vacuolization. Immunohistochemistry revealed there is no difference in hepatocyte activity and the ability of endothelia to contract and relax after reperfusion between dual grafts. Dual grafts made a rapid amelioration of liver function after reperfusion. 7 rats survived more than 7 days with survival rate of 58.3.%. Using "Y" type vein and bile duct prosthesis, we

Dual drug-loaded paclitaxel–thymoquinone nanoparticles for effective breast cancer therapy

Energy Technology Data Exchange (ETDEWEB)

Soni, Parth; Kaur, Jasmine; Tikoo, Kulbhushan, E-mail: tikoo.k@gmail.com [National Institute of Pharmaceutical Education and Research (NIPER), Laboratory of Epigenetics and Diseases, Department of Pharmacology and Toxicology (India)

2015-01-15

The present study highlights the beneficial synergistic blend of anticancer drug paclitaxel (PTX) and thymoquinone (TQ) in MCF-7 breast cancer cells. We aimed to augment the therapeutic index of PTX using a polymeric nanoparticle system loaded with PTX and TQ. PLGA nanoparticles encapsulating the two drugs, individually or in combination, were prepared by single emulsion solvent evaporation method. The formulated nanoparticles were homogenous with an overall negative charge and their size ranging between 200 and 300 nm. Entrapment efficiency of PTX and TQ in the dual drug-loaded nanoparticles was found to be 82.4 ± 2.18 and 65.8 ± 0.45 %, respectively. The release kinetics of PTX and TQ from the nanoparticles exhibited a biphasic pattern characterised by an initial burst, followed by a gradual and continuous release. The anticancer activity of nanoparticles encapsulating both the drugs was higher as compared to the free drugs in MCF-7 breast cancer cells. The combination index for the dual drug-loaded NPs was found to be 0.688 which is indicative of synergistic interaction. Thus, here, we propose the synthesis and use of dual drug-loaded TQ and PTX NPs which exhibits enhanced anticancer activity and can additionally help to alleviate the toxic effects of PTX by lowering its effective dose.

Dual drug-loaded paclitaxel–thymoquinone nanoparticles for effective breast cancer therapy

International Nuclear Information System (INIS)

Soni, Parth; Kaur, Jasmine; Tikoo, Kulbhushan

2015-01-01

The present study highlights the beneficial synergistic blend of anticancer drug paclitaxel (PTX) and thymoquinone (TQ) in MCF-7 breast cancer cells. We aimed to augment the therapeutic index of PTX using a polymeric nanoparticle system loaded with PTX and TQ. PLGA nanoparticles encapsulating the two drugs, individually or in combination, were prepared by single emulsion solvent evaporation method. The formulated nanoparticles were homogenous with an overall negative charge and their size ranging between 200 and 300 nm. Entrapment efficiency of PTX and TQ in the dual drug-loaded nanoparticles was found to be 82.4 ± 2.18 and 65.8 ± 0.45 %, respectively. The release kinetics of PTX and TQ from the nanoparticles exhibited a biphasic pattern characterised by an initial burst, followed by a gradual and continuous release. The anticancer activity of nanoparticles encapsulating both the drugs was higher as compared to the free drugs in MCF-7 breast cancer cells. The combination index for the dual drug-loaded NPs was found to be 0.688 which is indicative of synergistic interaction. Thus, here, we propose the synthesis and use of dual drug-loaded TQ and PTX NPs which exhibits enhanced anticancer activity and can additionally help to alleviate the toxic effects of PTX by lowering its effective dose

Stable narrow spacing dual-wavelength Q-switched graphene oxide embedded in a photonic crystal fiber

International Nuclear Information System (INIS)

Ahmad, H; Soltanian, M R K; Alimadad, M; Harun, S W

2014-01-01

An ultra-stable dual-wavelength saturable absorber based on a cladding-embedded commercial graphene oxide (GO) solution by capillary action in a solid core photonic crystal fiber (PCF) is demonstrated for the first time. The saturation absorption property is achieved through evanescent coupling between the guided light and the cladding-filled graphene layers. Stable spacing dual-wavelength fiber lasing is attained by controlling the polarization state of a simple 0.9 m long ring of highly doped Leikki Er80-8/125 erbium-doped fiber as the primary gain medium with PCF, polarization controller and tunable bandpass filter. Embedded GO is used to generate the desired pulsed output, and the laser is capable of generating pulses having a repetition rate of 24 kHz with an average output power and pulse energy of 0.167 mW and 8.98 nJ, respectively, at the maximum pump power of 220 mW. (paper)

NP-184[2-(5-methyl-2-furyl) benzimidazole], a novel orally active antithrombotic agent with dual antiplatelet and anticoagulant activities.

Science.gov (United States)

Kuo, Heng-Lan; Lien, Jin-Cherng; Chung, Ching-Hu; Chang, Chien-Hsin; Lo, Shyh-Chyi; Tsai, I-Chun; Peng, Hui-Chin; Kuo, Sheng-Chu; Huang, Tur-Fu

2010-06-01

The established antiplatelet and anticoagulant agents show beneficial effects in the treatment of thromboembolic diseases; however, these drugs still have considerable limitations. The effects of NP-184, a synthetic compound, on platelet functions, plasma coagulant activity, and mesenteric venule thrombosis in mice were investigated. NP-184 concentration-dependently inhibited the human platelet aggregation induced by collagen, arachidonic acid (AA), and U46619, a thromboxane (TX)A(2) mimic, with IC(50) values of 4.5 +/- 0.2, 3.9 +/- 0.1, and 9.3 +/- 0.5 microM, respectively. Moreover, NP-184 concentration-dependently suppressed TXA(2) formations caused by collagen and AA. In exploring effects of NP-184 on enzymes involved in TXA(2) synthesis, we found that NP-184 selectively inhibited TXA(2) synthase activity with an IC(50) value of 4.3 +/- 0.2 microM. Furthermore, NP-184 produced a right shift of the concentration-response curve of U46619, indicating a competitive antagonism on TXA(2)/prostaglandin H(2) receptor. Intriguingly, NP-184 also caused a concentration-dependent prolongation of the activated partial thromboplastin time (aPTT) with no changes in the prothrombin and thrombin time, indicating that it selectively impairs the intrinsic coagulation pathway. Oral administration of NP-184 significantly inhibited thrombus formation of the irradiated mesenteric venules in fluorescein sodium-treated mice without affecting the bleeding time induced by tail transection. However, after oral administration, NP-184 inhibited the ex vivo mouse platelet aggregation triggered by collagen and U46619 and also prolonged aPTT. Taken together, the dual antiplatelet and anticoagulant activities of NP-184 may have therapeutic potential as an oral antithrombotic agent in the treatment of thromboembolic disorders.

Indirect effects in dual radiation action

International Nuclear Information System (INIS)

Zaider, M.; Rossi, H.H.

1988-01-01

The basic aim in this paper is to establish the link between indirect effects of radiation action and the spatial distribution of radicals at the time of energy deposition as well as throughout subsequent diffusion and interaction. The fact that radicals diffuse for a finite distance before damaging a biomolecule has dramatic effects on their subsequent probability to result in lesions. Thus at very low DMSO concentrations, where p = 0.5, one expects - all other things being equal - some 75% of the lesions to result from indirect or semidirect lesions. The number calculated here is lower (15%), a direct result of the fact that such lesions involve proximity functions modulated by diffusion. At higher DMSO concentrations this percentage becomes progressively smaller, as expected. It appears thus that for low-LET radiation, the relative amount of indirect damage in single tracks (also termed intratrack or single events) action is very small. By contrast, intertrack (or two-event) contributions will have the ratio between direct and (indirect + semidirect) contributions given by p 2 /(1-p 2 ). The reason for this is that sublesions from different tracks are uniformly distributed throughout the cell nucleus; their probability of interaction should not depend on any previous diffusional processes. For the example given above (p = 0.5) they do expect 65% of intertrack (two-hit) lesions to have resulted from indirect or semidirect mechanisms. This contrast between the almost exclusively direct character of intratrack lesions and the dominant role of indirect action in intertrack lesions produced by low-LET radiation is an important conclusion of this study

Both novelty and expertise increase action observation network activity

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Sook-Lei eLiew

2013-09-01

Full Text Available Our experiences with others affect how we perceive their actions. In particular, activity in bilateral premotor and parietal cortices during action observation, collectively known as the action observation network (AON, is modulated by one’s expertise with the observed actions or individuals. However, conflicting reports suggest that AON activity is greatest both for familiar and unfamiliar actions. The current study examines the effects of different types and amounts of experience (e.g., visual, interpersonal, personal on AON activation. fMRI was used to scan 16 healthy participants without prior experience with individuals with amputations (novices, 11 experienced occupational therapists (OTs who had varying amounts of experience with individuals with amputations, and one individual born with below-elbow residual limbs (participant CJ, as they viewed video clips of goal-matched actions performed by an individual with residual limbs and by an individual with hands. Participants were given increased visual exposure to actions performed by both effectors midway through the scanning procedure. Novices demonstrated a large AON response to the initial viewing of an individual with residual limbs compared to one with hands, but this signal was attenuated after they received visual exposure to both effectors. In contrast, OTs, who had moderate familiarity with residual limbs, demonstrated a lower AON response upon initial viewing—similar to novices after they received visual exposure. At the other extreme, CJ, who has extreme familiarity with residual limbs both visually and motorically, shows a largely increased left-lateralized AON response, exceeding that of novices and experienced OTs, when viewing the residual limb compared to hand actions. These results suggest that a nuanced model of AON engagement is needed to explain how cases of both extreme experience (CJ and extreme novelty (novices can result in the greatest AON activity.

Additional chemical polymerization of dual resin cements: reality or a goal to be achieved?

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Luzia Sakaguti UMETSUBO

Full Text Available Abstract Introduction This study serves as a warning to dentists and researchers that dual-cured resin cements may not polymerize completely under some prosthetic crowns. Objective The aim of this study was to analyse the polymerization degree of dual-cured resin cements under prosthetic barrier, by microhardness test. Material and method Three cements (Bistite II, RelyX ARC and Variolink II were light-cured through different barriers, placed between the cement and the light source: G1: without barrier; G2: composite resin (Cesead; G3: Inceram alumina; G4: IPS Empress; G5: Inceram zirconia; G6: tooth fragment. Photopolymerization was carried out using a halogen light unit (650 mW/cm2; microhardness was evaluated using the Microhardness Tester FM 700, under a load of 50gf with a dwell time of 15s, at two evaluation times (30min and 24h. Result The results were submitted to ANOVA and Tukey tests (5%. Both Inceram alumina and Inceram zirconia ceramic barriers hindered polymerization. Bistite, followed by RelyX and Variolink, exhibited the highest microhardness values (p<0.05. As the highest values were obtained without a barrier, it was determined that the barrier, followed by the tooth, influenced microhardness. Both Empress and Cesead had the smallest microhardness values but with no statistically significant difference between them. Conclusion The barrier negatively affected the microhardness of dual-cured resin cements; evaluation time did not affect microhardness values for most of the conditions tested. There is a limited effect of the chemical activator on the polymerization of some dual-cured cements, and their performance is product specific.

Professionals’ perception on the management of patients with dual disorders

Science.gov (United States)

Roncero, Carlos; Szerman, Néstor; Terán, Antonio; Pino, Carlos; Vázquez, José María; Velasco, Elena; García-Dorado, Marta; Casas, Miguel

2016-01-01

Background There is a need to evaluate the professionals’ perception about the consequences of the lack of therapeutic adherence in the evolution of patients with co-occurring disorders. Methods An online survey, released on the Socidrogalcohol [Spanish Scientific Society for Research on Alcohol, Alcoholism and other Drug Addictions] and Sociedad Española de Patología Dual [the Spanish Society of Dual Pathology] web pages, was answered by 250 professionals who work in different types of Spanish health centers where dual diagnosis patients are assisted. Results Most professionals perceived the existence of noncompliance among dual diagnosis patients. Almost all of these professionals (99%) perceived that noncompliance leads to a worsening of the progression of the patient’s disorder, in both the exacerbation of mental disorders and the consumption of addictive substances. Most of the professionals (69.2%) considered therapeutic alliance as the main aspect to take into account to improve the prognosis in this population. The primary purpose of treatment must be the improvement of psychotic-phase positive symptoms, followed by the control of behavior disorders, reduction of craving, improvement of social and personal performances, and reduction of psychotic-phase negative symptoms. Conclusion Most professionals perceived low adherence among dual diagnosis patients. This lack of adherence is associated with a worsening of their disease evolution, which is reflected in exacerbations of the psychopathology and relapse in substance use. Therefore, we propose to identify strategies to improve adherence. PMID:27698553

The Dual Antioxidant/Prooxidant Effect of Eugenol and Its Action in Cancer Development and Treatment

Directory of Open Access Journals (Sweden)

Daniel Pereira Bezerra

2017-12-01

Full Text Available The formation of reactive oxygen species (ROS during metabolism is a normal process usually compensated for by the antioxidant defense system of an organism. However, ROS can cause oxidative damage and have been proposed to be the main cause of age-related clinical complications and diseases such as cancer. In recent decades, the relationship between diet and cancer has been more studied, especially with foods containing antioxidant compounds. Eugenol is a natural compound widely found in many aromatic plant species, spices and foods and is used in cosmetics and pharmaceutical products. Eugenol has a dual effect on oxidative stress, which can action as an antioxidant or prooxidant agent. In addition, it has anti-carcinogenic, cytotoxic and antitumor properties. Considering the importance of eugenol in the area of food and human health, in this review, we discuss the role of eugenol on redox status and its potential use in the treatment and prevention of cancer.

Early Birds by Light at Night: Effects of Light Color and Intensity on Daily Activity Patterns in Blue Tits.

Science.gov (United States)

de Jong, Maaike; Caro, Samuel P; Gienapp, Phillip; Spoelstra, Kamiel; Visser, Marcel E

2017-08-01

Artificial light at night disturbs the daily rhythms of many organisms. To what extent this disturbance depends on the intensity and spectral composition of light remain obscure. Here, we measured daily activity patterns of captive blue tits ( Cyanistes caeruleus) exposed to similar intensities of green, red, or white light at night. Birds advanced their onset of activity in the morning under all light colors but more under red and white light than under green light. Offset of activity was slightly delayed in all light colors. The total activity over a 24-h period did not change but birds moved a part of their daily activity into the night. Since the effect of red and white lights are comparable, we tested the influence of light intensity in a follow-up experiment, where we compared the activity of the birds under different intensities of green and white light only. While in the higher range of intensities, the effects of white and green light were comparable; at lower intensities, green light had a less disturbing effect as compared with white light on daily rhythms in blue tits. Our results show that the extent of this disturbance can be mitigated by modulating the spectral characteristics and intensity of outdoor lighting, which is now feasible through the use of LED lighting.

Self-dual spin-3 and 4 theories

International Nuclear Information System (INIS)

Aragone, C.; Khoudeir, A.

1991-08-01

We present self-dual pure spin-3 and 4 actions using the physical relevant Dreibein fields. Since these actions start with a Chern-Simons like kinetic term (and therefore cannot be obtained through dimensional reduction) one might wonder whether they need the presence of auxiliary, ghost-killing fields. It turns out that they must contain, also in this three dimensional case, auxiliary fields. Auxiliary scalars do not break self-duality; their free action does not contain kinetic terms. (author). 12 refs

The light wave flow effect in a plane-parallel layer with a quasi-zero refractive index under the action of bounded light beams

International Nuclear Information System (INIS)

Gadomsky, O. N.; Shchukarev, I. A.

2016-01-01

It is shown that external optical radiation in the 450–1200 nm range can be efficiently transformed under the action of bounded light beams to a surface wave that propagates along the external and internal boundaries of a plane-parallel layer with a quasi-zero refractive index. Reflection regimes with complex and real angles of refraction in the layer are considered. The layer with a quasi-zero refractive index in this boundary problem is located on a highly reflective metal substrate; it is shown that the uniform low reflection of light is achieved in the wavelength range under study.

Induction of DNA-protein crosslinks in human cells by ultraviolet and visible radiations: action spectrum

International Nuclear Information System (INIS)

Peak, J.G.; Peak, M.J.; Sikorski, R.S.; Jones, C.A.

1985-01-01

DNA-protein crosslinking was induced in cultured human P3 teratocarcinoma cells by irradiation with monochromatic radiation with wavelengths in the range 254-434 nm (far-UV, near-UV, and blue light). Wavelength 545 nm green light did not induce these crosslinks, using the method of alkaline elution of the DNA from membrane filters. The action spectrum for the formation of DNA-protein crosslinks revealed two maxima, one in the far-UV spectrum that closely coincided with the relative spectrum of DNA at 254 and 290 nm, and one in the visible light spectrum at 405 nm, which has no counterpart in the DNA spectrum. The primary events for the formation of DNA-protein crosslinks by such long-wavelength radiation probably involve photosensitizers. This dual mechanism for DNA-protein crosslink formation is in strong contrast to the single mechanism for pyrimidine dimer formation in DNA, which apparently has no component in the visible light spectrum

Nonthermal effects of therapeutic ultrasound: the frequency resonance hypothesis.

Science.gov (United States)

Johns, Lennart D

2002-07-01

To present the frequency resonance hypothesis, a possible mechanical mechanism by which treatment with non-thermal levels of ultrasound stimulates therapeutic effects. The review encompasses a 4-decade history but focuses on recent reports describing the effects of nonthermal therapeutic levels of ultrasound at the cellular and molecular levels. A search of MEDLINE from 1965 through 2000 using the terms ultrasound and therapeutic ultrasound. The literature provides a number of examples in which exposure of cells to therapeutic ultrasound under nonthermal conditions modified cellular functions. Nonthermal levels of ultrasound are reported to modulate membrane properties, alter cellular proliferation, and produce increases in proteins associated with inflammation and injury repair. Combined, these data suggest that nonthermal effects of therapeutic ultrasound can modify the inflammatory response. The concept of the absorption of ultrasonic energy by enzymatic proteins leading to changes in the enzymes activity is not novel. However, recent reports demonstrating that ultrasound affects enzyme activity and possibly gene regulation provide sufficient data to present a probable molecular mechanism of ultrasound's nonthermal therapeutic action. The frequency resonance hypothesis describes 2 possible biological mechanisms that may alter protein function as a result of the absorption of ultrasonic energy. First, absorption of mechanical energy by a protein may produce a transient conformational shift (modifying the 3-dimensional structure) and alter the protein's functional activity. Second, the resonance or shearing properties of the wave (or both) may dissociate a multimolecular complex, thereby disrupting the complex's function. This review focuses on recent studies that have reported cellular and molecular effects of therapeutic ultrasound and presents a mechanical mechanism that may lead to a better understanding of how the nonthermal effects of ultrasound may be

Efficacy and mode of action of a noise-sensor light alarm to decrease noise in the pediatric intensive care unit: a prospective, randomized study.

Science.gov (United States)

Jousselme, Chloé; Vialet, Renaud; Jouve, Elisabeth; Lagier, Pierre; Martin, Claude; Michel, Fabrice

2011-03-01

To determine whether a sound-activated light-alarm device could reduce the noise in the central area of our pediatric intensive care unit and to determine whether this reduction was significant enough to decrease the noise that could be perceived by a patient located in a nearby room. The secondary objective was to determine the mode of action of the device. In a 16-bed pediatric and neonatal intensive care unit, a large and clearly noticeable sound-activated light device was set in the noisiest part of the central area of our unit, and noise measurements were made in the central area and in a nearby room. In a prospective, quasi-experimental design, sound levels were compared across three different situations--no device present, device present and turned on, and device present but turned off--and noise level measurements were made over a total of 18 days. None. Setting a sound-activated light device on or off. When the device was present, the noise was about 2 dB lower in the central area and in a nearby room, but there was no difference in noise level with the device turned on vs. turned off. The noise decrease in the central area was of limited importance but was translated in a nearby room. The sound-activated light device did not directly decrease noise when turned on, but repetition of the visual signal throughout the day raised staff awareness of noise levels over time.

Oxidative desulfurization of model diesel via dual activation by a protic ionic liquid

Energy Technology Data Exchange (ETDEWEB)

Lü, Hongying, E-mail: hylv@ytu.edu.cn; Wang, Shunan; Deng, Changliang; Ren, Wanzhong; Guo, Baocun

2014-08-30

Highlights: • A protic ionic liquid, [Hnmp]HCOO, was used as in ODS. • The mechanism of ODS was involved in dual activation by the PIL. • The [Hnmp]HCOO exhibited high catalytic activity in ODS. • The amounts of PILs and oxidant dosage play vital roles in desulfurization system. • This system can be recycled five times with an unnoticeable decrease in activity. - Abstract: A novel and green carboxylate-anion-based protic ionic liquid (PIL), [Hnmp]HCOO, was prepared through a simple and atom economic neutralization reaction between N-methyl-2-pyrrolidonium (NMP) and formic acids. Both FT-IR spectra and {sup 1}H NMR confirmed its simple salt structure. [Hnmp]HCOO exhibited so high catalytic activity that the dibenzothiophene (DBT) removal reached 99% at 50 °C in 3 h under conditions of V{sub PIL}/V{sub model} {sub oil} = 1:10 and H{sub 2}O{sub 2}/DBT (O/S, molar ratio) = 5. The catalytic oxidation reactivity of S-compounds was found to be in the order of DBT > 4,6-dimethyldibenzothiophene (4,6-DMDBT) > benzothiophene (BT). The investigation on mechanism showed that oxidative desulfurization was realized through dual activation of PIL. Moreover, [Hnmp]HCOO can be recycled for five times with an unnoticeable decrease in desulfurization activity.

Oxidative desulfurization of model diesel via dual activation by a protic ionic liquid

International Nuclear Information System (INIS)

Lü, Hongying; Wang, Shunan; Deng, Changliang; Ren, Wanzhong; Guo, Baocun

2014-01-01

Highlights: • A protic ionic liquid, [Hnmp]HCOO, was used as in ODS. • The mechanism of ODS was involved in dual activation by the PIL. • The [Hnmp]HCOO exhibited high catalytic activity in ODS. • The amounts of PILs and oxidant dosage play vital roles in desulfurization system. • This system can be recycled five times with an unnoticeable decrease in activity. - Abstract: A novel and green carboxylate-anion-based protic ionic liquid (PIL), [Hnmp]HCOO, was prepared through a simple and atom economic neutralization reaction between N-methyl-2-pyrrolidonium (NMP) and formic acids. Both FT-IR spectra and 1 H NMR confirmed its simple salt structure. [Hnmp]HCOO exhibited so high catalytic activity that the dibenzothiophene (DBT) removal reached 99% at 50 °C in 3 h under conditions of V PIL /V model oil = 1:10 and H 2 O 2 /DBT (O/S, molar ratio) = 5. The catalytic oxidation reactivity of S-compounds was found to be in the order of DBT > 4,6-dimethyldibenzothiophene (4,6-DMDBT) > benzothiophene (BT). The investigation on mechanism showed that oxidative desulfurization was realized through dual activation of PIL. Moreover, [Hnmp]HCOO can be recycled for five times with an unnoticeable decrease in desulfurization activity

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

Science.gov (United States)

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

2018-08-01

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

Spectrophotometric flow-injection analysis assay of tetracycline antibiotics using a dual light-emitting diode based detector

Directory of Open Access Journals (Sweden)

Prinya Masawat

2008-02-01

Full Text Available In this paper, a small dual light-emitting diode (LED-based detector for FIA process analyser has been designed. The detector’s optical parts comprise a flow-through cell, a dual-blue LED and a photodiode. Neither mirrors nor lenses are used. The optical path for the first LED detects the blank, while the other LED detects the sample. The detector’s electronic components including a signal amplifier and an A/D converter are integrated on one small board connected to a PC for measuring the results. The designed spectrophotometric detector was used for the determination of tetracycline antibiotics. Uranyl acetate was used as a reagent forming orange-red complexes with the drugs in N,N– dimethylformamide. The complexes show absorption maxima at 410, 416 and 408 nm for tetracycline hydrochloride (TCH, chlortetracycline hydrochloride (CTCH, and doxycycline hydrochloride (DCH, respectively. The detection limit was found to be 0.38, 0.75, 1.44 µg mL-1 and the linear range was obtained at 1.0-3.0, 3.0-5.0, and 3.0-10.0 µg mL-1 for TCH, CTCH and DCH, respectively. The proposed method has been successfully applied to the determination of tetracycline antibiotic residues in milk samples. Moreover, this method is an environmentally friendly approach and suitable for routine analysis.

Converging Light, Energy and Hormonal Signaling Control Meristem Activity, Leaf Initiation, and Growth1[CC-BY

Science.gov (United States)

Mohammed, Binish; Bilooei, Sara Farahi; Grove, Elliot; Railo, Saana; Palme, Klaus

2018-01-01

The development of leaf primordia is subject to light control of meristematic activity. Light regulates the expression of thousands of genes with roles in cell proliferation, organ development, and differentiation of photosynthetic cells. Previous work has highlighted roles for hormone homeostasis and the energy-dependent Target of Rapamycin (TOR) kinase in meristematic activity, yet a picture of how these two regulatory mechanisms depend on light perception and interact with each other has yet to emerge. Their relevance beyond leaf initiation also is unclear. Here, we report the discovery that the dark-arrested meristematic region of Arabidopsis (Arabidopsis thaliana) experiences a local energy deprivation state and confirm previous findings that the PIN1 auxin transporter is diffusely localized in the dark. Light triggers a rapid removal of the starvation state and the establishment of PIN1 polar membrane localization consistent with auxin export, both preceding the induction of cell cycle- and cytoplasmic growth-associated genes. We demonstrate that shoot meristematic activity can occur in the dark through the manipulation of auxin and cytokinin activity as well as through the activation of energy signaling, both targets of photomorphogenesis action, but the organ developmental outcomes differ: while TOR-dependent energy signals alone stimulate cell proliferation, the development of a normal leaf lamina requires photomorphogenesis-like hormonal responses. We further show that energy signaling adjusts the extent of cell cycle activity and growth of young leaves non-cellautonomously to available photosynthates and leads to organs constituted of a greater number of cells developing under higher irradiance. This makes energy signaling perhaps the most important biomass growth determinant under natural, unstressed conditions. PMID:29284741

Therapeutic treatments potentially mediated by melatonin receptors: potential clinical uses in the prevention of osteoporosis, cancer and as an adjuvant therapy.

Science.gov (United States)

Witt-Enderby, Paula A; Radio, Nicholas M; Doctor, John S; Davis, Vicki L

2006-11-01

Melatonin's therapeutic potential is grossly underestimated because its functional roles are diverse and its mechanism(s) of action are complex and varied. Melatonin produces cellular effects via a variety of mechanisms in a receptor independent and dependent manner. In addition, melatonin is a chronobiotic agent secreted from the pineal gland during the hours of darkness. This diurnal release of melatonin impacts the sensitivity of melatonin receptors throughout a 24-hr period. This changing sensitivity probably contributes to the narrow therapeutic window for use of melatonin in treating sleep disorders, that is, at the light-to-dark (dusk) or dark-to-light (dawn) transition states. In addition to the cyclic changes in melatonin receptors, many genes cycle over the 24-hr period, independent or dependent upon the light/dark cycle. Interestingly, many of these genes support a role for melatonin in modulating metabolic and cardiovascular physiology as well as bone metabolism and immune function and detoxification of chemical agents and cancer reduction. Melatonin also enhances the actions of a variety of drugs or hormones; however, the role of melatonin receptors in modulating these processes is not known. The goal of this review is to summarize the evidence related to the utility of melatonin as a therapeutic agent by focusing on its other potential uses besides sleep disorders. In particular, its use in cancer prevention, osteoporosis and, as an adjuvant to other therapies are discussed. Also, the role that melatonin and, particularly, its receptors play in these processes are highlighted.

White organic light-emitting devices based on blue fluorescent dye combined with dual sub-monolayer

Energy Technology Data Exchange (ETDEWEB)

Yang, Huishan, E-mail: yanghuishan1697@163.com

2013-10-15

White organic light-emitting devices have been realized by using highly blue fluorescent dye 4,4′-Bis(2,2-diphenyl-ethen-1-yl)-4,4′-di-(tert-butyl)phenyl(p-TDPVBi) and [2-methyl-6-[2-(2, 3,6,7-tetrahydro-1H, red fluorescent dye 5H-benzo[ij] quinolizin-9-yl) ethenyl]-4H-pyran-4-ylidene] propane-dinitrile(DCM2), together with well known green fluorescent dye quinacridone (QAD). The fabrication of multilayer WOLEDs did not involve the hard-to-control doping process. The structure of the device is ITO/m-MTDATA (45 nm)/NPB(8 nm)/p-TDPVBi(15 nm)/DCM2(x nm)/Alq{sub 3} (5 nm)/QAD(y nm)/Alq{sub 3}(55 nm)/LiF(1 nm)/Al, where 4,4′,4′′-tris{N,-(3-methylphenyl)-N-phenylamine}triphenylamine (m-MTDATA) acts as a hole injection layer, N,N′-bis-(1-naphthyl)-N, N′-diphenyl-1, 1′-biph-enyl-4, 4′-diamine (NPB) acts as a hole transport layer, p-TDPVBi acts as a blue emitting layer, DCM2 acts as a red emitting layer, QAD acts as a green emitting layer, tris-(8-hydroxyquinoline) aluminum (Alq{sub 3}) acts as an electron transport layer, and WOLEDs of devices A, B, C and D are different in layer thickness of DCM2 and QAD, respectively. To change the thickness of dual sub-monolayer DCM2 and QAD, the WOLEDs were obtained. When x, y=0.05, 0.1, the Commission Internationale de 1’Eclairage (CIE) coordinates of the device change from (0.4458, 0.4589) at 3 V to (0.3137, 0.3455) at 12 V that are well in the white region, and the color temperature and color rendering index were 5348 K and 85 at 8 V, respectively. Its maximum luminance was 35260 cd/m{sup 2} at 12 V, and maximum current efficiency and maximum power efficiency were 13.54 cd/A at 12 V and 6.68 lm/W at 5 V, respectively. Moreover, the current efficiency is largely insensitive to the applied voltage. The electroluminescence intensity of white EL devices varied only little at deferent dual sub-monolayer. Device D exhibited relatively high color rendering index (CRI) in the range of 88–90, which was essentially

Light-dependent electrogenic activity of cyanobacteria.

Directory of Open Access Journals (Sweden)

John M Pisciotta

2010-05-01

Full Text Available Cyanobacteria account for 20-30% of Earth's primary photosynthetic productivity and convert solar energy into biomass-stored chemical energy at the rate of approximately 450 TW [1]. These single-cell microorganisms are resilient predecessors of all higher oxygenic phototrophs and can be found in self-sustaining, nitrogen-fixing communities the world over, from Antarctic glaciers to the Sahara desert [2].Here we show that diverse genera of cyanobacteria including biofilm-forming and pelagic strains have a conserved light-dependent electrogenic activity, i.e. the ability to transfer electrons to their surroundings in response to illumination. Naturally-growing biofilm-forming photosynthetic consortia also displayed light-dependent electrogenic activity, demonstrating that this phenomenon is not limited to individual cultures. Treatment with site-specific inhibitors revealed the electrons originate at the photosynthetic electron transfer chain (P-ETC. Moreover, electrogenic activity was observed upon illumination only with blue or red but not green light confirming that P-ETC is the source of electrons. The yield of electrons harvested by extracellular electron acceptor to photons available for photosynthesis ranged from 0.05% to 0.3%, although the efficiency of electron harvesting likely varies depending on terminal electron acceptor.The current study illustrates that cyanobacterial electrogenic activity is an important microbiological conduit of solar energy into the biosphere. The mechanism responsible for electrogenic activity in cyanobacteria appears to be fundamentally different from the one exploited in previously discovered electrogenic bacteria, such as Geobacter, where electrons are derived from oxidation of organic compounds and transported via a respiratory electron transfer chain (R-ETC [3], [4]. The electrogenic pathway of cyanobacteria might be exploited to develop light-sensitive devices or future technologies that convert solar

A Dual Luciferase Reporter System for B. burgdorferi Measures Transcriptional Activity during Tick-Pathogen Interactions

Directory of Open Access Journals (Sweden)

Philip P. Adams

2017-05-01

Full Text Available Knowledge of the transcriptional responses of vector-borne pathogens at the vector-pathogen interface is critical for understanding disease transmission. Borrelia (Borreliella burgdorferi, the causative agent of Lyme disease in the United States, is transmitted by the bite of infected Ixodes sp. ticks. It is known that B. burgdorferi has altered patterns of gene expression during tick acquisition, persistence and transmission. Recently, we and others have discovered in vitro expression of RNAs found internal, overlapping, and antisense to annotated open reading frames in the B. burgdorferi genome. However, there is a lack of molecular genetic tools for B. burgdorferi for quantitative, strand-specific, comparative analysis of these transcripts in distinct environments such as the arthropod vector. To address this need, we have developed a dual luciferase reporter system to quantify B. burgdorferi promoter activities in a strand-specific manner. We demonstrate that constitutive expression of a B. burgdorferi codon-optimized Renilla reniformis luciferase gene (rlucBb allows normalization of the activity of a promoter of interest when fused to the B. burgdorferi codon-optimized Photinus pyralis luciferase gene (flucBb on the same plasmid. Using the well characterized, differentially regulated, promoters for flagellin (flaBp, outer surface protein A (ospAp and outer surface protein C (ospCp, we document the efficacy of the dual luciferase system for quantitation of promoter activities during in vitro growth and in infected ticks. Cumulatively, the dual luciferase method outlined herein is the first dual reporter system for B. burgdorferi, providing a novel and highly versatile approach for strand-specific molecular genetic analyses.

Active Light Shaping using GPC

DEFF Research Database (Denmark)

Glückstad, Jesper; Palima, Darwin; Villangca, Mark Jayson

security, parallel laser marking and labelling and recently in contemporary biophotonics applications such as for adaptive and parallel two-photon optogenetics and neurophotonics. We will present our most recent GPC developments geared towards these applications. First, a compact GPC Light Shaper...... implementation based on our latest theoretical derivations is used to demonstrate the benefits for typical applications where lasers have to be actively shaped into particular light patterns. We then show the potential of GPC for biomedical and multispectral applications where we experimentally demonstrate...

Green functions in a super self-dual Yang-Mills background

International Nuclear Information System (INIS)

McArthur, I.N.

1984-01-01

In euclidean supersymmetric theories of chiral superfields and vector superfields coupled to a super-self-dual Yang-Mills background, we define Green functions for the Laplace-type differential operators which are obtained from the quadratic parot the action. These Green functions are expressed in terms of the Green function on the space of right chiral superfields, and an explicit expression for the right chiral Green function in the fundamental representation of an SU(n) gauge group is presented using the supersymmetric version of the ADHM formalism. The superfield kernels associated with the Laplace-type operators are used to obtain the one-loop quantum corrections to the super-self-dual Yang-Mills action, and also to provide a superfield version of the super-index theorems for the components of chiral superfields in a self-dual background. (orig.)

Dual-systems and the development of reasoning: competence-procedural systems.

Science.gov (United States)

Overton, Willis F; Ricco, Robert B

2011-03-01

Dual-system, dual-process, accounts of adult cognitive processing are examined in the context of a self-organizing relational developmental systems approaches to cognitive growth. Contemporary adult dual-process accounts describe a linear architecture of mind entailing two split-off, but interacting systems; a domain general, content-free 'analytic' system (system 2) and a domain specific highly contextualized 'heuristic' system (system 1). In the developmental literature on deductive reasoning, a similar distinction has been made between a domain general competence (reflective, algorithmic) system and a domain specific procedural system. In contrast to the linear accounts offered by empiricist, nativist, and/or evolutionary explanations, the dual competence-procedural developmental perspective argues that the mature systems emerge through developmental transformations as differentiations and intercoordinations of an early relatively undifferentiated action matrix. This development, whose microscopic mechanism is action-in-the-world, is characterized as being embodied, nonlinear, and epigenetic. WIREs Cogni Sci 2011 2 231-237 DOI: 10.1002/wcs.120 For further resources related to this article, please visit the WIREs website. © 2010 John Wiley & Sons, Ltd.

The therapeutic potential of CRTH2/DP2 beyond allergy and asthma.

Science.gov (United States)

Jandl, Katharina; Heinemann, Akos

2017-11-01

Prostaglandin (PG) D 2 has been in the focus of research for quite a long time, but its biological effects and its roles in human disease are still not fully characterized. When in 2001 a second major PGD 2 receptor termed chemoattractant receptor homologue expressed on Th2 cells (CRTH2; alternative name DP2) was discovered, diverse investigations started to shed more light on the complex and often controversial actions of the prostaglandin. With various immunomodulating effects, such as induction of migration, activation, and cytokine release of leukocytes observed both in vivo and in vitro, CRTH2 has emerged as a promising target for the treatment of allergic diseases. However, with more and more research being performed on CRTH2, it has also become clear that its biological actions are far more diverse than expected at the beginning. In this review, we aim to summarize the roles that PGD 2 - and CRTH2 in particular - might play in diseases of the central nervous system, kidney, intestine, lung, hair and skin, bone and cartilage, and in cancer. Based on current data we propose that blocking CRTH2 might be a potential therapeutic approach to numerous conditions beyond classical allergic diseases and asthma. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Dual beam vidicon digitizer

International Nuclear Information System (INIS)

Evans, T.L.

1976-01-01

A vidicon waveform digitizer which can simultaneously digitize two independent signals has been developed. Either transient or repetitive waveforms can be digitized with this system. A dual beam oscilloscope is used as the signal input device. The light from the oscilloscope traces is optically coupled to a television camera, where the signals are temporarily stored prior to digitizing

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

Science.gov (United States)

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

2010-12-15

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

Linear biocompatible glyco-polyamidoamines as dual action mode virus infection inhibitors with potential as broad-spectrum microbicides for sexually transmitted diseases

Science.gov (United States)

Mauro, Nicolò; Ferruti, Paolo; Ranucci, Elisabetta; Manfredi, Amedea; Berzi, Angela; Clerici, Mario; Cagno, Valeria; Lembo, David; Palmioli, Alessandro; Sattin, Sara

2016-09-01

The initial steps of viral infections are mediated by interactions between viral proteins and cellular receptors. Blocking the latter with high-affinity ligands may inhibit infection. DC-SIGN, a C-type lectin receptor expressed by immature dendritic cells and macrophages, mediates human immunodeficiency virus (HIV) infection by recognizing mannose clusters on the HIV-1 gp120 envelope glycoprotein. Mannosylated glycodendrimers act as HIV entry inhibitors thanks to their ability to block this receptor. Previously, an amphoteric, but prevailingly cationic polyamidoamine named AGMA1 proved effective as infection inhibitor for several heparan sulfate proteoglycan-dependent viruses, such as human papilloma virus HPV-16 and herpes simplex virus HSV-2. An amphoteric, but prevailingly anionic PAA named ISA23 proved inactive. It was speculated that the substitution of mannosylated units for a limited percentage of AGMA1 repeating units, while imparting anti-HIV activity, would preserve the fundamentals of its HPV-16 and HSV-2 infection inhibitory activity. In this work, four biocompatible linear PAAs carrying different amounts of mannosyl-triazolyl pendants, Man-ISA7, Man-ISA14, Man-AGMA6.5 and Man-AGMA14.5, were prepared by reaction of 2-(azidoethyl)-α-D-mannopyranoside and differently propargyl-substituted AGMA1 and ISA23. All mannosylated PAAs inhibited HIV infection. Both Man-AGMA6.5 and Man-AGMA14.5 maintained the HPV-16 and HSV-2 activity of the parent polymer, proving broad-spectrum, dual action mode virus infection inhibitors.

Dual pressurized light water reactor producing 2000 M We

Energy Technology Data Exchange (ETDEWEB)

NONE

2010-10-15

The dual unit optimizer 2000 M We (Duo2000) is proposed as a new design concept for large nuclear power plant. Duo is being designed to meet economic and safety challenges facing the 21 century green and sustainable energy industry. Duo2000 has two nuclear steam supply systems (NSSS) of the unit nuclear optimizer (Uno) pressurized water reactor (PWR) in a single containment so as to double the capacity of the plant. Uno is anchored to the optimized power reactor 1000 M We (OPR1000) of the Korea Hydro and Nuclear Power Co., Ltd. The concept of Duo can be extended to any number of PWRs or pressurized heavy water reactors (PHWR s), or even boiling water reactor (BWRs). Once proven in water reactors, the technology may even be expanded to gas cooled, liquid metal cooled, and molten salt cooled reactors. In particular, since it is required that the small and medium sized reactors (SMRs) be built as units, the concept of Duo2000 will apply to SMRs as well. With its in-vessel retention as severe accident management strategy, Duo can not only put the single most querulous PWR safety issue to end, but also pave ways to most promising large power capacity dispensing with huge redesigning cost for generation III + nuclear systems. The strengths of Duo2000 include reducing the cost of construction by decreasing the number of containment buildings from two to one, minimizing the cost of NSSS and control systems by sharing between the dual units, and lessening the maintenance cost by uniting NSSS. The technology can further be extended to coupling modular reactors as dual, triple, or quadruple units to increase their economics, thus accelerating the commercialization as well as the customization of SMRs. (Author)

Uncertainty Driven Action (UDA) model: A foundation for unifying perspectives on design activity

DEFF Research Database (Denmark)

Cash, Philip; Kreye, Melanie

2017-01-01

are linked via uncertainty perception. The foundations of the UDA model in the design literature are elaborated in terms of the three core actions and their links to designer cognition and behaviour, utilising definitions and concepts from Activity Theory. The practical relevance and theoretical......This paper proposes the Uncertainty Driven Action (UDA) model, which unifies the fragmented literature on design activity. The UDA model conceptualises design activity as a process consisting of three core actions: information action, knowledge-sharing action, and representation action, which...... contributions of the UDA model are discussed. This paper contributes to the design literature by offering a comprehensive formalisation of design activity of individual designers, which connects cognition and action, to provide a foundation for understanding previously disparate descriptions of design activity....

Light-Intensity Physical Activity and All-Cause Mortality.

Science.gov (United States)

Loprinzi, Paul D

2017-07-01

Research demonstrates that moderate-to-vigorous physical activity (MVPA) is associated with a reduced risk of all-cause mortality. Few studies have examined the effects of light-intensity physical activity on mortality. Therefore, the purpose of this study was to examine the association between objectively measured light-intensity physical activity and all-cause mortality risk. Longitudinal. National Health and Nutrition Examination Survey 2003-2006 with follow-up through December 31, 2011. Five thousand five hundred seventy-five U.S. adults. Participants wore an accelerometer for at least 4 days and completed questionnaires to assess sociodemographics and chronic disease information, with blood samples taken to assess biological markers. Follow-up mortality status was assessed via death certificate data from the National Death Index. Cox proportional hazard model. After adjusting for accelerometer-determined MVPA, age, gender, race-ethnicity, cotinine, weight status, poverty level, C-reactive protein, and comorbid illness, for every 60-minute increase in accelerometer-determined light-intensity physical activity, participants had a 16% reduced hazard of all-cause mortality (hazard ratio = .84; 95% confidence interval: .78-.91; p physical activity was inversely associated with all-cause mortality risk, independent of age, MVPA, and other potential confounders. In addition to MVPA, promotion of light-intensity physical activity is warranted.

Dual fluorescence of single LH2 antenna nanorings

International Nuclear Information System (INIS)

Freiberg, A.; Raetsep, M.; Timpmann, K.; Trinkunas, G.

2004-01-01

A dual nature of fluorescence from LH2 pigment-protein complexes, which is a part of the light harvesting system of purple bacteria, is confirmed by fluorescence-lifetime dependence on recording wavelength and spectrally selective spectroscopy. An analysis based on the Holstein molecular crystal model, modified by allowing diagonal disorder, suggests coexistence of large- and small-radius self-trapped excitons, which serve as the origin of the dual fluorescence

The therapeutic physical Culture in the rehabilitation to asthmatic students

Directory of Open Access Journals (Sweden)

Manuel Alejandro Romero-León

2016-05-01

Full Text Available Treating asthmatic students in the university environment has been a ministerial concern. Multiple actions aimed at preparing teachers to conduct the teaching of therapeutic physical culture are developed from the methodological work. In it offered theoretical, methodological and experiential tools for therapeutic exercises generate a developer student learning. Nevertheless, there are still limitations that reveal the need to give continuity to these intentions. One is the traditional approach of the exercises for therapeutic purposes. If we consider that today's society demands the formation of a subject becomes heir and transmitter of a culture of physical activity that achieves deal with their conditions, increasing growing life expectancy, then more than rehabilitation the physical must achieve a comprehensive educational impact.

Application of Conformational Space Search in Drug Action | Adikwu ...

African Journals Online (AJOL)

The role of conformational space in drug action is presented. Two examples of molecules in different therapeutic groups are presented. Conformational space search will lead to isolating the exact conformation with the desired medicinal properties. Many conformations of a plant isolate may exist which are active, weakly ...

Social Justice Activism: Feminism and Strategies for Action

Science.gov (United States)

Fernflores, Rachel

2016-01-01

Success in social justice activism often hinges on judging when to employ the most effective strategy for action. Strategies for action include militancy, peaceful protest, and sometimes, engaging in a longer term program of "marginal gains." The militant feminism of many 19th century suffragettes, such as Emmeline Pankhurst, is a good…

Marijuana-based Drugs: Innovative Therapeutics or Designer Drugs of Abuse?

OpenAIRE

Seely, Kathryn A.; Prather, Paul L.; James, Laura P.; Moran, Jeffery H.

2011-01-01

Marijuana has been used recreationally and medicinally for centuries. The principle psychoactive component, Δ9-tetrahydrocannabinol (Δ9-THC), activates CB1 cannabinoid receptors (CB1Rs). CB1R agonists and antagonists could potentially treat a wide variety of diseases; unfortunately, therapeutic doses produce unacceptable psychiatric effects. “K2” or “Spice” (K2/Spice), an emerging drug of abuse, exhibits psychotropic actions via CB1R activation. Because of structural dissimilarity to Δ9-THC, ...

Dual-color bioluminescent sensor proteins for therapeutic drug monitoring of antitumor antibodies

NARCIS (Netherlands)

van Rosmalen, M.; Ni, Y.; Vervoort, D.F.M.; Arts, R.; Ludwig, S.K.J.; Merkx, M.

2018-01-01

Monitoring the levels of therapeutic antibodies in individual patients would allow patient-specific dose optimization, with the potential for major therapeutic and financial benefits. Our group recently developed a new platform of bioluminescent sensor proteins (LUMABS; LUMinescent AntiBody Sensor)

Investigation of naphthofuran moiety as potential dual inhibitor against BACE-1 and GSK-3β: molecular dynamics simulations, binding energy, and network analysis to identify first-in-class dual inhibitors against Alzheimer's disease.

Science.gov (United States)

Kumar, Akhil; Srivastava, Gaurava; Srivastava, Swati; Verma, Seema; Negi, Arvind S; Sharma, Ashok

2017-08-01

BACE-1 and GSK-3β are potential therapeutic drug targets for Alzheimer's disease. Recently, both the targets received attention for designing dual inhibitors for Alzheimer's disease. Until now, only two-scaffold triazinone and curcumin have been reported as BACE-1 and GSK-3β dual inhibitors. Docking, molecular dynamics, clustering, binding energy, and network analysis of triazinone derivatives with BACE-1 and GSK-3β was performed to get molecular insight into the first reported dual inhibitor. Further, we designed and evaluated a naphthofuran series for its ability to inhibit BACE-1 and GSK-3β with the computational approaches. Docking study of naphthofuran series showed a good binding affinity towards both the targets. Molecular dynamics, binding energy, and network analysis were performed to compare their binding with the targets and amino acids responsible for binding. Naphthofuran series derivatives showed good interaction within the active site residues of both of the targets. Hydrogen bond occupancy and binding energy suggested strong binding with the targets. Dual-inhibitor binding was mostly governed by the hydrophobic interactions for both of the targets. Per residue energy decomposition and network analysis identified the key residues involved in the binding and inhibiting BACE-1 and GSK-3β. The results indicated that naphthofuran series derivative 11 may be a promising first-in-class dual inhibitor against BACE-1 and GSK-3β. This naphthofuran series may be further explored to design better dual inhibitors. Graphical abstract Naphthofuran derivative as a dual inhibitor for BACE-1 and GSK-3β.

Spatially Resolved Imaging and Spectroscopy of Candidate Dual Active Galactic Nuclei

Science.gov (United States)

McGurk, R. C.; Max, C. E.; Medling, A. M.; Shields, G. A.; Comerford, J. M.

2015-09-01

When galaxies merge, both central supermassive black holes are immersed in a dense and chaotic environment. If there is sufficient gas in the nuclear regions, one expects to see close pairs of active galactic nuclei (AGNs), or dual AGNs, in a fraction of galaxy mergers. However, finding them remains a challenge. The presence of double-peaked [O iii] emission lines has been proposed as a technique to select dual AGNs efficiently. We studied a sample of double-peaked narrow [O iii] emitting AGNs from Sloan Digital Sky Survey (SDSS) DR7. By obtaining new and archival high spatial resolution images taken with the Keck II Laser Guide Star Adaptive Optics system and the near-infrared camera NIRC2, we show that 30% of 140 double-peaked [O iii] emission line SDSS AGNs have two spatial components within a 3″ radius. However, spatially resolved spectroscopy or X-ray observations are needed to confirm these galaxy pairs as systems containing two AGNs. We followed up three spatially double candidate dual AGNs with integral field spectroscopy from Keck OSIRIS and 10 candidates with long-slit spectroscopy from the Shane Kast Double Spectrograph at Lick Observatory. We find that the double-peaked emission lines in our sample of 12 candidates are caused by: one dual AGN (SDSS J114642.47+511029.6), one confirmed outflow and four likely outflows, two pairs of star-forming galaxies, one candidate indeterminate due to sky line interference, and three AGNs with spatially coincident double [O iii] peaks, likely due to unresolved complex narrow line kinematics, outflows, binary AGN, or small-scale jets.

SPATIALLY RESOLVED IMAGING AND SPECTROSCOPY OF CANDIDATE DUAL ACTIVE GALACTIC NUCLEI

Energy Technology Data Exchange (ETDEWEB)

McGurk, R. C.; Max, C. E. [Astronomy Department and UCO-Lick Observatory, University of California, Santa Cruz, CA 95064 (United States); Medling, A. M. [Research School of Astronomy and Astrophysics, Australian National University, Mount Stromlo Observatory, Cotter Road, Weston Creek, ACT 2611 (Australia); Shields, G. A. [Laguna Falls Institute for Astrophysics, Austin, TX 78746 (United States); Comerford, J. M., E-mail: rosalie.mcgurk@gmail.com, E-mail: max@ucolick.org, E-mail: anne.medling@anu.edu.au, E-mail: shields@lfastro.org, E-mail: julie.comerford@colorado.edu [Department of Astrophysical and Planetary Sciences, University of Colorado, Boulder, CO 80309 (United States)

2015-09-20

When galaxies merge, both central supermassive black holes are immersed in a dense and chaotic environment. If there is sufficient gas in the nuclear regions, one expects to see close pairs of active galactic nuclei (AGNs), or dual AGNs, in a fraction of galaxy mergers. However, finding them remains a challenge. The presence of double-peaked [O iii] emission lines has been proposed as a technique to select dual AGNs efficiently. We studied a sample of double-peaked narrow [O iii] emitting AGNs from Sloan Digital Sky Survey (SDSS) DR7. By obtaining new and archival high spatial resolution images taken with the Keck II Laser Guide Star Adaptive Optics system and the near-infrared camera NIRC2, we show that 30% of 140 double-peaked [O iii] emission line SDSS AGNs have two spatial components within a 3″ radius. However, spatially resolved spectroscopy or X-ray observations are needed to confirm these galaxy pairs as systems containing two AGNs. We followed up three spatially double candidate dual AGNs with integral field spectroscopy from Keck OSIRIS and 10 candidates with long-slit spectroscopy from the Shane Kast Double Spectrograph at Lick Observatory. We find that the double-peaked emission lines in our sample of 12 candidates are caused by: one dual AGN (SDSS J114642.47+511029.6), one confirmed outflow and four likely outflows, two pairs of star-forming galaxies, one candidate indeterminate due to sky line interference, and three AGNs with spatially coincident double [O iii] peaks, likely due to unresolved complex narrow line kinematics, outflows, binary AGN, or small-scale jets.

SPATIALLY RESOLVED IMAGING AND SPECTROSCOPY OF CANDIDATE DUAL ACTIVE GALACTIC NUCLEI

International Nuclear Information System (INIS)

McGurk, R. C.; Max, C. E.; Medling, A. M.; Shields, G. A.; Comerford, J. M.

2015-01-01

When galaxies merge, both central supermassive black holes are immersed in a dense and chaotic environment. If there is sufficient gas in the nuclear regions, one expects to see close pairs of active galactic nuclei (AGNs), or dual AGNs, in a fraction of galaxy mergers. However, finding them remains a challenge. The presence of double-peaked [O iii] emission lines has been proposed as a technique to select dual AGNs efficiently. We studied a sample of double-peaked narrow [O iii] emitting AGNs from Sloan Digital Sky Survey (SDSS) DR7. By obtaining new and archival high spatial resolution images taken with the Keck II Laser Guide Star Adaptive Optics system and the near-infrared camera NIRC2, we show that 30% of 140 double-peaked [O iii] emission line SDSS AGNs have two spatial components within a 3″ radius. However, spatially resolved spectroscopy or X-ray observations are needed to confirm these galaxy pairs as systems containing two AGNs. We followed up three spatially double candidate dual AGNs with integral field spectroscopy from Keck OSIRIS and 10 candidates with long-slit spectroscopy from the Shane Kast Double Spectrograph at Lick Observatory. We find that the double-peaked emission lines in our sample of 12 candidates are caused by: one dual AGN (SDSS J114642.47+511029.6), one confirmed outflow and four likely outflows, two pairs of star-forming galaxies, one candidate indeterminate due to sky line interference, and three AGNs with spatially coincident double [O iii] peaks, likely due to unresolved complex narrow line kinematics, outflows, binary AGN, or small-scale jets

Slow light based on plasmon-induced transparency in dual-ring resonator-coupled MDM waveguide system

International Nuclear Information System (INIS)

Zhan, Shiping; Li, Hongjian; He, Zhihui; Li, Boxun; Yang, Hui; Cao, Guangtao

2014-01-01

We report a theoretical and numerical investigation of the plasmon-induced transparency (PIT) effect in a dual-ring resonator-coupled metal–dielectric–metal waveguide system. A transfer matrix method (TMM) is introduced to analyse the transmission and dispersion properties in the transparency window. A tunable PIT is realized in a constant separation design. The phase dispersion and slow-light effect are discussed in both the resonance and non-resonance conditions. Finally, a propagation constant based on the TMM is derived for the periodic system. It is found that the group index in the transparency window of the proposed structure can be easily tuned by the period p, which provides a new understanding, and a group index ∼51 is achieved. The quality factor of resonators can also be effective in adjusting the dispersion relation. These observations could be helpful to fundamental research and applications for integrated plasmonic devices. (paper)

Impaired bacterial attachment to light activated Ni-Ti alloy

International Nuclear Information System (INIS)

Chrzanowski, Wojciech; Valappil, Sabeel P.; Dunnill, Charles W.; Abou Neel, Ensanya A.; Lee, Kevin; Parkin, Ivan P.; Wilson, Michael; Armitage, David A.; Knowles, Jonathan C.

2010-01-01

Ni-Ti alloy due to its unique mechanical properties, is used for many types of implants. Failure of these implants can be attributed to many different factors; however infections are a common problem. In this paper, the attachment of the bacteria, Staphylococcus aureus, to the Ni-Ti surface modified by a range of processes with and without of light activation (used to elicit antimicrobial properties of materials) was assessed and related to different surface characteristics. Before the light activation the number of bacterial colony forming units was the greatest for the samples thermally oxidised at 600 deg. C. This sample and the spark oxidised samples showed the highest photocatalytic activity but only the thermally oxidised samples at 600 deg. C showed a significant drop of S. aureus attachment. The findings in this study indicate that light activation and treating samples at 600 deg. C is a promising method for Ni-Ti implant applications with inherent antimicrobial properties. Light activation was shown to be an effective way to trigger photocatalytic reactions on samples covered with relatively thick titanium dioxide via accumulation of photons in the surface and a possible increase in defects which may result in free oxygen. Moreover, light activation caused an increase in the total surface energy.

Nuclear data for the production of therapeutic radionuclides. Summary report of third research coordination meeting

International Nuclear Information System (INIS)

Sublet, J.-Ch.; Capote Noy, R.

2006-08-01

A summary is given of the Third Research Coordination Meeting on Nuclear Data for the Production of Therapeutic Radionuclides. The new library of evaluated cross-section will cover reactor and accelerator production of therapeutic radionuclides to appropriate specific activities and purity, along with the relevant decay data. A few new reactions were added at this meeting. Technical discussions and the resulting work plan to conclude the data evaluation activities are summarized for every reaction path. Timescales and agreed actions to deliver the database and Technical Report are also given. (author)

Dual-layer ultrathin film optics: I. Theory and analysis

International Nuclear Information System (INIS)

Wang, Qian; Lim, Kim Peng

2015-01-01

This paper revisits dual-layer ultrathin film optics, which can be used for functional graded refractive index thin film stack. We present the detailed derivation including s-polarized and p-polarized light under arbitrary incidence angle showing the equivalence between the dual-layer ultrathin films and a negative birefringent thin film and also the approximations made during the derivation. Analysis of the approximations shows the influence of thickness of dual-layer thin films, the incidence angle and desired refractive index of the birefringent film. Numerical comparison between the titanium dioxide/aluminum oxide based dual-layer ultrathin film stack and the equivalent birefringent film verifies the theoretical analysis. The detailed theoretical study and numerical comparison provide a physical insight and design guidelines for dual-layer ultrathin film based optical devices. (paper)

A bio-behavioral model of addiction treatment: applying dual representation theory to craving management and relapse prevention.

Science.gov (United States)

Matto, Holly

2005-01-01

A bio-behavioral approach to drug addiction treatment is outlined. The presented treatment model uses dual representation theory as a guiding framework for understanding the bio-behavioral processes activated during the application of expressive therapeutic methods. Specifically, the treatment model explains how visual processing techniques can supplement traditional relapse prevention therapy protocols, to help clients better manage cravings and control triggers in hard-to-treat populations such as chronic substance-dependent persons.

Dual blockade of HER2 in HER2-overexpressing tumor cells does not completely eliminate HER3 function.

Science.gov (United States)

Garrett, Joan T; Sutton, Cammie R; Kuba, María Gabriela; Cook, Rebecca S; Arteaga, Carlos L

2013-02-01

Dual blockade of HER2 with trastuzumab and lapatinib or with pertuzumab is a superior treatment approach compared with single-agent HER2 inhibitors. However, many HER2-overexpressing breast cancers still escape from this combinatorial approach. Inhibition of HER2 and downstream phosphoinositide 3-kinase (PI3K)/AKT causes a transcriptional and posttranslational upregulation of HER3 which, in turn, counteracts the antitumor action of the HER2-directed therapies. We hypothesized that suppression of HER3 would synergize with dual blockade of HER2 in breast cancer cells sensitive and refractory to HER2 antagonists. Inhibition of HER2/HER3 in HER2(+) breast cancer cell lines was evaluated by Western blotting. We analyzed drug-induced apoptosis and two- and three-dimensional growth in vitro. Growth inhibition of PI3K was examined in vivo in xenografts treated with combinations of trastuzumab, lapatinib, and the HER3-neutralizing monoclonal antibody U3-1287. Treatment with U3-1287 blocked the upregulation of total and phosphorylated HER3 that followed treatment with lapatinib and trastuzumab and, in turn, enhanced the antitumor action of the combination against trastuzumab-sensitive and -resistant cells. Mice bearing HER2(+) xenografts treated with lapatinib, trastuzumab, and U3-1287 exhibited fewer recurrences and better survival than mice treated with lapatinib and trastuzumab. Dual blockade of HER2 with trastuzumab and lapatinib does not eliminate the compensatory upregulation of HER3. Therapeutic inhibitors of HER3 should be considered as part of multidrug combinations aimed at completely and rapidly disabling the HER2 network in HER2-overexpressing breast cancers.

Dual-modality single particle orientation and rotational tracking of intracellular transport of nanocargos.

Science.gov (United States)

Sun, Wei; Gu, Yan; Wang, Gufeng; Fang, Ning

2012-01-17

The single particle orientation and rotational tracking (SPORT) technique was introduced recently to follow the rotational motion of plasmonic gold nanorod under a differential interference contrast (DIC) microscope. In biological studies, however, cellular activities usually involve a multiplicity of molecules; thus, tracking the motion of a single molecule/object is insufficient. Fluorescence-based techniques have long been used to follow the spatial and temporal distributions of biomolecules of interest thanks to the availability of multiplexing fluorescent probes. To know the type and number of molecules and the timing of their involvement in a biological process under investigation by SPORT, we constructed a dual-modality DIC/fluorescence microscope to simultaneously image fluorescently tagged biomolecules and plasmonic nanoprobes in living cells. With the dual-modality SPORT technique, the microtubule-based intracellular transport can be unambiguously identified while the dynamic orientation of nanometer-sized cargos can be monitored at video rate. Furthermore, the active transport on the microtubule can be easily separated from the diffusion before the nanocargo docks on the microtubule or after it undocks from the microtubule. The potential of dual-modality SPORT is demonstrated for shedding new light on unresolved questions in intracellular transport.

Dual recycling for GEO 600

International Nuclear Information System (INIS)

Grote, H; Freise, A; Malec, M; Heinzel, G; Willke, B; Lueck, H; Strain, K A; Hough, J; Danzmann, K

2004-01-01

Dual recycling is the combination of signal recycling and power recycling; both optical techniques improve the shot-noise-limited sensitivity of interferometric gravitational-wave detectors. In addition, signal recycling can reduce the loss of light power due to imperfect interference and allows us, in principle, to beat the standard quantum limit. The interferometric gravitational-wave detector GEO 600 is the first of the kilometre-scale detectors to use signal recycling. We have recently equipped the detector with a signal-recycling mirror with a transmittance of 1%. In this paper, we present details of the detector commissioning and the first locks of the dual-recycled interferometer

Dual-source dual-energy CT angiography with virtual non-enhanced images and iodine map for active gastrointestinal bleeding: Image quality, radiation dose and diagnostic performance

International Nuclear Information System (INIS)

Sun, Hao; Hou, Xin-Yi; Xue, Hua-Dan; Li, Xiao-Guang; Jin, Zheng-Yu; Qian, Jia-Ming; Yu, Jian-Chun; Zhu, Hua-Dong

2015-01-01

Highlights: • GIB is a common gastrointestinal emergency with a high mortality rate. • Detection and localization of GIB source are important for imaging modality. • DSDECTA using a dual-phase scan protocol is clinically feasible. • DSDECTA with VNE and iodine map images can diagnose the active GIB source accurately. • DSDECTA can reduce radiation dose compared with conventional CT examination in GIB. - Abstract: Objectives: To evaluate the clinical feasibility of dual-source dual-energy CT angiography (DSDECTA) with virtual non-enhanced images and iodine map for active gastrointestinal bleeding (GIB). Methods: From June 2010 to December 2012, 112 consecutive patients with clinical signs of active GIB underwent DSDECTA with true non-enhanced (TNE), arterial phase with single-source mode, and portal-venous phase with dual-energy mode (100 kVp/230 mAs and Sn 140 kVp/178 mAs). Virtual non-enhanced CT (VNE) image sets and iodine map were reformatted from ‘Liver VNC’ software. The mean CT number, noise, signal to noise ratio (SNR), image quality and radiation dose were compared between TNE and VNE image sets. Two radiologists, blinded to clinical data, interpreted images from DSDECTA with TNE (protocol 1), and DSDECTA with VNE and iodine map (protocol 2) respectively, with discordant interpretation resolved by consensus. The standards of reference included digital subtraction angiography, endoscopy, surgery, or final pathology reports. Receiver–operating characteristic (ROC) analysis was undertaken and the area under the curve (AUC) calculated for CT protocols 1 and 2, respectively. Results: There was no significant difference in mean CT numbers of all organs (including liver, pancreas, spleen, kidney, abdominal aorta, and psoas muscle) (P > 0.05). Lower noise and higher SNR were found on VNE images than TNE images (P < 0.05). Image quality of VNE was lower than that of TNE without significant difference (P > 0.05). The active GIB source was identified

Dual-source dual-energy CT angiography with virtual non-enhanced images and iodine map for active gastrointestinal bleeding: Image quality, radiation dose and diagnostic performance

Energy Technology Data Exchange (ETDEWEB)

Sun, Hao, E-mail: sunhao_robert@126.com [Department of Radiology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Shuaifuyuan No. 1, Wangfujing Street, Dongcheng District, Beijing 100730 (China); Hou, Xin-Yi, E-mail: hxy_pumc@126.com [Department of Radiology, Beijing Tiantan Hospital, Capital Medical University, Beijing (China); Xue, Hua-Dan, E-mail: bjdanna95@hotmail.com [Department of Radiology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Shuaifuyuan No. 1, Wangfujing Street, Dongcheng District, Beijing 100730 (China); Li, Xiao-Guang, E-mail: xglee88@126.com [Department of Radiology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Shuaifuyuan No. 1, Wangfujing Street, Dongcheng District, Beijing 100730 (China); Jin, Zheng-Yu, E-mail: zhengyu_jin@126.com [Department of Radiology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Shuaifuyuan No. 1, Wangfujing Street, Dongcheng District, Beijing 100730 (China); Qian, Jia-Ming, E-mail: qjiaming57@gmail.com [Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing (China); Yu, Jian-Chun, E-mail: yu-jch@163.com [Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing (China); Zhu, Hua-Dong, E-mail: huadongzhu@hotmail.com [Department of Emergency, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing (China)

2015-05-15

Highlights: • GIB is a common gastrointestinal emergency with a high mortality rate. • Detection and localization of GIB source are important for imaging modality. • DSDECTA using a dual-phase scan protocol is clinically feasible. • DSDECTA with VNE and iodine map images can diagnose the active GIB source accurately. • DSDECTA can reduce radiation dose compared with conventional CT examination in GIB. - Abstract: Objectives: To evaluate the clinical feasibility of dual-source dual-energy CT angiography (DSDECTA) with virtual non-enhanced images and iodine map for active gastrointestinal bleeding (GIB). Methods: From June 2010 to December 2012, 112 consecutive patients with clinical signs of active GIB underwent DSDECTA with true non-enhanced (TNE), arterial phase with single-source mode, and portal-venous phase with dual-energy mode (100 kVp/230 mAs and Sn 140 kVp/178 mAs). Virtual non-enhanced CT (VNE) image sets and iodine map were reformatted from ‘Liver VNC’ software. The mean CT number, noise, signal to noise ratio (SNR), image quality and radiation dose were compared between TNE and VNE image sets. Two radiologists, blinded to clinical data, interpreted images from DSDECTA with TNE (protocol 1), and DSDECTA with VNE and iodine map (protocol 2) respectively, with discordant interpretation resolved by consensus. The standards of reference included digital subtraction angiography, endoscopy, surgery, or final pathology reports. Receiver–operating characteristic (ROC) analysis was undertaken and the area under the curve (AUC) calculated for CT protocols 1 and 2, respectively. Results: There was no significant difference in mean CT numbers of all organs (including liver, pancreas, spleen, kidney, abdominal aorta, and psoas muscle) (P > 0.05). Lower noise and higher SNR were found on VNE images than TNE images (P < 0.05). Image quality of VNE was lower than that of TNE without significant difference (P > 0.05). The active GIB source was identified

Discrete radioisotopic relays of a cyclic action

International Nuclear Information System (INIS)

Klempner, K.S.; Vasil'ev, A.G.

1975-01-01

A functional diagram of discrete radioisotopic relay equipment (RRP) with cyclic action was examined. An analysis of its rapid action and reliability under stationary conditions and transition regimes is presented. A structural diagram of radioisotopic relay equipment shows three radiation detectors, a pulse standardizer, an integrator and a power amplifier with a threshold cut-off device. It was established that the basic properties of the RRP - rapid action and reliability - are determined entirely by the counting rate of the average frequency of pulses from the radiation detector, n 0 and n 1 , in the 0 and 1 states (absence of current in the electromagnetic relay winding and activation of the winding of the output relay), capacities N 1 and N 2 of the dual counters, and the frequency of the transition threshold, f, of the generator. Formulas are presented which allow making engineering calculations for determining the optimum RRP parameters. High speed and reliability are shown, which are determined by the production purposes of the relay

Active power filter for harmonic compensation using a digital dual-mode-structure repetitive control approach

DEFF Research Database (Denmark)

Zou, Zhixiang; Wang, Zheng; Cheng, Ming

2012-01-01

This paper presents an digital dual-mode-structure repetitive control approach for the single-phase shunt active power filter (APF), which aims to enhance the tracking ability and eliminate arbitrary order harmonic. The proposed repetitive control scheme blends the characteristics of both odd......-harmonic repetitive control and even-harmonic repetitive control. Moreover, the convergence rate is faster than conventional repetitive controller. Additionally, the parameters have been designed and optimized for the dual-mode structure repetitive control to improve the performance of APF system. Experimental...

Therapeutic enhancement: nursing intervention category for patients diagnosed with Readiness for Therapeutic Regimen Management.

Science.gov (United States)

Kelly, Cynthia W

2008-04-01

To present a new nursing intervention category called therapeutic enhancement. Fewer than half of North Americans follow their physician's recommendations for diet and exercise, even when such are crucial to their health or recovery. It is imperative that nurses consider new ways to promote healthy behaviours. Therapeutic enhancement is intended to provide such a fresh approach. Traditional intervention techniques focusing on education, contracts, social support and more frequent interaction with physicians appear not to be effective when used alone. Successful strategies have been multidisciplinary; and have included interventions by professional nurses who assist patients to understand their disease and the disease process and that helps them to develop disease-management and self-management skills. Therapeutic enhancement incorporates The Stages of Change Theory, Commitment to Health Theory, Motivational Interviewing techniques and instrumentation specifically designed for process evaluation of health-promoting interventions. This is a critical review of approaches that, heretofore, have not been synthesised in a single published article. Based on the commonly used Stages of Change model, therapeutic enhancement is useful for patients who are at the action stage of change. Using therapeutic enhancement as well as therapeutic strategies identified in Stages of Change Theory, such as contingency management, helping relationships, counterconditioning, stimulus control and Motivational Interviewing techniques, nursing professionals can significantly increase the chances of patients moving from action to the maintenance stage of change for a specific health behaviour. Using the nursing intervention category, therapeutic enhancement can increase caregivers' success in helping patients maintain healthy behaviours.

DUAL TIMELIKE NORMAL AND DUAL TIMELIKE SPHERICAL CURVES IN DUAL MINKOWSKI SPACE

OpenAIRE

ÖNDER, Mehmet

2009-01-01

Abstract: In this paper, we give characterizations of dual timelike normal and dual timelike spherical curves in the dual Minkowski 3-space and we show that every dual timelike normal curve is also a dual timelike spherical curve. Keywords: Normal curves, Dual Minkowski 3-Space, Dual Timelike curves. Mathematics Subject Classifications (2000): 53C50, 53C40. DUAL MINKOWSKI UZAYINDA DUAL TIMELIKE NORMAL VE DUAL TIMELIKE KÜRESEL EĞRİLER Özet: Bu çalışmada, dual Minkowski 3-...

Action Search: Learning to Search for Human Activities in Untrimmed Videos

KAUST Repository

Alwassel, Humam

2017-06-13

Traditional approaches for action detection use trimmed data to learn sophisticated action detector models. Although these methods have achieved great success at detecting human actions, we argue that huge information is discarded when ignoring the process, through which this trimmed data is obtained. In this paper, we propose Action Search, a novel approach that mimics the way people annotate activities in video sequences. Using a Recurrent Neural Network, Action Search can efficiently explore a video and determine the time boundaries during which an action occurs. Experiments on the THUMOS14 dataset reveal that our model is not only able to explore the video efficiently but also accurately find human activities, outperforming state-of-the-art methods.

Massive Born--Infeld and Other Dual Pairs

CERN Document Server

Ferrara, S

2015-01-01

We consider massive dual pairs of p-forms and (D-p-1)-forms described by non-linear Lagrangians, where non-linear curvature terms in one theory translate into non-linear mass-like terms in the dual theory. In particular, for D=2p and p even the two non-linear structures coincide when the non-linear massless theory is self-dual. This state of affairs finds a natural realization in the four-dimensional massive N=1 supersymmetric Born-Infeld action, which describes either a massive vector multiplet or a massive linear (tensor) multiplet with a Born-Infeld mass-like term. These systems should play a role for the massive gravitino multiplet obtained from a partial super-Higgs in N=2 Supergravity.

Light-intensity physical activity and cardiometabolic biomarkers in US adolescents.

Directory of Open Access Journals (Sweden)

Valerie Carson

Full Text Available BACKGROUND: The minimal physical activity intensity that would confer health benefits among adolescents is unknown. The purpose of this study was to examine the associations of accelerometer-derived light-intensity (split into low and high physical activity, and moderate- to vigorous-intensity physical activity with cardiometabolic biomarkers in a large population-based sample. METHODS: The study is based on 1,731 adolescents, aged 12-19 years from the 2003/04 and 2005/06 National Health and Nutrition Examination Survey. Low light-intensity activity (100-799 counts/min, high light-intensity activity (800 counts/min to <4 METs and moderate- to vigorous-intensity activity (≥ 4 METs, Freedson age-specific equation were accelerometer-derived. Cardiometabolic biomarkers, including waist circumference, systolic blood pressure, diastolic blood pressure, HDL-cholesterol, and C-reactive protein were measured. Triglycerides, LDL- cholesterol, insulin, glucose, and homeostatic model assessments of β-cell function (HOMA-%B and insulin sensitivity (HOMA-%S were also measured in a fasting sub-sample (n=807. RESULTS: Adjusted for confounders, each additional hour/day of low light-intensity activity was associated with 0.59 (95% CI: 1.18-0.01 mmHG lower diastolic blood pressure. Each additional hour/day of high light-intensity activity was associated with 1.67 (2.94-0.39 mmHG lower diastolic blood pressure and 0.04 (0.001-0.07 mmol/L higher HDL-cholesterol. Each additional hour/day of moderate- to vigorous-intensity activity was associated with 3.54 (5.73-1.35 mmHG lower systolic blood pressure, 5.49 (1.11-9.77% lower waist circumference, 25.87 (6.08-49.34% lower insulin, and 16.18 (4.92-28.53% higher HOMA-%S. CONCLUSIONS: Time spent in low light-intensity physical activity and high light-intensity physical activity had some favorable associations with biomarkers. Consistent with current physical activity recommendations for adolescents, moderate- to

Hamiltonian quantization of self-dual tensor fields and a bosonic Nielsen-Ninomiya theorem

International Nuclear Information System (INIS)

Tang Waikeung

1989-01-01

The quantization of self-dual tensor fields is carried out following the procedure of Batalin and Fradkin. The (anti) self-duality constraints (either fermionic or bosonic) in the action leads to the gravitational anomaly. In the process of gauge fixing, the impossibility of the co-existence of a positive hamiltonian and covariant action is shown. A version of the Nielsen-Ninomiya theorem applies to self-dual tensor fields viz. the lattice version of the theory shows species doubling with zero net chirality. (orig.)

On a gauge theory of the self-dual field and its quantization

International Nuclear Information System (INIS)

Srivastava, P.P.

1990-01-01

A gauge theory of self-dual fields is constructed by adding a Wess-Zumino term to the recently studied formulation based on a second-order scalar field lagrangian carrying with it an auxiliary vector field to take care of the self-duality constraint in a linear fashion. The two versions are quantized using the BRST formulation following the BFV procedure. No violation of microcausality occurs and the action of the ordinary scalar field may not be written as the sum of the actions of the self- and anti-self-dual fields. (orig.)

Dual-specificity phosphatase 3 deficiency or inhibition limits platelet activation and arterial thrombosis.

Science.gov (United States)

Musumeci, Lucia; Kuijpers, Marijke J; Gilio, Karen; Hego, Alexandre; Théâtre, Emilie; Maurissen, Lisbeth; Vandereyken, Maud; Diogo, Catia V; Lecut, Christelle; Guilmain, William; Bobkova, Ekaterina V; Eble, Johannes A; Dahl, Russell; Drion, Pierre; Rascon, Justin; Mostofi, Yalda; Yuan, Hongbin; Sergienko, Eduard; Chung, Thomas D Y; Thiry, Marc; Senis, Yotis; Moutschen, Michel; Mustelin, Tomas; Lancellotti, Patrizio; Heemskerk, Johan W M; Tautz, Lutz; Oury, Cécile; Rahmouni, Souad

2015-02-17

A limitation of current antiplatelet therapies is their inability to separate thrombotic events from bleeding occurrences. A better understanding of the molecular mechanisms leading to platelet activation is important for the development of improved therapies. Recently, protein tyrosine phosphatases have emerged as critical regulators of platelet function. This is the first report implicating the dual-specificity phosphatase 3 (DUSP3) in platelet signaling and thrombosis. This phosphatase is highly expressed in human and mouse platelets. Platelets from DUSP3-deficient mice displayed a selective impairment of aggregation and granule secretion mediated by the collagen receptor glycoprotein VI and the C-type lectin-like receptor 2. DUSP3-deficient mice were more resistant to collagen- and epinephrine-induced thromboembolism compared with wild-type mice and showed severely impaired thrombus formation on ferric chloride-induced carotid artery injury. Intriguingly, bleeding times were not altered in DUSP3-deficient mice. At the molecular level, DUSP3 deficiency impaired Syk tyrosine phosphorylation, subsequently reducing phosphorylation of phospholipase Cγ2 and calcium fluxes. To investigate DUSP3 function in human platelets, a novel small-molecule inhibitor of DUSP3 was developed. This compound specifically inhibited collagen- and C-type lectin-like receptor 2-induced human platelet aggregation, thereby phenocopying the effect of DUSP3 deficiency in murine cells. DUSP3 plays a selective and essential role in collagen- and C-type lectin-like receptor 2-mediated platelet activation and thrombus formation in vivo. Inhibition of DUSP3 may prove therapeutic for arterial thrombosis. This is the first time a protein tyrosine phosphatase, implicated in platelet signaling, has been targeted with a small-molecule drug. © 2014 American Heart Association, Inc.

The underlying mechanism of action for various medicinal properties of Piper betle (betel).

Science.gov (United States)

Haslan, H; Suhaimi, F H; Thent, Zar Chi; Das, S

2015-01-01

Piper betle (betel) plant belongs to the Piperaceae family. Piper. betle is widely known for its potent medicinal properties. Various active compounds are present in Piper. betle such as allylpyrocatechol, hydroxychavicol, piperbetol, ethylpiperbetol, piperol A, piperol B, chavibetol, and alkaloids which account for these beneficial medicinal properties. In the present narrative review, we looked into the various active compounds present in the Piper betle and attempted to understand their underlying mechanism of action. Proper understanding of the molecular biology involving the mechanism of action may help in better drug formulation and provide better therapeutic actions in the field of alternative and complementary medicine.

Towards Responsible Action through Agroecological Education

Directory of Open Access Journals (Sweden)

Geir Lieblein

2007-06-01

Full Text Available In the Agroecology MSc Program in the Nordic Region, conventional training of routine skills and memorizing facts, principles and theories are only two components of the educational activities.We have established a dual learning ladder metaphor to explore the expanded learning process. To establish context and build relevance, student teams begin their studies in agroecology by working with farmers and other key clients in the food system. After exploring the current situation, students can step down the learning ladder to acquire additional needed information and skills. Next they explore the links between theory and application, and we provide a safe space to experiment with putting knowledge into directed action. To help clients plan for a desirable future in farming and food systems, students step up the learning ladder to practice their ability to think creatively about the future, and then to evaluate the expected impacts and potential implications of alternative scenarios. Underlying the learning of skills, principles, and methods for action are the internal values and attitudes that will motivate and drive students in their future work. These include individual learning as a process of practicing, assimilating, connecting, creating, and acting with responsibility. In this paper we describe the educational process used in agroecology, with the dual learning ladder as metaphor for both cognitive learning and personal growth.

Towards Responsible Action through Agroecological Education

Directory of Open Access Journals (Sweden)

Geir Lieblein

Full Text Available In the Agroecology MSc Program in the Nordic Region, conventional training of routine skills and memorizing facts, principles and theories are only two components of the educational activities.We have established a dual learning ladder metaphor to explore the expanded learning process. To establish context and build relevance, student teams begin their studies in agroecology by working with farmers and other key clients in the food system. After exploring the current situation, students can step down the learning ladder to acquire additional needed information and skills. Next they explore the links between theory and application, and we provide a safe space to experiment with putting knowledge into directed action. To help clients plan for a desirable future in farming and food systems, students step up the learning ladder to practice their ability to think creatively about the future, and then to evaluate the expected impacts and potential implications of alternative scenarios. Underlying the learning of skills, principles, and methods for action are the internal values and attitudes that will motivate and drive students in their future work. These include individual learning as a process of practicing, assimilating, connecting, creating, and acting with responsibility. In this paper we describe the educational process used in agroecology, with the dual learning ladder as metaphor for both cognitive learning and personal growth.

Block copolymer micelles with a dual-stimuli-responsive core for fast or slow degradation.

Science.gov (United States)

Han, Dehui; Tong, Xia; Zhao, Yue

2012-02-07

We report the design and demonstration of a dual-stimuli-responsive block copolymer (BCP) micelle with increased complexity and control. We have synthesized and studied a new amphiphilic ABA-type triblock copolymer whose hydrophobic middle block contains two types of stimuli-sensitive functionalities regularly and repeatedly positioned in the main chain. Using a two-step click chemistry approach, disulfide and o-nitrobenzyle methyl ester groups are inserted into the main chain, which react to reducing agents and light, respectively. With the end blocks being poly(ethylene oxide), micelles formed by this BCP possess a core that can be disintegrated either rapidly via photocleavage of o-nitrobenzyl methyl esters or slowly through cleavage of disulfide groups by a reducing agent in the micellar solution. This feature makes possible either burst release of an encapsulated hydrophobic species from disintegrated micelles by UV light, or slow release by the action of a reducing agent, or release with combined fast-slow rate profiles using the two stimuli.

Active Affordance Learning in Continuous State and Action Spaces

NARCIS (Netherlands)

Wang, C.; Hindriks, K.V.; Babuska, R.

2014-01-01

Learning object affordances and manipulation skills is essential for developing cognitive service robots. We propose an active affordance learning approach in continuous state and action spaces without manual discretization of states or exploratory motor primitives. During exploration in the action

The Switch from Low-Pressure Sodium to Light Emitting Diodes Does Not Affect Bat Activity at Street Lights.

Directory of Open Access Journals (Sweden)

Elizabeth G Rowse

Full Text Available We used a before-after-control-impact paired design to examine the effects of a switch from low-pressure sodium (LPS to light emitting diode (LED street lights on bat activity at twelve sites across southern England. LED lights produce broad spectrum 'white' light compared to LPS street lights that emit narrow spectrum, orange light. These spectral differences could influence the abundance of insects at street lights and thereby the activity of the bats that prey on them. Most of the bats flying around the LPS lights were aerial-hawking species, and the species composition of bats remained the same after the switch-over to LED. We found that the switch-over from LPS to LED street lights did not affect the activity (number of bat passes, or the proportion of passes containing feeding buzzes, of those bat species typically found in close proximity to street lights in suburban environments in Britain. This is encouraging from a conservation perspective as many existing street lights are being, or have been, switched to LED before the ecological consequences have been assessed. However, lighting of all spectra studied to date generally has a negative impact on several slow-flying bat species, and LED lights are rarely frequented by these 'light-intolerant' bat species.

The Switch from Low-Pressure Sodium to Light Emitting Diodes Does Not Affect Bat Activity at Street Lights

Science.gov (United States)

Rowse, Elizabeth G.; Harris, Stephen; Jones, Gareth

2016-01-01

We used a before-after-control-impact paired design to examine the effects of a switch from low-pressure sodium (LPS) to light emitting diode (LED) street lights on bat activity at twelve sites across southern England. LED lights produce broad spectrum ‘white’ light compared to LPS street lights that emit narrow spectrum, orange light. These spectral differences could influence the abundance of insects at street lights and thereby the activity of the bats that prey on them. Most of the bats flying around the LPS lights were aerial-hawking species, and the species composition of bats remained the same after the switch-over to LED. We found that the switch-over from LPS to LED street lights did not affect the activity (number of bat passes), or the proportion of passes containing feeding buzzes, of those bat species typically found in close proximity to street lights in suburban environments in Britain. This is encouraging from a conservation perspective as many existing street lights are being, or have been, switched to LED before the ecological consequences have been assessed. However, lighting of all spectra studied to date generally has a negative impact on several slow-flying bat species, and LED lights are rarely frequented by these ‘light-intolerant’ bat species. PMID:27008274

Dyon Condensation and Dual Superconductivity in Abelian Higgs Model of QCD

Directory of Open Access Journals (Sweden)

B. S. Rajput

2010-01-01

Full Text Available Constructing the effective action for dyonic field in Abelian projection of QCD, it has been demonstrated that any charge (electrical or magnetic of dyon screens its own direct potential to which it minimally couples and antiscreens the dual potential leading to dual superconductivity in accordance with generalized Meissner effect. Taking the Abelian projection of QCD, an Abelian Higgs model, incorporating dual superconductivity and confinement, has been constructed and its representation has been obtained in terms of average of Wilson loop.

Naturally Occurring Anthraquinones: Chemistry and Therapeutic Potential in Autoimmune Diabetes

Directory of Open Access Journals (Sweden)

Shih-Chang Chien

2015-01-01

Full Text Available Anthraquinones are a class of aromatic compounds with a 9,10-dioxoanthracene core. So far, 79 naturally occurring anthraquinones have been identified which include emodin, physcion, cascarin, catenarin, and rhein. A large body of literature has demonstrated that the naturally occurring anthraquinones possess a broad spectrum of bioactivities, such as cathartic, anticancer, anti-inflammatory, antimicrobial, diuretic, vasorelaxing, and phytoestrogen activities, suggesting their possible clinical application in many diseases. Despite the advances that have been made in understanding the chemistry and biology of the anthraquinones in recent years, research into their mechanisms of action and therapeutic potential in autoimmune disorders is still at an early stage. In this paper, we briefly introduce the etiology of autoimmune diabetes, an autoimmune disorder that affects as many as 10 million worldwide, and the role of chemotaxis in autoimmune diabetes. We then outline the chemical structure and biological properties of the naturally occurring anthraquinones and their derivatives with an emphasis on recent findings about their immune regulation. We discuss the structure and activity relationship, mode of action, and therapeutic potential of the anthraquinones in autoimmune diabetes, including a new strategy for the use of the anthraquinones in autoimmune diabetes.

Oleanolic Acid and Its Derivatives: Biological Activities and Therapeutic Potential in Chronic Diseases

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Taiwo Betty Ayeleso

2017-11-01

Full Text Available The increasing demand for natural products as an alternative therapy for chronic diseases has encouraged research into the pharmacological importance of bioactive compounds from plants. Recently, there has been a surge of interest in the therapeutic potential of oleanolic acid (OA in the prevention and management of chronic diseases. Oleanolic acid is a pentacyclic triterpenoid widely found in plants, including fruits and vegetables with different techniques and chromatography platforms being employed in its extraction and isolation. Several studies have demonstrated the potential therapeutic effects of OA on different diseases and their symptoms. Furthermore, oleanolic acid also serves as a framework for the development of novel semi-synthetic triterpenoids that could prove vital in finding therapeutic modalities for various ailments. There are recent advances in the design and synthesis of chemical derivatives of OA to enhance its solubility, bioavailability and potency. Some of these derivatives have also been therapeutic candidates in a number of clinical trials. This review consolidates and expands on recent reports on the biological effects of oleanolic acid from different plant sources and its synthetic derivatives as well as their mechanisms of action in in vitro and in vivo study models. This review suggests that oleanolic acid and its derivatives are important candidates in the search for alternative therapy in the treatment and management of chronic diseases.

Nonlinear Gain Saturation in Active Slow Light Photonic Crystal Waveguides

DEFF Research Database (Denmark)

Chen, Yaohui; Mørk, Jesper

2013-01-01

We present a quantitative three-dimensional analysis of slow-light enhanced traveling wave amplification in an active semiconductor photonic crystal waveguides. The impact of slow-light propagation on the nonlinear gain saturation of the device is investigated.......We present a quantitative three-dimensional analysis of slow-light enhanced traveling wave amplification in an active semiconductor photonic crystal waveguides. The impact of slow-light propagation on the nonlinear gain saturation of the device is investigated....

On the scalar curvature of self-dual manifolds

International Nuclear Information System (INIS)

Kim, J.

1992-08-01

We generalize LeBrun's explicit ''hyperbolic ansatz'' construction of self-dual metrics on connected sums of conformally flat manifolds and CP 2 's through a systematic use of the theory of hyperbolic geometry and Kleinian groups. (This construction produces, for example, all self-dual manifolds with semi-free S 1 -action and with either nonnegative scalar curvature or positive-definite intersection form.) We then point out a simple criterion for determining the sign of the scalar curvature of these conformal metrics. Exploiting this, we then show that the sign of the scalar curvature can change on connected components of the moduli space of self-dual metrics, thereby answering a question raised by King and Kotschick. (author). Refs

Neuropharmacology of light-induced locomotor activation.

Science.gov (United States)

Amato, Davide; Pum, Martin E; Groos, Dominik; Lauber, Andrea C; Huston, Joseph P; Carey, Robert J; de Souza Silva, Maria A; Müller, Christian P

2015-08-01

Presentation of non-aversive light stimuli for several seconds was found to reliably induce locomotor activation and exploratory-like activity. Light-induced locomotor activity (LIA) can be considered a convenient simple model to study sensory-motor activation. LIA was previously shown to coincide with serotonergic and dopaminergic activation in specific cortical areas in freely moving and anesthetized animals. In the present study we explore the neuropharmacology of LIA using a receptor antagonist/agonist approach in rats. The non-selective 5-HT2-receptor antagonist ritanserin (1.5-6 mg/kg, i.p.) dose-dependently reduced LIA. Selective antagonism of either the 5-HT2A-receptor by MDL 11,939 (0.1-0.4 mg/kg, i.p.), or the 5-HT2C-receptor by SDZ SER 082 (0.125-0.5 mg/kg, i.p.), alone or in combination, had no significant influence on LIA. Also the selective 5-HT1A-receptor antagonist, WAY 100635 (0.4 mg/kg, i.p.) did not affect LIA. Neither did the preferential dopamine D2-receptor antagonist, haloperidol (0.025-0.1 mg/kg, i.p.) nor the D2/D3-receptor agonist, quinpirole (0.025-0.5 mg/kg, i.p.) affect the expression of LIA. However, blocking the glutamatergic NMDA-receptor with phencyclidine (PCP, 1.5-6 mg/kg, i.p.) dose-dependently reduced LIA. This effect was also observed with ketamine (10 mg/kg, i.p.). These findings suggest that serotonin and dopamine receptors abundantly expressed in the cortex do not mediate light-stimulus triggered locomotor activity. PCP and ketamine effects, however, suggest an important role of NMDA receptors in LIA. Copyright © 2015 Elsevier Ltd. All rights reserved.

Photosensitized herbicidal action

Energy Technology Data Exchange (ETDEWEB)

Zweig, A; Nachtigall, G W [American Cyanamid Co., Stamford, Conn.

1975-12-01

The herbicidal action produced by the colorless hydrocarbon fluoranthene sprayed on the leaves of growing plants did not occur when uv radiation was removed from the light to which the plants are exposed. If the uv component of the light under which the plants were grown was augmented, the herbicidal effect of fluoranthene was increased. The mechanism of this photodynamic action is discussed.

Cancer gene profiling in non-small cell lung cancers reveals activating mutations in JAK2 and JAK3 with therapeutic implications

Directory of Open Access Journals (Sweden)

Shuyu D. Li

2017-10-01

Full Text Available Abstract Background Next-generation sequencing (NGS of cancer gene panels are widely applied to enable personalized cancer therapy and to identify novel oncogenic mutations. Methods We performed targeted NGS on 932 clinical cases of non-small-cell lung cancers (NSCLCs using the Ion AmpliSeq™ Cancer Hotspot panel v2 assay. Results Actionable mutations were identified in 65% of the cases with available targeted therapeutic options, including 26% of the patients with mutations in National Comprehensive Cancer Network (NCCN guideline genes. Most notably, we discovered JAK2 p.V617F somatic mutation, a hallmark of myeloproliferative neoplasms, in 1% (9/932 of the NSCLCs. Analysis of cancer cell line pharmacogenomic data showed that a high level of JAK2 expression in a panel of NSCLC cell lines is correlated with increased sensitivity to a selective JAK2 inhibitor. Further analysis of TCGA genomic data revealed JAK2 gain or loss due to genetic alterations in NSCLC clinical samples are associated with significantly elevated or reduced PD-L1 expression, suggesting that the activating JAK2 p.V617F mutation could confer sensitivity to both JAK inhibitors and anti-PD1 immunotherapy. We also detected JAK3 germline activating mutations in 6.7% (62/932 of the patients who may benefit from anti-PD1 treatment, in light of recent findings that JAK3 mutations upregulate PD-L1 expression. Conclusion Taken together, this study demonstrated the clinical utility of targeted NGS with a focused hotspot cancer gene panel in NSCLCs and identified activating mutations in JAK2 and JAK3 with clinical implications inferred through integrative analysis of cancer genetic, genomic, and pharmacogenomic data. The potential of JAK2 and JAK3 mutations as response markers for the targeted therapy against JAK kinases or anti-PD1 immunotherapy warrants further investigation.

Preparing Students for (Inter-)Action with Activity Theory

DEFF Research Database (Denmark)

Bødker, Susanne; Klokmose, Clemens Nylandsted

2012-01-01

In this paper we explore recent developments in activity theoretical HCI with the purpose of preparing designers for action. The paper discusses two projects where students engaged in iterative design applying fundamental principles from Activity Theory. They had been introduced to these principles...

Phenformin-Induced Mitochondrial Dysfunction Sensitizes Hepatocellular Carcinoma for Dual Inhibition of mTOR.

Science.gov (United States)

Veiga, Sonia Rosa; Ge, Xuemei; Mercer, Carol A; Hernández-Alvarez, María Isabel; Thomas, Hala Elnakat; Hernández-Losa, Javier; Ramón Y Cajal, Santiago; Zorzano, Antonio; Thomas, George; Kozma, Sara C

2018-04-24

Hepatocellular carcinoma (HCC) ranks second in cancer mortality and has limited therapeutic options. We recently described the synergistic effect of allosteric and ATP-site competitive inhibitors against the mammalian target of rapamycin (mTOR) for the treatment of HCC. However, such inhibitors induce glycemia and increase mitochondrial efficiency. Here we determined whether the mitochondrial complex I inhibitor Phenformin could reverse both side effects, impose an energetic-stress on cancer cells and suppress the growth of HCC. Human HCC cell lines were used in vitro to access the signaling and energetic impact of mTOR inhibitors and Phenformin, either alone or in combination. Next, the therapeutic utility of these drugs alone or in combination was investigated pre-clinically in human orthotopic tumors implanted in mice, by analyzing their impact on the tumor burden and overall survival. We found Phenformin caused mitochondrial dysfunction and fragmentation, inducing a compensatory shift to glycolysis. In contrast, dual inhibition of mTOR impaired cell growth and glycolysis, while increasing mitochondrial fusion and efficiency. In a mouse model of human HCC, dual inhibition of mTOR, together with Phenformin, was highly efficacious in controlling tumor burden. However, more striking, pretreatment with Phenformin sensitized tumors to dual inhibition of mTOR, leading to a dramatic improvement in survival. Treatment of HCC cells in vitro with the biguanide Phenformin causes a metabolic shift to glycolysis, mitochondrial dysfunction and fragmentation, and dramatically sensitizes orthotopic liver tumors to dual inhibition of mTOR. We therefore propose this therapeutic approach should be tested clinically in HCC. Copyright ©2018, American Association for Cancer Research.

Fabrication of TiO{sub 2}/Ag{sub 2}O heterostructure with enhanced photocatalytic and antibacterial activities under visible light irradiation

Energy Technology Data Exchange (ETDEWEB)

Liu, Bingkun, E-mail: liubk2015@zzuli.edu.cn [School of Material and Chemical Engineering, Zhengzhou University of Light Industry, Zhengzhou 450002 (China); Mu, Lilong; Han, Bing [School of Material and Chemical Engineering, Zhengzhou University of Light Industry, Zhengzhou 450002 (China); Zhang, Jingtao [School of Food and Bioengineering, Zhengzhou University of Light Industry, Zhengzhou 450002 (China); Shi, Hengzhen, E-mail: shihz@zzuli.edu.cn [School of Material and Chemical Engineering, Zhengzhou University of Light Industry, Zhengzhou 450002 (China)

2017-02-28

Highlights: • TiO{sub 2}/Ag{sub 2}O composite photocatalyst was synthesized successfully. • The composites show better photocatalytic activity for MB under visible light. • The composites also possess good antibacterial properties. • The mechanism of enhanced photocatalytic activities was investigated. - Abstract: TiO{sub 2}/Ag{sub 2}O heterostructure prepared by a facile in situ precipitation route was used as an effective visible light-driven photocatalyst for degradation of methylene blue (MB) and inactivation of E. coli. X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), field emission scanning electron microscopy (FESEM) and transmission electron microscopy (TEM) revealed that Ag{sub 2}O nanoparticles were well distributed on the surface of TiO{sub 2} microspheres. The TiO{sub 2}/Ag{sub 2}O composite with optimal mass ratio of TiO{sub 2} and Ag{sub 2}O displayed extremely good photodegradation ability and antibacterial capability under visible light irradiation, which was mainly ascribed to the synergistic effect between Ag{sub 2}O and TiO{sub 2,} including highly dispersed smaller Ag{sub 2}O particles, increased visible light absorption and efficient separation of photo-induced charge carriers. Meanwhile, the roles of the radical species in the photocatalysis process were investigated. Our results showed that the TiO{sub 2}/Ag{sub 2}O could be used as a dual functional material in water treatment of removing the organic pollutant and killing the bacterium at the same time.

Improvement of water and light availability after thinning at a xeric site: which matters more? A dual isotope approach.

Science.gov (United States)

Giuggiola, Arnaud; Ogée, Jérôme; Rigling, Andreas; Gessler, Arthur; Bugmann, Harald; Treydte, Kerstin

2016-04-01

Thinning fosters individual tree growth by increasing the availability of water, light and nutrients. At sites where water rather than light is limiting, thinning also enhances soil evaporation and might not be beneficial. Detailed knowledge of the short- to long-term physiological response underlying the growth responses to thinning is crucial for the management of forests already suffering from recurrent drought-induced dieback. We applied a dual isotope approach together with mechanistic isotope models to study the physiological processes underlying long-term growth enhancement of heavily thinned Pinus sylvestris in a xeric forest in Switzerland. This approach allowed us to identify and disentangle thinning-induced changes in stomatal conductance and assimilation rate. At our xeric study site, the increase in stomatal conductance far outweighed the increase in assimilation, implying that growth release in heavily thinned trees is primarily driven by enhanced water availability rather than increased light availability. We conclude that in forests with relatively isohydric species (drought avoiders) that are growing close to their physiological limits, thinning is recommended to maintain a less negative water balance and thus foster tree growth, and ultimately the survival of forest trees under drought. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

Glycoengineering of therapeutic antibodies enhances monocyte/macrophage-mediated phagocytosis and cytotoxicity.

Science.gov (United States)

Herter, Sylvia; Birk, Martina C; Klein, Christian; Gerdes, Christian; Umana, Pablo; Bacac, Marina

2014-03-01

Therapeutic Abs possess several clinically relevant mechanisms of action including perturbation of tumor cell signaling, activation of complement-dependent cytotoxicity, Ab-dependent cellular cytotoxicity (ADCC), Ab-dependent cellular phagocytosis (ADCP), and induction of adaptive immunity. In view of the important role of phagocytic lineage cells in the mechanism of action of therapeutic Abs, we analyzed FcγR receptor-dependent effector functions of monocytes and macrophages triggered by glycoengineered (GE) Abs (having enhanced FcγRIIIa [CD16a] binding affinity) versus their wild-type (WT) counterparts under different experimental conditions. We first defined the precise FcγR repertoire on classical and nonclassical intermediate monocytes--M1 and M2c macrophage populations. We further show that WT and GE Abs display comparable binding and induce similar effector functions (ADCC and ADCP) in the absence of nonspecific, endogenous IgGs. However, in the presence of these IgGs (i.e., in a situation that more closely mimics physiologic conditions), GE Abs display significantly superior binding and promote stronger monocyte and macrophage activity. These data show that in addition to enhancing CD16a-dependent NK cell cytotoxicity, glycoengineering also enhances monocyte and macrophage phagocytic and cytotoxic activities through enhanced binding to CD16a under conditions that more closely resemble the physiologic setting.

The Explicit Determinations Of Dual Plane Curves And Dual Helices In Terms Of Its Dual Curvature And Dual Torsion

OpenAIRE

Lee Jae Won; Choi Jin Ho; Jin Dae Ho

2014-01-01

In this paper, we give the explicit determinations of dual plane curves, general dual helices and dual slant helices in terms of its dual curvature and dual torsion as a fundamental theory of dual curves in a dual 3-space

Vortex dynamics in self-dual Chern-Simons-Higgs systems

International Nuclear Information System (INIS)

Kim, Y.; Lee, K.

1994-01-01

We consider vortex dynamics in self-dual Chern-Simons-Higgs systems. We show that the naive Aharonov-Bohm phase is the inverse of the statistical phase expected from the vortex spin, and that the self-dual configurations of vortices are degenerate in energy but not in angular momentum. We also use the path integral formalism to derive the dual formulation of Chern-Simons-Higgs systems in which vortices appear as charged particles. We argue that in addition to the electromagnetic interaction, there is an additional interaction between vortices, the so-called Magnus force, and that these forces can be put together into a single ''dual electromagnetic'' interaction. This dual electromagnetic interaction leads to the right statistical phase. We also derive and study the effective action for slowly moving vortices, which contains terms both linear and quadratic in the vortex velocity. We show that vortices can be bounded to each other by the Magnus force

Analysis and Design of a Wireless Power Transfer System with Dual Active Bridges

Directory of Open Access Journals (Sweden)

Xin Liu

2017-10-01

Full Text Available Nowadays, work on Wireless Power Transfer (WPT systems with dual active bridges is attracting great attention due to their low conduction losses, power regulation, load transformation and reactance compensation. However, in these studies limitations such as overall analysis, design and realization techniques of the system were not considered properly. To address the aforementioned issues, this paper presents a detailed analysis, design and realization of a Series-Series (SS WPT system with dual active bridges, which will improve the overall performance. Three independent Phase Angles (PAs have been analyzed and designed in this study, one PA on the primary side and the other two PAs on the secondary side. This Multiple Degrees of Phase Control (MDPC method can achieve additional reactance compensation, load transformation and output regulation simultaneously. To realize the proposed method in practice, key implementation techniques have been investigated in detail, including additional reactance estimation, mutual inductance estimation, phase detection and synchronization. The feasibility and effectiveness of the proposed system is verified through simulation and experimental results.

Therapeutic Potential of Non-Psychotropic Cannabidiol in Ischemic Stroke

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Michihiro Fujiwara

2010-07-01

Full Text Available Cannabis contains the psychoactive component delta9-tetrahydrocannabinol (delta9-THC, and the non-psychoactive components cannabidiol (CBD, cannabinol, and cannabigerol. It is well-known that delta9-THC and other cannabinoid CB1 receptor agonists are neuroprotective during global and focal ischemic injury. Additionally, delta9-THC also mediates psychological effects through the activation of the CB1 receptor in the central nervous system. In addition to the CB1 receptor agonists, cannabis also contains therapeutically active components which are CB1 receptor independent. Of the CB1 receptor-independent cannabis, the most important is CBD. In the past five years, an increasing number of publications have focused on the discovery of the anti-inflammatory, anti-oxidant, and neuroprotective effects of CBD. In particular, CBD exerts positive pharmacological effects in ischemic stroke and other chronic diseases, including Parkinson’s disease, Alzheimer’s disease, and rheumatoid arthritis. The cerebroprotective action of CBD is CB1 receptor-independent, long-lasting, and has potent anti-oxidant activity. Importantly, CBD use does not lead to tolerance. In this review, we will discuss the therapeutic possibility of CBD as a cerebroprotective agent, highlighting recent pharmacological advances, novel mechanisms, and therapeutic time window of CBD in ischemic stroke.

Enantioselective Construction of 3-Hydroxypiperidine Scaffolds by Sequential Action of Light and Rhodium upon N-Allylglyoxylamides.

Science.gov (United States)

Ishida, Naoki; Nečas, David; Masuda, Yusuke; Murakami, Masahiro

2015-06-15

3-Hydroxypiperidine scaffolds were enantioselectively constructed in an atom-economical way by sequential action of light and rhodium upon N-allylglyoxylamides. In a formal sense, the allylic C-H bond was selectively cleaved and enantioselectively added across the ketonic carbonyl group with migration of the double bond (carbonyl-ene-type reaction). © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dual lattice representations for O(N and CP(N−1 models with a chemical potential

Directory of Open Access Journals (Sweden)

Falk Bruckmann

2015-10-01

Full Text Available We derive dual representations for O(N and CP(N−1 models on the lattice. In terms of the dual variables the partition sums have only real and positive contributions also at finite chemical potential. Thus the complex action problem of the conventional formulation is overcome and using the dual variables Monte Carlo simulations are possible at arbitrary chemical potential.

Wilsonian effective action of superstring theory

Energy Technology Data Exchange (ETDEWEB)

Sen, Ashoke [Harish-Chandra Research Institute,Chhatnag Road, Jhusi, Allahabad 211019 (India); Homi Bhabha National Institute,Training School Complex, Anushakti Nagar, Mumbai 400085 (India)

2017-01-25

By integrating out the heavy fields in type II or heterotic string field theory one can construct the effective action for the light fields. This effective theory inherits all the algebraic structures of the parent theory and the effective action automatically satisfies the Batalin-Vilkovisky quantum master equation. This theory is manifestly ultraviolet finite, has only light fields as its explicit degrees of freedom, and the Feynman diagrams of this theory reproduce the exact scattering amplitudes of light states in string theory to any arbitrary order in perturbation theory. Furthermore in this theory the degrees of freedom of light fields above certain energy scale are also implicitly integrated out. This energy scale is determined by a particular parameter labelling a family of equivalent actions, and can be made arbitrarily low, leading to the interpretation of the effective action as the Wilsonian effective action.

Exotic dual of type II double field theory

Directory of Open Access Journals (Sweden)

Eric A. Bergshoeff

2017-04-01

Full Text Available We perform an exotic dualization of the Ramond–Ramond fields in type II double field theory, in which they are encoded in a Majorana–Weyl spinor of O(D,D. Starting from a first-order master action, the dual theory in terms of a tensor–spinor of O(D,D is determined. This tensor–spinor is subject to an exotic version of the (self-duality constraint needed for a democratic formulation. We show that in components, reducing O(D,D to GL(D, one obtains the expected exotically dual theory in terms of mixed Young tableaux fields. To this end, we generalize exotic dualizations to self-dual fields, such as the 4-form in type IIB string theory.

Dual delivery systems based on polyamine analog BENSpm as prodrug and gene delivery vectors

Science.gov (United States)

Zhu, Yu

Combination drug and gene therapy shows promise in cancer treatment. However, the success of such strategy requires careful selection of the therapeutic agents, as well as development of efficient delivery vectors. BENSpm (N 1, N11-bisethylnorspermine), a polyamine analogue targeting the intracellular polyamine pathway, draws our special attention because of the following reasons: (1) polyamine pathway is frequently dysregulated in cancer; (2) BENSpm exhibits multiple functions to interfere with the polyamine pathway, such as to up-regulate polyamine metabolism enzymes and down-regulate polyamine biosynthesis enzymes. Therefore BENSpm depletes all natural polyamines and leads to apoptosis and cell growth inhibition in a wide range of cancers; (3) preclinical studies proved that BENSpm can act synergistically with various chemotherapy agents, making it a promising candidate in combination therapy; (4) multiple positive charges in BENSpm enable it as a suitable building block for cationic polymers, which can be further applied to gene delivery. In this dissertation, our goal was to design dual-function delivery vector based on BENSpm that can function as a gene delivery vector and, after intracellular degradation, as an active anticancer agent targeting dysregulated polyamine metabolism. We first demonstrated strong synergism between BENSpm and a potential therapeutic gene product TRAIL. Strong synergism was obtained in both estrogen-dependent MCF-7 breast cancer cells and triple-negative MDA-MB-231 breast cancer cells. Significant dose reduction of TRAIL in combination with BENSpm in MDA-MB-231 cells, together with the fact that BENSpm rendered MCF-7 cells more sensitive to TRAIL treatment verified our rationale of designing BENSpm-based delivery platform. This was expected to be beneficial for overcoming drug resistance in chemotherapy, as well as boosting the therapeutic effect of therapeutic genes. We first designed a lipid-based BENSpm dual vector (Lipo

Antimicrobial blue light: a drug-free approach for inactivating pathogenic microbes

Science.gov (United States)

Wang, Ying; Dai, Tianhong

2018-02-01

Due to the growing global threat of antibiotic resistance, there is a critical need for the development of alternative therapeutics for infectious diseases. Antimicrobial blue light (aBL), as an innovative non-antibiotic approach, has attracted increasing attention. This paper discussed the basic concepts of aBL and recent findings in the studies of aBL. It is commonly hypothesized that the antimicrobial property of aBL is attributed to the presence of endogenous photosensitizing chromophores in microbial cells, which produce cytotoxic reactive oxygen species upon light irradiation. A wide range of important microbes are found to be susceptible to aBL inactivation. Studies have also shown there exist therapeutic windows where microbes are selectively inactivated by aBL while host cells are preserved. The combination of aBL with some other agents result in synergistically improved antimicrobial efficacy. Future efforts should be exerted on the standardization of study design for evaluating aBL efficacy, further elucidation of the mechanism of action, optimization of the technical parameters, and translation of this technique to clinic.

Activation of dorsolateral prefrontal cortex in a dual neuropsychological screening test: An fMRI approach

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Tachibana Atsumichi

2012-05-01

Full Text Available Abstract Background The Kana Pick-out Test (KPT, which uses Kana or Japanese symbols that represent syllables, requires parallel processing of discrete (pick-out and continuous (reading dual tasks. As a dual task, the KPT is thought to test working memory and executive function, particularly in the prefrontal cortex (PFC, and is widely used in Japan as a clinical screen for dementia. Nevertheless, there has been little neurological investigation into PFC activity during this test. Methods We used functional magnetic resonance imaging (fMRI to evaluate changes in the blood oxygenation level-dependent (BOLD signal in young healthy adults during performance of a computerized KPT dual task (comprised of reading comprehension and picking out vowels and compared it to its single task components (reading or vowel pick-out alone. Results Behavioral performance of the KPT degraded compared to its single task components. Performance of the KPT markedly increased BOLD signal intensity in the PFC, and also activated sensorimotor, parietal association, and visual cortex areas. In conjunction analyses, bilateral BOLD signal in the dorsolateral PFC (Brodmann's areas 45, 46 was present only in the KPT. Conclusions Our results support the central bottleneck theory and suggest that the dorsolateral PFC is an important mediator of neural activity for both short-term storage and executive processes. Quantitative evaluation of the KPT with fMRI in healthy adults is the first step towards understanding the effects of aging or cognitive impairment on KPT performance.

Activation of dorsolateral prefrontal cortex in a dual neuropsychological screening test: an fMRI approach.

Science.gov (United States)

Tachibana, Atsumichi; Noah, J Adam; Bronner, Shaw; Ono, Yumie; Hirano, Yoshiyuki; Niwa, Masami; Watanabe, Kazuko; Onozuka, Minoru

2012-05-28

The Kana Pick-out Test (KPT), which uses Kana or Japanese symbols that represent syllables, requires parallel processing of discrete (pick-out) and continuous (reading) dual tasks. As a dual task, the KPT is thought to test working memory and executive function, particularly in the prefrontal cortex (PFC), and is widely used in Japan as a clinical screen for dementia. Nevertheless, there has been little neurological investigation into PFC activity during this test. We used functional magnetic resonance imaging (fMRI) to evaluate changes in the blood oxygenation level-dependent (BOLD) signal in young healthy adults during performance of a computerized KPT dual task (comprised of reading comprehension and picking out vowels) and compared it to its single task components (reading or vowel pick-out alone). Behavioral performance of the KPT degraded compared to its single task components. Performance of the KPT markedly increased BOLD signal intensity in the PFC, and also activated sensorimotor, parietal association, and visual cortex areas. In conjunction analyses, bilateral BOLD signal in the dorsolateral PFC (Brodmann's areas 45, 46) was present only in the KPT. Our results support the central bottleneck theory and suggest that the dorsolateral PFC is an important mediator of neural activity for both short-term storage and executive processes. Quantitative evaluation of the KPT with fMRI in healthy adults is the first step towards understanding the effects of aging or cognitive impairment on KPT performance.

The forgotten Elements of Action Learning

DEFF Research Database (Denmark)

Nunez, Heilyn Camacho; Aguirre, María

reflections. Through his work Revans was claiming several times that action learning goes further than other training methods and that its central ideas had been misunderstood. (Revans, 1982, p.531) He was claiming the need to develop the whole person in all its dimensions. From this perspective the Alpha...... system of action learning, where you explore your values, should not be taken as a light activity. It is the essence of action learning, where the person can explore all the significant aspects of his complete development which includes these moral, ethical and spiritual aspects.......The aim of this article is to provide a discussion and description of some topics of action learning that are not so commonly discussed in the literature and that I have called ‘the forgotten elements of action learning’. Those elements are dealing with Revans’ moral, spiritual and ethical...

Antidiarrheal and Antispasmodic Activities of Buddleja polystachya are Mediated Through Dual Inhibition of Ca(++) Influx and Phosphodiesterase Enzyme.

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Rehman, Najeeb-ur; Gilani, Anwarul-Hassan; Khan, Aslam; Nazneen, Maryam; El Gamal, Ali A; Fawzy, Ghada A; Al-Ati, Hanan Y; Abdel-kader, Maged S

2015-08-01

This study describes the antidiarrheal and antispasmodic activities of the hydro-alcoholic extract of Buddleja polystachya (Bp.Cr) with possible mode of action explored along with activity-directed fractionation. Bp.Cr and its aqueous (Bp.Aq) and organic fractions, petroleum ether (Bp.Pet), dichloromethane (Bp.DCM), ethylacetate (Bp.EtAc) and butanol (Bp.But), were tested using the in-vivo and in-vitro assays. The crude extract (100-300 mg/kg) showed 20 and 60% protection of castor oil-induced diarrhea in mice. In isolated rabbit jejunum, Bp.Cr like papaverine inhibited spontaneous and high K(+) (80 mM)-induced contractions equi-potently. In guinea-pig ileum, Bp.Cr showed a moderate spasmogenic effect. The activity-directed fractionation revealed that the spasmolytic activity was concentrated in the organic fractions and spasmogenic component in the aqueous fraction. Amongst the organic fractions, BP.DCM and Bp.Pet inhibited spontaneous and high K(+) -induced contractions equi-potently, while Bp.But, like verapamil was more potent against high K(+) . The crude extract and its organic fractions caused rightward shift in the Ca(++) -concentration response curves (CRCs), similar to verapamil, and all except Bp.But potentiated the isoprenaline-inhibitory CRCs to the left, similar to papaverine. The results of this study indicate that the crude extract of B. polystachya possesses antidiarrheal and antispasmodic activities, mediated possibly through dual inhibition of Ca(++) influx and phospodiesterase enzyme. Copyright © 2015 John Wiley & Sons, Ltd.

Misinterpreting the therapeutic effects of small interfering RNA caused by immune stimulation.

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Robbins, Marjorie; Judge, Adam; Ambegia, Ellen; Choi, Catherine; Yaworski, Ed; Palmer, Lorne; McClintock, Kevin; MacLachlan, Ian

2008-10-01

Activation of innate immunity has direct effects in modulating viral replication, tumor growth, angiogenesis, and inflammatory and other immunological processes. It is now established that unmodified siRNA can activate this innate immune response and therefore there is real potential for siRNA to elicit nonspecific therapeutic effects in a wide range of disease models. Here we demonstrate that in a murine model of influenza infection, the antiviral activity of siRNA is due primarily to immune stimulation elicited by the active siRNA duplexes and is not the result of therapeutic RNA interference (RNAi) as previously reported. We show that the misinterpretation stems from the use of a particular control green fluorescent protein (GFP) siRNA that we identify as having unusually low immunostimulatory activity compared with the active anti-influenza siRNA. Curiously, this GFP siRNA has served as a negative control for a surprising number of groups reporting therapeutic effects of siRNA. The inert immunologic profile of the GFP sequence was unique among a broad panel of published siRNAs, all of which could elicit significant interferon induction from primary immune cells. This panel included eight active siRNAs against viral, angiogenic, and oncologic targets, the reported therapeutic efficacy of which was based on comparison with the nonimmunostimulatory GFP siRNA. These results emphasize the need for researchers to anticipate, monitor, and adequately control for siRNA-mediated immune stimulation and calls into question the interpretation of numerous published reports of therapeutic RNAi in vivo. The use of chemically modified siRNA with minimal immunostimulatory capacity will help to delineate more accurately the mechanism of action underlying such studies.

Cyclic peptides as potential therapeutic agents for skin disorders.

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Namjoshi, Sarika; Benson, Heather A E

2010-01-01

There is an increasing understanding of the role of peptides in normal skin function and skin disease. With this knowledge, there is significant interest in the application of peptides as therapeutics in skin disease or as cosmeceuticals to enhance skin appearance. In particular, antimicrobial peptides and those involved in inflammatory processes provide options for the development of new therapeutic directions in chronic skin conditions such as psoriasis and dermatitis. To exploit their potential, it is essential that these peptides are delivered to their site of action in active form and in sufficient quantity to provide the desired effect. Many polymers permeate the skin poorly and are vulnerable to enzymatic degradation. Synthesis of cyclic peptide derivatives can substantially alter the physicochemical characteristics of the peptide with the potential to improve its skin permeation. In addition, cyclization can stabilize the peptide structure and thereby increase its stability. This review describes the role of cyclic peptides in the skin, examples of current cyclic peptide therapeutic products, and the potential for cyclic peptides as dermatological therapeutics and cosmeceuticals.

Dual-energy CT in assessing therapeutic response to radiofrequency ablation of renal cell carcinomas

Energy Technology Data Exchange (ETDEWEB)

Park, Sung Yoon; Kim, Chan Kyo, E-mail: chankyokim@skku.edu; Park, Byung Kwan

2014-02-15

Purpose: To investigate the utility of dual-energy (DE) CT using virtual noncontrast (VNC) and iodine overlay (IO) images to assess therapeutic response to radiofrequency ablation (RFA) for renal cell carcinomas (RCCs). Materials and methods: In this institutional review board-approved study (with waiver of informed consent), 47 patients with RCCs that underwent DECT after RFA were enrolled in this study. DECT protocols included true noncontrast (TNC), linearly blended DE corticomedullary and late nephrographic phase imaging. Two types of VNC and IO images were derived from corticomedullary and late nephrographic phases, respectively. To predict local tumor progression at RFA site, linearly blended and IO images were analyzed both qualitatively and quantitatively. Contrast-to-noise ratios (CNR) of renal cortex-to-RFA zones were calculated. The overall imaging quality of VNC images was compared with TNC images. Results: The IO images from corticomedullary and late nephrographic phases showed excellent diagnostic performance (each sensitivity 100% and each specificity 91.5%) for predicting local tumor progression. The degree of enhancement of local tumor progression was not significantly different between linearly blended and IO images (P > 0.05). The mean CT numbers were not significantly different between TNC and VNC images (P > 0.05). In renal cortex-to-RFA site, CNR between linearly blended and IO images was not significantly different (P > 0.05). The VNC imaging quality from the two phases was given a good rating. Conclusion: VNC and IO images from DECT may allow acceptable diagnostic performance with less radiation exposure as a follow-up imaging tool after RFA for RCC, compared to the linearly blended CT images.

Dual-energy CT in assessing therapeutic response to radiofrequency ablation of renal cell carcinomas

International Nuclear Information System (INIS)

Park, Sung Yoon; Kim, Chan Kyo; Park, Byung Kwan

2014-01-01

Purpose: To investigate the utility of dual-energy (DE) CT using virtual noncontrast (VNC) and iodine overlay (IO) images to assess therapeutic response to radiofrequency ablation (RFA) for renal cell carcinomas (RCCs). Materials and methods: In this institutional review board-approved study (with waiver of informed consent), 47 patients with RCCs that underwent DECT after RFA were enrolled in this study. DECT protocols included true noncontrast (TNC), linearly blended DE corticomedullary and late nephrographic phase imaging. Two types of VNC and IO images were derived from corticomedullary and late nephrographic phases, respectively. To predict local tumor progression at RFA site, linearly blended and IO images were analyzed both qualitatively and quantitatively. Contrast-to-noise ratios (CNR) of renal cortex-to-RFA zones were calculated. The overall imaging quality of VNC images was compared with TNC images. Results: The IO images from corticomedullary and late nephrographic phases showed excellent diagnostic performance (each sensitivity 100% and each specificity 91.5%) for predicting local tumor progression. The degree of enhancement of local tumor progression was not significantly different between linearly blended and IO images (P > 0.05). The mean CT numbers were not significantly different between TNC and VNC images (P > 0.05). In renal cortex-to-RFA site, CNR between linearly blended and IO images was not significantly different (P > 0.05). The VNC imaging quality from the two phases was given a good rating. Conclusion: VNC and IO images from DECT may allow acceptable diagnostic performance with less radiation exposure as a follow-up imaging tool after RFA for RCC, compared to the linearly blended CT images

Dual-energy CT in assessing therapeutic response to radiofrequency ablation of renal cell carcinomas.

Science.gov (United States)

Park, Sung Yoon; Kim, Chan Kyo; Park, Byung Kwan

2014-02-01

To investigate the utility of dual-energy (DE) CT using virtual noncontrast (VNC) and iodine overlay (IO) images to assess therapeutic response to radiofrequency ablation (RFA) for renal cell carcinomas (RCCs). In this institutional review board-approved study (with waiver of informed consent), 47 patients with RCCs that underwent DECT after RFA were enrolled in this study. DECT protocols included true noncontrast (TNC), linearly blended DE corticomedullary and late nephrographic phase imaging. Two types of VNC and IO images were derived from corticomedullary and late nephrographic phases, respectively. To predict local tumor progression at RFA site, linearly blended and IO images were analyzed both qualitatively and quantitatively. Contrast-to-noise ratios (CNR) of renal cortex-to-RFA zones were calculated. The overall imaging quality of VNC images was compared with TNC images. The IO images from corticomedullary and late nephrographic phases showed excellent diagnostic performance (each sensitivity 100% and each specificity 91.5%) for predicting local tumor progression. The degree of enhancement of local tumor progression was not significantly different between linearly blended and IO images (P>0.05). The mean CT numbers were not significantly different between TNC and VNC images (P>0.05). In renal cortex-to-RFA site, CNR between linearly blended and IO images was not significantly different (P>0.05). The VNC imaging quality from the two phases was given a good rating. VNC and IO images from DECT may allow acceptable diagnostic performance with less radiation exposure as a follow-up imaging tool after RFA for RCC, compared to the linearly blended CT images. Crown Copyright © 2013. Published by Elsevier Ireland Ltd. All rights reserved.

Supermembrane in D=5: component action

International Nuclear Information System (INIS)

Bellucci, S.; Kozyrev, N.; Krivonos, S.; Yeranyan, A.

2014-01-01

Based on the connection between partial breaking of global supersymmetry, coset approach, which realized the given pattern of supersymmetry breaking, and the Nambu-Goto actions for the extended objects, we have constructed on-shell component action for N=1,D=5 supermembrane and its dual cousins. We demonstrate that the proper choice of the components and the use of the covariant (with respect to broken supersymmetry) derivatives drastically simplify the action: it can be represented as a sum of four terms each having an explicit geometric meaning

Heteroreceptors Modulating CGRP Release at Neurovascular Junction: Potential Therapeutic Implications on Some Vascular-Related Diseases

Directory of Open Access Journals (Sweden)

Abimael González-Hernández

2016-01-01

Full Text Available Calcitonin gene-related peptide (CGRP is a 37-amino-acid neuropeptide belonging to the calcitonin gene peptide superfamily. CGRP is a potent vasodilator with potential therapeutic usefulness for treating vascular-related disease. This peptide is primarily located on C- and Aδ-fibers, which have extensive perivascular presence and a dual sensory-efferent function. Although CGRP has two major isoforms (α-CGRP and β-CGRP, the α-CGRP is the isoform related to vascular actions. Release of CGRP from afferent perivascular nerve terminals has been shown to result in vasodilatation, an effect mediated by at least one receptor (the CGRP receptor. This receptor is an atypical G-protein coupled receptor (GPCR composed of three functional proteins: (i the calcitonin receptor-like receptor (CRLR; a seven-transmembrane protein, (ii the activity-modifying protein type 1 (RAMP1, and (iii a receptor component protein (RCP. Although under physiological conditions, CGRP seems not to play an important role in vascular tone regulation, this peptide has been strongly related as a key player in migraine and other vascular-related disorders (e.g., hypertension and preeclampsia. The present review aims at providing an overview on the role of sensory fibers and CGRP release on the modulation of vascular tone.

The effect of polarized polychromatic noncoherent light (bioptron) therapy on patients with carpal tunnel syndrome.

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Raeissadat, Seyed Ahmad; Rayegani, Seyed Mansoor; Rezaei, Sajad; Sedighipour, Leyla; Bahrami, Mohammad Hasan; Eliaspour, Dariush; Karimzadeh, Afshin

2014-01-01

To study the effects of Polarized Polychromatic Noncoherent Light (Bioptron) therapy on patients with carpal tunnel syndrome (CTS). This study was designed as a randomized clinical trial. Forty four patients with mild or moderate CTS (confirmed by clinical and electrodiagnostic studies) were assigned randomly into two groups (intervention and control goups). At the beginning of the study, both groups received wrist splinting for 8 weeks. Bioptron light was applied for the intervention group (eight sessions, for 3/weeks). Bioptron was applied perpendicularly to the wrist from a 10 centimeter sdistance. Pain severity and electrodiagnostic measurements were compared from before to 8 weeks after initiating each treatment. Eight weeks after starting the treatments, the mean of pain severity based on Visual Analogue Scale (VAS) scores decreased significantly in both groups. Median Sensory Nerve Action Potential (SNAP) latency decreased significantly in both groups. However, other electrophysiological findings (median Compound Motor Action Potential (CMAP) latency and amplitude, also SNAP amplitude) did not change after the therapy in both groups. There was no meaningful difference between two groups regarding the changes in the pain severity. Bioptron with the above mentioned parameters led to therapeutic effects equal to splinting alone in patients with carpal tunnel syndrome. However, applying Bioptron with different therapeutic protocols and light parameters other than used in this study, perhaps longer duration of therapy and long term assessment may reveal different results favoring Bioptron therapy.

d-Lysergic Acid Diethylamide (LSD) as a Model of Psychosis: Mechanism of Action and Pharmacology.

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De Gregorio, Danilo; Comai, Stefano; Posa, Luca; Gobbi, Gabriella

2016-11-23

d-Lysergic Acid Diethylamide (LSD) is known for its hallucinogenic properties and psychotic-like symptoms, especially at high doses. It is indeed used as a pharmacological model of psychosis in preclinical research. The goal of this review was to understand the mechanism of action of psychotic-like effects of LSD. We searched Pubmed, Web of Science, Scopus, Google Scholar and articles' reference lists for preclinical studies regarding the mechanism of action involved in the psychotic-like effects induced by LSD. LSD's mechanism of action is pleiotropic, primarily mediated by the serotonergic system in the Dorsal Raphe, binding the 5-HT 2A receptor as a partial agonist and 5-HT 1A as an agonist. LSD also modulates the Ventral Tegmental Area, at higher doses, by stimulating dopamine D₂, Trace Amine Associate receptor 1 (TAAR₁) and 5-HT 2A . More studies clarifying the mechanism of action of the psychotic-like symptoms or psychosis induced by LSD in humans are needed. LSD's effects are mediated by a pleiotropic mechanism involving serotonergic, dopaminergic, and glutamatergic neurotransmission. Thus, the LSD-induced psychosis is a useful model to test the therapeutic efficacy of potential novel antipsychotic drugs, particularly drugs with dual serotonergic and dopaminergic (DA) mechanism or acting on TAAR₁ receptors.

Dual-window dual-bandwidth spectroscopic optical coherence tomography metric for qualitative scatterer size differentiation in tissues.